bluuebunny/crossref_metadata_2025 huggingface dataset:
Single neurons in thalamus and subthalamic nucleus process cardiac and respiratory signals in humans
Authors: De Falco Emanuela , Solcà Marco , Bernasconi Fosco , Babo-Rebelo Mariana , Young Nicole , Sammartino Francesco , Rezai Ali , Krishna Vibhor , Blanke Olaf
Published: July 2022

Visceral signals are constantly processed by our central nervous system, enable homeostatic regulation, and influence perception, emotion, and cognition. While visceral processes at cortical level have been extensively studied using non-invasive imaging techniques, very few studies have investigated how this information is processed at the single neuron level, both in humans and animals. Subcortical regions, relaying signals from peripheral interoceptors to cortical structures, are particularly understudied and how visceral information is processed in thalamic and subthalamic structures remains largely unknown. Here, we took advantage of intraoperative microelectrode recordings in patients undergoing surgery for deep brain stimulation (DBS) to investigate the activity of single neurons related to cardiac and respiratory functions in three subcortical regions: Ventral Intermedius nucleus (Vim) and Ventral caudalis nucleus (Vc) of the thalamus, and subthalamic nucleus (STN). We report that the activity of a large portion of the recorded neurons (about 70%) was modulated by either the heartbeat, the cardiac inter-beat interval, or the respiration. These cardiac and respiratory response patterns varied largely across neurons both in terms of timing and their kind of modulation. We observed neurons with increases or decreases in firing rate in response to either the heartbeat or the inter-beat interval. Peaks of neural activity were found at different phases of the cardiac and respiratory cycles. Whereas most neurons only responded to one of the tested signals, a substantial proportion of these visceral neurons (30%) was responsive to more than one of the tested signals, underlining specialization and integration of cardiac and respiratory signals in STN and thalamic neurons. By extensively describing for the first time single unit activity related to cardiorespiratory function in thalamic and subthalamic neurons, our results highlight the major role of these subcortical regions in the processing of visceral signals.
Genetic architecture of creativity and extensive genetic overlap with psychiatric disorders revealed from genome-wide association analyses of 241,736 individuals
Authors: Kim Hyejin , Ahn Yeeun , Yoon Joohyun , Jung Kyeongmin , Kim Soyeon , Shim Injeong , Park Tae Hwan , Ko Hyunwoong , Jung Sang-Hyuk , Kim Jaeyoung , Park Sanghyeon , Lee Dong June , Choi Sunho , Cha Soojin , Kim Beomsu , Cho Min Young , Cho Hyunbin , Kim Dan Say , Ihm Hong Kyu , Park Woong-Yang , Bakhshi Hasan , O’Connell Kevin S , Andreassen Ole A , Flint Jonathan , Kendler Kenneth S. , Myung Woojae , Won Hong-Hee
Published: July 2022

Creativity is heritable and exhibits familial aggregation with psychiatric disorders, but its genomic basis and genetic relationship with psychiatric disorders remain largely unknown. Here, we conducted a genome-wide association study (GWAS) using an expanded, machine learning-based definition of creativity in individuals of European ancestry from the UK Biobank (n= 241,736) and identified 25 creativity-associated loci. Extensive genetic overlap with psychiatric disorders, including schizophrenia, major depression, bipolar I disorder, attention deficit/hyperactivity disorder, and anorexia nervosa, was demonstrated by the genetic correlation, polygenic risk score, and MiXeR analyses. The condFDR and conjFDR analyses identified additional loci for creativity and psychiatric disorders, as well as shared genetic loci between creativity and psychiatric disorders. This GWAS showed significant correlations with GWASs using traditional definitions of creativity and GWASs adjusted for educational attainment. Our findings contribute to the understanding of the genetic architecture of creativity and reveal its polygenic relationships with psychiatric disorders.
mTORC1 is required for differentiation of germline stem cells in the Drosophila melanogaster testis
Authors: Clémot Marie , D’Alterio Cecilia , Kwang Alexa , Jones D. Leanne
Published: July 2022

Metabolism participates in the control of stem cell function and subsequent maintenance of tissue homeostasis. How this is achieved in the context of adult stem cell niches in coordination with other local and intrinsic signaling cues is not completely understood. The Target of Rapamycin (TOR) pathway is a master regulator of metabolism and plays essential roles in stem cell maintenance and differentiation. We observe differential expression of the Tor kinase in the Drosophila male germline, which correlates with restriction of mTORC1 activity to germline stem cells (GSCs) and early germ cells. Targeted RNAi-mediated downregulation of Tor in early germ cells causes a block and/or a delay in differentiation, resulting in an accumulation of germ cells with GSC-like features. These early germ cells also contain unusually large and dysfunctional autolysosomes. In addition, downregulation of Tor in adult male GSCs and early germ cells causes non-autonomous activation of mTORC1 in neighboring cyst cells, which correlates with a disruption in the coordination of germline and somatic differentiation. Our study identifies a previously uncharacterized role of the TOR pathway in regulating male germline differentiation.
Measures of epitope binding degeneracy from T cell receptor repertoires
Authors: Mayer Andreas , Callan Curtis G.
Published: July 2022

