bluuebunny/crossref_metadata_2025 huggingface dataset:
Muscle Flap Transposition for the Management of Intrathoracic Fistulas
Authors: Asaad Malke , Van Handel Amelia , Akhavan Arya A. , Huang Tony C. T. , Rajesh Aashish , Allen Mark A. , Shen K. Robert , Sharaf Basel , Moran Steven L.
Published: January 2020

Background:

Intrathoracic fistulas pose unique challenges for thoracic and reconstructive surgeons. To decrease the incidence of fistula recurrence, pedicled flaps have been suggested to buttress the repair site. The authors aimed to report their experience with muscle flap transposition for the management of intrathoracic fistulas.

Methods:

A retrospective review of all patients who underwent intrathoracic muscle flap transposition for the management of intrathoracic fistulas from 1990 to 2010 was conducted. Patient demographics, surgical characteristics, and complication rates were abstracted and analyzed.

Results:

A total of 198 patients were identified. Bronchopleural fistula was present in 156 of the patients (79 percent), and 48 had esophageal fistula (24 percent). A total of 238 flaps were used, constituting an average of 1.2 flaps per patient. After the initial fistula repair, bronchopleural fistula complicated the course of 34 patients (17 percent), and esophageal fistula occurred in 13 patients (7 percent). Partial flap loss was identified in 11 flaps (6 percent), and total flap loss occurred in four flaps (2 percent). Median follow-up was 27 months. At the last follow-up, 182 of the patients (92 percent) had no evidence of fistula, 175 (89 percent) achieved successful chest closure, and 164 (83 percent) had successful treatment. Preoperative radiation therapy and American Society of Anesthesiologists score of 4 or greater were identified as risk factors for unsuccessful treatment.

Conclusions:

Intrathoracic fistulas remain a source of major morbidity and mortality. Reinforcement of the fistula closure with vascularized muscle flaps is a viable option for preventing dehiscence of the repair site and can be potentially life-saving.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
Network-Level Correlates of Sexual Risk Among Male Sex Workers in the United States: A Dyadic Analysis
Authors: Biello Katie B. , Goedel William C. , Edeza Alberto , Safren Steven A. , Mayer Kenneth H. , Marshall Brandon D.L. , Latkin Carl , Mimiaga Matthew J.
Published: January 2020

Background:

Male sex workers (MSWs) are at increased risk of HIV infection in the United States. Research is limited on sexual and drug use network characteristics of MSWs.

Setting:

Community-based organization and health center in 2 US Northeast cities.

Methods:

One hundred MSWs completed a behavioral assessment and sexual and drug network inventory. Using dyadic analyses, we assessed whether network characteristics, including sex worker-male client age, race, and HIV status homophily and risk multiplexity (ie, overlap in drug-use and sex networks), were associated with condom use.

Results:

MSW participants' mean age was 33.6. Two-thirds identified as Black or Latino, 12% identified as heterosexual, and 90% reported recent drug use. Participants reported an average of 5.3 male clients in the past month (SD = 3.4), and having anal sex with 74% of these clients, at a rate of 2.2 times per month (SD = 4.6). Participants reported inconsistent condom use during anal sex with 53% of clients. In multivariable models, inconsistent condom use was more common in relationships with presumed HIV status homophily [odds ratio (OR): 1.25; 95% confidence interval (CI): 1.07 to 1.46] and sexual and drug network multiplexity (OR: 1.19; 95% CI: 1.09 to 1.30); and less common within relationships where the client is older than the MSW participant (OR: 0.83; 95% CI: 0.74 to 0.93). Number of multiplex relationships was positively associated with number of condomless anal sex acts with male clients (incidence rate ratio: 1.35; 95% CI: 1.19 to 1.54).

Conclusions:

Network characteristics may contribute to disproportionate HIV risk among MSWs. Modeling studies should include network characteristics when simulating HIV transmission, and future HIV interventions should address the role of networks.
Association Between Inflammatory Pathways and Phenotypes of Pulmonary Dysfunction Using Cluster Analysis in Persons Living With HIV and HIV-Uninfected Individuals
Authors: Qin Shulin , Vodovotz Lena , Zamora Ruben , Fitzpatrick Meghan , Kessinger Cathy , Kingsley Lawrence , McMahon Deborah , DeSensi Rebecca , Leader Joseph K. , Crothers Kristina , Huang Laurence , Morris Alison , Nouraie Mehdi
Published: January 2020

Background:

Persons living with HIV (PLWH) are at risk of developing different phenotypes of chronic lung disease, including chronic obstructive pulmonary disease. Mechanisms underlying these phenotypes are unclear.

Objective:

To identify clusters of peripheral inflammatory mediators associated with pulmonary function to determine inflammatory pathways and phenotypes of chronic obstructive pulmonary disease in PLWH and HIV-uninfected individuals.

Methods:

Study participants were PLWH and HIV-uninfected individuals enrolled in the Pittsburgh HIV Lung Cohort. Pulmonary function tests were performed for all participants. Chest computed tomographic scans were performed in a subset of PLWH. Plasma levels of 19 inflammatory mediators were measured by Luminex or ELISA. Clusters were identified based on the expression pattern of inflammatory mediators in PLWH and HIV-uninfected individuals, and the relationships among clinical parameters were evaluated within clusters by using cluster and network analyses.

