bluuebunny/crossref_metadata_2025 huggingface dataset:
High‐resolution microstructural and compositional analyses of shock deformed apatite from the peak ring of the Chicxulub impact crater
Authors: Cox Morgan A. , Erickson Timmons M. , Schmieder Martin , Christoffersen Roy , Ross Daniel K. , Cavosie Aaron J. , Bland Phil A. , Kring David A. ,   IODP–ICDP Expedition 364 Scientists
Published: August 2020

The mineral apatite, Ca5(PO4)3(F,Cl,OH), is a ubiquitous accessory mineral, with its volatile content and isotopic compositions used to interpret the evolution of H2O on planetary bodies. During hypervelocity impact, extreme pressures shock target rocks resulting in deformation of minerals; however, relatively few microstructural studies of apatite have been undertaken. Given its widespread distribution in the solar system, it is important to understand how apatite responds to progressive shock metamorphism. Here, we present detailed microstructural analyses of shock deformation in ~560 apatite grains throughout ~550 m of shocked granitoid rock from the peak ring of the Chicxulub impact structure, Mexico. A combination of high‐resolution backscattered electron (BSE) imaging, electron backscatter diffraction mapping, transmission Kikuchi diffraction mapping, and transmission electron microscopy is used to characterize deformation within apatite grains. Systematic, crystallographically controlled deformation bands are present within apatite, consistent with tilt boundaries that contain the  (axis) and result from slip in <> (direction) on (plane) during shock deformation. Deformation bands contain complex subgrain domains, isolated dislocations, and low‐angle boundaries of ~1° to 2°. Planar fractures within apatite form conjugate sets that are oriented within either {, {, {, or . Complementary electron microprobe analyses (EPMA) of a subset of recrystallized and partially recrystallized apatite grains show that there is an apparent change in MgO content in shock‐recrystallized apatite compositions. This study shows that the response of apatite to shock deformation can be highly variable, and that application of a combined microstructural and chemical analysis workflow can reveal complex deformation histories in apatite grains, some of which result in changes to crystal structure and composition, which are important for understanding the genesis of apatite in both terrestrial and extraterrestrial environments.
Kinetics in thermal evolution of Raman spectra of chondritic organic matter to evaluate thermal history of their parent bodies
Authors: Kiryu Kento , Kebukawa Yoko , Igisu Motoko , Shibuya Takazo , Zolensky Michael E. , Kobayashi Kensei
Published: August 2020

In order to establish kinetic expressions for Raman spectroscopic parameters of organic matter in chondritic meteorites with heating, a series of heating experiments (at 600–900 °C for 3–48 h) of the Murchison (CM2) meteorite was conducted. For comparison, several carbonaceous chondrites with various metamorphic degrees—Allende (CV3.2), Moss (CO3.6), Yamato (Y‐) 793321 (heated CM2), and Tagish Lake (ungrouped C2)—were also analyzed by the Raman spectrometer. Changes in the full width at half maximum of the D1 band (ΓD) of heated Murchison correlated well with temperature and time, and showed similar trends of chondrites with various metamorphic degrees. We obtained the kinetic expressions for the changes in ΓD by heating to estimate the time–temperature history of thermally metamorphosed type 3 chondrites and heated CM chondrites. Our results may also be useful for asteroids which are the targets of Hayabusa2 and OSIRIS‐REx missions.
Illuminating the impact of diel vertical migration on visual gene expression in deep‐sea shrimp
Authors: DeLeo Danielle M. , Bracken‐Grissom Heather D.
Published: August 2020

Diel vertical migration (DVM) of marine animals represents one of the largest migrations on our planet. Migrating fauna are subjected to a variety of light fields and environmental conditions that can have notable impacts on sensory mechanisms, including an organism's visual capabilities. Among deep‐sea migrators are oplophorid shrimp that vertically migrate hundreds of metres to feed in shallow waters at night. These species also have bioluminescent light organs that emit light during migrations to aid in camouflage. The organs have recently been shown to contain visual proteins (opsins) and genes that infer light sensitivity. Knowledge regarding the impacts of vertical migratory behaviour, and fluctuating environmental conditions, on sensory system evolution is unknown. In this study, the oplophorid Systellaspis debilis was either collected during the day from deep waters or at night from relatively shallow waters to ensure sampling across the vertical distributional range. De novo transcriptomes of light‐sensitive tissues (eyes/photophores) from the day/night specimens were sequenced and analysed to characterize opsin diversity and visual/light interaction genes. Gene expression analyses were also conducted to quantify expression differences associated with DVM. Our results revealed an expanded opsin repertoire among the shrimp and differential opsin expression that may be linked to spectral tuning during the migratory process. This study sheds light on the sensory systems of a bioluminescent invertebrate and provides additional evidence for extraocular light sensitivity. Our findings further suggest opsin co‐expression and subsequent fluctuations in opsin expression may play an important role in diversifying the visual responses of vertical migrators.
Warning bells: How clinicians leverage their discomfort to manage moments of uncertainty
Authors: Ilgen Jonathan S. , Teunissen Pim W. , de Bruin Anique B. H. , Bowen Judith L. , Regehr Glenn
Published: August 2020

Objectives

It remains unclear how medical educators can more effectively bridge the gap between trainees’ intolerance of uncertainty and the tolerance that experienced physicians demonstrate in practice. Exploring how experienced clinicians experience, appraise and respond to discomfort arising from uncertainty could provide new insights regarding the kinds of behaviours we are trying to help trainees achieve.

