bluuebunny/crossref_metadata_2025 huggingface dataset:
T-cell chimerism prior to graft-versus-host disease
Authors: Noguchi Misa , Shindo Takero , Yamada Yosuke , Date Hiroshi
Published: December 2020

Graft-versus-host disease (GVHD), a serious complication of haematopoietic stem cell transplantation, can occur following solid organ transplantation. However, diagnosing solid organ transplantation-associated GVHD is difficult, and its risk factors are not fully understood. Here, we report a GVHD case in a 59-year-old woman with dermatomyositis-associated interstitial pneumonia, who took immunosuppressants including corticosteroids before receiving right lung transplantation from a 13-year-old brain-dead male donor. She developed systemic erythema with desquamation and pancytopenia by day 20. Mixed chimerism with donor- and recipient-type cells in the bone marrow and skin led to the diagnosis of GVHD. Corticosteroid pulse therapy reduced the symptoms and decreased donor-type cell percentage. On day 50, the patient developed donor lung injury and was diagnosed with acute rejection, which was treated using steroid pulse therapy again. Although the granulocytes were recipient type, donor chimerism of peripheral blood T cells exacerbated on day 68. Subsequent deterioration of liver function and pulmonary injury in the patient’s own lung led to the diagnosis of relapsing GVHD. The patient died of multiple organ failure despite treatment with anti-thymocyte globulin. Thus, repeated steroid pulse therapy and age difference between donors and recipients may predispose to GVHD and T-cell mixed chimerism can be an important diagnostic indicator of GVHD.
Can International Law Survive a Rising China?
Authors: Chesterman Simon
Published: December 2020

The founding myth of international law is the sovereign equality of its member states. How, then, can and should it accommodate the rise of one potential hegemon and the decline of another? This review essay discusses an important new book by Cai Congyan, of Xiamen University, that tries to reconcile an international rule of law with rising powers in general and the rise of China in particular. The larger theoretical project is less successful than a more immediate one, which is describing and explaining China’s instrumentalist approach to the rule of law at the domestic and international levels. Though the tone of the book is assured and reassuring, Cai’s diplomacy at times leaves some interesting questions unanswered – and a few crucial ones unasked. It is, nonetheless, essential reading for anyone seeking to understand how China sees and uses international norms and institutions.
Belgium and the Fabrication of the International Legal Discipline
Authors: d’Aspremont Jean
Published: December 2020

In recounting the interventions of Belgian lawyers in the institutionalization of the discipline of international law at the end of the 19th century and the beginning of the 20th century, Vincent Genin’s Le laboratoire belge du droit international offers new materials and documentary evidence of the complicity between the construction of the international legal discipline and the colonial project. Taking his cue from Martti Koskenniemi’s Gentle Civilizer, Genin has produced a biographical and agent-based historicization of an unprecedented archival rigour, allowing international lawyers, and especially Belgian international lawyers, to take another hard look at the dark roots of their tradition.
Predicting difference in mean survival time from cause-specific hazard ratios for women diagnosed with breast cancer
Authors: Røssell Eeva-Liisa , Bornhøft Laura O , Lousdal Mette Lise , Støvring Henrik
Published: December 2020

Background

Relative reduction in breast cancer mortality is the preferred outcome measure for evaluation of mammography screening. However, mean survival time has been advocated as a better and more intuitive outcome for risk communication. We have previously introduced a method to predict difference in mean survival time from empirical hazard ratios for all-cause mortality. In this article, we aim to investigate the association between hazard ratios for breast cancer mortality and the difference in mean survival time for women diagnosed with breast cancer.

Methods

We retrieved data on all women diagnosed with first-time invasive breast cancer in Norway from 1960 through 2004. Women were followed until emigration or end of follow-up on 31 December 2015, whichever came first. Observed differences in mean survival times and hazard ratios for both breast cancer death and death from causes other than breast cancer were obtained for neighbouring time periods defined by women’s age and year of diagnosis. Based on previously developed methods, we fitted a linear relationship between observed differences in mean survival and logarithmic hazard ratios.

Results

A linear association was found between breast cancer-specific hazard ratios and difference in mean survival time for women diagnosed with breast cancer. This association was also estimated with adjustment for other causes of death than breast cancer.

Conclusions

The change in mean survival time could be predicted from an estimated reduction in breast cancer mortality. This outcome measure can contribute to better and more understandable risk information about the effect of mammography screening programmes.
In the Shadow of ‘Euthanasia’: The Long Road to the Nazi Murder of Tuberculosis Patients
Authors: Bernhard Patrick
Published: December 2020

The social stigmatization, persecution and murder of tuberculosis patients in Nazi Germany is a topic that has long been overshadowed by euthanasia crimes. Based on extensive archival research, this article shows that over 30,000 patients, labelled as deviant, became victims of forced detention. In so-called ‘special institutions’, which were part of the regime’s terror apparatus, these people suffered severe physical abuse. An estimated 4,000 were deliberately starved to death or murdered by overdoses of medication. As the article argues, a long road led to the Nazi murder of tuberculosis patients and began with medical experience gathered during the First World War and in the 1920s. When the regime’s handling of the disease and of tuberculosis patients is located within this much wider time frame, the notion that the exigencies of the Second World War caused the regime’s radicalization falters.
Renal Aging Resembles a Continuum Between Normal and Diseased Kidneys That Potentiates Inflammatory Response to Injury
Authors: Jung Su Woong , Kim Dong Jin , Kim Yang Gyun , Moon Ju-Young , Jeong Kyung Hwan , Lee Sang-Ho
Published: December 2020