Adaptive immunity is driven by specific binding of hyper-variable receptors to diverse molecular targets. The sequence diversity of receptors and targets are both individually known but, because multiple receptors can recognize the same target, a measure of the effective ‘functional’ diversity of the human immune system has remained elusive. Here, we show that sequence near-coincidences within T cell receptors that bind specific epitopes provide a new window into this problem, and allow the quantification of how binding probability co-varies with sequence. We find that near-coincidence statistics within epitope-specific repertoires imply a measure of binding degeneracy to amino acid changes in receptor sequence that is consistent across disparate experiments. Paired data on both chains of the heterodimeric receptor are particularly revealing since simultaneous near-coincidences are rare and we show how they can be exploited to estimate the number of epitope responses that created the memory compartment. In addition, we find that paired-chain coincidences are strongly suppressed across donors with different human leukocyte antigens, evidence for a central role of antigen-driven selection in making paired chain receptors public. These results demonstrate the power of coincidence analysis to reveal the sequence determinants of epitope binding in receptor repertoires.
Escherichia coliSPFH membrane microdomain proteins HflKC contribute to aminoglycoside and oxidative stress tolerance
Authors: Wessel Aimee K. , Yoshii Yutaka , Reder Alexander , Boudjemaa Rym , Szczesna Magdalena , Betton Jean-Michel , Bernal-Bayard Joaquin , Beloin Christophe , Lopez Daniel , Völker Uwe , Ghigo Jean-Marc
Published: July 2022

Many eukaryotic membrane-dependent functions are often spatially and temporally regulated by membrane microdomains (FMMs) also known as lipid rafts. These domains are enriched in polyisoprenoid lipids and scaffolding proteins belonging to the Stomatin, Prohibitin, Flotillin, and HflK/C (SPFH) protein superfamily that was also identified in Gram-positive bacteria. By contrast, little is still known about FMMs in Gram-negative bacteria. InEscherichia coliK12, 4 SPFH proteins, YqiK, QmcA, HflK, and HflC, were shown to localize in discrete polar or lateral inner-membrane locations, raising the possibility thatE. coliSPFH proteins could contribute to the assembly of inner-membrane FMMs and the regulation of cellular processes.

Here we studied the determinant of the localization of QmcA and HflC and showed that FMM-associated cardiolipin lipid biosynthesis is required for their native localization pattern. Using Biolog phenotypic arrays, we showed that a mutant lacking all SPFH genes displayed increased sensitivity to aminoglycosides and oxidative stress that is due to the absence of HflKC. Our study therefore provides further insights into the contribution of SPFH proteins to stress tolerance inE. coli.

IMPORTANCE

Eukaryotic cells often segregate physiological processes in cholesterol-rich functional membrane micro-domains. These domains are also called lipid rafts and contain proteins of the Stomatin, Prohibitin, Flotillin, and HflK/C (SPFH) superfamily, which are also present in prokaryotes but were mostly studied in Gram-positive bacteria. Here, we showed that the cell localization of the SPFH proteins QmcA and HflKC in the Gram-negative bacteriaE. coliis altered in absence of cardiolipin lipid synthesis. This suggests that cardiolipins contribute toE. colimembrane microdomain assembly. Using a broad phenotypic analysis, we also showed that HflKC contribute toE. colitolerance to aminoglycosides and oxidative stress. Our study, therefore, provides new insights into the cellular processes associated with SPFH proteins inE. coli.
Reducing environmentally mediated transmission to moderate impacts of an emerging wildlife disease
Authors: Hoyt Joseph R. , Parise Katy L. , DePue John E. , Kaarakka Heather M. , Redell Jennifer A. , Scullon William H. , O’Reskie Rich , Foster Jeffrey T. , Kilpatrick A. Marm , Langwig Kate E. , White J. Paul
Published: July 2022

Emerging infectious diseases are a serious threat to wildlife communities, and the ability of pathogens to survive in the environment can exacerbate disease impacts on hosts and increase the likelihood of species extinction. Targeted removal or control of these environmental reservoirs could provide an effective mitigation strategy for reducing disease impacts but is rarely used in wildlife disease control.

We examined the effectiveness of managing environmental transmission to reduce impacts of an emerging infectious disease of bats, white-nose syndrome. We used a chemical disinfectant, chlorine dioxide (ClO2), to experimentally reducePseudogymnoascus destructans, the fungal pathogen causing WNS, in the environment. We conducted laboratory experiments followed by three years of field trials at four abandoned mines to determine whether ClO2could effectively reduceP. destructansin the environment, reduce host infection, and limit population impacts.

ClO2was effective at killingP. destructans in vitroacross a range of concentrations. In field settings, higher concentrations of ClO2treatment sufficiently reduced viableP. destructansconidia in the environment.

The reduction in the environmental reservoir at treatment sites resulted in lower fungal loads on bats compared to untreated control populations. Survival following treatment was higher in little brown bats (Myotis lucifugus), and trended higher for tricolored bats (Perimyotis subflavus) compared to untreated sites.

