bluuebunny/crossref_metadata_2025 huggingface dataset:
Protection induced by anti-PD-1 and anti-PD-L1 treatment inLeishmania amazonensis-infected BALB/c mice
Authors: da Fonseca-Martins Alessandra M. , Ramos Tadeu D. , Pratti Juliana E.S. , Firmino-Cruz Luan , Gomes Daniel Claudio Oliveira , Soong Lynn , Saraiva Elvira M. , de Matos Guedes Herbert L.
Published: August 2019

Leishmaniasis is a neglected disease, for which current treatment presents numerous issues.Leishmania amazonensisis the etiological agent of cutaneous and diffuse cutaneous leishmaniasis. The roles of the programmed death-1 (PD-1) receptor on lymphocytes and its ligand (PD-L1) on antigen-presenting cells have been well studied in tumor and other infection models; but little is known about their roles in non-healing cutaneous leishmaniasis. Our previous report ofL. amazonensis-induced PD-L1 expression on dendritic cells, in combination with decreased IFN-γ production by CD4+T cells in C57BL/6 mice, led to a hypothesis that the formation of the PD-1/PD-L1 complex contributes to down-modulation of immune responses, especially T cell suppression, enabling parasite survival and persistence. In this study, we tested the therapeutic potential of anti-PD-1 and anti-PD-L1 monoclonal antibodies (MoAbs) against a non-healingL. amazonensisinfection in BALB/c mice. We observed thatL. amazonensisinduced PD-1 expression on both CD4+and CD8+T cells, and that anti-PD-1 and anti-PD-L1 treatment significantly increased IFN-γ-producing CD4+and CD8+T cells, respectively. Compared with infection controls, mice that received treatment with anti-PD-1 and anti-PD-L1, but not anti-PD-L2, displayed bigger lesions with significantly lower parasite loads. Treatment did not affect anti-Leishmaniaantibody or IL-10 production, but anti-PD-1 treatment reduced both IL-4 and TGF-β production. Together, our results highlight the therapeutic potential of an anti-PD-1-based treatment in promoting the reinvigoration of T cells for the control of parasite burden.
Negative selection on complex traits limits genetic risk prediction accuracy between populations
Authors: Durvasula Arun , Lohmueller Kirk E.
Published: August 2019

Accurate genetic risk prediction is a key goal for medical genetics and great progress has been made toward identifying individuals with extreme risk across several traits and diseases (Collins and Varmus, 2015). However, many of these studies are done in predominantly European populations (Bustamante et al., 2011; Popejoy and Fullerton, 2016). Although GWAS effect sizes correlate across ancestries (Wojcik et al., 2019), risk scores show substantial reductions in accuracy when applied to non-European populations (Kim et al., 2018; Martin et al., 2019; Scutari et al., 2016). We use simulations to show that human demographic history and negative selection on complex traits result in population specific genetic architectures. For traits under moderate negative selection, ~50% of the heritability can be accounted for by variants in Europe that are absent from Africa. We show that this directly leads to poor performance in risk prediction when using variants discovered in Europe to predict risk in African populations, especially in the tails of the risk distribution. To evaluate the impact of this effect in genomic data, we built a Bayesian model to stratify heritability between European-specific and shared variants and applied it to 43 traits and diseases in the UK Biobank. Across these phenotypes, we find ~50% of the heritability comes from European-specific variants, setting an upper bound on the accuracy of genetic risk prediction in non-European populations using effect sizes discovered in European populations. We conclude that genetic association studies need to include more diverse populations to enable to utility of genetic risk prediction in all populations.
Integrative x-ray structure and molecular modeling for the rationalization of procaspase-8 inhibitor potency and selectivity
Authors: Xu Janice H. , Eberhardt Jerome , Hill-Payne Brianna , González-Páez Gonzalo E. , Castellón José Omar , Cravatt Benjamin F. , Forli Stefano , Wolan Dennis W. , Backus Keriann M.
Published: August 2019

Caspases are a critical class of proteases involved in regulating programmed cell death and other biological processes. Selective inhibitors of individual caspases, however, are lacking, due in large part to the high structural similarity found in the active sites of these enzymes. We recently discovered a small-molecule inhibitor, 63-R, that covalently binds the zymogen, or inactive precursor (pro-form), of caspase-8, but not other caspases, pointing to an untapped potential of procaspases as targets for chemical probes. Realizing this goal would benefit from a structural understanding of how small molecules bind to and inhibit caspase zymogens. There have, however, been very few reported procaspase structures. Here, we employ x-ray crystallography to elucidate a procaspase-8 crystal structure in complex with 63-R, which reveals large conformational changes in active-site loops that accommodate the intramolecular cleavage events required for protease activation. Combining these structural insights with molecular modeling and mutagenesis-based biochemical assays, we elucidate key interactions required for 63-R inhibition of procaspase-8. Our findings inform the mechanism of caspase activation and its disruption by small molecules, and, more generally, have implications for the development of small molecule inhibitors and/or activators that target alternative (e.g., inactive precursor) protein states to ultimately expand the druggable proteome.
Quantitative assessment of fecal contamination in multiple environmental sample types in urban communities in Dhaka, Bangladesh using SaniPath microbial approach
Authors: Amin Nuhu , Rahman Mahbubur , Raj Suraja , Ali Shahjahan , Green Jamie , Das Shimul , Doza Solaiman , Mondol Momenul Haque , Wang Yuke , Islam Mohammad Aminul , Alam Mahbub-Ul , Huda Tarique Md. Nurul , Haque Sabrina , Unicomb Leanne , Joseph George , Moe Christine L.
Published: August 2019