Results:

In PLWH, we identified a distinct cluster with higher levels of Th1, Th2, and Th17 inflammatory mediators with increased complexity of these mediators and inferred presence of pathogenic Th17 cell types. Individuals in this cluster had worse airway obstruction and more radiographic emphysema. In HIV-uninfected individuals, a cluster with high-grade systemic inflammation also had worse diffusing capacity for carbon monoxide.

Conclusions:

Inflammatory pathways associated with pulmonary dysfunction in PLWH suggest multifaceted immune dysregulation involved in different phenotypes of pulmonary dysfunction with a potential specific contribution of the Th17 pathway to airway obstruction in PLWH. Identification of these associations may help in development of treatments that could alter the course of the disease.
Liposomal Delivery Improves the Efficacy of Prednisolone to Attenuate Renal Inflammation in a Mouse Model of Acute Renal Allograft Rejection
Authors: van Alem Carla M.A. , Schmidbauer Martina , Rong Song , Derlin Katja , Schmitz Jessica , Bräsen Jan H. , Thorenz Anja , Chen Rongjun , Ruben Jurjen M. , Winter Elizabeth M. , Schilperoort Maaike , Kooijman Sander , Lalai Reshma A. , Metselaar Josbert M. , Klemann Christian , Meier Martin , van Kooten Cees , Gueler Faikah , Rotmans Joris I.
Published: January 2020

Background.

Systemic exposure to high-dose corticosteroids effectively combats acute rejection after kidney transplantation, but at the cost of substantial side effects. In this study, a murine acute renal allograft rejection model was used to investigate whether liposomal-encapsulated prednisolone (LP) facilitates local exposure to enhance its therapeutic effect.

Methods.

Male BalbC recipients received renal allografts from male C57BL/6J donors. Recipients were injected daily with 5 mg/kg cyclosporine A and received either 10 mg/kg prednisolone (P), or LP intravenously on day 0, 3, and 6, or no additional treatment. Functional magnetic resonance imaging (fMRI) was performed on day 6 to study allograft perfusion and organs were retrieved on day 7 for further analysis.

Results.

Staining of polyethylene-glycol-labeled liposomes and high performance liquid chromatography analysis revealed accumulation in the LP treated allograft. LP treatment induced the expression of glucocorticoid responsive gene Fkbp5 in the allograft. Flow-cytometry of allografts revealed liposome presence in CD45+ cells, and reduced numbers of F4/80+ macrophages, and CD3+ T-lymphocytes upon LP treatment. Banff scoring showed reduced interstitial inflammation and tubulitis and fMRI analysis revealed improved allograft perfusion in LP versus NA mice.

Conclusions.

Liposomal delivery of prednisolone improved renal bio-availability, increased perfusion and reduced cellular infiltrate in the allograft, when compared with conventional prednisolone. Clinical studies should reveal if treatment with LP results in improved efficacy and reduced side effects in patients with renal allograft rejection.
Renal Transplantation in Patients Older Than 60 Years With High Comorbidity. Is There a Survival Benefit? A Multicenter Study in Argentina
Authors: Fragale Guillermo Daniel , Pujol Gervasio Soler , Laham Gustavo , Raffaele Pablo , Fortunato Marcela , Imperiali Nora , Giordani María C. , Taylor Marcelo , Ciappa Julio , Matamala Natalia , Maldonado Rafael , Trimarchi Hernán , Pomeranz Vanesa , Naser Sofia , De La Fuente Jorge , Bisigniano Liliana , Antik Ariel
Published: January 2020

Background.

The impact of renal transplantation (RT) in the elderly with many comorbid conditions is a matter of concern. The aim of our study was to assess the impact of RT on the survival of patients older than 60 years compared with those remaining on the waiting list (WL) according to their comorbidities.

Methods.

In this multicentric observational retrospective cohort study, we included all patients older than 60 years old admitted on the WL from 01 January 2006 to 31 December 2016. The Charlson comorbidity index (CCI) score was calculated for each patient at inclusion on the WL. Kidney donor risk index was used to assess donor characteristics.

Results.

One thousand and thirty-six patients were included on the WL of which 371 (36%) received an RT during a median follow-up period of 2.5 (1.4–4.1) years. Patient survival was higher after RT compared to patients remaining on the WL, 87%, 80%, and 72% versus 87%, 55%, and 30% at 1, 3, and 5 years, respectively. After RT survival at 5 years was 37% higher for patients with CCI ≥ 3, and 46% higher in those with CCI < 3, compared with patients remaining on the WL. On univariate and multivariate analysis, patient survival was independently associated with a CCI of ≥3 (hazard ratio 1.62; confidence interval 1.09-2.41; P < 0.02) and the use of calcineurin-based therapy maintenance therapy (hazard ratio 0.53; confidence interval 0.34-0.82; P < 0.004).

Conclusions.

