bluuebunny/crossref_metadata_2025 huggingface dataset:
Interhemispheric comparison of scale‐dependent spatial variation in the structure of intertidal rocky‐shore communities
Authors: Catalán Alexis M. , Valdivia Nelson , Scrosati Ricardo A.
Published: June 2020

In rocky intertidal habitats, the pronounced increase in environmental stress with elevation, caused by tides, generates significant vertical variation in community structure. Along coastlines, environmental changes generate horizontal biological variation, which, when measured at large sampling intervals, generally surpasses vertical biological variation. It is unknown, however, how vertical biological variation compares with horizontal biological variation when the latter is measured in environmentally similar habitats. We tested the hypothesis that, for sites experiencing similar environmental conditions along the shore, horizontal biological variation does not surpass vertical biological variation even when horizontal variation is measured at large sampling intervals along the coast. We compared vertical and horizontal variation in intertidal communities by surveying habitats experiencing the same wave exposure on the NW Atlantic and SE Pacific coasts. We measured biological variation based on differences in species richness, occurrence, and abundance between quadrats from low and high elevations (vertical variation) and between quadrats at three horizontal scales of sampling interval on both coasts: local (tens of cm between quadrats), meso‐ (˜100 km between quadrats), and regional (˜200 km between quadrats). We measured biological variation for all species combined, separately for sessile and mobile species, and for the numerically dominant species. The data analyses indicated that horizontal biological variation was never higher than vertical biological variation, not even at the regional scale, providing support for our hypothesis. Overall, our findings suggest that studies comparing spatial scales of biological variation should consider the underlying environmental variation in addition to simply scale alone.
Valorization of spent black tea by recovery of antioxidant polyphenolic compounds: Subcritical solvent extraction and microencapsulation
Authors: Rajapaksha D.S.W. , Shimizu Naoto
Published: June 2020

Spent black tea (SBT), waste remaining after producing tea beverages, is potentially an underutilized source of antioxidant phenolic compounds. This study evaluated the integrated processes of subcritical solvent extraction of polyphenols from SBT followed by microencapsulation to improve the stability of obtained extract. Optimization of extraction conditions was carried out by response surface methodology for the best recovery of antioxidant phenolic compounds. Two variables [temperature (°C) and ethanol concentration (%)] were used to design the optimization model using central composite inscribed. Extraction temperature of 180°C and ethanol concentration of 71% were optimal for the highest yield of total polyphenols (126.89 mg gallic acid equiv./g SBT) and 2,2‐diphenyl‐1‐picrylhydrazyl scavenging activity (69.08 mg gallic acid equiv./g SBT). The extract was encapsulated using pectin, sodium caseinate, and a blend of these compounds (ratio 1:1) as wall materials by spray drying. The wall material significantly influenced (p < .05) encapsulation efficiency, particle size, morphology, thermal stability, crystallinity, and storage stability. The blend of wall materials produced an amorphous powder with the highest phenolic retention (94.28%) in the accelerated storage at 45°C for 40 days. The microcapsules prepared with sodium caseinate were smaller with lowest mean diameter and highest thermal stability than the other types of materials. Obtained microencapsulates have potential use in different food systems to enhance their antioxidant property.
Zur Ermittlung von resultierenden Wasserdrücken auf Uferwände in Tidegebieten
Authors: Nuber Thomas , Pohl Martin
Published: June 2020

Bei der Bemessung von Uferwänden sind die aus den Grund‐ und Oberflächenwässern resultierenden Druck‐ und Strömungskräfte als Einwirkungen zu berücksichtigen. Für Tidegebiete sind in den EAU 2012 Näherungsansätze enthalten. Anhand dieser Näherungsansätze können für die einzelnen Bemessungssituationen die anzusetzenden Wasserstände abgeschätzt werden. Die Näherungsansätze sind allgemeingültig, sodass bei bestimmten hydraulischen Randbedingungen und örtlichen Verhältnissen die resultierenden Wasserdrücke weit auf der sicheren Seite liegen können. Vor diesem Hintergrund kann es sinnvoll sein, die resultierenden Wasserdrücke auf der Grundlage von Grundwasserstandsmessungen festzulegen. An einem Beispiel wird gezeigt, welche Auswerteansätze für die Verhältnisse in den norddeutschen Tidegebieten zu verfolgen sind, um die resultierenden Wasserdrücke zu ermitteln und zudem die hydrogeologischen Verhältnisse genauer zu erfassen. Hierbei liegen die resultierenden Wasserdrücke, die über eine Auswertung der Grundwasserstände und eine Grundwassermodellierung ermittelt wurden, weit unterhalb der Werte, die sich aus den EAU‐Näherungsansätzen ergeben. Somit wird über Messungen und Auswertungen von Grundwasserstandsdaten eine wirtschaftlichere Bemessung von Uferwänden in Tidegebieten ermöglicht, sodass für die norddeutschen Tidegebiete Grundwassermessungen grundsätzlich zu empfehlen sind.
62,406 and Counting
Authors: Berlinger Nancy
Published: June 2020

What will we remember, as scholars, practitioners, policy‐makers, educators, and citizens, about this acute phase of the catastrophe in the United States? The shocking federal failure concerning testing? That the first shortage was not of ventilators but protective gear? How infection rates and deaths in communities of color, immigrant neighborhoods, and nursing homes mercilessly exposed the relationship between social inequalities and health inequities? I hope we will remember that the field of bioethics did good work under pressure, learned that public health ethics and global health ethics are about securing the conditions for decent lives and decent work as well as saving lives, and committed ourselves to progress on the problem of inequality.
Learning from a Pandemic
Authors: Kaebnick Gregory E. , Haupt Laura
Published: June 2020

