bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimizing Translational Research for Exceptional Health and Life Span: A Systematic Narrative of Studies to Identify Translatable Therapeutic Target(s) for Exceptional Health Span in Humans
Authors: Raghavachari Nalini , Wilmot Beth , Dutta Chhanda
Published: March 2022

Background

Exceptional longevity as manifested by the lower incidence and delayed onset of age-related disabilities/diseases that include cardiovascular disease, Alzheimer’s disease, cancer is believed to be influenced by inherent protective molecular factors in exceptionally long-lived individuals. Unraveling these protective factors could lead to the discovery of therapeutic target(s) and interventions to promote healthy aging.

Methods

In this context, the National Institute on Aging has established a collection of translational longevity research projects (ie, the Long-Life Family Study, the Longevity Consortium, Longevity Genomics, and the Integrative Longevity Omics) which are generating large omics data sets spanning the human genome to phenome and have embarked on cross-species multiomic data analyses integrating human and nonhuman species that display wide variation in their life spans.

Results

It is expected that these studies will discover key signaling pathways that influence exceptional health span and identify therapeutic targets for translation to enhance health and life span. Other efforts related to translational longevity research include the “Comprehensive Evaluation of Aging-Related Clinical Outcomes and Geroproteins study,” which focuses on potential effects in humans of polypeptides/proteins whose circulating levels change with age, and for which experimental evidence indicates reversal or acceleration of aging changes. The “Predictive Human Mechanistic Markers Network” is devoted to the development of predictive markers of aging, for target engagement when testing novel interventions for healthy aging.

Conclusion

We describe here the significance, the unique study design, categories of data sets, analytical strategies, and a data portal to facilitate open science and sharing of resources from these longevity studies to identify and validate potential therapeutic targets for healthy aging.
Chromosome-level genome assembly, annotation, and phylogenomics of the gooseneck barnacle Pollicipes pollicipes
Authors: Bernot James P , Avdeyev Pavel , Zamyatin Anton , Dreyer Niklas , Alexeev Nikita , Pérez-Losada Marcos , Crandall Keith A
Published: March 2022

Background

The barnacles are a group of >2,000 species that have fascinated biologists, including Darwin, for centuries. Their lifestyles are extremely diverse, from free-swimming larvae to sessile adults, and even root-like endoparasites. Barnacles also cause hundreds of millions of dollars of losses annually due to biofouling. However, genomic resources for crustaceans, and barnacles in particular, are lacking.

Results

Using 62× Pacific Biosciences coverage, 189× Illumina whole-genome sequencing coverage, 203× HiC coverage, and 69× CHi-C coverage, we produced a chromosome-level genome assembly of the gooseneck barnacle Pollicipes pollicipes. The P. pollicipes genome is 770 Mb long and its assembly is one of the most contiguous and complete crustacean genomes available, with a scaffold N50 of 47 Mb and 90.5% of the BUSCO Arthropoda gene set. Using the genome annotation produced here along with transcriptomes of 13 other barnacle species, we completed phylogenomic analyses on a nearly 2 million amino acid alignment. Contrary to previous studies, our phylogenies suggest that the Pollicipedomorpha is monophyletic and sister to the Balanomorpha, which alters our understanding of barnacle larval evolution and suggests homoplasy in a number of naupliar characters. We also compared transcriptomes of P. pollicipes nauplius larvae and adults and found that nearly one-half of the genes in the genome are differentially expressed, highlighting the vastly different transcriptomes of larvae and adult gooseneck barnacles. Annotation of the genes with KEGG and GO terms reveals that these stages exhibit many differences including cuticle binding, chitin binding, microtubule motor activity, and membrane adhesion.