These findings support the management of environmental reservoirs as an effective control strategy for wildlife disease and provide a valuable tool for ongoing conservation efforts. More broadly, these results highlight how the intensity of environmental reservoirs can have cascading impacts on host infection and population declines.
Sample pooling inflates error rates in between-sample comparisons: an empirical investigation of the statistical properties of count-based data
Authors: Taylor Megan N. , Vega Nic M.
Published: July 2022

Heterogeneity is ubiquitous across individuals in biological data, and sample batching, a form of biological averaging, inevitably loses information about this heterogeneity. The consequences for inference from biologically averaged data are frequently opaque, particularly when the underlying populations are non-normal. Here we investigate a case where biological averaging is common - count-based measurement of bacterial load in individualCaenorhabditis elegans- to empirically determine the consequences of batching. We find that both central measures and measures of variation on individual-based data contain biologically relevant information that is useful for distinguishing between groups, and that batch-based inference readily produces both false positive and false negative results in these comparisons. These results support the use of individual rather than batched samples when possible, illustrate the importance of understanding distributions across individuals within a sample frame, and indicate the need to consider effect size when drawing conclusions from biologically averaged data.
CEO transformational leadership and firm innovation: the role of strategic flexibility and top management team knowledge diversity
Authors: Yin Kui , Li Can , Sheldon Oliver J. , Zhao Jing
Published: July 2022

Purpose

Drawing upon a dynamic managerial capabilities perspective, this study aims to unpack how and when chief experience officer (CEO) transformational leadership influences firm innovation. Specifically, a moderated mediation model linking CEO transformational leadership to firm innovation, which includes strategic flexibility as a mediator and top management team (TMT) knowledge diversity as a moderator, is theorized and empirically tested.

Design/methodology/approach

The authors conducted a survey of 354 TMT members and 62 CEOs from 62 firms in China’s construction industry to explore these relationships. Path analysis using Mplus 7.4 was undertaken to test our proposed moderated mediation model.

Findings

The results revealed that strategic flexibility mediates the positive relationship between CEO transformational leadership and firm innovation. Additionally, TMT knowledge diversity positively moderates the relationship between CEO transformational leadership and strategic flexibility.

Research limitations/implications

Taken together, these findings help advance and deepen our understanding of the mechanisms through which CEO transformational leadership influences firm innovation and boundary conditions under which CEO transformational leadership influences strategic flexibility. At the same time, this study also contributes to the literature on strategic flexibility and the CEO-TMT interface by revealing the interactive effect of CEO transformational leadership and TMT knowledge diversity on strategic flexibility.

Originality/value

Although the positive influence of CEO transformational leadership on firm innovation has been widely recognized, the specific mechanisms underlying this effect have yet to be fully theorized. This study proposes and tests a nuanced theoretical framework linking CEO transformational leadership to firm innovation via a firm’s strategic flexibility. It also argues that TMT knowledge diversity enhances the indirect effect of CEO transformational leadership on firm innovation through strategic flexibility; that is, this indirect effect is significant when TMT diversity is high, but not when TMT diversity is low.
Social learning and career navigation in the U.S. Military: the personal experiences, observations and socializations of servicewomen
Authors: Erwin Stephanie K.
Published: July 2022

Purpose

This paper aims to explore the interactions of social learning and career navigation and their associated implications for women in military service.

Design/methodology/approach

Social learning theory (Bandura, 1977) exposes and aids in understanding the ability of an organization’s members to reconcile their personal experiences, socialization and observations. Drawn from a larger qualitative study of gender in the US military, this study highlights the US military’s rigorous socialization practices and the reliance on communal memory and social learning including matters pertaining to gender including career navigation.

Findings

Military servicewomen use these processes to learn military culture, acceptable behaviors, institutional norms and organizational realities for career navigation reflective of gender.

Originality/value

This article presents a novel exploration of gender in the military as it pertains to social learning and career progression.
Smart tourism destinations really make sustainable cities: Benidorm as a case study
Authors: Aguirre Alexander , Zayas Antonio , Gómez-Carmona Diego , López Sánchez José Antonio
Published: July 2022

Purpose

Tourism sustainability is a challenge for 21st-century destinations – this paper aims to analyse smart destinations' sustainability through a case study of Benidorm, the first world destination to be certified under the UNE 178501 standard as smart tourism destination (STD).

Design/methodology/approach

The methodological component has been divided into developing a framework for measuring sustainability through economic, social and environmental open data. Moreover, studying the plan's contribution “Benidorm, Destino Turístico Inteligente y Sostenible” to the city's sustainability through a time series analysis.

Findings

The main contribution shows that Benidorm's transformation into an STD leads to more sustainable cities. Thus, the conversion of Benidorm into an STD has a sustained effect in the medium and long term, contributing to the sustainability of the city.

Research limitations/implications

An open question as a limitation is the subjectivity of the distribution of the relative weight of each indicator. However, statistical analyses are developed to explore the relationship between indicators and global sustainability.

Practical implications

The debate to contextualise this paper is bridging the gap between sustainability and tourism intelligence, giving an original framework for measuring destination sustainability that provides a reasonable starting point for comparing tourism sustainability in different destinations.

Social implications

Tourists in the 21st century prefer environmentally friendly tourism. Marketing campaigns based on destination sustainability must be based on data rather than mere slogans.

Originality/value

To the best of the authors’ knowledge, the originality of this paper provides a flexible framework for measuring sustainability from open data sources, being one of the first empirical analyses to study the effects on the sustainability of converting a mature destination into an STD.
Entrepreneurial ecosystems as contested spaces: a case study from the Galapagos islands
Authors: Carrick Oliver James
Published: July 2022

Purpose

Although research of entrepreneurial ecosystems has mainly focused on urban centers in developed nations, there is an emergent need to study the complexities of rural, regional and development contexts. Ecosystems in such settings are often characterized by the heightened importance assumed by environmental and social factors. This paper aims to document learning from participatory development and economic planning in the Galapagos, a setting in which the interplay between social, economic and ecological factors is critical.