Our study showed that RT improved survival in patients older than 60 years even those with high comorbidities. The survival after transplantation was also affected by comorbidities.
Association of Alemtuzumab Induction With a Significantly Lower Incidence of GVHD Following Intestinal Transplantation: Results of 445 Consecutive Cases From a Single Center
Authors: Vianna Rodrigo , Farag Ahmed , Gaynor Jeffrey J. , Selvaggi Gennaro , Tekin Akin , Garcia Jennifer , Pierce Conlan , Beduschi Thiago
Published: January 2020

Background.

In intestinal transplantation, graft versus host disease (GVHD), while relatively rare, remains a major cause of morbidity and mortality posttransplant. Because of its rarity of occurrence, no multivariable analysis of risk factors for GVHD development has previously been reported.

Methods.

We used Cox stepwise regression to determine the significant multivariable predictors of the hazard rate of developing biopsy-proven GVHD during the first 60 months posttransplant among 445 consecutive intestinal transplant cases at our center since 1994.

Results.

GVHD was observed in 8.8% (39/445); median time-to-GVHD development (range) was 1.5 months (0.5–17.3 mo) posttransplant. Sites of GVHD included skin (N = 21), skin/gastrointestinal tract (N = 6), gastrointestinal tract/rectum (N = 4), skin/liver (N = 4), skin/lung (N = 2), skin/rectum (N = 1), and skin/bone marrow (N = 1). Three factors were selected into the Cox model offering significant protection from GVHD development (listed in order of selection): isolated intestine or liver-intestine (LI) (versus modified multivisceral [MV] or MV) allograft (P = 0.00003), alemtuzumab (versus no induction, anti-CD25, rabbit antithymocyte globulin, or rabbit antithymocyte globulin/rituximab) induction (P = 0.004), and liver inclusion (LI or MV) (P = 0.009). These results remained unchanged even after accounting for the propensity to receive alemtuzumab induction. Observed GVHD incidence was 2.4% (3/125), 0.0% (0/38), 17.9% (7/39), and 11.9% (29/243) for isolated intestine, LI, modified MV, and MV allografts, and 2.7% (3/113) versus 10.8% (36/332) for those receiving versus not receiving alemtuzumab induction, respectively.

Conclusions.

These results may help advance the current state of knowledge about risk factors for GVHD development following intestinal transplantation.
Perceived Social Support in Individuals With Diabetic Foot Ulcers
Authors: Laopoulou Fotini , Kelesi Martha , Fasoi Georgia , Vasilopoulos Georgios , Polikandrioti Maria
Published: January 2020

PURPOSE:

Explore levels of perceived social support and the associated factors among patients with diabetic foot ulcers (DFUs).

DESIGN:

Cross-sectional survey.

SUBJECTS AND SETTING:

Outpatients (n = 140) with DFUs attending a diabetic clinic affiliated with a public hospital in Athens, Greece, for wound care and follow-up visits after healing.

METHODS:

Data collection included demographic, clinical, self-report, and perceived social support, measured with the Multidimensional Scale of Perceived Social Support (MSPSS), during one-on-one interviews at the post-healing follow-up visit.

RESULTS:

For perceived social support, 50% of patients (average age 70 years) scored above 24, 24, and 18 (median) on the MSPSS in the categories of receiving support from significant other, family, and friends, respectively, suggesting high levels of perceived social support. Other statistically significant associations were observed for perceived social support from significant other, family, and friends and marital status (P = .001, P = .001, and P = .004, respectively), patients level of information about their health (P =.002, P =.001, and P =.001, respectively), family level of information (P = .001, P = .001, and P = .004, respectively), and how closely they followed period foot checks (P = .001, P = .002, and P = .011, respectively) and diet (P = .001, P = .001, and P = .001, respectively).

CONCLUSIONS:

Data from our study show that higher levels of perceived social support from significant others, family, and friends were linked to patients and others, being better informed about health status, and other self-care behaviors. Findings underscore the need for health care providers to recognize that social support is an important component of overall DFU management and may guide future interventions to determine which are most effective in enhancing socially supportive behaviors.
Palaeophysiology of pH regulation in tetrapods
Authors: Janis Christine M. , Napoli James G. , Warren Daniel E.
Published: January 2020

The involvement of mineralized tissues in acid–base homeostasis was likely important in the evolution of terrestrial vertebrates. Extant reptiles encounter hypercapnia when submerged in water, but early tetrapods may have experienced hypercapnia on land due to their inefficient mode of lung ventilation (likely buccal pumping, as in extant amphibians). Extant amphibians rely on cutaneous carbon dioxide elimination on land, but early tetrapods were considerably larger forms, with an unfavourable surface area to volume ratio for such activity, and evidence of a thick integument. Consequently, they would have been at risk of acidosis on land, while many of them retained internal gills and would not have had a problem eliminating carbon dioxide in water. In extant tetrapods, dermal bone can function to buffer the blood during acidosis by releasing calcium and magnesium carbonates. This review explores the possible mechanisms of acid–base regulation in tetrapod evolution, focusing on heavily armoured, basal tetrapods of the Permo-Carboniferous, especially the physiological challenges associated with the transition to air-breathing, body size and the adoption of active lifestyles. We also consider the possible functions of dermal armour in later tetrapods, such as Triassic archosaurs, inferring palaeophysiology from both fossil record evidence and phylogenetic patterns, and propose a new hypothesis relating the archosaurian origins of the four-chambered heart and high systemic blood pressures to the perfusion of the osteoderms.