Renal aging is a natural process that can lead to structural changes and functional decline in the kidneys. These age-related changes are considered irreversible physiological processes, but resemble diseased kidneys. To enhance understanding of the molecular nature of renal aging, we first compared whole-kidney RNA sequencing between naturally aging mice (24-month-old) and adenine-induced nephropathy in young mice (2-month-old). Young mice (2-month-old) without intervention were used as the control group to investigate transcription alteration with aging or by adenine-enriched diet. Next, we compared the functional and structural renal consequences of aging and adenine-induced nephropathy between young (2-month-old) and old mice (18- to 22-month-old). C57BL/6 male mice were used in all experimental studies. Both aging kidneys and adenine-induced nephropathy showed similar transcriptional profiles characterized by upregulation in innate and adaptive immune system activation and inflammation, although these alterations were generally less significant in the aging kidneys. In contrast to aging kidneys, adenine-induced nephropathy showed prominent expression of the genes related to cytokines, T-cell activation, and fibrosis and decreased expression of the genes implicated in transporter activity and metabolism. The subclinical immunological micromilieu in aging kidneys potentially causes augmented kidney damage in response to injurious stimulus. When mice were fed with adenine-enriched diet, aging kidneys showed more extensive tubular injury and fibrosis with stronger inflammatory response than young kidneys. Taken together, our results suggest that renal aging may lie on a continuum between normal kidneys and diseased kidneys in the context of immune system upregulation that can worsen kidney damage upon injury.
State Standards for Insurance Access to Oncologists
Authors: Moore Catherine J , Shalowitz David I
Published: December 2020

As the market for health insurance plans expands, each state is responsible for setting standards to ensure that plans contain adequate coverage for cancer care. Little is currently known about what criteria states use for network adequacy of insurance plans. We contacted representatives of the Department of Insurance (or equivalent) for 50 states and the District of Columbia, as well as searched official state websites to compile data on network adequacy standards for cancer care nationwide. The standards of 16 (31.4%) states contained only qualitative elements for access to an oncologist (eg, “reasonable access”), 7 (13.7%) states included only quantitative elements (eg, travel distance and time restrictions), and 24 (47.1%) states included standards with both qualitative and quantitative elements. Standards from 4 states were not available. States should make certain that robust, transparent protections exist to ensure that patients are able to access high-quality cancer care without experiencing the financial toxicity associated with out-of-network billing.
PTEN Blocking Stimulates Corticospinal and Raphespinal Axonal Regeneration and Promotes Functional Recovery After Spinal Cord Injury
Authors: Bhowmick Saurav , Abdul-Muneer P M
Published: December 2020

The long-term disabilities associated with spinal cord injury (SCI) are primarily due to the absence of robust neuronal regeneration and functional plasticity. The inability of the axon to regenerate after SCI is contributed by several intrinsic factors that trigger a cascade of molecular growth program and modulates axonal sprouting. Phosphatase and tensin homolog (PTEN) is one of the intrinsic factors contributing to growth failure after SCI, however, the underlying mechanism is not well known. Here, we developed a novel therapeutic approach for treating SCI by suppressing the action of PTEN in a mouse model of hemisection SCI. We have used a novel peptide, PTEN antagonistic peptide (PAP) to block the critical domains of PTEN to demonstrate its ability to potentially promote axon growth. PAP treatment not only enhanced regeneration of corticospinal axons into the caudal spinal cord but also promoted the regrowth of descending serotonergic axons in SCI mice. Furthermore, expression levels of p-mTOR, p-S6, p-Akt, p-Erk, p-GSK, p-PI3K downstream of PTEN signaling pathway were increased significantly in the spinal cord of SCI mice systemically treated with PAP than control TAT peptide-treated mice. Our novel strategy of administering deliverable compounds postinjury may facilitate translational feasibility for central nervous system injury.
The Evolution of Merger Enforcement Intensity: What do the Data Show?
Authors: Macher Jeffrey T , Mayo John W
Published: December 2020