Rapid urbanization has led to a growing sanitation crisis in urban areas of Bangladesh and potential exposure to fecal contamination in the urban environment due to inadequate sanitation and poor fecal sludge management. Limited data are available on environmental fecal contamination associated with different exposure pathways in urban Dhaka. We conducted a cross-sectional study to explore the magnitude of fecal contamination in the environment in low-income, high-income, and transient/floating neighborhoods in urban Dhaka. Ten samples were collected from each of 10 environmental compartments in 10 different neighborhoods (4 low-income, 4 high-income and 2 transient/floating neighborhoods). These 1,000 samples were analyzed with the IDEXX-Quanti-Tray technique to determine most-probable-number (MPN) of E. coli. Samples of open drains (6.91 log10 MPN/100 mL), surface water (5.28 log10 MPN/100 mL), floodwater (4.60 log10 MPN/100 mL), produce (3.19 log10 MPN/serving), soil (2.29 log10 MPN/gram), and street food (1.79 log10 MPN/gram) had the highest mean log10E. coli contamination compared to other samples. The contamination concentrations did not differ between low-income and high-income neighborhoods for shared latrine swabs, open drains, municipal water, produce, and street foodsamples. E. coli contamination were significantly higher (p <0.05) in low-income neighborhoods compared to high-income for soil (0.91 log10 MPN/gram, 95% CI, 0.39, 1.43), bathing water (0.98 log10 MPN/100 mL, 95% CI, 0.41, 1.54), non-municipal water (0.64 log10 MPN/100 mL, 95% CI, 0.24, 1.04), surface water (1.92 log10 MPN/100 mL, 95% CI, 1.44, 2.40), and floodwater (0.48 log10 MPN/100 mL, 95% CI, 0.03, 0.92) samples. E. coli contamination were significantly higher (p<0.05) in low-income neighborhoods compared to transient/floating neighborhoods for drain water, bathing water, non-municipal water and surface water. Future studies should examine behavior that brings people into contact with the environment and assess the extent of exposure to fecal contamination in the environment through multiple pathways and associated risks.
Regulation of FLIP(L) and TRAIL-R2 signalling by the SCFSkp2Ubiquitin Ligase Complex
Authors: Roberts JZ , Holohan C , Sessler T , Fox J , Higgins C. , Espona-Fiedler G , Majkut J , Crawford N , Riley JS , Khawaja H , Humphreys LM , Ferris J , Evergren E , Moynagh P , McDade SS , Longley DB
Published: August 2019

Depending on its expression levels, the long splice form of the pseudo-caspase FLIP (FLIP(L)) can act as an inhibitor (high expression) or activator (low expression) of apoptosis induction by the TRAIL-R2 death-inducing signalling complex (DISC); its expression levels are therefore tightly regulated. Here, we demonstrate that the Skp1-Cullin-1-F-box (SCF) Cullin-Ring E3 Ubiquitin Ligase complex containing Skp2 (SCFSkp2) regulates the stability of FLIP(L) (but not the short splice form FLIP(S)), and, unusually, this is mediated by direct binding of FLIP(L) to Cullin-1 rather than via Skp2. By fine mapping the interaction of FLIP(L) with Cullin-1 to the large subunit of its pseudo-caspase domain, we found that the interaction is significantly stronger with FLIP(L)’s DISC-processed p43-form. Importantly, this interaction disrupts the ability of p43-FLIP to interact with FADD, caspase-8 and another DISC component, TRAF2. Moreover, we find that SCFSkp2associates with TRAIL-R2 constitutively and does so independently of FLIP(L) and other canonical DISC components. Inhibition of Cullin-1 expression (using siRNA) or activity (using a NEDDylation inhibitor, MLN4924) enhanced FLIP(L) and TRAF2 levels at the TRAIL-R2 DISC and enhanced caspase-8 processing. This suggests that processing of FLIP(L) to p43-FLIP at the TRAIL-R2 DISC enhances its interaction with co-localised SCFSkp2, leading to disruption of p43-FLIP’s association with the DISC thereby altering caspase-8 processing. These findings provide important new insights into how FLIP(L) expression and TRAIL-R2 signaling is controlled.
Magnesium, aluminum and zinc co-substituted hydroxyapatite: anti-corrosion properties
Authors: Šimková Lenka , Šulcová Petra
Published: August 2019

Purpose

The purpose of this study was to investigate the influence of doping ions Mg2+, Zn2+, Al3+ to the structure of hydroxyapatite (HAP; Ca10(PO4)6(OH)2) and subsequently to evaluate their adaptation in structure and their anticorrosive properties.

Design/methodology/approach

The substituted hydroxyapatite was synthesized by precipitation method that included the addition of Mg2+, Zn2+ and Al3+ containing precursors to partially replace Ca2+ ions in the hydroxyapatite structure. For precipitation synthesis, three ratios of Ca/P = 1; 1.67; 3 and two values of pH = 7 and 12 were selected. Samples 1 (Ca/P = 1; pH = 7), 2 (Ca/P = 1.67; pH = 7), 3 (Ca/P = 3; pH = 7) and 5 (Ca/P = 1.67; pH = 12) were chosen to monitor the influence of doping ions Mg2+, Zn2+ and Al3+ to the structure of hydroxyapatite and its anticorrosive properties.