Methods

We used a constructivist grounded theory approach to explore how emergency medicine faculty experienced, managed and responded to discomfort in settings of uncertainty. Using a critical incident technique, we asked participants to describe case‐based experiences of uncertainty immediately following a clinical shift. We used probing questions to explore cognitive, emotional and somatic manifestations of discomfort, how participants had appraised and responded to these cues, and how they had used available resources to act in these moments of uncertainty. Two investigators coded the data line by line using constant comparative analysis and organised transcripts into focused codes. The entire research team discussed relationships between codes and categories, and developed a conceptual framework that reflected the possible relationships between themes.

Results

Participants identified varying levels of discomfort in their case descriptions. They described multiple cues alerting them to problems that were evolving in unexpected ways or problems with aspects of management that were beyond their abilities. Discomfort served as a trigger for participants to monitor a situation with greater attention and to proceed more intentionally. It also served as a prompt for participants to think deliberately about the types of human and material resources they might call upon strategically to manage these uncertain situations.

Conclusions

Discomfort served as a dynamic means to manage and respond to uncertainty. To be ‘tolerant’ of uncertainty thus requires clinicians to embrace discomfort as a powerful tool with which to grapple with the complex problems pervasive in clinical practice.
Coordinated regulation of anthranilate metabolism and bacterial virulence by the GntR family regulator MpaR in Pseudomonas aeruginosa
Authors: Wang Tietao , Qi Yihang , Wang Zhihan , Zhao Jingru , Ji Linxuan , Li Jun , Cai Zhao , Yang Liang , Wu Min , Liang Haihua
Published: August 2020

The GntR family regulators are widely distributed in bacteria and play critical roles in metabolic processes and bacterial pathogenicity. In this study, we describe a GntR family protein encoded by PA4132 that we named MpaR (MvfR‐mediated PQS and anthranilate regulator) for its regulation of Pseudomonas quinolone signal (PQS) production and anthranilate metabolism in Pseudomonas aeruginosa. The deletion of mpaR increased biofilm formation and reduced pyocyanin production. RNA sequencing analysis revealed that the mRNA levels of antABC encoding enzymes for the synthesis of catechol from anthranilate, a precursor of the PQS, were most affected by mpaR deletion. Data showed that MpaR directly activates the expression of mvfR, a master regulator of pqs system, and subsequently promotes PQS production. Accordingly, deletion of mpaR activates the expression of antABC genes, and thus, increases catechol production. We also demonstrated that MpaR represses the rhl quorum‐sensing (QS) system, which has been shown to control antABC activity. These results suggested that MpaR function is integrated into the QS regulatory network. Moreover, mutation of mpaR promotes bacterial survival in a mouse model of acute pneumonia infection. Collectively, this study identified a novel regulator of pqs system, which coordinately controls anthranilate metabolism and bacterial virulence in P. aeruginosa.
Invasive Scedosporium and Lomentosora infections in the era of antifungal prophylaxis: A 20‐year experience from a single centre in Spain
Authors: Álvarez‐Uría Ana , Guinea Jesus Vicente , Escribano Pilar , Gómez‐Castellá Javier , Valerio Maricela , Galar Alicia , Vena Antonio , Bouza Emilio , Muñoz Patricia
Published: August 2020

Background

Non‐Aspergillus mould infections such as those caused by Scedosporium apiospermum or Lomentospora prolificans are an emerging threat. Few studies have monitored their long‐term incidence.

Objectives

To analyse the epidemiology, risk factors, clinical features and incidence of patients with proven and probable infections.

Patients/Methods

Patients admitted to Gregorio Marañón Hospital between 1998 and 2017 and from whom Scedosporium/Lomentospora was isolated were studied. Subjects were classified as having a probable/proven invasive fungal infection or colonization. Molecular identification and antifungal susceptibility testing of isolates causing infection were performed, as well as a description of the patients and incidence of infection.

Results

One or more Scedosporium/Lomentospora isolates were identified in 67 patients. Sixteen (23.9%) patients had developed infection: 11 scedosporiosis and 5 lomentosporiosis. Stable incidence was observed throughout the study period. Most patients were immunosuppressed and the most common underlying diseases were haematologic malignancy (25%), solid organ transplantation (25%) and chronic corticoid therapy (25%). Breakthrough infection occurred in four patients, 2/11 (18.2%) cases of scedosporiosis and 2/5 (40%) of lomentosporiosis. Overall mortality was 54.5% (6/11) and 80% (4/5) in subjects with scedosporiosis and lomentosporiosis, respectively. High MICs of amphotericin B and remarkable inter‐species susceptibility variability to triazoles was observed for most isolates.