A growing narrative has arisen that antitrust regulators have systematically relaxed enforcement over time. This narrative has led to calls for reinvigorated enforcement and the passage of new tougher antitrust legislation. In this paper, we employ data drawn directly from the antitrust agencies to examine this claim. Data collected from 1979 to 2017 indicate that, contrary to the popular narrative, regulators have become more likely to challenge proposed mergers over time. Controlling for the number of merger proposals submitted to the agencies, the likelihood of a merger challenge has more than doubled over this period. After remaining relatively constant over previous administrations, merger enforcement intensity (MEI) rose in the G.W. Bush and even more so in the Obama administrations. The data also reveal that MEI is positively influenced by the agency budget size. Were historical enforcement tendencies to continue, a ten percent increase in the agencies’ budgets would yield an eight percent increase in merger challenges. This finding suggests that, independent of any statutory changes to existing antitrust laws, variation in agency budgets provides a viable pathway to enhanced merger enforcement.
Initial Guidance on Use of Monoclonal Antibody Therapy for Treatment of Coronavirus Disease 2019 in Children and Adolescents
Authors: Wolf Joshua , Abzug Mark J , Wattier Rachel L , Sue Paul K , Vora Surabhi B , Zachariah Philip , Dulek Daniel E , Waghmare Alpana , Olivero Rosemary , Downes Kevin J , James Scott H , Pinninti Swetha G , Yarbrough April , Aldrich Margaret L , MacBrayne Christine E , Soma Vijaya L , Grapentine Steven P , Oliveira Carlos R , Hayes Molly , Kimberlin David W , Jones Sarah B , Bio Laura L , Morton Theodore H , Hankins Jane S , Maron Gabriela M , Timberlake Kathryn , Young Jennifer L , Orscheln Rachel C , Schwenk Hayden T , Goldman David L , Groves Helen E , Huskins W Charles , Rajapakse Nipunie S , Lamb Gabriella S , Tribble Alison C , Lloyd Elizabeth C , Hersh Adam L , Thorell Emily A , Ratner Adam J , Chiotos Kathleen , Nakamura Mari M
Published: December 2020

Background

In November 2020, the US Food and Drug Administration (FDA) provided Emergency Use Authorizations (EUA) for 2 novel virus-neutralizing monoclonal antibody therapies, bamlanivimab and REGN-COV2 (casirivimab plus imdevimab), for the treatment of mild to moderate coronavirus disease 2019 (COVID-19) in adolescents and adults in specified high-risk groups. This has challenged clinicians to determine the best approach to use of these products.

Methods

A panel of experts in pediatric infectious diseases, pediatric infectious diseases pharmacy, pediatric intensive care medicine, and pediatric hematology from 29 geographically diverse North American institutions was convened. Through a series of teleconferences and web-based surveys, a guidance statement was developed and refined based on review of the best available evidence and expert opinion.

Results

The course of COVID-19 in children and adolescents is typically mild and there is no high-quality evidence supporting any high-risk groups. There is no evidence for safety and efficacy of monoclonal antibody therapy for treatment of COVID-19 in children or adolescents, limited evidence of modest benefit in adults, and evidence for potential harm associated with infusion reactions or anaphylaxis.

Conclusions

Based on evidence available as of December 20, 2020, the panel suggests against routine administration of monoclonal antibody therapy (bamlanivimab, or casirivimab and imdevimab), for treatment of COVID-19 in children or adolescents, including those designated by the FDA as at high risk of progression to hospitalization or severe disease. Clinicians and health systems choosing to use these agents on an individualized basis should consider risk factors supported by pediatric-specific evidence and ensure the implementation of a system for safe and timely administration that does not exacerbate existing healthcare disparities.
A 20-year latency between hysterectomy for endometrial adenocarcinoma and solitary pulmonary metastasis: a case report
Authors: Kodia Karishma , Richards Stephanie , Pinto Andre , Pearson Joseph M , Nguyen Dao M
Published: December 2020

We present a rare case pulmonary metastasis of an early stage endometrial cancer nearly 20 years after curative surgical resection. Our patient had a remote history of hysterectomy for endometrial cancer in 1998 and later had Stage 1B right upper lobe lung cancer treated with lobectomy and adjuvant chemotherapy in 2014. She was found to have an enlarging nodule in the left upper lobe in 2018, which was thought to be another primary lung cancer. She underwent left upper lobe segmentectomy for an intraoperative diagnosis of adenocarcinoma by diagnostic wedge resection of the lung nodule. Final pathologic examination of the resected tumor demonstrated an endometrial adenocarcinoma. It is important for thoracic surgeons to remain vigilant, keeping secondary lung cancer in the differential diagnosis for patients with complex oncologic histories.
The 1993 World Conference on Human Rights and the retreat of a redistributive rights vision
Authors: Burke Roland
Published: December 2020

The 1993 UN World Conference on Human Rights, the second held in the history of the UN, and the sequel to the 1968 conference in Tehran, was convened as the faith in the liberal democratic human rights order was renascent. Economic and social rights, one of the dominant notes of Tehran a quarter century earlier, were—in comparative terms—marginal to Western priorities. This paper draws on new archival research to assess the new equilibrium in post-Cold War human rights that emerged from Vienna. The interrelationship between political, civil, and legal freedoms, and economic and social provisions was pared down to mere exhortation. After the transnational ‘Breakthrough’ of human rights NGOs in the 1970s, almost everyone had begun to transliterate their cause to the language of human rights—but it had become a language which required the excision of economic radicalism as a prerequisite for drawing on its newly inflated moral currency.
Evolution of gas disc–embedded intermediate mass ratio inspirals in theLISAband
Authors: Derdzinski A , D’Orazio D , Duffell P , Haiman Z , MacFadyen A
Published: December 2020