The Covid‐19 pandemic has highlighted connections between health and social structural phenomena that have long been recognized in bioethics but have never really been front and center—not just access to health care, but fundamental conditions of living that affect public health, from income inequality to political and environmental conditions. In March, as the pandemic spread globally, the field's traditional focus on health care and health policy, medical research, and biotechnology no longer seemed enough. The adequacy of bioethics seemed even less certain after the killing of George Floyd, whose homicide showed in an especially agonizing way how social institutions are in effect (and often intentionally) designed to make the lives of black people go poorly and end early. Whether bioethics needs to be expanded, redirected, and even reconceived is at the heart of the May‐June 2020 issue of the Hastings Center Report, which is devoted to questions provoked by and lessons emerging during this pandemic.
Ventilators, Guidelines, Judgment, and Trust
Authors: Gorovitz Samuel
Published: June 2020

Covid‐19 confronts us with tragic choices, in which every option is unacceptable. On the New York State Task Force on Life and the Law, I worked on guidelines for such situations. We did not envision the scale or character of Covid‐19. To minimize fear that the decisions made in these situations might be unfair, we all must know what guidelines or mandates inform them. Only with transparency about how decisions will be made, by whom, and according to what requirements can we have confidence that fairness prevails. We now face many related questions about process, goals, leadership, and trust. For example, how might ethical guidelines evolve as scientific understanding advances? Should guidelines vary with different venues? And if, as I have argued, judgment is necessary even with the best of guidelines, how can we prepare clinicians to make good judgments? Are there implications for better training of personnel in nonemergency times for what they might face in the worst of times?
Realigning Pakistan's Bioethics Center during Covid‐19
Authors: Moazam Farhat , Jafarey Aamir
Published: June 2020

The arrival of the Covid‐19 pandemic in Pakistan necessitated that the Centre of Biomedical Ethics and Culture in Karachi realign its activities to changing realities in the country. As Pakistan's only bioethics center, and with no guidelines available for allocation of scarce medical resources, CBEC developed “Guidelines for Ethical Healthcare Decision‐Making in Pakistan” with input from medical and civil society stakeholders. The CBEC blog connected to the center's bioethics programs for students from Pakistan and Kenya shifted to Covid‐related issues specific to the context of existing social and political realities within these countries. As part of its outreach activities, CBEC initiated a popular Facebook series, #HumansofCovid, as an experience‐sharing platform for health care professionals and members of the public. Narratives received vary from those by frustrated physicians under quarantine to those concerning street vendors left jobless and a transsexual person in whose opinion “social distancing” is not a new phenomenon for their communities.
Walls
Authors: Hauser Joshua M.
Published: June 2020

In a field that strives to care for patients and families together, what can palliative care clinicians do when patients’ families are physically absent? The Covid‐19 pandemic has put both literal and figurative walls between health care professionals and families. How health care workers respond to these disconnections might have a lasting impact on patients, on families, and on our practice. Recently, I saw this in the case of a patient our palliative care team was consulted to see. Mr. B was minimally responsive and dying from multisystem organ failure of unclear etiology. As in other cases during this pandemic, our team became a facilitator of interaction between the patient and the physically absent family, seeing an intimacy we normally would not, in this case, by being present while our intern held the phone to Mr. B's ear for an end‐of‐life call from his wife, son, and daughter. Such moments force us clinicians to be even more present for our families and patients, and they allow us to bear witness to the strength and sadness and love that we might otherwise miss.
Disability Rights as a Necessary Framework for Crisis Standards of Care and the Future of Health Care
Authors: Guidry‐Grimes Laura , Savin Katie , Stramondo Joseph A. , Reynolds Joel Michael , Tsaplina Marina , Burke Teresa Blankmeyer , Ballantyne Angela , Kittay Eva Feder , Stahl Devan , Scully Jackie Leach , Garland‐Thomson Rosemarie , Tarzian Anita , Dorfman Doron , Fins Joseph J.
Published: June 2020

In this essay, we suggest practical ways to shift the framing of crisis standards of care toward disability justice. We elaborate on the vision statement provided in the 2010 Institute of Medicine (National Academy of Medicine) “Summary of Guidance for Establishing Crisis Standards of Care for Use in Disaster Situations,” which emphasizes fairness; equitable processes; community and provider engagement, education, and communication; and the rule of law. We argue that interpreting these elements through disability justice entails a commitment to both distributive and recognitive justice. The disability rights movement's demand “Nothing about us, without us” requires substantive inclusion of disabled people in decision‐making related to their interests, including in crisis planning before, during, and after a pandemic like Covid‐19.
Interdependent Citizens: The Ethics of Care in Pandemic Recovery
Authors: Gary Mercer , Berlinger Nancy
Published: June 2020