Design/methodology/approach

This case study seeks to elaborate theory with qualitative data from an empirical context.

Findings

Reconstructed theory shows that in participatory development contexts, the entrepreneurial ecosystem constitutes a space in which competing interests contrast and conflict. Results from the Galapagos islands highlight the ability of local actors to successfully affect policy during local collaborative planning. The tensions between the economy, environment and society apparent in participatory dialogue indicate that a more nuanced approach to the interaction within entrepreneurial ecosystems is required.

Originality/value

This case study demonstrates the value of analyzing the processes and mechanisms for collaboration in the entrepreneurial ecosystem in sustainable development contexts. Results suggest implications for scholars researching entrepreneurial ecosystem networks.
Family physician leadership during the COVID-19 pandemic: roles, functions and key supports
Authors: Mathews Maria , Ryan Dana , Hedden Lindsay , Lukewich Julia , Marshall Emily Gard , Brown Judith Belle , Gill Paul S. , McKay Madeleine , Wong Eric , Wetmore Stephen J. , Buote Richard , Meredith Leslie , Moritz Lauren , Spencer Sarah , Alexiadis Maria , Freeman Thomas R. , Letto Aimee , Ryan Bridget L. , Sibbald Shannon L. , Terry Amanda Lee
Published: July 2022

Purpose

Strong leadership in primary care is necessary to coordinate an effective pandemic response; however, descriptions of leadership roles for family physicians are absent from previous pandemic plans. This study aims to describe the leadership roles and functions family physicians played during the COVID-19 pandemic in Canada and identify supports and barriers to formalizing these roles in future pandemic plans.

Design/methodology/approach

This study conducted semi-structured qualitative interviews with family physicians across four regions in Canada as part of a multiple case study. During the interviews, participants were asked about their roles during each pandemic stage and the facilitators and barriers they experienced. Interviews were transcribed and a thematic analysis approach was used to identify recurring themes.

Findings

Sixty-eight family physicians completed interviews. Three key functions of family physician leadership during the pandemic were identified: conveying knowledge, developing and adapting protocols for primary care practices and advocacy. Each function involved curating and synthesizing information, tailoring communications based on individual needs and building upon established relationships.

Practical implications

Findings demonstrate the need for future pandemic plans to incorporate formal family physician leadership appointments, as well as supports such as training, communication aides and compensation to allow family physicians to enact these key roles.

Originality/value

The COVID-19 pandemic presents a unique opportunity to examine the leadership roles of family physicians, which have been largely overlooked in past pandemic plans. This study’s findings highlight the importance of these roles toward delivering an effective and coordinated pandemic response with uninterrupted and safe access to primary care.
An mHealth‐Supported antenatal lifestyle intervention may be associated with improved maternal sleep in pregnancy: Secondary analysis from the PEARS trial
Authors: Bartels Helena C. , Kennelly Maria A. , Killeen Sarah Louise , Lindsay Karen L. , Crowley Rachel K. , McAuliffe Fionnuala M.
Published: July 2022

Objective

To investigate the effect of an antenatal diet and exercise intervention during pregnancy on sleep duration. As a secondary objective, associations between sleep duration and gestational weight gain (GWG), maternal metabolic parameters and pregnancy outcomes were assessed.

Design

Secondary analysis.

Setting

Large tertiary Maternity Hospital in Dublin, Ireland.

Population

326 women with overweight or obesity who participated in the Pregnancy Exercise And Nutrition Research Study (PEARS) randomised controlled trial between March 2013 and August 2016.

Methods

Secondary analysis of a randomised trial.

Main outcome measures

Impact of the PEARS intervention on sleep duration, and association of sleep duration and maternal metabolic parameters, and pregnancy outcomes.

Results

Participants had a mean age of 32.5 ± 4.5 years and median (interquartile range [IQR]) body mass index of 28.3 (26.6–31.2) kg/m2. The intervention group had a longer sleep duration in late pregnancy (mean difference 17.1 minutes (95% confidence interval [CI] 0.5–33.7) and a higher proportion achieving optimum sleep duration of 7–9 h (54.3 vs. 42.9%, relative risk [RR] 1.28 (95% CI 1.01–1.62). In late pregnancy, sleep duration of <6 h was associated with lower breastfeeding rates on discharge (RR 0.74, 95% CI 0.57–0.95) and higher triglyceride levels (mean difference 0.24, 95% CI 0.10–0.38). There were no significant associations between sleep and incidence of gestational diabetes mellitus or pre‐eclampsia/toxaemia, or other metabolic parameters assessed (insulin, fasting glucose, HOMA‐IR).

Conclusion

A diet and exercise intervention from early pregnancy may promote longer and optimal sleep duration, with maternal benefits such as lower triglyceride levels and higher breastfeeding rates.
Maternal alloimmune antibodies against HPA and HLA class I antigens are associated with reduced birthweight among healthy neonates delivered by Chinese women
Authors: Xue Yang , Xin Wenlong , Li Chao , Zeng Xing , Song Zhanyun , Cao Chen , Zhao Tongmao
Published: July 2022

Introduction

It is well known that HPA‐1a antibodies lead to fetal and neonatal alloimmune thrombocytopenia (FNAIT), and an association with reduced birthweight in boys has been reported. Although it remains unclear whether HLA antibodies cause FNAIT, an association between HLA class I antibodies and reduced birthweight in FNAIT neonates has been observed. The aim of this study was to investigate the incidence of platelet antibodies among Chinese women and the impact of maternal alloimmune antibodies on birthweight among healthy neonates.