Among the potential milliHz gravitational wave (GW) sources for the upcoming space-based interferometer LISA are extreme- or intermediate-mass ratio inspirals (EMRI/IMRIs). These events involve the coalescence of supermassive black holes in the mass range 105M⊙ ≲ M ≲ 107M⊙ with companion BHs of much lower masses. A subset of E/IMRIs are expected to occur in the accretion discs of active galactic nuclei (AGNs), where torques exerted by the disc can interfere with the inspiral and cause a phase shift in the GW waveform. Here we use a suite of 2D hydrodynamical simulations with the moving-mesh code disco to present a systematic study of disc torques. We measure torques on an inspiralling BH and compute the corresponding waveform deviations as a function of the binary mass ratio q ≡ M2/M1, the disc viscosity (α), and gas temperature (or equivalently Mach number; $\mathcal {M}$). We find that the absolute value of the gas torques is within an order of magnitude of previously determined planetary migration torques, but their precise value and sign depends non-trivially on the combination of these parameters. The gas imprint is detectable by LISA for binaries embedded in AGN discs with surface densities above $\Sigma _0\ge 10^{4-6} \rm \, g cm^{-2}$, depending on q, α, and $\mathcal {M}$. Deviations are most pronounced in discs with higher viscosities, and for E/IMRIs detected at frequencies where LISA is most sensitive. Torques in colder discs exhibit a noticeable dependence on the GW-driven inspiral rate as well as strong fluctuations at late stages of the inspiral. Our results further suggest that LISA may be able to place constraints on AGN disc parameters and the physics of disc–satellite interaction.
On the formation and stability of fermionic dark matter haloes in a cosmological framework
Authors: Argüelles Carlos R , Díaz Manuel I , Krut Andreas , Yunis Rafael
Published: December 2020

The formation and stability of collisionless self-gravitating systems are long-standing problems, which date back to the work of D. Lynden-Bell on violent relaxation and extends to the issue of virialization of dark matter (DM) haloes. An important prediction of such a relaxation process is that spherical equilibrium states can be described by a Fermi–Dirac phase-space distribution, when the extremization of a coarse-grained entropy is reached. In the case of DM fermions, the most general solution develops a degenerate compact core surrounded by a diluted halo. As shown recently, the latter is able to explain the galaxy rotation curves, while the DM core can mimic the central black hole. A yet open problem is whether these kinds of astrophysical core–halo configurations can form at all, and whether they remain stable within cosmological time-scales. We assess these issues by performing a thermodynamic stability analysis in the microcanonical ensemble for solutions with a given particle number at halo virialization in a cosmological framework. For the first time, we demonstrate that the above core–halo DM profiles are stable (i.e. maxima of entropy) and extremely long-lived. We find the existence of a critical point at the onset of instability of the core–halo solutions, where the fermion-core collapses towards a supermassive black hole. For particle masses in the keV range, the core-collapse can only occur for $M_{\rm vir} \gtrsim 10^{9}{\, \mathrm{M}_\odot}$ starting at zvir ≈ 10 in the given cosmological framework. Our results prove that DM haloes with a core–halo morphology are a very plausible outcome within non-linear stages of structure formation.
Metabolomic and secretomic approach to the resistance features of the fungus Aspergillus niger IOC 4687 to copper stress
Authors: Perdigão Cota de Almeida Silas , Rozas Enrique Eduardo , Oller do Nascimento Cláudio Augusto , Dias Meriellen , Mendes Maria Anita
Published: December 2020

Metabolomic and secretomic analyses of Aspergillus niger IOC 4687 indicated the features of resistance of this strain to copper stress. To investigate the metabolites produced under oxidative stress conditions, gas chromatography–mass spectrometry analysis was performed. The secretome principal component analysis results showed that mannitol could be the main metabolite responsible for conferring resistance to the fungus, and gluconic acid is the possible cause of copper desorption because of its chelating ability. The meta-analysis of the metabolome of A. niger IOC 4687 indicated that a low concentration of sorbitol and ribonolactone during growth may be an indicator of oxidative stress.
The role of inflammation in mesenchymal stromal cell therapy in osteoarthritis, perspectives for post-traumatic osteoarthritis: a review
Authors: Theeuwes Wessel F , van den Bosch Martijn H J , Thurlings Rogier M , Blom Arjen B , van Lent Peter L E M
Published: December 2020

OA is a complex and highly prevalent degenerative disease affecting the whole joint, in which factors like genetic predisposition, gender, age, obesity and traumas contribute to joint destruction. ∼50–80% of OA patients develop synovitis. OA-associated risk factors contribute to joint instability and the release of cartilage matrix fragments, activating the synovium to release pro-inflammatory factors and catabolic enzymes in turn damaging the cartilage and creating a vicious circle. Currently, no cure is available for OA. Mesenchymal stromal cells (MSCs) have been tested in OA for their chondrogenic and anti-inflammatory properties. Interestingly, MSCs are most effective when administered during synovitis. This review focusses on the interplay between joint inflammation and the immunomodulation by MSCs in OA. We discuss the potential of MSCs to break the vicious circle of inflammation and describe current perspectives and challenges for clinical application of MSCs in treatment and prevention of OA, focussing on preventing post-traumatic OA.
The effect of sleep deprivation and restriction on mood, emotion, and emotion regulation: three meta-analyses in one
Authors: Tomaso Cara C , Johnson Anna B , Nelson Timothy D
Published: December 2020

Study Objectives

New theory and measurement approaches have facilitated nuanced investigation of how sleep loss impacts dimensions of affective functioning. To provide a quantitative summary of this literature, three conceptually related meta-analyses examined the effect of sleep restriction and sleep deprivation on mood, emotion, and emotion regulation across the lifespan (i.e. from early childhood to late adulthood).