Conclusions

In contrast to previous studies, the incidence of scedosporiosis and lomentosporiosis has not increased at our hospital over the years. The tendency to cause disseminated infection and a reduced susceptibility to most antifungal agents leads to high mortality.
The analysis of epidermal nerve fibre spatial distribution improves the diagnostic yield of skin biopsy
Authors: Piscosquito G. , Provitera V. , Mozzillo S. , Caporaso G. , Borreca I. , Stancanelli A. , Manganelli F. , Santoro L. , Nolano M.
Published: August 2020

Aim

Small fibre neuropathy (SFN) diagnosis represents a challenge for neurologists. The diagnostic gold standard is intraepidermal nerve fibre (IENF) density, but in about 10–20% of patients with symptoms/signs and abnormalities on functional tests, it remains within normal range. We propose an adjunctive parameter to improve the efficiency of skin biopsy diagnosis.

Methods

We recruited 31 patients with SFN symptoms/signs, normal nerve conduction study, abnormal quantitative sensory testing and normal IENF density. We also included 31 healthy controls and 31 SFN patients with reduced IENF density as control groups.

Results

We measured the distance between consecutive IENFs in the three groups. Mean inter‐fibre distances did not differ between patients with normal counts and healthy controls (66.7 ± 14.5 μm vs. 76.7 ± 13.4 μm; P = 0.052), while the relative standard deviation was significantly (P < 0.001) higher in patients (79.3 ± 29.9) compared to controls (51.6 ± 12.2). Using ROC analysis, we identified an inter‐fibre distance of 350 µm as the measure that better differentiated patients from controls (AUC = 0.85, sensitivity: 74%, specificity: 94%). At least one such segment was also observed in all patients with reduced IENF count.

Conclusion

Irregular spatial distribution is an SFN intrinsic feature preceding actual nerve loss. The presence of a stretch of denervated epidermis longer than 350 µm is a parameter able to increase the diagnostic efficiency of skin biopsy.
Critical care nurses' experiences of nursing intoxicated patients after abuse of drugs
Authors: Wedin Adam , Sandström Stina , Sandström Linda , Forsberg Angelica
Published: August 2020

Background

Patients intoxicated after abusing illicit drugs constitute a significant proportion of patients cared for in intensive care units. Intensive critical care nurses who nurse accidentally intoxicated patients face complex and demanding situations, and there is a lack of studies regarding this topic.

Aims and objectives

To illuminate Swedish intensive critical care nurses' experiences of nursing accidentally intoxicated patients after abuse of illicit drugs.

Design

A qualitative design with an inductive approach was used.

Methods

Semi‐structured interviews were conducted with eight intensive critical care nurses at an intensive care unit in Sweden. Data were analysed using qualitative content analysis.

Findings

The themes found illuminate intensive critical care nurses' experiences of nursing accidentally intoxicated patients after their abuse of illicit drugs: feeling empathy and a wish to provide dignified care; dreading nursing the patient and feeling a lack of empathy; feeling frustration and questioning the care; lacking knowledge about a complex and challenging situation.

Conclusions

It is essential to respond to intoxicated patients with empathy and dignity. Intensive critical care nurses should learn how to identify factors that lead to provocation and agitation in order to reduce the occurrence of dangerous situations in intensive care units.

Relevance to clinical practice

To create a caring environment where the interaction becomes more positive and harmonious, an intensive care nurse needs a deep understanding of what a drug abuse disorder means. Moreover, the ability to see the person behind the abuse and to provide non‐judgemental support is required.

What is known about this topic

Patients intoxicated after abuse of illicit drugs constitute a significant proportion of patients cared for in ICUs worldwide.

Intensive critical nurses who nurse accidentally intoxicated patients face complex and demanding situations, and few studies have addressed this topic.

What this paper contributes

It is essential to respond to intoxicated patients who are admitted to the ICU with empathy and dignity, as well as to learn how to identify factors that lead to provocation and agitation in order to reduce the occurrence of dangerous situations.

Education is warranted and must be enhanced, including knowledge about drug abuse and training in communication and empathy

Nursing should include an understanding of what the disease of drug abuse means and the development of the ability to see the person behind the abuse and to provide non‐judgemental support.
Insights on arrhythmia termination and type 2 breaks after ICD therapy delivery
Authors: Gagno Giulia , Zoppo Franco
Published: August 2020

Introduction of anti‐tachycardia pacing (ATP) therapy and longer detection intervals delivery have allowed to safely reduce unnecessary shocks, improving survival and quality of life in implantable cardioverter defibrillator (ICD) patients. However, there are still outstanding issues, especially regarding the mode of arrhythmias termination after ATP or shock delivery. Regardless of ICD therapy efficacy, the arrhythmia interruption does not always occur abruptly, indeed both nonsustained tachy‐ or bradyarrhythmias have been described after ICD therapy delivery, being the former classified as type 2 interruption. Several physiopathological mechanisms have been suggested to be responsible for this phenomenon. Our aim is to review current data on postshock and post‐ATP arrhythmias and to give insights on their possible mechanisms.
Early cutis marmorata telangiectatica congenita masquerading as ulcerated retiform purpura: a diagnostic trap
Authors: MacGibeny Margaret A. , John Ann M. , Milgraum David M. , Wassef Cindy , Milgraum Sandy S.
Published: August 2020