Material and methods

In this retrospective observational cohort study, platelet antibody screening was performed among women hospitalized for delivery from March 2019 to November 2020. A portion of each serum sample was used to distinguish HLA class I antibodies from HPA antibodies. Based on neonatal sex, gestational age and maternal age, platelet antibody‐negative women who were hospitalized for delivery during the same period were randomly selected as reference groups at a 1:1 ratio for comparisons of the birthweights of healthy neonates delivered by women who were positive or negative for platelet antibodies.

Results

Among 15 156 women, 1008 (6.7%) were positive for platelet antibodies; the incidences of positive platelet antibody were 1.2%, 1.9%, 1.6% and 2.0% among women with 1, 2, 3 and >3 pregnancies, respectively. Among 787 platelet antibody‐positive serum samples available for further analysis, 548 (69.6%) were positive for HLA class I antibodies bound to platelets, and 239 (30.4%) were positive for HPA antibodies. The average birthweight of healthy neonates delivered by women who were positive for platelet antibodies, HLA class I antibodies or HPA antibodies was 161–483 g lower than that of neonates delivered by women who were negative for these antibodies (P < 0.001). Regarding birthweight reduction, there was no significant difference among women who were positive for these antibodies or between boys and girls (P > 0.05).

Conclusions

This study is the first to report that maternal HPA and HLA class I antibodies are associated with reduced birthweight among healthy neonates delivered by Chinese women. This finding provides information for the study of the effect of maternal alloimmune antibodies on fetal development.
Choice matters: Pupils' stress regulation, brain development and brain function in an outdoor education project
Authors: Dettweiler Ulrich , Gerchen Martin , Mall Christoph , Simon Perikles , Kirsch Peter
Published: July 2022

Background

Education outside the classroom (EOtC) is considered beneficial to children's physical and mental health. Especially, stress resilience has been linked to nature experience.

Aims

This study experimentally explored the effects of pupils' autonomy support (AUT) and physical activity (PA) on their biological stress responses and brain development in EOtC.

Sample

The study comprised 48 fifth and sixth graders.

Methods

The intervention consisted of one day/week taught in a forest over one school year. Structural magnetic resonance imaging (MRI) was conducted at the beginning and the end of the school year, functional MRI under a stress condition at the end. Regions of interest were amygdala, hippocampus and the anterior cingulate cortex (ACC). All other measures were obtained at the beginning, at mid‐term and at the end of the school year. PA was measured using accelerometry. Cortisol levels were obtained three times during the examined school days. AUT was measured with a paper‐based survey. Data were analysed using Bayesian multivariate models.

Results

EOtC students exhibit more efficient regulation of biological stress‐reactivity and show a reduction of cortisol over the day associated with light PA in the forest. Cortisol is further associated with amygdala activation in the stress condition. Cerebral structural change is best explained by age; however, AUT has a positive direct effect on the maturation of the ACC, which is stronger in EOtC.

Conclusions

Our results support the idea that autonomy supportive teaching fosters cerebral maturation and that EOtC can have a positive effect on biological stress regulation.
AtypicalTDP‐43 protein expression in anALSpedigree carrying a p.Y374Xtruncation mutation inTARDBP
Authors: Cooper‐Knock Johnathan , Julian Thomas H. , Feneberg Emily , Highley J. Robin , Sidra Maurice , Turner Martin R. , Talbot Kevin , Ansorge Olaf , Allen Scott P. , Moll Tobias , Shelkovnikova Tatyana , Castelli Lydia , Hautbergue Guillaume M. , Hewitt Christopher , Kirby Janine , Wharton Stephen B. , Mead Richard J. , Shaw Pamela J.
Published: July 2022

We describe an autosomal dominant, multi‐generational, amyotrophic lateral sclerosis (ALS) pedigree in which disease co‐segregates with a heterozygous p.Y374X nonsense mutation within TDP‐43. Mislocalization of TDP‐43 and formation of insoluble TDP‐43‐positive neuronal cytoplasmic inclusions is the hallmark pathology in >95% of ALS patients. Neuropathological examination of the single case for which CNS tissue was available indicated typical TDP‐43 pathology within lower motor neurons, but classical TDP‐43‐positive inclusions were absent from motor cortex. The mutated allele is transcribed and translated in patient fibroblasts and motor cortex tissue, but overall TDP‐43 protein expression is reduced compared to wild‐type controls. Despite absence of TDP‐43‐positive inclusions we confirmed deficient TDP‐43 splicing function within motor cortex tissue. Furthermore, urea fractionation and mass spectrometry of motor cortex tissue carrying the mutation revealed atypical TDP‐43 protein species but not typical C‐terminal fragments. We conclude that the p.Y374X mutation underpins a monogenic, fully penetrant form of ALS. Reduced expression of TDP‐43 combined with atypical TDP‐43 protein species and absent C‐terminal fragments extends the molecular phenotypes associated with TDP‐43 mutations and with ALS more broadly. Future work will need to include the findings from this pedigree in dissecting the mechanisms of TDP‐43‐mediated toxicity.
Cutaneous eyelid melanoma with lacrimal sac metastasis: the potential role of lacrimal fluid as a metastatic pathway
Authors: Nakamura Yoshio , Tanese Keiji , Kameyama Kaori , Ota Yu , Fusumae Takaiyuki , Hirai Ikuko , Fukuda Keitaro , Funakoshi Takeru
Published: July 2022