This article is part of the theme issue ‘Vertebrate palaeophysiology’.
Uncoupling of sarcoendoplasmic reticulum calcium ATPase pump activity by sarcolipin as the basis for muscle non-shivering thermogenesis
Authors: Bal Naresh C. , Periasamy Muthu
Published: January 2020

Thermogenesis in endotherms relies on both shivering and non-shivering thermogenesis (NST). The role of brown adipose tissue (BAT) in NST is well recognized, but the role of muscle-based NST has been contested. However, recent studies have provided substantial evidence for the importance of muscle-based NST in mammals. This review focuses primarily on the role of sarcoplasmic reticulum (SR) Ca
2+
-cycling in muscle NST; specifically, it will discuss recent data showing how uncoupling of sarcoendoplasmic reticulum calcium ATPase (SERCA) (inhibition of Ca
2+
transport but not ATP hydrolysis) by sarcolipin (SLN) results in futile SERCA pump activity, increased ATP hydrolysis and heat production contributing to muscle NST. It will also critically examine how activation of muscle NST can be an important factor in regulating metabolic rate and whole-body energy homeostasis. In this regard, SLN has emerged as a powerful signalling molecule to promote mitochondrial biogenesis and oxidative metabolism in muscle. Furthermore, we will discuss the functional interplay between BAT and muscle, especially with respect to how reduced BAT function in mammals could be compensated by muscle-based NST. Based on the existing data, we argue that SLN-mediated thermogenesis is an integral part of muscle NST and that muscle NST potentially contributed to the evolution of endothermy within the vertebrate clade.

This article is part of the theme issue ‘Vertebrate palaeophysiology’.
Thermophysiologies of Jurassic marine crocodylomorphs inferred from the oxygen isotope composition of their tooth apatite
Authors: Séon Nicolas , Amiot Romain , Martin Jeremy E. , Young Mark T. , Middleton Heather , Fourel François , Picot Laurent , Valentin Xavier , Lécuyer Christophe
Published: January 2020

Teleosauridae and Metriorhynchidae were thalattosuchian crocodylomorph clades that secondarily adapted to marine life and coexisted during the Middle to Late Jurassic. While teleosaurid diversity collapsed at the end of the Jurassic, most likely as a result of a global cooling of the oceans and associated marine regressions, metriorhynchid diversity was largely unaffected, although the fossil record of Thalattosuchia is poor in the Cretaceous. In order to investigate the possible differences in thermophysiologies between these two thalattosuchian lineages, we analysed stable oxygen isotope compositions (expressed as δ18O values) of tooth apatite from metriorhynchid and teleosaurid specimens. We then compared them with the δ18O values of coexisting endo-homeothermic ichthyosaurs and plesiosaurs, as well as ecto-poikilothermic chondrichthyans and osteichthyans. The distribution of δ18O values suggests that both teleosaurids and metriorhynchids had body temperatures intermediate between those of typical ecto-poikilothermic vertebrates and warm-blooded ichthyosaurs and plesiosaurs, metriorhynchids being slightly warmer than teleosaurids. We propose that metriorhynchids were able to raise their body temperature above that of the ambient environment by metabolic heat production, as endotherms do, but could not maintain a constant body temperature compared with fully homeothermic ichthyosaurs and plesiosaurs. Teleosaurids, on the other hand, may have raised their body temperature by mouth-gape basking, as modern crocodylians do, and benefited from the thermal inertia of their large body mass to maintain their body temperature above the ambient one. Endothermy in metriorhynchids might have been a by-product of their ecological adaptations to active pelagic hunting, and it probably allowed them to survive the global cooling of the Late Jurassic, thus explaining the selective extinction affecting Thalattosuchia at the Jurassic–Cretaceous boundary.

This article is part of the theme issue ‘Vertebrate palaeophysiology'.
Optimizing Clinical Outcome and Toxicity in Lung Cancer Using a Genomic Marker of Radiosensitivity
Authors: Scott Jacob G. , Sedor Geoff , Kattan Michael W. , Peacock Jeffrey , Grass G. Daniel , Mellon Eric A. , Thapa Ram , Schell Michael , Waller Anthony , Poppen Sean , Andl George , Eschrich Steven A. , Dilling Thomas J. , Dalton William S. , Harrison Louis B. , Fox Tim , Torres-Roca Javier F.
Published: January 2020