Conclusion

This study provides high-quality genomic resources for a key group of crustaceans. This is especially valuable given the roles P. pollicipes plays in European fisheries, as a sentinel species for coastal ecosystems, and as a model for studying barnacle adhesion as well as its key position in the barnacle tree of life. A combination of genomic, phylogenetic, and transcriptomic analyses here provides valuable insights into the evolution and development of barnacles.
The crustal and uppermost mantle dynamics of the Tengchong–Baoshan region revealed by P-wave velocity and azimuthal anisotropic tomography
Authors: Shen Wenhao , Liu Shaolin , Yang Dinghui , Wang Wenshuai , Xu Xiwei , Yang Shuxin
Published: March 2022

The Tengchong–Baoshan region (TBR) is located at the margin of the southeastern Tibetan Plateau (SETP) and is subject to the complex interaction among multiple tectonic blocks. Therefore, the TBR is approximate for investigating the mechanism responsible for the interaction among the SETP and its surrounding blocks. Based on eikonal equation-based seismic tomography, we obtain high-resolution P-wave velocity and azimuthal anisotropy at depths of 0–40 km beneath the TBR. We discover a large magma reservoir (with horizontal scale of ∼50 km and vertical scale of ∼15 km) in the middle-lower crust beneath the Tengchong volcanic zone, which is directly fed by hot materials from the uppermost mantle. We also detect a shallow magma chamber in the uppermost crust above the large reservoir. These magma reservoirs at different depths constitute a multiscale magma system. Furthermore, we observe a low-velocity belt beneath the Weixi–Qiaohou–Weishan and Nantinghe faults and postulate that it corresponds to lower crustal flow and hot mantle upwelling. Additionally, we infer that two M > 7.0 earthquakes that have occurred in Baoshan block nucleated in the transition zone between low- and high-velocity anomalies. Based on the azimuthal anisotropy tomography results, we consider that incoherent deformation in the crust causes the uneven accumulation of stress, which facilitated the occurrence of these two events. The 2021 Ms 6.4 Yangbi earthquake also occurred in the transition zone between low- and high-velocity anomalies. Based on the P-wave velocity tomography results, we suggest that hot material decreases the fault strength and leads to the instability of the fault.
The Human Rights Implications of the Use of AI in the Digital Welfare State: Lessons Learned from the Dutch SyRI Case
Authors: Rachovitsa Adamantia , Johann Niclas
Published: March 2022

The article discusses the human rights implications of algorithmic decision-making in the social welfare sphere. It does so against the background of the 2020 Hague’s District Court judgment in a case challenging the Dutch government’s use of System Risk Indication—an algorithm designed to identify potential social welfare fraud. Digital welfare state initiatives are likely to fall short of meeting basic requirements of legality and protecting against arbitrariness. Moreover, the intentional opacity surrounding the implementation of algorithms in the public sector not only hampers the effective exercise of human rights but also undermines proper judicial oversight. The analysis unpacks the relevance and complementarity of three legal/regulatory frameworks governing algorithmic systems: data protection, human rights law and algorithmic accountability. Notwithstanding these frameworks’ invaluable contribution, the discussion casts doubt on whether they are well-suited to address the legal challenges pertaining to the discriminatory effects of the use of algorithmic systems.
Artificial Intelligence Program to Predict p53 Mutations in Ulcerative Colitis–Associated Cancer or Dysplasia
Authors: Noguchi Tatsuki , Ando Takumi , Emoto Shigenobu , Nozawa Hiroaki , Kawai Kazushige , Sasaki Kazuhito , Murono Koji , Kishikawa Junko , Ishi Hiroaki , Yokoyama Yuichiro , Abe Shinya , Nagai Yuzo , Anzai Hiroyuki , Sonoda Hirofumi , Hata Keisuke , Sasaki Takeshi , Ishihara Soichiro
Published: March 2022

Background

The diagnosis of colitis-associated cancer or dysplasia is important in the treatment of ulcerative colitis. Immunohistochemistry of p53 along with hematoxylin and eosin (H&E) staining is conventionally used to accurately diagnose the pathological conditions. However, evaluation of p53 immunohistochemistry in all biopsied specimens is expensive and time-consuming for pathologists. In this study, we aimed to develop an artificial intelligence program using a deep learning algorithm to investigate and predict p53 immunohistochemical staining from H&E-stained slides.

Methods

We cropped 25 849 patches from whole-slide images of H&E-stained slides with the corresponding p53-stained slides. These slides were prepared from samples of 12 patients with colitis-associated neoplasia who underwent total colectomy. We annotated all glands in the whole-slide images of the H&E-stained slides and grouped them into 3 classes: p53 positive, p53 negative, and p53 null. We used 80% of the patches for training a convolutional neural network (CNN), 10% for validation, and 10% for final testing.