The crisis of Covid‐19 has forced us to notice two things: our human interdependence and American society's tolerance for what Nancy Krieger has called “inequalities embodied in health inequities,” reflected in data on Covid‐19 mortality and geographies. Care is integral to our recovery from this catastrophe and to the development of sustainable public health policies and practices that promote societal resilience and reduce the vulnerabilities of our citizens. Drawing on the insights of Joan Tronto and Eva Feder Kittay, we argue that the ethics of care offers a critical alternative to utilitarian and deontological approaches and provides a street‐ready framework for integration into public health deliberations to anchor public policy and investments concerning the recovery and future well‐being of America's citizens and society.
Black Lives in a Pandemic: Implications of Systemic Injustice for End‐of‐Life Care
Authors: Elbaum Alan
Published: June 2020

In recent months, Covid‐19 has devastated African American communities across the nation, and a Minneapolis police officer murdered George Floyd. The agents of death may be novel, but the phenomena of long‐standing epidemics of premature black death and of police violence are not. This essay argues that racial health and health care disparities, rooted as they are in systemic injustice, ought to carry far more weight in clinical ethics than they generally do. In particular, this essay examines palliative and end‐of‐life care for African Americans, highlighting the ways in which American medicine, like American society, has breached trust. In the experience of many African American patients struggling against terminal illness, health care providers have denied them a say in their own medical decision‐making. In the midst of the Covid‐19 pandemic, African Americans have once again been denied a say with regard to the rationing of scarce medical resources such as ventilators, in that dominant and ostensibly race‐neutral algorithms sacrifice black lives. Is there such thing as a “good” or “dignified” death when African Americans are dying not merely of Covid‐19 but of structural racism?
Avoiding Ineffective End‐of‐Life Care: A Lesson from Triage?
Authors: Latham Stephen R.
Published: June 2020

Ethicists and physicians all over the world have been working on triage protocols to plan for the possibility that the Covid‐19 pandemic will result in shortages of intensive care unit beds, ventilators, blood products, or medications. In reflecting on those protocols, many health care workers have noticed that, outside the pandemic shortage situation, we routinely supply patients in the ICU with invasive and painful care that will not help the patients survive even their hospitalization. This is the kind of pointless care that even the most basic protocol would triage against. Perhaps this widespread reflection on triage standards will draw our attention to our ongoing custom of supplying burdensome and inefficacious care to those near the end of life—care that most health care providers would not want for themselves. This essay argues that reflecting on triage could help us improve end‐of‐life care.
Reassessing the Three Rs?
Authors: Challenger Melanie
Published: June 2020

In recent years, the established paradigm of the three Rs of animal research—refinement, replacement, and reduction—has come under scrutiny. A crucial weakness in use of the three Rs is uncertainty about how they should be prioritized. Events like pandemics have the power to alter the research landscape, fast‐tracking innovation and setting new precedents. Existential threats can raise perceptions of social benefit and can lower animal‐welfare thresholds. The rush to develop new research models may also undermine progress in reducing or replacing animal models. By circumventing the barrier posed by animal models that are poorly matched to human conditions, new technologies like CRISPR can enhance the refinement component while undermining reduction and replacement. This pandemic has exposed the need for an urgent review of the efficacy of the three Rs, with the potential to establish a new set of protocols for animal research, both inside and beyond the context of an emergency.
Recognizing Moral Injury: Toward Legal Intervention for Physician Burnout
Authors: Lennon Robert P. , Day Philip G. , Marra Janelle
Published: June 2020

The writers respond to the commentary “Physician Burnout Calls for Legal Intervention,” by Sharona Hoffman, in the November‐December 2019 issue of the Hastings Center Report.
Health for Whom? Bioethics and the Challenge of Justice for Genomic Medicine
Authors: Reynolds Joel Michael
Published: June 2020

The guiding premise from which this special report begins is the conviction and hope that justice is at the normative heart of medicine and that it is the perpetual task of bioethics to bring concerns of justice to bear on medical practice. On such an account, justice is medicine's lifeblood, that by which it contributes to life as opposed to diminishing it. It is in this larger, historical, intersectional, critical, and ethically minded context that we must approach pressing questions facing medicine, including the question of the import and role of genomic knowledge for human life. The second premise is that, at least in principle, the knowledge generated by genomics can be a gift or a weight, or both at the same time. That is to say that, on the one hand, genomic knowledge is a gift, creating novel insights into the genetic drivers of disease and into the geographical paths of our ancestors. And on the other hand, it is a weight, creating new obligations, new forms of social classification, and new forms of surveillance. Because it is in many ways the “common sense” of the day that genomic knowledge is a gift, this special report, which contains nine essays, concentrates on the ways in which such knowledge can be a weight, a weight that has the potential to thwart—and historically has thwarted—medicine from genuinely advancing justice.
Coding the Self: The Infopolitics and Biopolitics of Genetic Sciences
Authors: Koopman Colin
Published: June 2020

This essay compares three models for conceptualizing the political and ethical challenges of contemporary genetics, genomics, and postgenomics. The three analytical approaches are referred to as the state‐politics model, the biopolitical model, and the infopolitical model. Each of these models is valuable for different purposes. In terms of their influence in contemporary discussions, the first is by far the dominant approach, the second is gaining in importance, and the third is almost entirely neglected. The widespread neglect of the infopolitical dimensions of genetic sciences that are the focus of the third model is puzzling in light of the fact that genetics, genomics, and postgenomics are all preeminent information sciences. The infopolitical model thus aims to bring into clearer view the specific political and ethical problems engendered by this informational nature of the genetic sciences. This model offers a way of understanding how ethically salient and politically fraught conceptual assumptions can be embedded in informational architectures such as algorithms and the formats (or data structures) upon which they rely.
Evaluating integrated use of information technologies in secondary schools of Ethiopia using design‐reality gap analysis: A school‐level study
Authors: Bati Tesfaye Bayu , Workneh Anteneh Wasyhun
Published: June 2020