Cancer sequencing efforts have demonstrated that cancer is the most complex and heterogeneous disease that affects humans. However, radiation therapy, one of the most common cancer treatments, is prescribed based on an empiric one-size-fits all approach. We propose that the field of radiation oncology is operating under an outdated null hypothesis: that all patients are biologically similar and should uniformly respond to the same dose of radiation. We have previously developed the Genomic Adjusted Radiation Dose (GARD), a method which accounts for biological heterogeneity and can be utilized to predict optimal RT dose for an individual patient. In this article, we utilize GARD to characterize the biological imprecision of one-size-fits-all RT dosing schemes which result in both over- and under-dosing for the majority of patients treated with RT. To elucidate this inefficiency, and therefore the opportunity for improvement using a personalized dosing scheme, we develop a patient-specific competing hazards-style mathematical model combining the canonical equations for tumor control (TCP) and normal tissue complication probabilities (NTCP). This model simultaneously optimizes tumor control and toxicity by personalizing RT dose using patient-specific genomics. Using data from two prospectively collected cohorts of patients with non-small-cell lung cancer, we validate the competing hazards model by demonstrating that it predicts the results of RTOG 0617. We show how 0617 failure can be explained by the biological imprecision of empiric uniform dose escalation which results in 80% of patients being over-exposed to normal tissue toxicity without potential tumor control benefit. In conclusion, our data reveals a tapestry of radiosensitivity heterogeneity, provides a biological framework that explains the failure of empiric RT dose escalation, and quantifies the opportunity to improve clinical outcomes in lung cancer by incorporating genomics into RT.
Using text mining to track outbreak trends in global surveillance of emerging diseases: ProMED-mail
Authors: You Jingxian , Expert Paul , Costelloe Céire
Published: January 2020

Objectives

ProMED-mail (Program for Monitoring Emerging Disease, also abbreviated ProMED) is an international disease outbreak monitoring and early warning system. Every year, users contribute thousands of reports that include reference to infectious diseases and toxins, and these reports are then distributed to all subscribers of ProMED. However, the corpus of reports has not been well studied so far. Thus, we propose to apply text mining methods to derive information pertinent to the characterisation of the stage of an epidemic outbreak from the reports.

Methods

A retrospective study was conducted in ProMED reports in three steps: reports filtering, keywords extraction from reports and finally word co-occurrence network analysis. The keyword extraction was performed with the TextRank algorithm, keywords co-occurrence networks were then produced using the top keywords from each document and multiple network centrality measures were computed to analyse the co-occurrence networks. We used two major outbreaks in recent years, Ebola 2014 and Zika 2015, as cases to illustrate and validate the process.

Results

We found that the information structures extracted at different stages of outbreaks from ProMED are consistent with response strategies as well as situation reports of the World Health Organisation.

Conclusion

This study shows that ProMED provides large valuable information to characterise the evolution of epidemic outbreaks. Our research presents a pipeline that can extract and organise this information in a meaningful way. It also highlights the potential for ProMED mail to be utilised in monitoring, evaluating and improving responses to outbreaks.
Phase Transition of RNA-protein Complexes into Ordered Hollow Condensates
Authors: Alshareedah Ibraheem , Moosa Mahdi Muhammad , Raju Muralikrishna , Potoyan Davit , Banerjee Priya R.
Published: January 2020

Liquid-liquid phase separation of multivalent intrinsically disordered protein-RNA complexes is ubiquitous in both natural and biomimetic systems. So far, isotropic liquid droplets are the most commonly observed topology of RNA-protein condensates in experiments and simulations. Here, by systematically studying the phase behavior of RNA-protein complexes across varied mixture compositions, we report a hollow vesicle-like condensate phase of nucleoprotein assemblies that is distinct from RNA-protein droplets. We show that these vesicular condensates are stable at specific mixture compositions and concentration regimes within the phase diagram and are formed through the phase separation of anisotropic protein-RNA complexes. Similar to membranes composed of amphiphilic lipids, these nucleoprotein-RNA vesicular membranes exhibit local ordering, size-dependent permeability, and selective encapsulation capacity without sacrificing their dynamic formation and dissolution in response to physicochemical stimuli. Our findings suggest that protein-RNA complexes can robustly create lipid-free vesicle-like enclosures by phase separation.

Significance statement

Vesicular assemblies play crucial roles in subcellular organization as well as in biotechnological applications. Classically, the ability to form such assemblies were primarily assigned to lipids and lipid-like amphiphilic molecules. Here, we show that disordered RNA-protein complexes can form vesicle-like ordered assemblies at disproportionate mixture compositions. We also show that the ability to form vesicular assemblies is generic to multi-component systems where phase separation is driven by heterotypic interactions. We speculate that such vesicular assemblies play crucial roles in the formation of dynamic multi-layered subcellular membrane-less organelles and can be utilized to fabricate novel stimuli-responsive microscale systems.
Division of labor between YAP and TAZ in non-small cell lung cancer
Authors: Shreberk-Shaked Michal , Dassa Bareket , Sinha Sanju , Agostino Silvia Di , Azuri Ido , Aylon Yael , Blandino Giovanni , Ruppin Eytan , Oren Moshe
Published: January 2020

Lung cancer is the leading cause of cancer-related deaths worldwide. The paralogous transcriptional cofactors Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ, also called WWTR1), the main downstream effectors of the Hippo signal transduction pathway, are emerging as pivotal determinants of malignancy in lung cancer. Traditionally, studies have tended to consider YAP and TAZ as functionally redundant transcriptional cofactors, with similar biological impact. However, there is growing evidence that each of them also possesses distinct attributes. Here, we sought to systematically characterize the division of labor between YAP and TAZ in non-small cell lung cancer (NSCLC), the most common histological subtype of lung cancer. Employing representative NSCLC cell lines, as well as patient-derived data, we show that the two paralogs orchestrate non-overlapping transcription programs in this cancer type: whereas YAP preferentially regulates gene sets associated with cell division and cell cycle progression, TAZ preferentially regulates genes associated with extracellular matrix organization. Concordantly, depletion of YAP, but not TAZ, leads to growth arrest, while YAP overexpression promotes cell proliferation. Likewise, depletion of TAZ, but not YAP, compromises cell migration, whereas TAZ overexpression enhances migration. Importantly, the differential effects of YAP vs TAZ on key cellular processes are also associated with differential response to anti-cancer therapies. Uncovering the different activities and downstream effects of YAP and TAZ may thus facilitate better stratification of lung cancer patients for anti-cancer therapies.
Beyond the forest-grassland dichotomy: the gradient-like organization of habitats in forest-steppes
Authors: Erdős László , Török Péter , Szitár Katalin , Bátori Zoltán , Tölgyesi Csaba , Kiss Péter János , Bede-Fazekas Ákos , Kröel-Dulay György
Published: January 2020