Results

The trained CNN glands were classified into 2 or 3 classes according to p53 positivity, with a mean average precision of 0.731 to 0.754. The accuracy, sensitivity (recall), specificity, positive predictive value (precision), and F-measure of the prediction of p53 immunohistochemical staining of the glands detected by the trained CNN were 0.86 to 0.91, 0.73 to 0.83, 0.91 to 0.92, 0.82 to 0.89, and 0.77 to 0.86, respectively.

Conclusions

Our trained CNN can be used as a reasonable alternative to conventional p53 immunohistochemical staining in the pathological diagnosis of colitis-associated neoplasia, which is accurate, saves time, and is cost-effective.
Advances and Challenges in Paleobiological Reconstructions of Joint Mobility
Authors: Manafzadeh Armita R , Gatesy Stephen M
Published: March 2022

Paleobiological reconstructions of joint mobility are an essential component of functional analyses of extinct animals. Over the past half-decade, the methods underlying mobility studies have advanced rapidly in three main areas: increasing complexity of virtual joint manipulation, formalizing pose viability criteria, and constructing more rigorous quantitative frameworks. Here we contextualize and review the recent history of this field, and call attention to remaining challenges and potential future directions. Additionally, we make available and describe a set of user-friendly scripts for the animation software Autodesk Maya. In doing so, we aim to make many of the latest approaches for virtual mobility reconstruction more easily accessible to other researchers, encouraging their broader adoption and collaborative improvement.
Demersal fish and invertebrate catches relative to construction and operation of North America's first offshore wind farm
Authors: Wilber Dara H , Brown Lorraine , Griffin Matthew , DeCelles Gregory R , Carey Drew A
Published: March 2022

Effects of offshore wind farm (OSW) development in the US on fishery resources have been predicted based on European experience. A seven-year study of the first US OSW documented the response of demersal fish and invertebrates to construction and operation. Local fishermen and scientists designed a monthly demersal trawl survey using a Before-After-Control-Impact (BACI) design to assess potential effects of Block Island Wind Farm (BIWF), a pilot scale 30 MW project completed in 2016. Common species did not exhibit statistically significant (α = 0.10) BACI interactions in catch per unit effort (CPUE) due to BIWF operation. CPUE of structure-oriented species, such as black sea bass (Centropristis striata) and Atlantic cod (Gadus morhua), increased at BIWF following turbine installation. Fall and spring biomass varied synchronously between BIWF and a regional survey for several species including longfin squid (Loligo pealeii) and winter flounder (Pseudopleuronectes americanus). Spatial-temporal interaction between reference areas provided an estimate of the minimum effect sizes (approximately 40% to 63% among the fish evaluated) that may be considered ecologically significant when assessing potential OSW impacts. Results from this first North American OSW fisheries monitoring study provide valuable information for future OSW development on the northeastern US coastline.
Small-c constitutional rights
Authors: Chilton Adam , Versteeg Mila
Published: March 2022

Although constitutions establish countries’ fundamental laws, identifying which legal materials are constitutional is not a straightforward task. Empirical studies in comparative law have focused on countries’ formal, written constitutions—the “large-C” constitutions—while often ignoring the broader body of constitutional rules—the “small-c” constitutions. This oversight occurs because incorporating small-c constitutional law into comparative research requires overcoming the conceptual challenge of identifying which legal sources should be considered constitutional and the practical challenge of quantifying those sources across jurisdictions. In this article, we address both of these challenges. We address the conceptual challenge by outlining three approaches to identifying small-c constitutions: an entrenchment-based approach that emphasizes whether given rules are more deeply entrenched than conventional laws, an external approach that emphasizes exogenously defined core constitutional functions, and an internal approach that emphasizes local understandings of constitutional law. We then partially address the practical challenge by using an internal approach to collect data on one aspect of constitutional law: constitutional rights. We collected this data for 123 countries by conducting an expert survey of constitutional law scholars and practitioners. Our data reveals that although the large-C constitution is the primary source of constitutional rights in a majority of countries, the small-c constitution is still a notable source of rights, especially in older constitutional systems. But although our data offers new evidence about small-c constitutional rights around the world, it also points to several substantial obstacles that any efforts to code small-c constitutions are likely to face.
Plasmodium falciparuminAotus nancymaae: A New Model for Placental Malaria
Authors: Sharma Ankur , Jenkins Bethany , Akue Adovi , Lambert Lynn E , Orr-Gonzalez Sachy , Thomas Marvin L , Mahamar Almahamoudou , Diarra Bacary S , Dicko Alassane , Fried Michal , Duffy Patrick E
Published: March 2022