The purpose of this study was to examine the level of readiness of Ethiopian secondary education systems in terms of access to technologies and preparedness in skills and motivation for the integrated use of information communication technologies (ICT) for quality education. To serve this end, a Design‐Reality Gap Analysis approach was employed. Relevant data were collected from teachers, students, and school leaders through a questionnaire survey, and the result was cross‐examined against the national goals and strategies. The Design‐Reality Gap Analysis of integrated use of ICT in classroom teaching in Ethiopian secondary schools thus far revealed fewer successes and widespread challenges in the country's discourse to achieve the 2016‐2020 national targets. The study showed that students have better access to mobile phones and other technologies at home and outside of schools. Major school‐level factors for the gap observed were delay in implementation of a nationwide e‐cloud based ICT infrastructure, lack of coordination for the pedagogical use of ICT, and insufficient capacity building training for teachers and school leaders. This suggests the importance of a strategy that integrates inside‐ and outside of schools ICT resources and services for improved use of ICT in student learning.
Copper homeostasis: Emerging target for cancer treatment
Authors: Li Yueqin
Published: June 2020

Copper (Cu) is an essential micronutrient involved in a variety of fundamental biological processes. Recently, disorder of Cu homeostasis can be observed in many malignancies. Elevated Cu levels in serum and tissue are correlated with cancer progression. Hence, targeting Cu has emerged as a novel strategy in cancer treatment. This review provides an overview of physiological Cu metabolism and its homeostasis, followed by a discussion of the dysregulation of Cu homeostasis in cancer and the effects of Cu on cancer progression. Finally, recent therapeutic advances using Cu coordination complexes as anticancer agents, as well as the mechanisms of their anti‐cancer action are discussed. This review contributes full comprehension to the role of Cu in cancer and demonstrates the broad application prospect of Cu coordination compounds as potential therapeutic agents.
Inhibition of Osteoclast Differentiation by 1.25-D and the Calcimimetic KP2326 Reveals 1.25-D Resistance in Advanced CKD
Authors: Bernardor Julie , Flammier Sacha , Ranchin Bruno , Gaillard Ségolène , Platel Diane , Peyruchaud Olivier , Machuca-Gayet Irma , Bacchetta Justine
Published: June 2020

Active vitamin D analogs and calcimimetics are the main therapies used for treating secondary hyperparathyroidism (SHPT) in patients with chronic kidney disease (CKD). Peripheral blood mononuclear cells of 19 pediatric patients with CKD1-5D and 6 healthy donors (HD) were differentiated into mature osteoclasts with receptor activator of NF-κB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). The effects of single or combined treatment with active vitamin D (1.25-D) and/or calcimimetic KP2326 were evaluated on osteoclastic differentiation and osteoclastic-mediated bone resorption. Although 1.25-D inhibited osteoclastic differentiation, a significant resistance to 1.25-D was observed when glomerular filtration rate decreased. A significant albeit less important inhibitory effect of KP2326 on osteoclastic differentiation was also found both in cells derived from HD and CKD patients, through a putative activation of the Erk pathway. This inhibitory effect was not modified by CKD stage. Combinatorial treatment with 1.25-D and KP2326 did not result in synergistic effects. Last, KP2326 significantly inhibited osteoclast-mediated bone resorption. Both 1.25-D and KP2326 inhibit osteoclastic differentiation, however, to a different extent. There is a progressive resistance to 1.25-D in advanced CKD that is not found with KP2326. KP2326 also inhibits bone resorption. Given that 1.25-D has no effect on osteoclastic resorption activity and that calcimimetics also have direct anabolic effects on osteoblasts, there is an experimental rationale that could favor the use of decreased doses of 1.25-D with low doses of calcimimetics in SHPT in dialysis to improve the underlying osteodystrophy. However, this last point deserves confirmatory clinical studies. © 2020 American Society for Bone and Mineral Research.
Hydrocarbon production by addition of Cu‐ZnO on g‐C3N4 for CO2 conversion
Authors: Zhu Zhen , Chen Chin‐Yuan , Wu Ren‐Jang
Published: June 2020

In this study, copper/zinc oxide/graphite nitrogen carbide (Cu/ZnO/g‐C3N4) is prepared using a hydrothermal method and applied as a photocatalyst for CO2 photoreduction. The morphology and structural properties of the obtained Cu/ZnO/g‐C3N4 are systematically characterized through X‐ray powder diffraction, ultraviolet–visible absorption spectroscopy, transmission electronic microscopy, and photoluminescence spectroscopy. A 3 wt% Cu/ZnO/g‐C3N4 photocatalyst exhibits high CH4 (40.7 μmol g−1 hr−1), CO (65.1 μmol g−1 hr−1), and CH3OH (92.5 μmol g−1 hr−1) production rates, which are 38.3, 77.1, and 58.1 fold higher than the pure g‐C3N4. The production rate is higher than those for bulk g‐C3N4 and ZnO/g‐C3N4. Finally, the reaction mechanism of Cu/ZnO/C3N4 is proposed in this study.
Evaluation of autoantibodies and immunoglobulin G subclasses in women with suspected macroprolactinemia
Authors: Yu Chao , Fan Fei , Hu Siqi , Meng Lingxin , Xu Dong , Wang Juan , Chen Lu , Liu Jingrui , Dong Ying , Lu Yifan , Shen Min , Zhai Yanhong , Cao Zheng
Published: June 2020

Background

Macroprolactin mostly composed of an immunoglobulin G (IgG) and a monomeric prolactin (PRL) represents the major circulating PRL form in the patients with macroprolactinemia that are usually asymptomatic and may not require treatment. In this study, we aimed to evaluate the prevalence of antithyroid and antinuclear antibodies, as well as the IgG subclass distributions in the patients suspected for macroprolactinemia.