Featuring a transitional zone between closed forests and treeless steppes, forest-steppes cover vast areas and have outstanding conservation importance. The components of this mosaic ecosystem can conveniently be classified into two basic types, forests and grasslands. However, this dichotomic classification may not fit reality as habitat organization can be much more complex. In this study, our aim was to find out if the main habitat types can be grouped into two distinct habitat categories (which would support the dichotomic description), or a different paradigm better fits this complex ecosystem. We selected six main habitats of sandy forest-steppes, and, using 176 relevés, we compared their vegetation based on species composition (NMDS ordination, number of common species of the studied habitats), relative ecological indicator values (mean indicators for temperature, soil moisture, and light availability), and functional species groups (life-form categories, geoelement types, and phytosociological preference groups). According to the species composition, we found a well-defined gradient, with the following habitat order: large forest patches – medium forest patches – small forest patches – north-facing edges – south-facing edges – grasslands. A considerable number of species were shared among all habitats, while the number of species restricted to certain habitat types was also numerous, especially for north-facing edges. The total (i.e., pooled) number of species peaked near the middle of the gradient, in north-facing edges. The relative ecological indicator values and functional species groups showed mostly gradual changes from the large forest patches to the grasslands. Our results indicate that the widely used dichotomic categorization of forest-steppe habitats into forest and grassland patches is too simplistic, potentially resulting in a considerable loss of information. We suggest that forest-steppe vegetation better fits the gradient-based paradigm of landscape structure, which is able to reflect continuous variations.
New intranuclear symbiotic bacteria from macronucleus ofParamecium putrinum—CandidatusGortzia yakutica
Authors: Beliavskaia Alexandra , Logacheva Maria , Garushyants Sofya , Gong Jun , Zou Songbao , Gelfand Mikhail , Rautian Maria
Published: January 2020

Holospora-like bacteria are obligate intracellularAlphaproteobacteria, inhabiting nuclei ofParameciumciliates and other protists.Alphaproteobacteriahave drawn significant attention, as both closest existing relatives of bacteria that gave rise to mitochondria, as well as a class of intracellular bacteria with numerous important pathogens.

HLB clade includes two genera –Holospora(Hafkine 1980) andcandidatusGortzia (Boscaro 2013). These bacteria have a peculiar life cycle with two morphological forms, a strict specificity to the host species and the type of nucleus they inhabit.

Here we describe a new species of HLB –candidatusGortzia yakutica sp. nov., a symbiont from macronucleus ofParamecium putrinum, the first known HLB for thisParameciumspecies. The new symbiont shows morphological similarities with other HLB. The phylogenetic analysis of SSU rDNA gene places it intocandidatusGortzia clade.
Surface topography is a context-dependent activator of TGF-β signaling in mesenchymal stem cells
Authors: Vermeulen Steven , Roumans Nadia , Honig Floris , Carlier Aurélie , Hebels Dennie G.A.J. , Dede Eren Aysegul , ten Dijke Peter , Vasilevich Aliaksei , de Boer Jan
Published: January 2020

We previously found that surface topographies induce the expression of theScxagene, encoding Scleraxis in tenocytes. BecauseScxais a TGF-β responsive gene, we investigated the link between mechanotransduction and TGF-β signaling. We discovered that mesenchymal stem cells exposed to both micro-topographies and TGF-β2 display synergistic induction of SMAD phosphorylation and transcription of the TGF-β target genesSCXA,a-SMA, andSOX9. Pharmacological perturbations revealed that Rho/ROCK/SRF signaling is required for this synergistic response. We further found an activation of the early response genesSRFandEGR1during the early adaptation phase on micro-topographies, which coincided with higher expression of the TGF-β type-II receptor gene. Of interest, PKC activators Prostratin and Ingenol-3, known for inducing actin reorganization and activation of serum response elements, were able to mimic the topography-induced TGF-β response. These findings provide novel insights into the convergence of mechanobiology and TGF-β signaling, which can lead to improved culture protocols and therapeutic applications.
Impact of a resistance gene against a fungal pathogen on the plant host residue microbiome: the case of theLeptosphaeria maculans-Brassica napuspathosystem
Authors: Kerdraon Lydie , Barret Matthieu , Balesdent Marie-Hélène , Suffert Frédéric , Laval Valérie
Published: January 2020