Methods

A total of 241 effect sizes from 64 studies were selected for inclusion, and multilevel meta-analytic techniques were used when applicable.

Results

There was a moderate, positive effect of sleep loss on negative mood (g = 0.45), which was stronger for studies with younger samples, as well as a large, negative effect of sleep loss on positive mood (g = −0.94). For negative mood only, studies that used total sleep deprivation had larger effect sizes than studies that restricted sleep. After correcting for publication bias, a modest but significant negative effect for sleep loss on emotion (g = −0.11) was found; the valence of emotional stimuli did not change the direction of this effect, and type of sleep manipulation was also not a significant moderator. Finally, sleep restriction had a small, negative effect on adaptive emotion regulation (g = −0.32), but no significant impact on maladaptive emotion regulation (g = 0.14); all studies on adaptive emotion regulation were conducted with youth samples.

Conclusions

Sleep loss compromises optimal affective functioning, though the magnitude of effects varies across components. Findings underscore the importance of sleep for healthy affective outcomes.
How do children with autism spectrum disorder form gist memory during sleep? A study of slow oscillation–spindle coupling
Authors: Kurz Eva-Maria , Conzelmann Annette , Barth Gottfried Maria , Renner Tobias J , Zinke Katharina , Born Jan
Published: December 2020

Sleep is assumed to support memory through an active systems consolidation process that does not only strengthen newly encoded representations but also facilitates the formation of more abstract gist memories. Studies in humans and rodents indicate a key role of the precise temporal coupling of sleep slow oscillations (SO) and spindles in this process. The present study aimed at bolstering these findings in typically developing (TD) children, and at dissecting particularities in SO-spindle coupling underlying signs of enhanced gist memory formation during sleep found in a foregoing study in children with autism spectrum disorder (ASD) without intellectual impairment. Sleep data from 19 boys with ASD and 20 TD boys (9–12 years) were analyzed. Children performed a picture-recognition task and the Deese–Roediger–McDermott (DRM) task before nocturnal sleep (encoding) and in the next morning (retrieval). Sleep-dependent benefits for visual-recognition memory were comparable between groups but were greater for gist abstraction (recall of DRM critical lure words) in ASD than TD children. Both groups showed a closely comparable SO-spindle coupling, with fast spindle activity nesting in SO-upstates, suggesting that a key mechanism of memory processing during sleep is fully functioning already at childhood. Picture-recognition at retrieval after sleep was positively correlated to frontocortical SO-fast-spindle coupling in TD children, and less in ASD children. Critical lure recall did not correlate with SO-spindle coupling in TD children but showed a negative correlation (r = −.64, p = .003) with parietal SO-fast-spindle coupling in ASD children, suggesting other mechanisms specifically conveying gist abstraction, that may even compete with SO-spindle coupling.
Diagnostic Yield of Bronchoalveolar Lavage in Immunocompromised Children
Authors: Wong Jeff Chin Pang , Hon Kam Lun Ellis , Leung Karen Ka Yan , Qian Suyun , Leung Alexander K C
Published: December 2020

Results from early studies in the diagnostic yield of bronchoalveolar lavage (BAL) in immunocompromised adults and children were variable. This prospective study aimed to determine the diagnostic yield of BALs in immunocompromised children over the first 18 months of service at a newly established children’s hospital. Relationship between BAL results and changes in antimicrobial management was also studied. Twenty-one bronchoscopic BALs were performed on 18 children; 14 BALs (66.7%) yielded at least 1 pathogen and 7 (33.3%) yielded no pathogen. Two pathogens were found in 2 samples, and 1 pathogen was identified in 12 samples. Bacteria (n = 7 patients), viruses (n = 8 patients) and fungus (Pneumocycstis jirovecii in one patient) were yielded. Of the 21 BALs, 8 (38.1%) were associated with changes in antimicrobial management (Fisher’s exact test, p = 0.018). No significant side effects such as pneumothorax or pulmonary hemorrhages were observed in this series. In conclusion, BAL in immunocompromised children is rewarding and has potential to impact on antimicrobial management.
Emerging global novelty in phyllobothriidean tapeworms (Cestoda: Phyllobothriidea) from sharks and skates (Elasmobranchii)
Authors: Caira Janine N , Bueno Veronica , Jensen Kirsten
Published: December 2020

New genera are erected for three clades of tapeworms originally discovered using molecular sequence data. The morphological features of each are characterized after examination of specimens with light and scanning electron microscopy. Rockacestus gen. nov. parasitizes skates. Ruhnkebothrium gen. nov. parasitizes hammerhead sharks. Yamaguticestus gen. nov. parasitizes small squaliform sharks and catsharks. The novelty of these genera is supported by a taxonomically comprehensive molecular phylogenetic analysis of the D1–D3 region of the 28S rDNA gene, which, with the addition of newly generated sequence data, is the first to include representation of 15 of the 18 genera of phyllobothriideans plus the three new genera. Five new species are described from elasmobranchs in the western Atlantic Ocean, the Gulf of California, Chile, the Falkland Islands and South Africa to help circumscribe the new genera. Two of the genera provide appropriate generic homes for ten species of phyllobothriideans from catsharks and skates with uncertain generic affinities and thus resolve longstanding taxonomic issues. Given that these genera parasitize some of the most poorly sampled groups of elasmobranchs (i.e. hammerhead sharks, squaliform sharks, catsharks and skates), based on the strict degree of host specificity observed, we predict that further work on other members of these groups will yield as many as 200 additional species in these three genera of tapeworms globally. This brings the total number of genera in the Phyllobothriidea to 21.
2020 Visionary Leader Ferlie Villacorte
Authors: Ellis Sharon
Published: December 2020