Methods

From January to July in 2018, totally 317 patients with elevated PRL were subjected to the polyethylene glycol (PEG) precipitation assay. The patients with recovery rates of ≤60% were subjected for IgG subclass determination and autoantibody testing including thyroid peroxidase antibody (aTPO), antithyroglobulin antibody (aTG), and antinuclear antibodies (ANA).

Results

The higher the post‐PEG PRL recovery rates, the less typical hyperprolactinemia symptoms and the higher prevalence of autoantibodies were observed. The IgG1 and IgG3 were the predominant subclasses in the PRL‐IgG complexes according to the immunoprecipitation experiments.

Conclusion

The patients with post‐PEG PRL recovery rates of <40% and 40%‐60% were likely to represent two distinct populations of different clinical presentations. The prevalence of autoantibodies and IgG subclasses distribution suggested their pathogenic significance in the development of macroprolactinemia.
Population Pharmacokinetic Analysis of Quizartinib in Healthy Volunteers and Patients With Relapsed/Refractory Acute Myeloid Leukemia
Authors: Kang Dongwoo , Ludwig Elizabeth , Jaworowicz David , Huang Hannah , Fiedler‐Kelly Jill , Cortes Jorge , Ganguly Siddhartha , Khaled Samer , Krämer Alwin , Levis Mark , Martinelli Giovanni , Perl Alexander , Russell Nigel , Abutarif Malaz , Choi Youngsook , Mendell Jeanne , Yin Ophelia
Published: June 2020

Quizartinib is an FMS‐like tyrosine kinase 3 (FLT3) inhibitor that has shown robust clinical activity in patients with FLT3‐internal tandem duplication–mutated relapsed/refractory acute myeloid leukemia (AML). This analysis evaluated the population pharmacokinetics (PK) of quizartinib and its active metabolite, AC886, in a pooled analysis of data from 649 healthy volunteers or patients with AML from 8 clinical trials including the phase 3 QuANTUM‐R study. Quizartinib was given as a single dose or multiple once‐daily doses of 20, 30, 60, or 90 mg. Nonlinear mixed‐effects modeling was performed using observed concentrations of quizartinib and AC886. Strong CYP3A inhibitor use resulted in an 82% increase in the area under the curve (AUC) and a 72% increase in the maximum concentration (Cmax) of quizartinib. Albumin level, age, and body surface area were statistically significant covariates on quizartinib PK. However, their individual effects on quizartinib AUC and Cmax were <20%. For AC886, strong CYP3A inhibitor use, body surface area and black/African American race were significant covariates. Except for strong CYP3A inhibitor use, the effects on the overall exposure (AUC of quizartinib + AC886) were <20%. The population PK model provided an adequate description of the observed concentrations of quizartinib and AC886 in both healthy volunteers and patients with AML. Only concomitant use of strong CYP3A inhibitors had a clinically meaningful effect on quizartinib PK exposure.
DNMT1 and p38γ are inversely expressed in reactive non‐metastatic lymph nodes burdened with colorectal adenocarcinoma
Authors: Zhang Xu Hannah , Yin Zhirong , Zhang Aimin , Pillai Raju , Armstrong Brian , Rosen Steven T
Published: June 2020

Lymph nodes are important front‐line defense immune tissues, which also act against inflammatory diseases and cancer. Lymph nodes undergo extensive upheavals within newly formed germinal centers (GCs) when exposed to antigens, the molecular mechanisms of which remain elusive. Recently, p38γ was identified as an important target for multiple cancers, including cutaneous T‐cell lymphoma (CTCL). We previously observed that p38γ is overexpressed in CTCL versus normal cells, but it is not clear if p38γ is expressed in B or T lymphocytes of GCs of patients in response to a stress such as cancer. Therefore, in this study, we obtained non‐metastatic reactive lymph nodes adjacent to cancer lesions (colorectal adenocarcinoma), then performed multicolor immunohistochemical staining for p38γ and other relevant markers. We observed for the first time that p38γ was expressed in the light zone of activated B cells and T helper cells in GCs, whereas DNA‐methyltransferase 1 (DNMT1), a marker for GC B cells, was highly expressed in centrocytes and in the dark zone of GCs. This inverse relationship suggests a novel function for p38γ in T cells that cross‐talk to B cells in response to stress.
Bacteria associated with marine macroorganisms as potential source of quorum‐sensing antagonists
Authors: Singh Aparna A. , Singh Anil K. , Nerurkar Anuradha
Published: June 2020