Oilseed rape residues are a crucial determinant of stem canker epidemiology, as they support the sexual reproduction of the fungal pathogenLeptosphaeria maculans. The aim of this study was to characterise the impact of a resistance gene againstL. maculansinfection on residue microbial communities and to identify micro-organisms interacting with this pathogen during residue degradation. We used near-isogenic lines to obtain healthy and infected host plants. The microbiome associated with the two types of plant residues was characterised by metabarcoding. A combination of linear discriminant analysis and ecological network analysis was used to compare the microbial communities and to identify micro-organisms interacting withL. maculans. Fungal community structure differed between the two lines at harvest, but not subsequently, suggesting that the presence/absence of the resistance gene influences the microbiome at the base of the stem whilst the plant is alive, but that this does not necessarily lead to differential colonisation of the residues by fungi. Direct interactions with other members of the community involved many fungal and bacterial ASVs (amplicon sequence variants).L. maculansappeared to play a minor role in networks, whereas one ASV affiliated toPlenodomus biglobosus(synonymLeptosphaeria biglobosa) from theLeptosphaeriaspecies complex may be considered a keystone taxon in the networks at harvest. This approach could be used to identify and promote micro-organisms with beneficial effects against residue-borne pathogens, and more broadly, to decipher the complex interactions between multi-species pathosystems and other microbial components in crop residues.
Identification of a Δ11 desaturase from the arbuscular mycorrhizal fungusRhizophagus irregularis
Authors: Cheeld Henry , Bhutada Govindprasad , Beaudoin Frederic , Eastmond Peter J
Published: January 2020

Arbuscular mycorrhizal fungi are oleaginous organisms and the most abundant fatty acyl moiety usually found in their lipids is palmitvaccenic acid (16:1Δ11cis). However, it is not known how this uncommon fatty acid species is made. Here we have cloned two homologs of Lepidopteran fatty acyl-CoenzymeA Δ11 desaturases fromRhizophagus irregularis. BothDES1andDES2are expressed in intraradicle mycelium and can complement the unsaturated fatty acid-requiring auxotrophic growth phenotype of theSaccharomyces cerevisiae ole1Δmutant. DES1 expression leads almost exclusively to oleic acid (18:1Δ9cis) production, whereas DES2 expression results in the production of 16:1Δ11cisand vaccenic acid (18:1Δ11cis).DES2therefore encodes a Δ11 desaturase that is likely to be responsible for the synthesis of 16:1Δ11cisinR. irregularis.
Clinical competence assessment: development of a mobile app to enhance patient centerderness
Authors: Lucio-Ramirez César Alberto , Nigenda Juan Pablo , Garcia-Garcia Marisol , Olivares Silvia Lizett
Published: January 2020

Purpose

The current emphasis within education is on collaboration, data-driven decision-making, and assessment driven accountability. Medical education is now being oriented to guarantee patient-centered care. Having appropriate data from student outcomes is crucial for decision making on both educational and health care institutions. This paper describes the development of a mobile app to assess the clinical competencies of medical students for timely and quality feedback.

Design

The app development included 4 phases. The conceptual model was designed on collaborative and multidisciplinary focus groups with clinicians, information technology professionals, hospital directors, and change managers. The prototype was an app with functional and friendly features to assess students with Patient-Centered Learning perspectives. Innovative features included student profiles, multiple examiners, customizable instruments, and data reports. The pilot started with faculty training and monitoring by information technology professionals. For a broader implementation, detailed rubrics were applied to assess the clinical competencies on bedside (ambulatory care, surgical procedures and emergency skills) and non-bedside learning moments (case discussions and rounds).

Findings

Non-bedside learning moments had the highest frequency (55.3 vs 28.8 per cent) of the records. Case discussions represented 40.7 per cent of assessments while rounds accounted for 14.6 per cent. In contrast, regarding the bedside learning moments, the emergency department had the lowest figures (3.5 per cent). It seems that faculty prefers to grade students on academic activities rather than complex student patient encounters.

Originality

Obtaining multiple results from real-time feedback promoted awareness of patient centeredness on medical students. Both the medical school and the hospital now have accountable information for decision making.
Micro-credentials: the potential of personalized professional development
Authors: Hunt Tiffany , Carter Richard , Zhang Ling , Yang Sohyun
Published: January 2020

Purpose

The purpose of this article is to introduce micro-credentials as an innovative, personalized professional development modality. With traditional time bound professional development (PD) offering largely whole group instruction with little feedback or a focus on skill mastery, micro-credentials have the ability to develop educator skills, provide relevant content, encourage flexibility, and measure earner mastery. Although relatively new, state leaders and administrators are exploring the use of micro-credentials to improve educator practice at the individual level. Such efforts encourage systems change aligned with new technologies and advancements.

Design/methodology/approach

This article is designed to review the impetus for the use of micro-credentials in education and the potential this personalized professional development has to change and improve traditional support of educators' professional growth and skill development. We structured the article to first introduce the possibilities micro-credentials (MCs) have in initiating systems change in education. We then define MCs and explore their use in state policy. Additionally, we present the benefits MCs offer and how an individual would select and complete one. To conclude, we connect all elements in the article and emphasize the need for further research and analysis.