Findings

The chosen synthesis conditions are appropriate for the formation of crystalline HAP substituted by elements Mg, Zn and Al. Only for one sample (1-Mg), two different phases (hydroxyapatite and whitlockite) were identified in the phase composition. On the basis of preliminary corrosion tests, pigments were divided into three groups pursuant to their anticorrosion effectivity: pigments with high corrosion-inhibition efficiency; pigments without anticorrosive properties; and pigments that promote corrosion processes.

Originality/value

In addition, no doping effect can be observed except for the sample 1-Mg, which consists of two phases (hydroxyapatite and whitlockite). Preliminary corrosion tests prove that some samples of HAP have extremely high anticorrosive effectivity as effectivity of the commercial pigments. The accelerated corrosion test showed that HAP samples have insufficient corrosion-inhibition properties for coating applications compared with the commercial pigment.
Transparency of public private partnership (PPP): the extent of mandatory information disclosure
Authors: Ismail Suhaiza , Musawa Mubarak Shehu , Ahmad Hawa
Published: August 2019

Purpose

The purpose of this paper is to examine the extent public listed construction firms in Malaysia disclose mandatory information on public private partnership (PPP) projects. This paper is important as the level of disclosure of PPP information reflects the extent of transparency as practiced by the companies involved in PPP projects.

Design/methodology/approach

In achieving the aim, a content analysis procedure was carried out to analyse the 2015 annual reports of the construction companies. Descriptive statistics including the mean score, frequency and percentage were employed to analyse the disclosure of the annual report.

Findings

The overall mean disclosure score of the sampled companies is 40 per cent, which connotes a low level of disclosure of mandatory information on PPP. The companies also tend to disclose more mandatory financial information than non-financial information.

Originality/value

This paper is one of the few studies that investigated the level of mandatory disclosure of PPP information, thus contributing to the scanty literature on PPP transparency not only in Malaysia but also internationally.
Supply chain transparency and willingness-to-pay for refurbished products
Authors: Duan Yanji , Aloysius John A.
Published: August 2019

Purpose

Researchers in supply chain transparency have called to expand the boundaries by disclosing various types of information to multiple stakeholders. The purpose of this paper is to explore the effect of transparency about supply chain sustainability on consumers as critical stakeholders and investigate the effectiveness of message characteristics.

Design/methodology/approach

This study utilizes two scenario-based experiments grounded in a refurbished goods context: Study 1, which employs a 2×2 between-subject experiment investigates the effects of product type and sustainable information provision on consumers evaluations, and Study 2, which employs a 2×1 between-subject experiment examines the effects of sustainable information direction on consumer evaluations. A total of 348 participants were recruited from the Amazon M-Turk platform across the two experiments. Data are analyzed with regression analysis using the PROCESS macro in SPSS and the Johnson–Neyman technique.

Findings

Contrary to prior research that assumes that refurbished products are associated with lower quality, quality perceptions are moderated by individuals’ environmental involvement (EI) and the information presented by the firm. More importantly, consumer evaluations are influenced by specific characteristics of sustainable supply chain messages: high EI individuals have higher willingness-to-pay a premium (WTPP) when the message is consistent with original beliefs (pro-attitudinal). In contrast to prior theory, there was no difference in the WTPP of consumers with high EI and low EI for counter-attitudinal messages.

Practical implications

The study shows that what to say, how to say it and to whom, are critical for firms who seek to nudge consumers to support their sustainable practices.

Originality/value

The value of communicating information on sustainability has been well established. However, little is known about such association when the information provided trades off environmental benefits and product quality. This research addresses the gap in a refurbished product context. The research studies the effect of sustainable supply chain transparency and message characteristics on stakeholders’ evaluations.
Tell us a story: teaching religion with picturebooks
Authors: Gillikin Margaret Wilson , Hubbard Koti L. , Stapleton Joy N.
Published: August 2019

Purpose

The purpose of this paper is to present a method to incorporate teaching about religion into K–12 social studies classes. A central tenet of social studies education is preparing students to be engaged citizens, and religious literacy is essential to this. Yet, teachers often feel uncomfortable teaching about religion. One way to approach this is by centering discussion about religion around understanding who our neighbors are.

Design/methodology/approach

This paper employs the Inquiry Design Model to outline lessons for early, middle and upper grades, each centered around the compelling question, “Who are my Muslim neighbors?” Beginning with a picturebook depicting a Muslim American child, the lessons explore supporting questions with academically appropriate sources, culminate with an evidence-based response to the compelling question and suggest an opportunity for students to take informed action.

Findings

While religion does not appear in many social studies standards, teaching about religion has strong connections to civics standards. In an increasingly diverse USA, students need to understand the beliefs and religious behaviors of their neighbors and how those traditions provide a sense of belonging within the faith community. This paper provides the necessary tools for teachers to teach this content. In addition to teaching these as outlined here, teachers can also select resources from across the three units in order to customize an inquiry for a particular group of students.