Samples were collected from different undisturbed areas along the coast of Gujarat like Okha, Diu, Veraval, and Somnath. A total of 68 marine isolates were obtained out of which 53 were associated with various marine macroorganisms like sponges, gastropods, and algae, whereas 15 were free living. Quorum‐quenching ability of all the isolates was tested against Chromobacterium violaceum MK by co‐culture technique as a way to simultaneously detect signal‐degrading as well as nondegrading quorum‐sensing inhibitors. Nineteen macroorganism‐associated bacteria and eight free‐living bacteria were found to possess quorum‐sensing inhibitory activity against C. violaceum MK without affecting its growth. Isolate OA22 from grape alga and OA10 from purple sponge (Haliclona sp.) were found to possess the highest C6‐HSL degradation activity and extracellular non‐N‐acyl‐homoserine lactone degrading QSI activity, respectively. OA22 was also found to degrade 3‐oxo‐C12 homoserine lactone. Acid recovery of both the C6‐ and C12‐HSL after degradation by OA22 indicated the presence of lactonase enzyme in the isolate. Cell‐free supernatant of OA10 was extracted with ethyl acetate to obtain the quorum‐quenching compound. Pigment inhibition in C. violaceum MK treated with OA10 extract was demonstrated in various ways and was indicative of QSI activity of the extract without degradation of the quorum‐sensing signaling molecule. The isolates OA22 and OA10 were identified as Desemzia incerta and Bacillus sp., respectively, by 16S ribosomal DNA sequence analysis.
The digital transformation of preventive telemedicine in France based on the use of connected wearable devices
Authors: Quévat Alexandre , Heinze Aleksej
Published: June 2020

France has a large and well‐organized health‐care system, however, before the restrictions caused by the COVID‐19 pandemic, telemedicine was largely seen as a cost‐effective method of making specialist skills available to socially isolated groups, and to patients who live in remote locations. Here, we present the findings of an exploratory study that examined what a preventative telemedicine system, based around a centralized platform and connected wearable devices, might look like. The data were collected during 2019, ahead of the pandemic, and include interviews with three key stakeholders: a doctor working in a hospital emergency room, the director of a service providing mobile resuscitation teams, and a user of a wearable device who discovered, through the device, that he had a serious cardiac pathology. The study uses the HINGE digital transformation model both as a methodology, and as a structure for presenting an outline of the key features of our proposed approach. We conclude by highlighting some of the benefits of our system, both in light of the context for the original study, and in the light of the COVID‐19 pandemic that occurred afterward.
The Effects of Prolonged Exposure on Substance Use in Patients With Posttraumatic Stress Disorder and Substance Use Disorders
Authors: Peirce Jessica M. , Schacht Rebecca L. , Brooner Robert K.
Published: June 2020

Despite research demonstrating the benefit of exposure‐based therapy for posttraumatic stress disorder (PTSD) in patients with co‐occurring substance use disorders, there remains a strong clinical expectation that this treatment will exacerbate substance use or other psychiatric symptoms. The present study evaluated within‐session and session‐to‐session changes in (a) craving and use of substances for a range of drug classes and (b) symptoms of PTSD and other psychiatric distress in a sample of 44 SUD patients who received prolonged exposure (PE) therapy for PTSD. Visual analog scales showed no within‐session increases in craving, except for cocaine, within Session 8. Across sessions, craving scores dropped for heroin, methadone, benzodiazepines, and cocaine; no increases in craving were found. Past‐week substance use reported at each session did not differ. The severity of PTSD symptoms and self‐reported serious emotional problems decreased from Session 1 to subsequent sessions, with no increases or decreases in other psychiatric, social, or medical problems. Finally, PTSD severity was unrelated to substance use reported 1 or 2 weeks later. Substance use during the past week was associated with higher PTSD severity scores at the next session, B = 6.86 (SE = 2.87), p = .018, but was not associated 2 weeks later. These findings indicate that the concern that exposure therapy for PTSD will increase SUD patients’ substance use or other psychiatric symptoms may be unwarranted, and, thus, SUD patients, including those who are actively using, should have access to effective treatments for PTSD, like PE.
Life and death of Crocosphaera sp. in the Pacific Ocean: Fine scale predator–prey dynamics
Authors: Dugenne Mathilde , Henderikx Freitas Fernanda , Wilson Samuel T. , Karl David M. , White Angelicque E.
Published: June 2020

In the North Pacific Subtropical Gyre, the daily pulse of photosynthetic carbon (C) fixation is closely balanced by losses. This concert of growth and loss is driven by a diverse assemblage of plankton, including the diazotroph Crocosphaera sp. While primary production is relatively well characterized in this ecosystem, the extent of C transfer to secondary producers is poorly constrained. Here, we use automated imaging flow cytometry and population modeling to study the coupling of C production by Crocosphaera and subsequent grazing by nanoplanktonic protists. Crocosphaera cells represent on average 30% of the nanoplankton detected by the Imaging FlowCytoBot in the surface layer of mesoscale eddies during summertime. The size spectra show a maximum in the frequency of Crocosphaera doublet cells just prior to mitotic division at midday, with an average estimated growth rate of 0.8 ± 0.5 d−1. We also identified potential predators by fitting a Lotka–Volterra model to plankton time series observations. Significant predators include the dinoflagellates Protoperidinium and Dinophysis as well as the ciliate Strombidium, which were all imaged with Crocosphaera in food vacuoles. The estimated C demand of the main grazers fluctuated between 25% and 250% of Crocosphaera new production in an anticyclonic eddy where we observed the onset of a Crocosphaera‐driven bloom. Heterotrophic Protoperidinium drove most of the estimated C demand, with grazing rates nearly equivalent to Crocosphaera growth rates (0.6 ± 0.4 d−1 on average), but saturating at high prey concentrations. Our novel results demonstrate tight coupling between specific protistan predators and a diazotrophic prey.
Elastic and Thermoreversible Iongels by Supramolecular PVA/Phenol Interactions
Authors: Luque Gisela C. , Picchio Matías L. , Martins Ana P. S. , Dominguez‐Alfaro Antonio , Tomé Liliana C. , Mecerreyes David , Minari Roque J.
Published: June 2020