Findings

Findings from our review indicate that 9 states are currently exploring the use of micro-credentials in their state ESSA plans. We recognize that there are several benefits of micro-credentials that make them appealing to state leaders and administrators. These include personalization, competency, flexibility, cost efficiency, and collaboration. It is noted that a large number of organizations are offering micro-credentials and it is most often the responsibility of educators to determine which micro-credentials meet their needs and may be utilized for continuing education credit. Steps in earning micro-credentials are similar across platforms, though content, assessment expectations, and depth vary widely.

Originality/value

Rapid strides in technology have created change and advancements to societal norms, required workforce skillsets, and personalization. As a result, leaders in education are exploring new and innovative ways to provide professional development to educators. This article will introduce the concept of micro-credentials and explore their focus on personalization, competency-based learning, flexibility and skill development. Individuals interested in shifting the delivery and methodology of traditional PD will be intrigued by the potential micro-credentials offer and the work that is currently being done to explore this PD option.
Futures Triangle 2.0: integrating the Futures Triangle with Scenario Planning
Authors: Fergnani Alessandro
Published: January 2020

Purpose

The purpose of this paper is to introduce the Futures Triangle 2.0, a methodological advancement of the Futures Triangle method (Inayatullah, 2008), which better integrates the original method with Scenario Planning by visually representing scenarios against the three dimensions of the Triangle, i.e. pulls, pushes and weights.

Design/methodology/approach

The paper explains the theoretical rationale behind the creation of the method, outlines the steps required to use it in a futures workshop or in a futures research project with a step-by-step procedure and reports a case study of its application in practice.

Findings

The Futures Triangle 2.0 encourages a deliberate and systematic discussion on the three dimensions of the Futures Triangle in each scenario and on whether scenarios differ in these attributes. The method allows the foresight researcher/practitioner to capture the valuable tensions between weights on the past on one hand and pushes of the present/pulls of the futures on the other hand, and to make sure that the scenarios differ substantially in these three attributes.

Originality/value

The method integrates the Futures Triangle and Scenario Planning in an intuitive, easily reproducible and visually pleasant graphical procedure.
Audit quality, media coverage, environmental, social, and governance disclosure and firm investment efficiency
Authors: Hammami Ahmad , Hendijani Zadeh Mohammad
Published: January 2020

Purpose

The purpose of this study is twofold: first, to introduce two determinants of environmental, social and governance (ESG) disclosure transparency, namely, audit quality and public media exposure; and second, to investigate the impact of ESG transparency on firm-level investment efficiency.

Design/methodology/approach

Ordinary least square (OLS) regressions are applied to explore the relationship between the two variables of interest (audit quality and public media exposure) and ESG transparency on a sample of publicly listed Canadian firms during the period 2008 to 2017. Then, an econometric model is used to investigate the association between ESG transparency and investment efficiency under two identified scenarios, under-investment and over-investment.

Findings

Results show that audit quality and public media exposure are two main drivers of ESG transparency, hence, commitment to high-quality audits and exposure to high public media coverage drive firms to disclose more extensive and transparent ESG information. The authors also find a negative association between ESG transparency and firm-level investment inefficiency. Thus, ESG transparency generates influential incremental information that helps mitigate the information asymmetry between firms and stakeholders while fostering better resource allocation through investment efficiency.

Originality/value

This study contributes to the corporate social responsibility (CSR) and ESG literature by identifying audit quality and public media exposure as two determinants of ESG transparency; and by noting that higher ESG transparency has a significant economic effect on capital investment decisions through higher firm-level investment efficiency.
Integrated STEM teaching competencies and performances as perceived by secondary teachers in South Korea
Authors: Song Miran
Published: January 2020

Purpose

The purpose of this paper is to explore what key competencies and characteristics of teachers are needed for integrated Science, Technology, Engineering and Mathematics (STEM) teaching and to investigate teachers’ perceptions on how important those competencies are and how often they are executed.

Design/methodology/approach

An exploratory sequential mixed methods approach was used to investigate key characteristics of integrated STEM teaching competencies and the level of their importance and performance as perceived by teachers. By using behavioral event interview technique, qualitative data were collected from professional secondary teachers in science, math and technology subjects. An instrument was constructed based on the result of qualitative research; and a survey was conducted with 48 STEM teachers working in South Korea. The mean values between importance and performance of integrated STEM teaching competencies were compared. A perceived importance level of each item was compared with a practice level by using importance-performance analysis.

Findings

As a result of qualitative research, in total 21 items were constructed as detailed characteristics of each domain of integrated STEM teaching competencies, which provide insights about teachers’ perceptions of teaching competencies that are critical for integrated STEM education. A comparison of means between importance and performance of integrated STEM teaching competencies showed that whereas teachers considered each of these items to be of significant importance in their overall evaluation of the integrated STEM teaching competencies, they are not performing at a level that reflects the assigned importance.

Practical implications

This research results provide information for future research on how to implement an integrated STEM education initiative at the secondary school level, for planning teacher training programs, pre-service teacher education and related educational policies.

Originality/value

South Korea has focused on integrated STEM education to raise talented human resources in the fields of science and technology. However, many teachers have experienced serious difficulties and troubles in executing integrated STEM education. It is necessary to figure out key competencies and characteristics of teachers to facilitate integrated STEM teaching.