Cutis marmorata telangiectatica congenita (CMTC) is a rare congenital cutaneous vascular anomaly with a reticular marbled erythematous pattern, which can result in isolated benign skin lesions or less commonly be associated with systemic anomalies. Occasionally, the characteristic pattern of CMTC lesions is masked on initial presentation, creating a diagnostic conundrum that can result in unnecessary workups to rule out vasculopathy. We present the case of a female newborn with a red‐blue ulcerated skin lesion on the right leg and foot, which initially appeared as retiform purpura but evolved to exhibit the mottled pattern of CMTC by 5 days of age. Clinicians must be made aware of this potential diagnostic trap in early CMTC to avoid invasive skin biopsies and unnecessary laboratory testing in neonates.
Adversarial Classification: Impact of Agents’ Faking Cost on Firms and Agents
Authors: Cezar Asunur , Raghunathan Srinivasan , Sarkar Sumit
Published: August 2020

Classification of agents such as suppliers and customers into good and bad types based on their attributes is ubiquitous in business. In adversarial classification contexts, firms face agents who fake their attributes to receive favorable decisions from the classifier; for instance, suppliers could misrepresent their safety or quality features in order to qualify as a firm’s accredited vendor. Anticipating such faking by agents, firms may strategically design their classifiers and may also verify the information presented by agents. We examine the impact of agents’ faking on the firm and on agents in a context in which agents of two types—good‐risk and bad‐risk—have possibly different faking costs. We find that the firm is hurt when bad‐risk agents’ faking costs decrease, and the firm benefits when good‐risk agents’ faking costs decrease. We find that agents do not always benefit when faking becomes easier. Further, a decrease in faking costs of one type will sometimes benefit the other type. We show that when the faking costs decrease the firm may be better off using some attributes that do not offer a positive value to the firm at the higher faking cost. Though supplementing a strategic classifier with verification of the agents’ information could benefit the firm, 100% verification may not be optimal even if there was no cost incurred in conducting verification. Experiments conducted using a Naive Bayes classifier on a real‐world dataset demonstrate that our findings hold for extant (and potentially non‐optimal) commercial classifiers.
Green hay transfer for grassland restoration: species capture and establishment
Authors: Wagner Markus , Hulmes Sarah , Hulmes Lucy , Redhead John W. , Nowakowski Marek , Pywell Richard F.
Published: August 2020

Green hay transfer from species‐rich donor sites is now commonly used in Europe to restore species‐rich semi‐natural grassland, both on ex‐arable land and on former intensive grassland. However, species transfer rates are usually well below 100%, and due to lack of further colonization by additional target species after initial restoration, continued progress toward the target plant community is often very slow. We used data from a restoration experiment aiming to reestablish species‐rich grazed meadows of the MG5 grassland type according to the British National Vegetation Classification to investigate relationships between species abundance at a donor site, species capture by green hay and its seed content, and success of species establishment on experimental plots in formerly intensively managed species‐poor grassland undergoing restoration. Our results show that species with higher abundance at the donor site were more likely captured as seed in green hay, and were more likely to establish after hay application at the recipient site. Species with low abundance at the donor site that also possessed specific germination requirements that might prevent immediate establishment after green hay transfer were particularly unlikely to get established after transfer. These findings can provide guidance for additional measures aimed at ensuring establishment of a wider range of target species. Such measures could include targeted sowing of species in addition to green hay application, and management of restored grassland swards to extend or reopen an initial window of opportunity for the establishment of green hay species that might not be germinable immediately after hay transfer.
Action capability constrains visuo‐motor complexity during planning and performance in on‐sight climbing
Authors: van Knobelsdorff Marlene H. , van Bergen Nikki G. , van der Kamp John , Seifert Ludovic , Orth Dominic
Published: August 2020

The capability to adapt to changing conditions is crucial for safe and successful performance in physical activities and sports. According to the affordance‐based control perspective, individuals act in such a way as to take into account the limits of their capability to act. However, it is not clear how strength interacts with skill in shaping performer‐environment interactions. We, therefore, determined whether fingertip strength influences patterns of gaze and climbing behavior on new routes of ever‐increasing difficulty. We expected that comparatively weaker climbers would show less complex behavior because of an inability to perceive and act. Stronger climbers would show more complex visuo‐motor behavior because more opportunities for action remain, even as route difficulty increases. For very strong climbers the route would not be challenging enough, and less complex patterns suffice. Twenty climbers, ranging from lower grade to elite level participated. Maximum fingertip strength was obtained. Participants previewed and then climbed two separate 3 m long traverses, gradually decreasing in edge depth. Gaze and hip positions were collected for subsequent computation of gaze transition entropy (during preview) and hip displacement entropy (during climbing). Data revealed statistically significant curvilinear relationships between both fingertip strength and gaze transition entropy, and fingertip strength, and hip displacement entropy. Visuo‐motor complexity is scaled by how close the individual must act relative to boundaries of what the environment affords and does not afford for action given the individual constraints. Future research should examine in greater detail relationships between action capabilities and functional movement variability.
A universal parallel scheduling approach to polyline and polygon vector data buffer analysis on conventional GIS platforms
Authors: Guo Mingqiang , Han Chengde , Guan Qingfeng , Huang Ying , Xie Zhong
Published: August 2020