Originality/value

Teachers are often hesitant to teach about religion. This paper offers a concrete method for doing so. Incorporating religion into social studies classes is necessary for preparing students for civic engagement.
Developing entrepreneurial learning triggered by factory tours
Authors: Bonfanti Angelo , Castellani Paola , Giaretta Elena , Brunetti Federico
Published: August 2019

Purpose

This paper aims to examine the content dimensions and methods of accelerating the entrepreneurial learning (EL) triggered by participating in learning events, such as factory tours. It particularly focuses on the Italian case of Open Factory – an open-doors event of industrial manufacturing culture.

Design/methodology/approach

This study adopted a qualitative approach using the “Gioia” methodology. Data were mainly collected through semi-structured interviews with firms participating in and organising Open Factory.

Findings

The dimensions of EL are learning from critical reflection, experience and external sources, while the enablers of EL (factors that accelerate learning) are varied and connected to organisational learning in the form of individual-, team- and institutional-level learning. Based on these results, this paper proposes a model for developing EL triggered by participating in learning events.

Practical implications

This research suggests developing appropriate organisational conditions inside firms, especially by entrepreneurs. These conditions are connected to sharing organisational values to foster learning, such as trust, commitment, involvement, awareness, sharing of experiences, exchange, autonomy and freedom. In addition, this study suggests ways that the EL model proposed in this research can be adapted to other learning events.

Originality/value

This is the first study to connect factory tours to learning events and EL. It highlights the ways that participating in the Open Factory event created the chance to develop learning across organisational levels inside firms.
How to intentionally forget rules in newly introduced agile projects
Authors: Volland Marcel F.
Published: August 2019

Purpose

While much empirical research has examined how routines are unlearned, little is known about the intentional forgetting of rules in organizations. This paper aims to combine the literature on organizational rules and that on intentional forgetting with the aim of studying the relationship between power types of rule imposition and the process of intentional forgetting.

Design/methodology/approach

This study is a single-case analysis carried out in a multinational automotive company that introduced an agile project into the development department. The case was chosen because the introduction of agility was grounded on a dominantly created set of rules. Access to unique data was provided to study processes of intentional forgetting when actors have to apply new rules. In all, 33 interviews and further observations were conducted in a two-year study. Qualitative comparative analysis (QCA) was used for data analysis.

Findings

This case study demonstrates the importance of two forms of power, domination and self-organization, when it comes to forgetting rules intentionally. A rule will be intentionally forgotten if it is created by domination, does not originate from conventional working practices and does not determine an organizational unit (development team). Furthermore, the findings point to the importance of self-organization when it comes to intentional forgetting.

Research limitations/implications

This research relies on a single-case study and presents first results on intentionally forgetting rules.

Practical implications

Organizations implementing new forms of working such as agile working in their existing structures should be aware that processes of intentional forgetting can occur. Managers should consider why organizational members stop following dominantly created rules. Ignoring such a phenomenon could be a threat to the organization’s success.

Originality/value

While many studies examined the process of unlearning routines, little is known about the intentional forgetting of rules in organizations. Rules are different from routines because they are imposed and encompass a normative component. The imposition of a rule is based on power. Two forms of power are presented in this article: domination and self-organization. In addition, the QCA was carried out at a micro-level.
Postmenopausal craniofacial hyperhidrosis treated with botulinum toxin type B
Authors: Cabreus Philip , Swartling Carl , Rystedt Alma
Published: August 2019

Hyperhidrosis can seriously impair patients’ quality of life. Medical history, including heredity and hyperhidrosis during youth, as well as current age and time elapsed since menopause, is important to consider when distinguishing between postmenopausal hyperhidrosis and vasomotor symptoms to enable adequate treatment. This report concerns a subgroup of eight postmenopausal patients participating in a randomized controlled trial regarding botulinum toxin (Btx) type B treatment in craniofacial hyperhidrosis. Even though the sample size is small and the enrolment is not yet completed, the promising data collected hitherto are interesting to present in advance because this subtype of craniofacial hyperhidrosis is often underrecognized and challenging to treat. Patients were randomized to receive Btx type B or placebo. Measurements were performed before treatment and 3 ± 1 weeks after. The Dermatology Life Quality Index (DLQI) score was improved for all patients after Btx type B treatment (n = 3) with a median decrease of 9 points (90% median improvement). The placebo group (n = 5) had a median increase of 2 points (–18% median decline). When the same group (n = 5) received Btx type B (open) the DLQI score decreased with a median of 7 points compared with baseline (91% median improvement). Treatment‐related adverse events were temporary and did not prevent improvement of life quality. Furthermore, background data evaluation uncovered interesting findings regarding vasomotor symptoms in relation to postmenopausal hyperhidrosis. In conclusion, the results indicated that Btx type B seems to be a safe and effective treatment in postmenopausal craniofacial hyperhidrosis. Further research is encouraged.
Litter quality and site characteristics interact to affect the response of priming effect to temperature in subtropical forests
Authors: Lyu Maokui , Nie Yangyi , Giardina Christian P. , Vadeboncoeur Matthew A. , Ren Yinbang , Fu Zuoqin , Wang Minhuang , Jin Changshan , Liu Xiuming , Xie Jinsheng
Published: August 2019

Forest litter inputs to soil can stimulate the decomposition of older soil organic matter (SOM) via a priming effect (PE). The magnitude and underlying mechanisms driving PE are poorly understood, with especially little know about how litter quality and site conditions affect PE in situ. Further, very few studies have examined PE in tropical and subtropical soils.