The following manuscript is the winning 2020 Richard Hader Visionary Leader Award entry submitted to Nursing Management in recognition of Ferlie Villacorte, MPH, MSN, RN, CNS, clinical nursing director of ambulatory care services at Harbor-UCLA Medical Center in California.
Hearing Status Affects Children’s Emotion Understanding in Dynamic Social Situations: An Eye-Tracking Study
Authors: Tsou Yung-Ting , Li Boya , Kret Mariska E. , Frijns Johan H. M. , Rieffe Carolien
Published: December 2020

Objectives:

For children to understand the emotional behavior of others, the first two steps involve emotion encoding and emotion interpreting, according to the Social Information Processing model. Access to daily social interactions is prerequisite to a child acquiring these skills, and barriers to communication such as hearing loss impede this access. Therefore, it could be challenging for children with hearing loss to develop these two skills. The present study aimed to understand the effect of prelingual hearing loss on children’s emotion understanding, by examining how they encode and interpret nonverbal emotional cues in dynamic social situations.

Design:

Sixty deaf or hard-of-hearing (DHH) children and 71 typically hearing (TH) children (3–10 years old, mean age 6.2 years, 54% girls) watched videos of prototypical social interactions between a target person and an interaction partner. At the end of each video, the target person did not face the camera, rendering their facial expressions out of view to participants. Afterward, participants were asked to interpret the emotion they thought the target person felt at the end of the video. As participants watched the videos, their encoding patterns were examined by an eye tracker, which measured the amount of time participants spent looking at the target person’s head and body and at the interaction partner’s head and body. These regions were preselected for analyses because they had been found to provide cues for interpreting people’s emotions and intentions.

Results:

When encoding emotional cues, both the DHH and TH children spent more time looking at the head of the target person and at the head of the interaction partner than they spent looking at the body or actions of either person. Yet, compared with the TH children, the DHH children looked at the target person’s head for a shorter time (b = −0.03, p = 0.030), and at the target person’s body (b = 0.04, p = 0.006) and at the interaction partner’s head (b = 0.03, p = 0.048) for a longer time. The DHH children were also less accurate when interpreting emotions than their TH peers (b = −0.13, p = 0.005), and their lower scores were associated with their distinctive encoding pattern.

Conclusions:

The findings suggest that children with limited auditory access to the social environment tend to collect visually observable information to compensate for ambiguous emotional cues in social situations. These children may have developed this strategy to support their daily communication. Yet, to fully benefit from such a strategy, these children may need extra support for gaining better social-emotional knowledge.
Physical activity and gastric cancer risk: a case-control study in the Amazon region of Brazil
Authors: Fagundes Marcela A. , Peres Stela V. , Assumpção Paulo P. , Curado Maria P.
Published: December 2020

Gastric cancer is the fifth most common cancer worldwide. Investigations of lifestyle factors such as physical activity may identify risk patterns in this population. Thus, the aim of this study was to analyze the level of habitual physical activity and its association with the risk of gastric adenocarcinoma in the Amazon region. We conducted a hospital-based case-control study. Questionnaires investigating sociodemographic characteristics and physical activity were applied between July 2017 and April 2019. To assess habitual physical activity, we used the Baecke Physical Activity Questionnaire, which assessed physical exercise (PE), occupational physical activity, and leisure and locomotion activity (LLA). The Chi-square association test was applied and univariate and multiple binary logistic regression models were used for odds ratio analysis. The descriptive level of 5% (P < 0.05) was selected for statistical significance. The sample consisted of 297 individuals, with 147 cases and 150 controls. Those who performed PE at the second percentile level for 5 years before the interview were 71% less likely to develop gastric cancer (P = 0.012). Individuals with the highest LLA levels during the preceding 10 and 15 years were 76 and 78% less likely to have gastric cancer, respectively. In this study, physical activity related to sport and to leisure and locomotion was an independent protective factor that was inversely associated with gastric cancer.
Consumption of meat containing ractopamine might enhance tumor growth through induction of asparagine synthetase
Authors: Fan Frank S.
Published: December 2020

There is currently no evidence of the carcinogenic effect of the β-adrenergic agonist ractopamine added in finishing swine and cattle feed for promoting leanness. Nonetheless, it has the capability of stimulating expression of asparagine synthetase (ASNS) through activating transcription factor 5, and many other genes involved in the stress reaction in the skeletal muscle of pigs according to published scientific articles. Because overexpression of ASNS has been detected as a key player in amino acid response and unfolded protein response during the development of not a few malignant diseases, especially those with KRAS mutations, and found to be closely related to tumor proliferation, invasion and metastasis, it seems reasonable to hypothesize that intake of ractopamine residue in meat might bring negative effects to cancer patients.
Cigarettes smoking and androgen receptor-positive breast cancer
Authors: Pizzato Margherita , Carioli Greta , Rosso Stefano , Zanetti Roberto , Negri Eva , La Vecchia Carlo
Published: December 2020

Objectives

Cigarette smoking is related to higher levels of circulating androgens, but its association with androgen receptor (AR) status is still unaddressed.