Here we present a patient with cutaneous eyelid melanoma patient with lacrimal sac metastasis. Clinicopathological findings in this case support the theory that lacrimal fluid can be a metastatic pathway for tumour cells. Dermatologists should be aware of the possibility that cutaneous eyelid melanoma may involve the nasolacrimal system and should examine it during the perioperative period and in postoperative follow-up.
Acupuncture and osteopathic medicine for atopic dermatitis: a three-armed, randomized controlled explorative clinical trial
Authors: Rotter Gabriele , Ahnert Moritz W. , Geue Anne V. , Icke Katja , Binting Sylvia , Tissen-Diabaté Tatjana , Roll Stephanie , Ortiz Miriam , Reinhold Thomas , Kass Benjamin , Staab Doris , Pfab Florian , Willich Stefan N. , Brinkhaus Benno
Published: July 2022

Background

Patients with atopic dermatitis (AD) frequently use acupuncture (ACU) and osteopathic medicine (OM), although their therapeutic benefits are unclear.

Aim

To investigate the effectiveness of ACU and OM in patients with AD.

Methods

In a three-armed, single-centre, randomized controlled open explorative clinical trial, adult patients with AD received ACU, OM or no study intervention (control group; CG) plus routine care. Outcomes included disease severity (SCORing Atopic Dermatitis; SCORAD), itching intensity (visual analogue scale; VAS), frequency of topical corticosteroid (TCS) use over 7 days and cost-effectiveness. Endpoints were analysed by analysis of covariance adjusted for the respective baseline value and TCS use.

Results

Overall, 121 patients (92 women, 29 men) with a mean ± SD age of 31.4 ± 10.5 years were randomized. After 12 weeks, the adjusted means (95% CI) for ACU, OM and control were, respectively, 22.3 (18.3–26.3), 26.4 (22.6–30.2) and 23.7 (19.9–27.5) for SCORAD (P = 0.32); 27.9 (19.5–36.4), 35.0 (26.9–43.0) and 42.3 (34.7–50.0) for VAS itching (P < 0.05); and 2.3 (0.8–3.9), 1.9 (0.4–3.5) and 4.3 (2.6–6.0), for TCS use (P = 0.10). ACU and OM were not cost-effective compared with the CG.

Conclusion

Although no differences in disease severity were found, our findings indicate that ACU might reduce itching in patients with AD. Furthermore, ACU and OM showed a trend towards reducing TCS use.
Systemic sclerosis mortality trends in Spain from 1980 to 2019: age–period–cohort and joinpoint analysis
Authors: Hernández-Rodríguez Juan-Carlos , Sendín-Martín Mercedes , Durán-Romero Antonio-José , Álvarez Juan Ortiz , Conejo-Mir Julián , Pereyra-Rodríguez José-Juan
Published: July 2022

Background

Systemic sclerosis (SSc) is an autoimmune chronic rheumatic disease with a high mortality rate, which continues to be a challenge for clinicians today.

Aim

To assess changes in mortality trends in the Spanish SSc population between 1980 and 2019, taking into account the independent effects of sex, age, time period and birth cohort.

Methods

SSc death records and mid-year population data were collected from the National Statistics Institute. Age-standardized mortality rates were calculated for the overall population and for each sex (male, female) and age group (5-year groups). Significant changes in mortality trends were identified by joinpoint regressions. An age–period–cohort (APC) analysis and potential years of life lost (PYLL) analysis were performed to identify the burden of SSc.

Results

Age-standardized mortality rates due to SSc increased from 1.87 (95% CI 1.00–3.02) per 1 000 000 inhabitants between 1980 and 1984, to 2.47 (95% CI 1.74–3.02) per 1 000 000 inhabitants between 2015 and 2019. The relative risk of mortality fell in all groups in cohorts born after 1990. The PYLL rates showed a gradual rise for both sexes.

Conclusion

There was an increase in overall SSc mortality in Spain during the 39 years evaluated, although there was a progressive drop for men.
Identification of peptides from protease‐fermented milk protein and immunomodulatory effect in vivo against lipopolysaccharide‐induced inflammation
Authors: Xie Yujia , Li Mingyi , Zhang Shaohui
Published: July 2022

Food‐derived peptides exhibit potential immunomodulatory effects and become popular functional ingredients in food industry. However, the in vivo effect varies from in vitro while the optimal utilisation content remains unclear. This study aimed to identify novel peptides from protease‐facilitated fermentation, to evaluate their immunomodulatory effect and effect‐dose relationship in vivo. Totally 2045 peptides were screened by liquid chromatography mass spectrometry (LC–MS/MS), and in silico methods were applied to predict the potential bioactivity through Peptide Ranker, GRAVY Calculator and PepDraw. In vivo assay indicated that 200 mg kg−1 milk‐derived peptides showed the optimal regulation on lipopolysaccharide‐induced inflammation by enhancing the immune function of spleen and regulating immunoglobulin and cytokine production. These peptides contributed to the prevention of inflammation through the oral route and could be further applied in functional food development.
Effect of dandelion root polysaccharide on structure, rheology and retrogradation properties of corn starch during storage
Authors: Wang Libo , Zhu Ling , Gao Jingyu , Zhang Fengjie , Li Lianyu , Yang Yu , Xu Yaqin
Published: July 2022