With the increasing volume of spatial data, conventional vector data buffer analysis algorithms cannot meet the demands of fast data processing, so parallel computing is introduced to accelerate vector data analysis. However, it is difficult for these GIS platforms to adopt parallel approaches to conduct buffer analysis due to their conventional data format and vector buffer analysis algorithms. To address the problem, a universal parallel scheduling approach to buffer analysis on conventional GIS platforms is proposed in this study. First, the key impacting factor of buffer analysis computing time is identified. The relationship between the impacting factor and the buffer analysis computing time is analyzed to generate computational intensity transformation functions. Then, computational intensity grids (CIGs) of polyline and polygon are constructed by partially computing the computational intensity of a lattice. Using the corresponding CIGs, a two‐stage adaptive spatial decomposition method for parallel buffer analysis is developed. Firstly, the whole domain of the spatial vector dataset is divided into sub‐domains, with the computational intensity of each sub‐domain being equal as far as possible; secondly, the features are evenly assigned within the sub‐domains into parallel buffer analysis tasks for load balance. The experiments demonstrate that the approach presented in this article can effectively evaluate and spatially represent the computational intensity of buffer analysis for polylines and polygons. Compared with typical spatial adaptive decomposition methods and regular domain decomposition methods, the new approach accomplishes greater balanced decomposition of computational intensity for parallel buffer analysis and achieves near‐linear speedups. The new approach achieves excellent performance on three conventional GIS platforms, indicating that our approach is an effective parallel scheduling approach to vector data buffer analysis for conventional GIS platforms.
Secondary bacterial culture of platelets to mitigate transfusion‐associated sepsis: A 3‐year analysis at a large academic institution
Authors: Fenwick Alexander J. , Gehrie Eric A. , Marshall Christi E. , Tobian Aaron A. R. , Shrestha Ruchee , Kacker Seema , Brunker Patricia A. R. , Shifflett Lisa , Carroll Karen C. , Gozelanczyk Donna , Goel Ruchika , Ness Paul M. , Bloch Evan M.
Published: August 2020

Background

In 2019, the United States Food and Drug Administration published its final recommendations to mitigate bacterial contamination of platelets. We sought to evaluate our secondary bacterial culture (SBC) strategy in light of those recommendations.

Study Design and Methods

A retrospective analysis was conducted of SBC data (October 2016‐2019) at our institution. SBC was performed upon receipt (Day 3 after collection); 5 mL of platelet product was inoculated aseptically into an aerobic bottle and incubated at 35°C for 3 days. For 8 months, a 10‐mL inoculum was trialed. No quarantine was applied. All positive cultures underwent Gram staining and repeat culture of the platelet product (if available). A probable true positive was defined as concordant positive culture between the initial and repeat culture. The incidence of probable true‐ and false‐positive cultures were reported descriptively and differences evaluated by sampling volume.

Results

Over 3 years, 55 896 platelet products underwent SBC, yielding 30 initial positive results (approx. 1/1863 platelets); 25 (83.3%) signaled within 24 hours of SBC. The rates of probable true positive, false positive, and indeterminate for 5 mL were 0.027% (1/3771), 0.002% (1/45 251) and 0.018% (1/5656), respectively. The respective rates for 10 mL were 0.018% (1/5323), 0.07% (1/1521), and 0%. Seven of eight (87.5%) false‐positive SBCs occurred with a 10‐mL inoculum. No septic transfusion reactions were reported.

Conclusion

SBC continues to interdict bacterially contaminated units of platelets. Our findings suggest higher rates of false positivity using large‐volume inocula.
Dynamics of shape recovery by stored red blood cells during washing at the single cell level
Authors: Lu Madeleine , Shevkoplyas Sergey S.
Published: August 2020

Background

Hypothermic storage transforms red blood cells (RBC) from smooth biconcave discocytes into increasingly spherical spiculated echinocytes and, ultimately, fragile spherocytes (S). Individual cells undergo this transformation at different rates, producing a heterogeneous mixture of RBCs at all stages of echinocytosis in each unit of stored blood. Here we investigated how washing (known to positively affect RBC properties) changes morphology of individual RBCs at the single‐cell level.

Study Design and Methods

We tracked the change in shape of individual RBCs (n = 2870; drawn from six 4‐ to 6‐week‐old RBC units) that were confined in an array of microfluidic wells during washing in saline (n = 1095), 1% human serum albumin (1% HSA) solution (n = 999), and the autologous storage supernatant (control, n = 776).

Results

Shape recovery proceeded through the disappearance of spicules followed by the progressive smoothening of the RBC contour, with the majority of changes occurring within the initial 10 minutes of being exposed to the washing solution. Approximately 57% of all echinocytes recovered by at least one morphologic class when washed in 1% HSA (36% for normal saline), with 3% of cells in late‐stage echinocytosis restoring their discoid shape completely. Approximately one‐third of all spherocytic cells were lysed in either washing solution. Cells washed in their autologous storage supernatant continued to deteriorate during washing.