Methods

We analysed, with a case-only approach, smoking habits according to AR status in 112 cases of invasive female breast cancer, from the Piedmont Cancer Registry. We used a multivariate logistic regression model to estimate the odds ratio (OR) and the corresponding confidence interval (CI).

Results

The OR of AR-positive breast cancer (versus AR-negative) for ever smokers (versus never) was 2.85 (95% CI 1.02–7.96).

Conclusion

Smoking is related to AR-positive breast cancer.
Family Planning Performance in Selected States and Union Territories of India: Evidence from NFHS 2019-20
Authors: Chaurasia Aalok Ranjan
Published: December 2020

This paper uses a new composite index to measure family planning performance in 22 states/Union Territories of India for which latest data on family planning use are available from NFHS 2019-2020. The analysis reveals that family planning performance in meeting the family planning needs of the people remains poor and there are significant inter-state/Union Territory variation in the performance. The paper calls for reinvigorating family planning efforts by treating family planning as a development strategy.
Early start of oral clarithromycin is associated with better outcome in COVID-19 of moderate severity: the ACHIEVE open-label trial
Authors: Tsiakos Konstantinos , Tsakiris Antonios , Tsibris Georgios , Voutsinas Pantazis , Panagopoulos Periklis , Kosmidou Maria , Petrakis Vasileios , Gravvani Areti , Gkavogianni Theologia , Klouras Eleftherios , Katrini Konstantina , Koufargyris Panagiotis , Rapti Iro , Karageorgos Athanassios , Vrentzos Emmanouil , Damoulari Christina , Zarkada Vagia , Sidiropoulou Chrysanthi , Artemi Sofia , Ioannidis Anastasios , Papapostolou Androniki , Michelakis Evangelos , Georgiopoulou Maria , Myrodia Dimitra-Melia , Tsiamalos Panteleimon , Syrigos Konstantinos , Chrysos George , Nitsotolis Thomas , Milionis Haralampos , Poulakou Garyphallia , Giamarellos-Bourboulis Evangelos J.
Published: December 2020

Background

To study the efficacy of oral clarithromycin in moderate COVID-19.

Methods

An open-label non-randomized trial in 90 patients with COVID-19 of moderate severity was conducted between May and October 2020. The primary endpoint was defined at the end-of-treatment (EOT) as no need for hospital re-admission and no progression into lower respiratory tract infection (LRTI) for patients with upper respiratory tract infection; and as at least 50% decrease of the respiratory symptoms score the without progression into severe respiratory failure (SRF) for patients with LRTI. Viral load, biomarkers, the function of mononuclear cells, and safety were assessed.

Results

The primary endpoint was attained in 86.7% of patients treated with clarithromycin (95% CIs 78.1-92.2%); this was 91.7% and 81.4% among patients starting clarithromycin the first 5 days from symptoms onset or later (odds ratio after multivariate analysis 6.62; p: 0.030). The responses were better for patients infected by non-B1.1 variants. Clarithromycin use was associated with decreases in circulating C-reactive protein, tumour necrosis factor-alpha and interleukin (IL)-6; by increase of Th1 to Th2 mononuclear responses; and by suppression of SARS-CoV-2 viral load. No safety concerns were reported.

Conclusions

Early clarithromycin treatment provides most of clinical improvement in moderate COVID-19 (Trial Registration: ClinicalTrials.gov, NCT04398004)
Marine community metabolomes carry fingerprints of phytoplankton community composition
Authors: Heal Katherine R. , Durham Bryndan , Boysen Angela K. , Carlson Laura T. , Qin Wei , Ribalet François , White Angelicque E. , Bundy Randelle M. , Armbrust E. Virginia , Ingalls Anitra Eiding
Published: December 2020

Phytoplankton transform inorganic carbon into thousands of biomolecules that represent an important pool of fixed carbon, nitrogen, and sulfur in the surface ocean. Metabolite production differs between phytoplankton, and the flux of these molecules through the microbial food web depends on compound-specific bioavailability to members of a wider microbial community. Yet relatively little is known about the diversity or concentration of metabolites within marine plankton. Here we compare 313 polar metabolites in 21 cultured phytoplankton species and in natural planktonic communities across environmental gradients to show that bulk community metabolomes reflect chemical composition of the phytoplankton community. We also show that groups of compounds have similar patterns across space and taxonomy suggesting that the concentrations of these compounds in the environment are controlled by similar sources and sinks. We quantify several compounds in the surface ocean that represent substantial understudied pools of labile carbon. For example, the N-containing metabolite homarine was up to 3% of particulate carbon and is produced in high concentrations by culturedSynechococcus, and S-containing gonyol accumulated up to 2.5 nM in surface particles and likely originates from dinoflagellates. Our results show that phytoplankton composition directly shapes the carbon composition of the surface ocean. Our findings suggest that in order to access these pools of bioavailable carbon, the wider microbial community must be adapted to phytoplankton community composition.