Iongels have attracted much attention over the years as ion‐conducting soft materials for applications in several technologies including stimuli‐responsive drug release and flexible (bio)electronics. Nowadays, iongels with additional functionalities such as electronic conductivity, self‐healing, thermo‐responsiveness, or biocompatibility are actively being searched for high demanding applications. In this work, a simple and rapid synthetic pathway to prepare elastic and thermoreversible iongels is presented. These iongels are prepared by supramolecular crosslinking between polyphenols biomolecules with a hydroxyl‐rich biocompatible polymer such as poly(vinyl alcohol) (PVA) in the presence of ionic liquids. Using this strategy, a variety of iongels are obtained by combining different plant‐derived polyphenol compounds (PhC) such as gallic acid, pyrogallol, and tannic acid with imidazolium‐based ionic liquids, namely 1‐ethyl‐3‐methylimidazolium dicyanamide and 1‐ethyl‐3‐methylimidazolium bromide. A suite of characterization tools is used to study the structural, morphological, mechanical, rheological, and thermal properties of the supramolecular iongels. These iongels can withstand large deformations (40% under compression) with full recovery, revealing reversible transitions from solid to liquid state between 87 and 125 °C. Finally, the polyphenol‐based thermoreversible iongels show appropriated properties for their potential application as printable electrolytes for bioelectronics.
Enhancing the intergranular corrosion resistance of high Mg‐alloyed Al–Mg alloy by Y addition
Authors: Li Xinlei , Xia Weijun , Yan Hongge , Chen Jihua , Su Bin , Li Xinyu
Published: June 2020

Microalloying is thought to improve the performance of Al–Mg alloys commonly used in transport applications. The effect of Y addition (0–0.4%) on the microstructure, mechanical properties, and corrosion resistance of Al–9.2Mg–0.7Mn alloy is investigated for potential use in engineering applications. The generation of the β‐Al3Mg2 phase along the grain boundaries is suppressed in the as‐cast alloy due to the formation of the AlMgY ternary phase. The average intergranular corrosion mass loss of the alloy with 0.1% Y addition decreases about 53.1% almost at no expense of mechanical performance in the as‐rolled alloy after annealing. Moreover, the alloy with 0.1% Y addition shows the corrosion mass loss about 30.2% lower than the Y‐free alloy in the sensitized state. The enhanced corrosion resistance of the alloy can be ascribed to the reduced β‐Al3Mg2 precipitation along the grain boundaries associated with Y addition.
The anoxic corrosion behaviour of carbon steel in anoxic alkaline environments simulating a Swiss L/ILW repository environment
Authors: Senior Nicholas A. , Martino Taylor , Diomidis Nikitas
Published: June 2020

The Swiss waste management programme foresees that low‐ and intermediate‐level radioactive waste will be disposed of in a deep geological repository constructed in Opalinus Clay. Gas generation is expected in the repository due to the decomposition of organic materials and the corrosion of metals, with carbon steel being the primary source. The corrosion behaviour of mild steel under anoxic conditions has been studied over the course of several years to better understand the long‐term hydrogen evolution profile under anticipated repository conditions. Steel, either bare or encased within mortar, was tested in water vapour or immersed in electrolytes representative of aged cement waters at 50°C. The corrosion rate was measured indirectly through the hydrogen analysis using a solid‐state probe. The hydrogen evolution behaviour of grout was also monitored to more accurately determine the hydrogen generating from the corrosion of the embedded steel. For steel in water vapour or in alkaline environments, embedded in cementitious material or immersed in simulated aged cement pore water, corrosion rates were invariably <1 nm/year after several years of analysis.
Expanding the phenotype of STRA6‐related disorder to include left ventricular non‐compaction
Authors: Sun Hairui , Yu Shaomei , Zhou Xiaoxue , Han Lu , Zhang Hongjia , He Yihua
Published: June 2020

Background

Syndromic microphthalmia‐9 (MCOPS9) is a rare autosomal recessive disorder caused by mutations in STRA6, an important regulator of vitamin A and retinoic acid metabolism. This disorder is characterized by bilateral clinical anophthalmia, pulmonary hypoplasia/aplasia, cardiac malformations, and diaphragmatic defects. The clinical characteristics of this disorder have not been fully determined because of the rarity of clinical reports.

Methods

A comprehensive genotyping examination including copy number variation sequencing (CNV‐Seq) and whole‐exome sequencing (WES) was applied to a fetus of Han Chinese with bilateral anophthalmia, bilateral pulmonary agenesis, interrupted aortic arch type A, and left ventricular non‐compaction (LVNC).