Conclusion

Our findings suggest that the replacement of storage supernatant with a washing solution during washing induces actual shape recovery for RBCs in all stages of echinocytosis, except for S that undergo lysis instead.
Richardson Extrapolation: An Info-Gap Analysis of Numerical Uncertainty
Authors: Ben-Haim Yakov , Hemez François
Published: August 2020

Computational modeling and simulation is a central tool in science and engineering, directed at solving partial differential equations for which analytical solutions are unavailable. The continuous equations are generally discretized in time, space, energy, etc., to obtain approximate solutions using a numerical method. The aspiration is for the numerical solutions to asymptotically converge to the exact-but-unknown solution as the discretization size approaches zero. A generally applicable procedure to assure convergence is unavailable. The Richardson extrapolation is the main method for dealing with this challenge, but its assumptions introduce uncertainty to the resulting approximation. We use info-gap decision theory to model and manage its main uncertainty, namely, in the rate of convergence of numerical solutions. The theory is illustrated with a numerical application to Hertz contact in solid mechanics.
Carbonization of 3D printed polymer structures for CMOS-compatible electrochemical sensors
Authors: Haque Mohammad Aminul , Lavrik Nickolay V. , Hedayatipour Ava , Hensley Dale , Briggs Dayrl P. , McFarlane Nicole
Published: August 2020

Carbon based electrodes suitable for integration with CMOS readout electronics are of great importance for a variety of emerging applications. In this study, we have looked into the prerequisites for the optimized pyrolytic conversion of 3D printed polymer microstructures and nanostructures with the goal of developing sensing electrodes for a lab-on-CMOS electrochemical system. As a result, we identified conditions for a sequence of anneals in oxidative and inert environments that yield carbonized structures on metallized substrates with improved shape retention, while also providing electrical insulation of the surrounding metal stack. We demonstrated that titanium metal layers can be conveniently used to form electrically insulating titanium oxide on the substrate outside the carbonized structures in a self-aligned fashion. However, significant shrinkage of polymer structures formed by 3D printing or stereolithography is inevitable during their pyrolysis. Furthermore, the catalytically active titanium oxide present during initial stages of carbonization leads to additional loss of carbon and significant artifacts in the resulting structures. To minimize these adverse effects of titanium oxide on the shape retention of the carbonized structures, we developed an optimized processing sequence. Various processing steps in this sequence were characterized in terms of their effects on titanium oxide growth and geometrical changes in the 3D printed structures, while impedance and Raman spectroscopy were performed to evaluate their degree of pyrolytic conversion and, therefore, potential for electrochemical sensing.
Coordinating a neutrophil swarm
Authors: VanHook Annalisa M.
Published: August 2020

Ca
2+
and ATP signaling control the self-organized, collective behaviors of neutrophils at wound sites.
Genetic Reprogramming of the Ergot Alkaloid Pathway of Metarhizium brunneum
Authors: Davis Kyle A. , Sampson Jessi K. , Panaccione Daniel G.
Published: August 2020

Ergot alkaloids derived from LA or DHLA are the bases for numerous pharmaceuticals with applications in the treatment of dementia, migraines, hyperprolactinemia, and other conditions. However, extraction of ergot alkaloids from natural sources is inefficient, and their chemical synthesis is expensive. The ability to control and redirect ergot alkaloid synthesis in fungi may allow more efficient production of these important chemicals and facilitate research on novel derivatives. Our results show that
Metarhizium brunneum
can be engineered to efficiently produce and secrete LA and DHLA and, also, to produce a novel derivative of DHLA not previously found in nature. The engineering of dihydroergot alkaloids, including a novel species, is important because very few natural sources of these compounds are known. Our approach establishes a platform with which to use
M. brunneum
to study the production of other ergot alkaloids, specifically those classified as lysergic acid amides and dihydroergot alkaloids.
Paracellular Pathway-Mediated Mycoplasma hyopneumoniae Migration across Porcine Airway Epithelial Barrier under Air-Liquid Interface Conditions
Authors: Wang Haiyan , Zhang Zhenzhen , Xie Xing , Liu Beibei , Wei Yanna , Gan Yuan , Yuan Ting , Ni Bo , Wang Jia , Zhang Lei , Xiong Qiyan , Shao Guoqing , Feng Zhixin
Published: August 2020

Mycoplasma hyopneumoniaeis an important respiratory pathogen of pigs that causes persistent and secondary infections. However, the mechanisms by which this occurs are unclear. In this study, we established air-liquid interface culture systems for pig bronchial epithelial cells (ALI-PBECs) that were comparable to the conditions in the native bronchusin vivo. We used this ALI-PBECs model to study the infection and migration characteristics ofM. hyopneumoniaein vitro.
Integrative Analysis of Proteome and Transcriptome Dynamics during Bacillus subtilis Spore Revival
Authors: Swarge Bhagyashree , Abhyankar Wishwas , Jonker Martijs , Hoefsloot Huub , Kramer Gertjan , Setlow Peter , Brul Stanley , de Koning Leo J.
Published: August 2020

This study demonstrated the progress of macromolecular synthesis during
Bacillus subtilis
spore germination and outgrowth. The transcriptome analysis has additionally allowed us to trace gene expression during this transformation process. For the first time, the basic survival kit for spore-based life has been identified. In addition, in this analysis based on monitoring of protein levels in germinating and outgrowing spores, the transition from (ribo)nucleotide and amino acid biosynthesis to the restoration of all metabolic pathways can be clearly seen. The integrative multi-omics approach applied in this study thus has helped us to achieve a comprehensive overview of the molecular mechanisms at the basis of spore germination and outgrowth as well as to identify important knowledge gaps in need of further study.
Tn-Seq Analysis Identifies Genes Important for Yersinia pestis Adherence during Primary Pneumonic Plague
Authors: Eichelberger Kara R. , Sepúlveda Victoria E. , Ford John , Selitsky Sara R. , Mieczkowski Piotr A. , Parker Joel S. , Goldman William E.
Published: August 2020