Here, we established low and high elevation sites (600 vs. 1,400 m a.s.l.) in the subtropical Wuyishan National Park, China, that differed with respect to mean annual temperature (MAT; ∆MAT = 4.2°C), vegetation, soil texture and soil moisture. We conducted a 1‐year field incubation study at these two sites to compare PE induced by adding low‐ and high‐quality 13C‐labelled leaf litter to soils.

At the low elevation site, additions of high‐quality (low C/N) litter caused a PE that was 140% greater than the PE observed following additions of low‐quality (high C/N) litter. In contrast, we saw no significant differences in PE between litter types at the high elevation site, perhaps because PE was not limited by substrate quality at this cooler, finer textured and higher soil moisture coniferous site. In addition, we found a negative relationship between home‐field advantage (HFA) for litter decomposition and PE, indicating that specialized litter decomposer community driving HFA may not accelerate SOM decomposition via PE in the same way.

In line with our observed strong relationship between PE and the efficiency of priming (PE size per unit of mineralized litter C), PEs induced by the high‐ and low‐quality litters were directed to microbial phosphorus (P) mining rather than nitrogen (N) mining. This interpretation aligns with observed increases in the activity of P acquiring extracellular enzymes, often described as phosphatases (P‐tases), as well as the positive relationship between the PE, P‐tase activity and the activity of C acquiring extracellular enzymes.

Overall, this PE study across two contrasting sites highlights the important role of site characteristics and litter quality in regulating PE size. Further, we suggest that MAT may be a dominant driver of soil priming, through both the direct effects of litter quantity on labile substrate supply and the indirect effects of litter quality changes on downstream decomposer communities.

A free Plain Language Summary can be found within the Supporting Information of this article.
Correlation between the shoot‐cutting behavior of the acorn weevil and the reproductive traits of host fagaceous trees
Authors: Hirayama Daisuke , Okada Minetaka , Nanami Satoshi , Itoh Akira
Published: August 2019

Many fagaceous species mature acorns during the second autumn after flowering and are called “2‐year species.” In 2‐year species of subgenus Cyclobalanopsis (genus Quercus), alternate bearing (2‐year seed production cycle) is prominent, but this has not been reported for other 2‐year species in the genera of Lithocarpus and Castanopsis. We tested the hypothesis that the difference in reproduction of 2‐year species is linked to the weevil, Mechoris ursulus. After ovipositing on acorns, this insect cuts the shoots to which the acorns are attached. We examined the host preference of M. ursulus and reproductive traits of fagaceous 2‐year species. Percentage infestation was remarkably high in the subgenus Cyclobalanopsis, whereas Lithocarpus and Castanopsis species suffered almost no damage. Furthermore, unlike Lithocarpus and Castanopsis, most of the acorn‐producing shoots in subgenus Cyclobalanopsis had no current‐year shoots. The clear relationship suggests that alternate bearing in subgenus Cyclobalanopsis is an adaptation to the shoot‐cutting behavior of M. ursulus.
Short‐term outcomes of typical versus atypical lung segmentectomy by minimally invasive surgeries
Authors: Xie Boheng , Sun Xiao , Qin Yi , Liu Ao , Miao Shuncheng , Jiao Wenjie
Published: August 2019

Background

Segmentectomy is increasingly used to resect lung nodules. Robotic‐assisted thoracic surgery (RATS) is considered a safe and practical method for segmentectomy. Few studies have compared robotic surgery and video‐assisted thoracic surgery (VATS) for lung segmentectomy.

Method

We retrospectively examined 215 consecutive patients who underwent typical (88 patients) or atypical (128 patients) segmentectomy by either robotic surgery or VATS. The postoperative characteristics including operation time, blood loss, pneumonia, tumor size, lymph nodes harvested, chest tube duration, prolonged air leak, atrial fibrillation, and postoperative hospital stay were recorded.

Results

A total of 88 patients underwent typical segmentectomy, while 127 patients underwent atypical segmentectomy. A greater number of lymph nodes were resected via RATS than by VATS (13.24 ± 4.84 vs. 11.71 ± 3.89; P = 0.018). The operation time for typical segmentectomy was shorter than that for atypical segmentectomy (115.69 ± 22.32 vs. 131.68 ± 22.52; P = 0). No significant differences were found between RATS and VATS in terms of chest drainage duration and postoperative hospital stay. The incidence of postoperative complications including prolonged air leak and atrial fibrillation was not significantly different between typical segmentectomy and atypical segmentectomy.