Results

No aneuploidy or pathogenic CNV were identified by CNV‐seq. WES analysis revealed a previously reported homozygous splice site (NM_022369.4:c.113+3_113+4del) in the STRA6 gene. This variant was confirmed by Sanger sequencing. The diagnosis of MCOPS9 was confirmed given the identification of the STRA6 mutation and the association of bilateral anophthalmia, pulmonary agenesis, and cardiac malformations.

Conclusion

This case adds to the phenotypic spectrum of MCOPS9, supporting the association with LVNC, and the presence of interruption of aortic arch further demonstrates the variability of the cardiac malformations.
Identification of novel splice mutation in SMAD3 in two Cypriot families with nonsyndromic thoracic aortic aneurysm. Two case reports
Authors: Keravnou Anna , Bashiardes Evy , Barberis Vassilis , Michailidou Kyriaki , Soteriou Marinos , Tanteles George A. , Cariolou Marios A.
Published: June 2020

Background

Thoracic aortic aneurysm and dissection (TAA/D) represents a potentially lethal disease group characterized by an increased risk of dissection or rupture. Only a small percentage (approximately 30%) of individuals with nonsyndromic familial TAA/D have a pathogenic variant in one of the genes that have been found to be associated with the disease.

Methods

A targeted sequencing panel and direct sequencing approach were used to identify causative mutations in the index patients and other family members.

Results

In this study we report two apparently unrelated Cypriot families with nonsyndromic familial TAA/D. The proband A is a female patient diagnosed with TAA/D and intracranial aneurysm and opted for an elective intervention. The proband B is a male patient who was diagnosed with TAA/D and underwent cardiac surgery. Sequencing analysis identified a novel splice site variant (c.871+1G>A) in SMAD3 which is shown to be associated with the disease. Analysis of mRNA from the patient's tissue confirmed aberrant splicing and exon 6 skipping.

Conclusion

Our findings expand the mutation spectrum of variants that have been shown to be associated with nonsyndromic familial TAA/D. This study demonstrates the importance of a comprehensive clinical and genetic evaluation aiming at early diagnosis and intervention.
Modeling of active shimming of metallic needles for interventional MRI
Authors: Sengupta Saikat
Published: June 2020

Purpose

Artifacts caused by large magnetic susceptibility differences between metallic needles and tissue are a persistent problem in many interventional MRI applications. The signal void caused by the needle can hide procedure targets and prevent accurate image‐based monitoring. In this paper, a solution to this problem is presented in the form of an active shim insert inspired from degaussing coils used in naval vessels, that is designed to correct the field disturbance (ΔB0) caused by the needle.

Methods

The ΔB0 induced by a 10 gauge hollow single‐beveled titanium needle at 3T is modeled in different orientations. A set of 63 orthogonal coil pairs with unique tip paths are evaluated for shimming performance, and an optimal coil pair is chosen. Shimming performance and current demands are evaluated over a range of needle orientations.

Results

Robust correction of the titanium needle induced ΔB0 is predicted using a flat no‐loop coil combined with an orthogonal 1½ turn loop coil angled at the bevel angle for most orientations, with currents well below 1 amp per coil. Reductions in ΔB0 standard deviations with shimming ranged from ~49% to ~10% depending on needle orientation, with performance worsening as the needle is aligned more along B0.

Conclusion

Simulations predict that it is possible to minimize metallic probe induced ΔB0 and signal losses using externally supplied direct current shim coil inserts in arbitrary orientations for potential benefits in many interventional MRI applications.
New iterative and staggered solution schemes for incompressible fluid‐structure interaction based on Dirichlet‐Neumann coupling
Authors: Dettmer Wulf G. , Lovrić Aleksander , Kadapa Chennakesava , Perić Djordje
Published: June 2020

In the presence of strong added mass effects, partitioned solution strategies for incompressible fluid‐structure interaction are known to lack robustness and computational efficiency. A number of strategies have been proposed to address this challenge. However, these strategies are often complicated or restricted to certain problem classes and generally require intrusive modifications of existing software. In this work, the well‐known Dirichlet‐Neumann coupling is revisited and a new combined two‐field relaxation strategy is proposed. A family of efficient staggered schemes based crucially on a force predictor is formulated alongside the classical iterative approach. Both methodologies are rigorously analyzed on the basis of a linear model problem derived from a simplified fluid‐conveying elastic tube. The investigation suggests that both the robustness and the efficiency of a partitioned Dirichlet‐Neumann coupling scheme can be improved by a relatively small nonintrusive modification of a standard implementation. The relevance of the model problem analysis for finite element‐based computational fluid‐structure interaction is demonstrated in detail for a submerged cylinder subject to an external force.
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Authors: Provenzano Aldesia , Palazzo Viviana , Reho Paolo , Pagliazzi Angelica , Marozza Annabella , Farina Antonio , Zuffardi Orsetta , Giglio Sabrina
Published: June 2020

The front cover image is based on the Research Letter Noninvasive prenatal diagnosis in a family at risk for Fraser syndrome by Aldesia Provenzano et al., https://doi.org/10.1002/pd.5700.

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Cover Image
Authors: Wang Yu , Zhang Jiaqi , Feng Wei , Cao Haiyan , He Qiaoyue , Xu Jinzhi , Zeng He , Xie Mingxing
Published: June 2020

The back cover image is based on the Original Article Description of misdiagnosis and missed diagnosis of fetal complex heart malformations by prenatal echocardiography combined with postnatal cardiovascular casting by Yu Wang et al., https://doi.org/10.1002/pd.5689.

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