Colonization of the lung by
Yersinia pestis
is a critical first step in establishing infection during primary pneumonic plague, a disease characterized by high lethality. However, the mechanisms by which
Y. pestis
adheres in the lung after inhalation remain elusive. Here, we used Tn-seq to identify
Y. pestis
genes important for adherence early during primary pneumonic plague. Our mutant enrichment strategy resulted in the identification of genes important for regulation and assembly of genes and proteins rather than adhesin genes themselves. These results reveal that there may be multiple
Y. pestis
adhesins or redundancy among adhesins. Identifying the adhesins regulated by the genes identified in our enrichment screen may reveal novel therapeutic targets for preventing
Y. pestis
adherence and the subsequent development of pneumonic plague.
Multidisciplinary approach in medicine: successful pregnancy in a patient with hyperinsulinism/hyperammonaemia (HI/HA) syndrome
Authors: Benner Bernadette J M , Bazelmans Mijke , Huidekoper Hidde , Langeveld Mirjam , Langendonk Janneke , Schoenmakers Sam
Published: August 2020

This case illustrates the importance of multidisciplinary counselling and management of pregnancies in women with complex medical conditions, especially concerning women with cognitive impairment. We present a woman with hyperinsulinism/hyperammonaemia (HI/HA) syndrome. This syndrome is characterised by recurrent episodes of hypoglycaemia and elevated ammonia levels, which are potentially harmful to both the patient and a developing fetus. We describe a successful multidisciplinary approach during the pregnancy of a mentally challenged patient with HI/HA syndrome. This case illustrates the importance of personalised counselling during the preconception period and emphasises to include all disciplines involved in the medical and daily care of such a patient. In our case, the extensive multidisciplinary care during the preconception period, pregnancy, delivery and postpartum period resulted in a good maternal and neonatal outcome.
Helicobacter pylori infection in children
Authors: Aguilera Matos Idalmis , Diaz Oliva Sarah Esther , Escobedo Angel A , Villa Jiménez Oscar Manuel , Velazco Villaurrutia Yamila del Carmen
Published: August 2020

Helicobacter pylori infection affects more than half of the world population and it occurs generally in childhood. It is associated with gastroduodenal ulcer, gastric atrophy, intestinal metaplasia, gastric adenocarcinoma and lymphoid tissue-associated lymphoma. It is difficult to eradicate this bacterium due to its high antimicrobial resistance. In children, the infection is asymptomatic in the majority of cases and complications are less common. Probable inverse relationships with allergic diseases and inflammatory bowel diseases are being studied. These reasons mean that the decision to diagnose and treat the infection in children is only considered in specific circumstances in which it provides true benefits. This review focuses on some current considerations regarding epidemiology, diagnosis and treatment of childhood infection, emphasising outcomes and treatment schemes in children.
Tumor infiltrating lymphocytes (TIL) therapy in metastatic melanoma: boosting of neoantigen-specific T cell reactivity and long-term follow-up
Authors: van den Berg Joost H , Heemskerk Bianca , van Rooij Nienke , Gomez-Eerland Raquel , Michels Samira , van Zon Maaike , de Boer Renate , Bakker Noor A M , Jorritsma-Smit Annelies , van Buuren Marit M , Kvistborg Pia , Spits Hergen , Schotte Remko , Mallo Henk , Karger Matthias , van der Hage Joris A , Wouters Michel W J M , Pronk Loes M , Geukes Foppen Marnix H , Blank Christian U , Beijnen Jos H , Nuijen Bastiaan , Schumacher Ton N , Haanen John B A G
Published: August 2020

Treatment of metastatic melanoma with autologous tumor infiltrating lymphocytes (TILs) is currently applied in several centers. Robust and remarkably consistent overall response rates, of around 50% of treated patients, have been observed across hospitals, including a substantial fraction of durable, complete responses.

Purpose

Execute a phase I/II feasibility study with TIL therapy in metastatic melanoma at the Netherlands Cancer Institute, with the goal to assess feasibility and potential value of a randomized phase III trial.

Experimental

Ten patients were treated with TIL therapy. Infusion products and peripheral blood samples were phenotypically characterized and neoantigen reactivity was assessed. Here, we present long-term clinical outcome and translational data on neoantigen reactivity of the T cell products.

Results

Five out of 10 patients, who were all anti-PD-1 naïve at time of treatment, showed an objective clinical response, including two patients with a complete response that are both ongoing for more than 7 years. Immune monitoring demonstrated that neoantigen-specific T cells were detectable in TIL infusion products from three out of three patients analyzed. For six out of the nine neoantigen-specific T cell responses detected in these TIL products, T cell response magnitude increased significantly in the peripheral blood compartment after therapy, and neoantigen-specific T cells were detectable for up to 3 years after TIL infusion.