Conclusion

Atypical segmentectomy is more complicated than typical segmentectomy, which may lead to increases in complications and operation time. Robotic surgery was safe and practical for segmentectomy compared to VATS and more lymph nodes could be dissected by RATS without increasing the risk of postoperative complications.
Trade credit use and bank loan access: an agency theory perspective
Authors: Ma Liangbo , Ma Shiguang
Published: August 2019

In this study we find that firms’ use of trade credit significantly facilitates their access to bank loans in the future, suggesting a complementary relationship. Such a relationship is more profound for firms with higher perceived agency costs, i.e., firms with opaque corporate information, firms located in regions with less developed external institutions, and firms at an early stage of existence. Firms switch from trade credit to bank loans as the main source of debt financing as they age. However, the process is slower for firms with a greater level of corporate information opacity and firms located in regions with weak external institutions.
Thymic hyperplasia following double immune checkpoint inhibitor therapy in two patients with stage IV melanoma
Authors: Mencel Justin , Gargett Tessa , Karanth Narayan , Pokorny Adrian , Brown Michael P. , Charakidis Michail
Published: August 2019

Hyperplasia of the thymus is commonly seen in myasthenia gravis and other autoimmune disorders. Thymic size also varies with age, corticosteroid use, infections, and inflammatory disease. Although thymic hyperplasia has been described following chemotherapy, there is no known association of true thymic hyperplasia with immune checkpoint inhibitor therapy. We present two cases of suspected true thymic hyperplasia in patients with stage IV melanoma who were treated with the combination of nivolumab and ipilimumab, which was complicated by immune‐related toxicity requiring corticosteroid therapy, and then subsequently also by secondary hypoadrenalism requiring replacement hydrocortisone. In one patient, histological and flurocytometric analyses of an incisional biopsy of the thymus revealed findings consistent with true thymic hyperplasia. In the other case, the stable fluorodeoxyglucose positron emission tomography/Computed tomography (FDG‐PET/CT) findings were consistent also with true thymic hyperplasia. These are the first described cases of true thymic hyperplasia following combination immune checkpoint inhibitor therapy for metastatic melanoma. We hypothesize that the true thymic hyperplasia in these cases results from initial lymphocyte depletion caused by intense corticosteroid therapy followed by rebound thymic hyperplasia during the period of relative hypocortisolism, which may have been aggravated by the onset of secondary hypoadrenalism.
Bone mineral density is preserved in men with idiopathic infertility
Authors: Antonio L. , Priskorn L. , Nordkap L. , Bang A. K. , Jensen T. K. , Skakkebæk N. E. , Petersen J. H. , Vanderschueren D. , Jørgensen N.
Published: August 2019

Background

Lower semen quality is associated with increased mortality and morbidity, which may include osteoporosis.

Objective

To assess whether infertile men have a lower bone mineral density (BMD) compared with fertile men at the time of fertility workup.

Methods

A total of 146 men from infertile couples with unexplained impaired semen quality, characterized by sperm concentration < 20 million/mL, progressive motility < 50% or < 12% morphologically normal spermatozoa. Men with infertility due to a genetic etiology or a condition that could cause testicular damage were excluded. A total of 271 men from couples with an ongoing naturally conceived pregnancy served as a control group. Lumbar, femoral, and total body BMD were measured by dual X‐ray absorptiometry.

Results

Infertile men had similar BMD compared with fertile men (Beta coefficient (g/cm2) and 95% confidence interval for the difference between the two groups: −0.02 (−0.05; 0.01) for lumbar BMD, −0.02 (−0.05; 0.01) for femoral neck BMD, −0.01 (−0.04; 0.02) for total femur BMD, and −0.01 (−0.03; 0.01) for total body BMD). Semen parameters were not associated with BMD measurements. Furthermore, BMD did not differ between infertile men with the lowest semen quality vs. infertile men with better semen quality nor between infertile men with low testosterone vs. fertile men with normal testosterone levels.

Conclusion

Bone mineral density is preserved in men with unexplained infertility at the time of fertility workup.
Annotation: travel and thrombosis
Authors: Czuprynska Julia , Arya Roopen
Published: August 2019

Travel appears to be a weak risk factor for venous thromboembolism (VTE) and is more relevant for passengers with additional VTE risk factors. The association is not limited to air travel and is related to duration of travel. Life‐threatening pulmonary embolism (PE) is rare. There is limited evidence to support interventions, including ‘sensible measures’, graduated compression stockings (GCS) and low‐molecular‐weight heparin (LMWH). It is difficult to confidently define a population who would benefit from thromboprophylaxis and no validated risk assessment exists for this purpose. LMWH has traditionally been used for flight thromboprophylaxis but a direct oral anticoagulant (DOAC) would be a more appealing oral option.
Modulating macrophage polarization on titanium implant surface by poly(dopamine)‐assisted immobilization of IL4
Authors: Wang Yulan , Qi Haoning , Miron Richard J. , Zhang Yufeng
Published: August 2019

Background

In the past few decades, very little research has been carried out to modify implant surfaces to improve osteointegration through the regulation of immune cells.

Purpose

The aim of this study is to investigate whether the poly(dopamine) (pDA)‐assisted immobilization of IL4 on titanium surfaces could modulate the inflammatory profile of macrophages in vitro and search for the possibility of enhancing implant integration in this way.

Material and Methods

The surface composition, topography, and roughness of SLA, SLA‐pDA, and SLA‐pDA‐IL4 discs were examined by scanning electron microscope (SEM) and energy dispersive spectrometer (EDS). Then the releasing profile of the SLA‐pDA‐IL4 implants was recorded for 1 week and the bioactivity of released IL4 was investigated by ELISA. Then macrophage polarization was investigated via three methods including: (a) surface marker via immunofluorescence; (b) mRNA levels of M1 and M2 polarization markers via real‐time PCR, and (c) cytokine release via ELISA.