The influence of dandelion root polysaccharide (DRP) on the retrogradation characteristics of corn starch (CS) in the process of storage was studied. Compared with native corn starch gel, the blue value (BV), hardness and syneresis were significantly decreased with the increasing of DRP concentration. Fourier transform infrared (FT‐IR) and X‐ray diffraction (XRD) showed that DRP addition inhibited the recrystallisation of CS during retrogradation. In addition, the dynamic rheological behaviours confirmed that DRP could enhance the shear stability and reduce the elastic properties of corn starch gel. These data showed DRP had potential application value in delaying starch retrogradation and improving food texture.
The structural rearrangement and depolymerisation induced by high‐pressure homogenisation inhibit the thermal aggregation of myofibrillar protein
Authors: Su Chang , He Zhifei , Wang Zefu , Zhang Dong , Li Hongjun
Published: July 2022

The effects of heating on the dissolution and aggregation of high‐pressure homogenisation (HPH)‐treated myofibrillar protein (MP) in low ionic strength medium were investigated in this study. Upon heating, HPH‐treated MP (HTMP) had a greater solubility and lower turbidity than control MP (P < 0.05). The rheological measurement exhibited that the thermal aggregation ability of HTMP was hampered due to lower storage modulus (G′) and loss modulus (G″), except near 50 °C. The increased G′ and G″ of HTMP at near 50 °C could be attributed to structural rearrangement induced by HPH. The analysis of proteomics indicated that HPH destroyed the cytoskeletal proteins in myofibrillar structure, made MP structure more swollen and flexible, promoted MP rearrangement and formation of oligomers with higher negative charge, which produced stronger steric hindrance and electrostatic repulsion between molecules, thus inhibiting thermally induced MP aggregation. The depolymerisation effect induced by HPH destroyed myosin head and tail portion, hampered the assembly of myosin into filaments and therefore suppressed the formation of strand‐type aggregates under heating. The in vitro digestion suggested that the depolymerisation and rearrangement effect significantly improved MP digestibility (P < 0.05) regardless of whether the protein was heat treated or not.
Fagiolina del Trasimeno, an Italian cowpea landrace: effect of different cooking techniques and domestic storage on chemical and biological features
Authors: Acito Mattia , Palomba Martina , Fatigoni Cristina , Villarini Milena , Sancineto Luca , Santi Claudio , Moretti Massimo
Published: July 2022

The aim of this work was a chemical and biological characterisation of Fagiolina del Trasimeno (Italian cowpea landrace) in its coloured and white variants. After opening the package (T0), samples were addressed to a set of chemical and biological assays. Analyses were also conducted on cooked, 6‐month‐stored (T1) and commercial products. Chemical composition was comparatively analysed by nuclear magnetic resonance (NMR) of the proton. At both T0 and T1, raw coloured Fagiolina del Trasimeno showed statistically higher values in terms of phenolic content (T0: 11.51 mg GAE/g, T1: 9.34 mg GAE/g) and antioxidant activity (DPPH T0: 27.40 μmol TE/g, T1: 20.15 μmol TE/g; ABTS T0: 37.98 μmol CE/g, T1: 27.24 μmol CE/g) when compared with white/commercial variants. Globally, boiling, pressure‐cooking, and storage led to a loss in phenolic content and antioxidant activity. However, values in coloured samples generally remained higher than those observed in the other products. Finally, Fagiolina del Trasimeno extracts were shown to inhibit cyclooxygenase activity in HepG2 cells (up to −41.96%). In summary, these results highlighted interesting chemical and biological features of this product, showing the impact of routine procedures, as well.
Evaluation of 11C‐choline positron emission tomography/computed tomography for determining treatment response in castration‐resistant prostate cancer patients
Authors: Kimura Kazuhiko , Kitajima Kazuhiro , Kawanaka Yusuke , Yokoyama Hiroyuki , Komoto Hisashi , Fujiwara Masayuki , Furukawa Yoshitaka , Kanematsu Akihiro , Yamamoto Shingo , Miyake Hideaki , Yamakado Koichiro
Published: July 2022

Objective

The utility of 11C‐choline positron emission tomography/computed tomography for determining treatment response as compared with prostate‐specific antigen response and prognosis prediction in castration‐resistant prostate cancer patients was investigated.

Methods

Eighty‐four 11C‐choline‐positron emission tomography/computed tomography scans before/after treatments with abiraterone (n = 12 patients), enzalutamide (n = 3), docetaxel (n = 9), cabazitaxel (n = 5), radiation therapy alone (n = 3), radiation therapy, enzalutamide, and/or abiraterone (n = 5), radium‐223 (n = 4), and radiofrequency ablation (n = 1) in 42 castration‐resistant prostate cancer patients were retrospectively examined. Prostate‐specific antigen values were determined before and after treatment. Using the Kaplan–Meier method, the correlation of Positron Emission Tomography Response Criteria In Solid Tumors with prostate‐specific antigen response and prognostic impact was evaluated.