Conclusion

The clinical results from this study confirm the robustness of TIL therapy in metastatic melanoma and the potential role of neoantigen-specific T cell reactivity. In addition, the data from this study supported the rationale to initiate an ongoing multicenter phase III TIL trial.
An open-label, phase II multicohort study of an oral hypomethylating agent CC-486 and durvalumab in advanced solid tumors
Authors: Taylor Kirsty , Loo Yau Helen , Chakravarthy Ankur , Wang Ben , Shen Shu Yi , Ettayebi Ilias , Ishak Charles A , Bedard Philippe L , Abdul Razak Albiruni , R Hansen Aaron , Spreafico Anna , Cescon Dave , Butler Marcus O , Oza Amit M , Lheureux Stephanie , Stjepanovic Neda , Van As Brendan , Boross-Harmer Sarah , Wang Lisa , Pugh Trevor J , Ohashi Pamela S , Siu Lillian L , De Carvalho Daniel D
Published: August 2020

Purpose

To evaluate whether administration of the oral DNA hypomethylating agent CC-486 enhances the poor response rate of immunologically ‘cold’ solid tumors to immune checkpoint inhibitor durvalumab.

Experimental design

PD-L1/PD-1 inhibitor naïve patients with advanced microsatellite stable colorectal cancer; platinum resistant ovarian cancer; and estrogen receptor positive, HER2 negative breast cancer were enrolled in this single-institution, investigator-initiated trial. Two 28 day regimens, regimen A (CC-486 300 mg QD Days 1–14 (cycles 1–3 only) in combination with durvalumab 1500 mg intravenous day 15) and regimen B (CC-486 100 mg QD days 1–21 (cycle 1 and beyond), vitamin C 500 mg once a day continuously and durvalumab 1500 mg intravenous day 15) were investigated. Patients underwent paired tumor biopsies and serial peripheral blood mononuclear cells (PBMCs) collection for immune-profiling, transcriptomic and epigenomic analyzes.

Results

A total of 28 patients were enrolled, 19 patients treated on regimen A and 9 on regimen B. The combination of CC-486 and durvalumab was tolerable. Regimen B, with a lower dose of CC-486 extended over a longer treatment course, showed less grade 3/4 adverse effects. Global LINE-1 methylation assessment of serial PBMCs and genome-wide DNA methylation profile in paired tumor biopsies demonstrated minimal changes in global methylation in both regimens. The lack of robust tumor DNA demethylation was accompanied by an absence of the expected ‘viral mimicry’ inflammatory response, and consequently, no clinical responses were observed. The disease control rate was 7.1%. The median progression-free survival was 1.9 months (95% CI 1.5 to 2.3) and median overall survival was 5 months (95% CI 4.5 to 10).

Conclusions

The evaluated treatment schedules of CC-486 in combination with durvalumab did not demonstrate robust pharmacodynamic or clinical activity in selected immunologically cold solid tumors. Lessons learned from this biomarker-rich study should inform continued drug development efforts using these agents.

Trial registration number

NCT02811497.
Benefit of primary percutaneous coronary interventions in the elderly with ST segment elevation myocardial infarction
Authors: Fernández-Bergés Daniel , Degano Irene R , Gonzalez Fernandez Reyes , Subirana Isaac , Vila Joan , Jiménez-Navarro Manuel , Perez-Fernandez Silvia , Roqué Mercé , Bayes-Genis Antoni , Fernandez-Aviles Francisco , Mayorga Antonio , Bertomeu-Gonzalez Vicente , Sanchis Juan , Rodríguez Esteban Marcos , Sanchez-Hidalgo Antonio , Sanchez-Insa Esther , Elorriaga Ane , Abu Assi Emad , Nuñez Alberto , Garcia Ruiz Jose Manuel , Morrondo Valdeolmillos Pedro , Bosch-Portell Daniel , Lekuona Iñaki , Carrillo-Lopez Andres , Zamora Alberto , Vega-Hernandez Berta , Alameda Serrano Javier , Rubert Catalina , Ruiz-Valdepeñas Luis , Quintas Laura , Rodríguez-Padial Luis , Vaquero Jessica , Martinez Dolz Luis , Barrabes Jose A , Sanchez Pedro L , Sionis Alessandro , Martí-Almor Julio , Elosua Roberto , Lidon Rosa-María , Garcia-Dorado David , Marrugat Jaume
Published: August 2020

Objective

Primary percutaneous coronary intervention (P-PCI) has demonstrated its efficacy in patients with ST segment elevation myocardial infarction (STEMI). However, patients with STEMI ≥75 years receive less P-PCI than younger patients despite their higher in-hospital morbimortality. The objective of this analysis was to determine the effectiveness of P-PCI in patients with STEMI ≥75 years.

Methods

We included 979 patients with STEMI ≥75 years, from theATención HOspitalaria del Síndrome coronariostudy, a registry of 8142 consecutive patients with acute coronary syndrome admitted at 31 Spanish hospitals in 2014–2016. We calculated a propensity score (PS) for the indication of P-PCI. Patients that received or not P-PCI were matched by PS. Using logistic regression, we compared the effectiveness of performing P-PCI versus non-performance for the composite primary event, which included death, reinfarction, acute pulmonary oedema or cardiogenic shock during hospitalisation.

Results

Of the included patients, 81.5 % received P-PCI. The matching provided two groups of 169 patients with and without P-PCI. Compared with its non-performance, P-PCI presented a composite event OR adjusted by PS of 0.55 (95% CI 0.34 to 0.89).

Conclusions

Receiving a P-PCI was significantly associated with a reduced risk of major intrahospital complications in patients with STEMI aged 75 years or older.