Results

SEM and EDS revealed that pDA and IL4 were coated successfully on SLA surfaces. The ELISA results showed that IL4 remained its bioactivity on SLA surface and were immobilized on the SLA surface. The immobilization of IL4 through pDA has no significant influence on the attachment, morphology, and proliferation of macrophages, while it increased the M2/M1 proportion in human macrophages revealed by immunofluorescence. The real‐time PCR and ELISA results demonstrated that SLA‐pDA‐IL4 surface reduced the pro‐inflammatory profile compared with SLA‐pDA and SLA surfaces.

Conclusions

The SLA‐pDA‐IL4 surfaces described here is able to activate adherent macrophages into M2 phenotype and reduce the release of pro‐inflammatory cytokines. Immobilization of IL4 via pDA is convenient and effective, thus providing an applicable way to control macrophage behavior upon implant insertion and is anticipated to accelerating further bone integration.
Dermoscopic features of lichen planopilaris in Northern Iran: a prospective observational study
Authors: Eftekhari Hojat , Azimi Seyyede Zeinab , Rafiei Rana , Darjani Abbas , Alizadeh Narges , Rafiei Elahe , Ghadarjani Reyhaneh , Gharaei Nejad Kaveh
Published: August 2019

Background

Dermoscopy can be helpful in assessing nonpigmented lesions and inflammatory processes like lichen planopilaris (LPP).

Material & Methods

In this observational prospective study, 81 patients with a cicatricial alopecic patch on their scalp were included and underwent dermatologic examination. A biopsy was taken from the active part of the lesion based on dermoscopy evaluation.

Results

Analysis of 44 patients with definite diagnosis of LPP revealed that the mean age at the time of presentation was 44.05 ± 12.62 years. More than 77% of patients had at least one form of the follicular opening disorder. About 75% of patients had shaft disorders. The most common pattern of pigmentation was milky‐red (97.73%). The irregular and ectatic vascular network were seen in 59.09% of patients. Patients with coiled and twisted hairs, small yellow dots, large yellow dots, and peripilar sign were more likely to have shorter disease duration (P < 0.05). Those with overall shaft disorders were younger (P = 0.02). Small yellow dots (P = 0.025) and peripilar sign (P = 0.039) were more common in female patients.

Conclusion

Dermoscopy can be a helpful diagnostic tool in differentiating LPP among patients with primary cicatricial alopecia (PCA). Larger cohort studies are recommended to find the role of demographic factors in predicting the dermoscopic patterns among LPP patients.
A perspective on causation of the chronic fatigue syndrome by considering its nosology
Authors: White Peter Denton
Published: August 2019

The causes of chronic fatigue syndrome (CFS) remain unknown, with many failures to replicate new findings. This may be because the condition is hard to diagnose, difficult to classify, or because of its heterogeneous nature. Authors have problems in differentiating CFS from myalgic encephalomyelitis (ME), which leads many to label it as a hybrid CFS/ME or ME/CFS. Attempts to validate the many published criterion‐based definitions have ended in failure. The International Classification of Diseases provide several different descriptions to choose from, although the latest 11th edition has narrowed this down.

This paper describes conventional attempts to define and classify the illness, suggesting that this may be what leads to a failure to replicate putative causes. The approach to CFS/ME may require a shift in the assumption that the illness is homogeneous. An alternative approach is provided by studies suggesting that the condition is heterogeneous.

Conclusion

The way forward may be to be over‐inclusive regarding the diagnosis as a first step, while subdividing the condition into likely subgroups as a means of finding valid and reliable associations with potential causes. Studies of aetiology must involve prospective designs since cross‐sectional studies cannot inform either aetiology or pathophysiology.
Learning values in shared decision‐making in undergraduate paramedic education
Authors: Eaton Georgette
Published: August 2019

Rationale

While professional values are seen as a fundamental part of element of shared decision‐making, there is little research on how they are learnt within the paramedic profession.

Aims and objectives

This study sought to understand how student paramedics developed their professional values within the ambulance practicum.

Method

37 paramedic students and 5 paramedic educators submitted diary entries and took part in focus groups.

Results

There was a general consensus between participants that the study of professional values was viewed as a scholarly activity within the university, and the practicum subsequently viewed as unacademic. Students identified that much of their learning replicated values of the environment they were in, and educators voiced their concerns that this may not always result in the understanding behind professional values.

Conclusion

This study has highlighted that professional values would be worthy of being explored within the paramedic undergraduate curriculum, in an effort to enable students to understand and develop their values during their education and appreciate the importance of values within shared decision‐making.
Histovariability in human clavicular cortical bone microstructure and its mechanical implications
Authors: Crane Matthew A. , Kato Kyle M. , Patel Biren A. , Huttenlocker Adam K.
Published: August 2019