IMPORTANCE

Microscopic phytoplankton transform 100 million tons of inorganic carbon into thousands of different organic compounds each day. The structure of each chemical is critical to its biological and ecosystem function, yet, the diversity of biomolecules produced by marine microbial communities remained mainly unexplored, especially small polar molecules which are often considered the currency of the microbial loop. Here we explore the abundance and diversity of small biomolecules in planktonic communities across ecological gradients in the North Pacific and within 21 cultured phytoplankton species. Our work demonstrates that phytoplankton diversity is an important determinant of the chemical composition of the highly bioavailable pool of organic carbon in the ocean, and we highlight understudied yet abundant compounds in both the environment and cultured organisms. These findings add to understanding of how the chemical makeup of phytoplankton shapes marine microbial communities where the ability to sense and use biomolecules depends on the chemical structure.
MHC Haplotyping of SARS-CoV-2 patients: HLA subtypes are not associated with the presence and severity of Covid-19 in the Israeli population
Authors: Ben Shachar Shay , Barda Noam , Manor Sigal , Israeli Sapir , Dagan Noa , Haber Adam , Carmi Shai , Balicer Ran , Zisser Bracha , Louzoun Yoram
Published: December 2020

HLA haplotypes were found to be associated with increased risk for viral infections or disease severity in various diseases, including SARS. Several genetic variants are associated with Covid-19 severity. However, no clear association between HLA and Covid-19 incidence or severity has been reported. We conducted a large scale HLA analysis of Israeli individuals who tested positive for SARS-CoV-2 infection by PCR. Overall, 72,912 individuals with known HLA haplotypes were included in the study, of whom 6,413 (8.8%) were found to have SARS-CoV-2 by PCR. a Total of 20,937 subjects were of Ashkenazi origin (at least 2/4 grandparents). One hundred eighty-one patients (2.8% of the infected) were hospitalized due to the disease. None of the 66 most common HLA loci (within the five HLA subgroups; A, B, C, DQB1, DRB1) was found to be associated with SARS-CoV-2 infection or hospitalization. Similarly, no association was detected in the Ashkenazi Jewish subset. Moreover, no association was found between heterozygosity in any of the HLA loci and either infection or hospitalization.

We conclude that HLA haplotypes are not a major risk/protecting factor among the Israeli population for SARS-CoV-2 infection or severity.
Changes in inflammatory and immune drivers in response to immunomodulatory therapies in COVID-19
Authors: Wang Stephen Y. , Chang C-Hong , Meizlish Matthew L. , Bahel Parveen , Rinder Henry M. , Lee Alfred I. , Chun Hyung J.
Published: December 2020

As the global community strives to discover effective therapies for COVID-19, immunomodulatory strategies have emerged as a leading contender to combat the cytokine storm and improve clinical outcomes in patients with severe disease. Systemic corticosteroids and selective cytokine inhibitory agents have been utilized both as empiric therapies and in clinical trials. While multiple randomized, placebo controlled trials have now demonstrated that corticosteroids improve survival in patients with COVID-19,1, 2 IL-6 inhibition, which gained significant early interest based on observational studies, has not demonstrated reliable efficacy in randomized, placebo controlled trials.3, 4 To better understand the mechanistic basis of immunomodulatory therapies being implemented for treatment of COVID-19, we assessed longitudinal biochemical changes in response to such approaches in hospitalized patients with COVID-19. We demonstrate broad suppression of multiple immunomodulatory factors associated with adverse clinical outcomes in COVID-19 in patients who received corticosteroids, but no such response was seen in patients who either received tocilizumab or no immunomodulatory therapy. Our findings provide early insights into molecular signatures that correlate with immunomodulatory therapies in COVID-19 which may be useful in understanding clinical outcomes in future studies of larger patient cohorts.
Genomic characterization of a novel SARS-CoV-2 lineage from Rio de Janeiro, Brazil
Authors: Voloch Carolina M , Silva F Ronaldo da , de Almeida Luiz G P , Cardoso Cynthia C , Brustolini Otavio J. , Gerber Alexandra L , Guimarães Ana Paula de C , Mariani Diana , Costa Raissa Mirella da , Ferreira Orlando C. ,   Covid19-UFRJ Workgroup,   LNCC-Workgroup, Cavalcanti Adriana Cony , Frauches Thiago Silva , de Mello Claudia Maria Braga , Galliez Rafael Mello , Faffe Débora Souza , Castiñeiras Terezinha M P P , Tanuri Amilcar , de Vasconcelos Ana Tereza R
Published: December 2020

In this study, we report the sequencing of 180 new viral genomes obtained from different municipalities of the state of Rio de Janeiro from April to December 2020. We identified a novel lineage of SARS-CoV-2, originated from B.1.1.28, distinguished by five single-nucleotide variants (SNVs): C100U, C28253U, G28628U, G28975U, and C29754U. The SNV G23012A (E484K), in the receptor-binding domain of Spike protein, was widely spread across the samples. This mutation was previously associated with escape from neutralizing antibodies against SARS-CoV-2. This novel lineage emerged in late July being first detected by us in late October and still mainly restricted to the capital of the state. However, as observed for other strains it can be rapidly spread in the state. The significant increase in the frequency of this lineage raises concerns about public health management and continuous need for genomic surveillance during the second wave of infections.

Article Summary Line

We identified a novel circulating lineage of SARS-CoV-2 in the state of Rio de Janeiro Brazil originated from B.1.1.28 lineage.