Results

Pretreatment 11C‐choline‐positron emission tomography/computed tomography findings identified local, lymph node, bone, and visceral metastasis in 12, 12, 29, and five patients, respectively. Following treatments, complete metabolic response was noted in one, partial metabolic response in eight, stable metabolic disease in 13, and progressive metabolic disease in 20. Mean prostate‐specific antigen change for complete metabolic response, partial metabolic response, stable metabolic disease and progressive metabolic disease was −48.9%, −55.0% (range −92.4% to −19.1%), −4.2% (−33.2% to 35.1%), and 142.7% (30.7% to 373.8%), respectively, significantly greater in the progressive metabolic disease cases (P < 0.01). Positron Emission Tomography Response Criteria In Solid Tumors was well correlated with prostate‐specific antigen change. Patients with no progression (complete metabolic response/partial metabolic response/stable metabolic disease) showed significantly longer cancer‐specific survival than progressive metabolic disease (P < 0.005). Using pretreatment 11C‐choline‐positron emission tomography/computed tomography results to divide into three groups; (a) local and/or lymph node metastasis without bone metastasis (n = 10), (b) <6 bone metastasis sites (n = 16), (c) ≥6 bone metastasis sites and/or visceral metastasis (n = 16), cancer‐specific survival showed significant stratification (P < 0.001).

Conclusions

11C‐choline‐positron emission tomography/computed tomography may reflect castration‐resistant prostate cancer metastatic lesion activity for treatment response and prognosis evaluations.
Constitutively‐expressed and induced immune effectors in the house fly (Musca domestica) and the transcription factors that may regulate them
Authors: Asgari Danial , Saski Christopher A. , Meisel Richard P. , Nayduch Dana
Published: July 2022

Insects possess both infection‐induced and constitutively expressed innate immune defences. Some effectors, such as lysozymes and antimicrobial peptides (AMPs), are constitutively expressed in flies, but expression patterns vary across tissues and species. The house fly (Musca domestica L.) has an impressive immune repertoire, with more effector genes than any other flies. We used RNA‐seq to explore both constitutive and induced expression of immune effectors in flies. House flies were fed either Pseudomonas aeruginosa or Escherichia coli, or sterile control broth, and gene expression in the gut and carcass was analysed 4 h post‐feeding. Flies fed either bacterium did not induce AMP expression, but some lysozyme and AMP genes were constitutively expressed. Prior transcriptome data from flies injected with bacteria also were analysed, and these constitutively expressed genes differed from those induced by bacterial injection. Binding sites for the transcription factor Myc were enriched upstream of constitutively expressed AMP genes, while upstream regions of induced AMPs were enriched for NF‐κB binding sites resembling those of the Imd‐responsive transcription factor Relish. Therefore, we identified at least two expression repertoires for AMPs in the house fly: constitutively expressed genes that may be regulated by Myc, and induced AMPs likely regulated by Relish.
Development of inflammatory bowel disease patient education and medical information sheets: serving an unmet need
Authors: Al‐Ani Aysha ,   GESA IBD Patient Information Materials Working Group*, Garg Mayur
Published: July 2022

Inflammatory bowel disease is a chronic gastrointestinal condition that necessitates life‐long healthcare engagement and management. Empowering patients with knowledge is fundamental to enhance health literacy, improve health outcomes and facilitate complex decision‐making regarding medication and potential surgery. A working group was formed to develop concise, comprehensive patient information sheets to meet this unmet need in the Australian setting.
Who donates and how? New evidence on the tax incentives in the canton of Geneva, Switzerland
Authors: Lideikyte Huber Giedre , Pittavino Marta
Published: July 2022

The present study is the first large‐scale empirical legal analysis of tax incentives for charitable giving in Switzerland, and one of the few studies globally. Using unique longitudinal data including household income and wealth of the entire taxpayers' population of the Canton of Geneva, Switzerland, we study patterns of charitable deductions and characteristics of donors making such deductions. Our study period extends over a decade (2001‐2011), this period also encompassing a legal reform that raised ceilings for charitable deductions. We observe that an overwhelming majority of donors make deductions that never reach the legal ceiling, especially after the reform. Nonetheless, we identify a subset of donors that are potentially tax‐incentive sensitive, because their deductions constantly reach (or exceed) this ceiling. Deductions made by those donors amount to 30%–54% of all such deductions in the canton of Geneva. If compared to all donors, the donors in this particular subset are older (in their mid‐late 60s), mostly single, wealthier and more regular givers (deducters). Analyzing the deduction patterns in the entire donors' population, we observe that deducting charitable donations have become increasingly popular during the study period. In addition, we find that donors' relative generosity tends to decrease when their income and wealth increase. Those results have important tax policy implications and relevance in modeling tax incentives for charitable giving, in both Switzerland and elsewhere.
Upstream market structure and downstream partial ownership
Authors: Shuai Jie , Xia Mengyuan , Zeng Chenhang
Published: July 2022

Existing studies on partial ownership usually overlook the effects of vertically related markets. Our paper highlights the importance of the upstream market on downstream firms' incentives to acquire partial ownership and the consequent welfare implications. In the main model, we assume that there are three firms in the downstream market, two of which may form a partial ownership arrangement. We find several results that are in contrast to those in the literature. First, the two firms will engage in partial ownership if the upstream market is an oligopoly (triopoly or duopoly). Second, partial ownership may raise total production, consumer surplus, and social welfare. This happens when the upstream market consists of a duopoly and the two firms involved in partial ownership are supplied by different suppliers. Third, the outsider, commonly known as a free rider in the literature, may become a victim of partial ownership. Our results are robust to several extensions, including a general ‐firm framework, product differentiation, and uniform pricing by upstream firms. We also provide the conditions under which the curvature of the demand function and the convexity of the cost function motivate firms to form partial ownership.