The human clavicle (i.e. collarbone) is an unusual long bone due to its signature S‐shaped curve and variability in macrostructure observed between individuals. Because of the complex nature of how the upper limb moves, as well as due to its complex musculoskeletal arrangement, the biomechanics, in particular the mechanical loadings, of the clavicle are not fully understood. Given that bone remodeling can be influenced by bone stress, the histologic organization of Haversian bone offers a hypothesis of responses to force distributions experienced across a bone. Furthermore, circularly polarized light microscopy can be used to determine the orientation of collagen fibers, providing additional information on how bone matrix might organize to adapt to direction of external loads. We examined Haversian density and collagen fiber orientation, along with cross‐sectional geometry, to test whether the clavicle midshaft shows unique adaptation to atypical load‐bearing when compared with the sternal (medial) and acromial (lateral) shaft regions. Because fractures are most common at the midshaft, we predicted that the cortical bone structure would show both disparities in Haversian remodeling and nonrandomly oriented collagen fibers in the midshaft compared with the sternal and acromial regions. Human clavicles (n = 16) were sampled via thin‐sections at the sternal, middle, and acromial ends of the shaft, and paired sample t‐tests were employed to evaluate within‐individual differences in microstructural or geometric properties. We found that Haversian remodeling is slightly but significantly reduced in the middle of the bone. Analysis of collagen fiber orientation indicated nonrandom fiber orientations that are overbuilt for tensile loads or torsion but are poorly optimized for compressive loads throughout the clavicle. Geometric properties of percent bone area, polar second moment of area, and shape (Imax/Imin) confirmed the conclusions drawn by existing research on clavicle macrostructure. Our results highlight that mediolateral shape changes might be accompanied by slight changes in Haversian density, but bone matrix organization is predominantly adapted to resisting tensile strains or torsion throughout and may be a major factor in the risk of fracture when experiencing atypical compression.
Methodology of blood pressure measurements casts doubt on the validity of the conclusions
Authors: Jolobe O. M. P.
Published: August 2019

Click here to view the Letter to the Editor by Y. Shang and W. Xu.
Functional gastrointestinal disorders in women with systemic lupus erythematosus: A case‐control study
Authors: García‐Carrasco Mario , Mendoza‐Pinto Claudia , Munguía‐Realpozo Pamela , Méndez‐Valderrabano Fabiola , Méndez Martínez Socorro , Etchegaray Morales Ivet , Montiel‐Jarquín Álvaro , López‐Colombo Aurelio , Schmulson Max
Published: August 2019

Background

Systemic lupus erythematosus (SLE) is an autoimmune disease with multisystemic involvement. Gastrointestinal (GI) manifestations are frequent but functional gastrointestinal disorders (FGIDs) have scarcely been studied in SLE. To determine the prevalence of FGIDs and their potential risk factors in SLE female patients vs controls.

Methods

Systemic lupus erythematosus patients meeting the American College of Rheumatology (ACR) criteria and controls completed the Rome III questionnaire for FGIDs and a structured interview to assess sociodemographic, clinical, and treatment variables after excluding organic GI diseases. Logistic regression was used to determine risk factors (ie, alcohol drinking, medications) for FGIDs.

Key Results

Responders included 113 SLE patients and 122 age‐matched controls. The presence of at least one FGIDs was higher in SLE (73.4%) vs controls (54.1%), P = .003. The most frequent FGIDs in SLE patients were nausea and vomiting disorders (NVD), belching disorders, globus, anorectal pain, functional heartburn (FH), and functional bloating (FB). After adjustment for confounding variables, SLE was associated with NVD (OR: 7.1, 95% CI: 2.7‐19.1) globus (3.5, 1.3‐9.3), anorectal pain (3.4, 1.4‐8.4), and FH (2.5, 1.5‐4.4). The simultaneous presence of >1 FGID was more common in SLE patients than controls (69.8% vs 31.8%). Glucocorticoids (5.2, 1.3‐19.9) and non‐steroidal anti‐inflammatory drugs (NSAIDs; 3.0, 1.1‐8.0) were associated with any FGID in SLE patients while alcohol drinking with gallbladder/sphincter of Oddi disorders 7.4 (1.1‐47.3).

Conclusions and Inferences

Functional gastrointestinal disorders are more frequent in SLE patients compared with controls. Medication that may alter gastrointestinal homeostasis, such as glucocorticoids and NSAIDs, are potential risk factors for FGIDs in SLE.
Interacting maternal and spatial cues influence natal – dispersal out of social groups
Authors: Yip Eric C. , Rao Dinesh , Smith Deborah R. , Lubin Yael
Published: August 2019

Proximate cues for animal dispersal are complex and varied. Multiple cues may provide information about different aspects of habitat quality, and these aspects may interact with each other, as well as with population density in different ways. We examined how individuals incorporate multiple cues in their decisions to emigrate and immigrate in the colonial orb‐weaving spider,Cyrtophora citricola. We manipulated maternal feeding as a cue for prey abundance and measured the size of the maternal web, which provides a limited space for philopatric offspring and a second potential dispersal cue. In addition, we recorded all immigration events to determine dispersal distances and the cues juveniles may use in settlement. Dispersal increased when mothers were poorly fed, web sizes were small and clutch sizes were large. In addition to these overall effects, maternal feeding also interacted with web size, indicating that offspring from well‐fed mothers were more tolerant of high sibling densities. We also detected a threshold for the effect of clutch size on dispersal for the first egg sac: below 20 offspring, there was no effect of clutch size, but dispersal increased with clutch size for larger clutches. Dispersal distances were often short, and immigrants preferred sheltered trees and those occupied by adult females. Dispersal not only depended on multiple cues, but these cues interacted, and the importance of web size suggested that saturation of the natal web might force dispersal, at least for spiders with poorly‐fed mothers. How one aspect of habitat quality influences dispersal can therefore depend on the state of other aspects of habitat quality. In particular, some natal resources, such as a nest or territory, may become saturated and limit group size, but this limit will also depend on other factors, such as prey availability.