Plasmodium falciparum-infected erythrocytes that display the variant surface antigen VAR2CSA bind chondroitin sulfate A (CSA) to sequester in placental intervillous spaces, causing severe sequelae for mother and offspring. Here, we establish a placental malaria (PM) monkey model. Pregnant Aotus infected with CSA-binding P. falciparum CS2 parasites during the third trimester developed pronounced sequestration of late-stage parasites in placental intervillous spaces that express VAR2CSA and bind specifically to CSA. Similar to immune multigravid women, a monkey infected with P. falciparum CS2 parasites over successive pregnancies acquired antibodies against VAR2CSA, with potent functional activity that was boosted upon subsequent pregnancy infections. Aotus also developed functional antibodies after multiple acute PM episodes and subsequent VAR2CSA immunization. In summary, P. falciparum infections in pregnant Aotus monkeys recapitulate all the prominent features of human PM infection and immunity, and this model can be useful for basic mechanistic studies and preclinical studies to qualify candidate PM vaccines.

Clinical Trials Registration: NCT02471378.
School-Based Malaria Screening and Treatment Reduces Plasmodium falciparum Infection and Anemia Prevalence in Two Transmission Settings in Malawi
Authors: Cohee Lauren M , Peterson Ingrid , Buchwald Andrea G , Coalson Jenna E , Valim Clarissa , Chilombe Moses , Ngwira Andrew , Bauleni Andy , Schaffer-DeRoo Sarah , Seydel Karl B , Wilson Mark L , Taylor Terrie E , Mathanga Don P , Laufer Miriam K
Published: March 2022

Background

In areas highly endemic for malaria, Plasmodium falciparum infection prevalence peaks in school-age children, adversely affecting health and education. School-based intermittent preventive treatment reduces this burden but concerns about cost and widespread use of antimalarial drugs limit enthusiasm for this approach. School-based screening and treatment is an attractive alternative. In a prospective cohort study, we evaluated the impact of school-based screening and treatment on the prevalence of P. falciparum infection and anemia in 2 transmission settings.

Methods

We screened 704 students in 4 Malawian primary schools for P. falciparum infection using rapid diagnostic tests (RDTs), and treated students who tested positive with artemether-lumefantrine. We determined P. falciparum infection by microscopy and quantitative polymerase chain reaction (qPCR), and hemoglobin concentrations over 6 weeks in all students.

Results

Prevalence of infection by RDT screening was 37% (9%–64% among schools). An additional 9% of students had infections detected by qPCR. Following the intervention, significant reductions in infections were detected by microscopy (adjusted relative reduction [aRR], 48.8%; P < .0001) and qPCR (aRR, 24.5%; P < .0001), and in anemia prevalence (aRR, 30.8%; P = .003). Intervention impact was reduced by infections not detected by RDT and new infections following treatment.

Conclusions

School-based screening and treatment reduced P. falciparum infection and anemia. This approach could be enhanced by repeating screening, using more-sensitive screening tests, and providing longer-acting drugs.

Clinical Trials Registration

NCT04858087.
Rates of underreported needlestick and sharps injuries among healthcare workers in Turkey: in the light of Infection Control Committee data
Authors: Korkmaz Nesibe , Şentürk Gönül Çiçek , Tekin Asiye , Gürbüz Yunus , Sevinç Ganime , Tütüncü Emin Ediz , Şencan İrfan
Published: March 2022

Objective

Doctors and nurses are frequently exposed to needlestick and sharps injuries (NSIs) because of their work. It is estimated that NSIs are more common than the rates reported to Infection Control Committee. The purpose of this study was to determine the incidence and reporting rates of NSIs in our hospital.

Methods

After their consent forms were obtained for the questionnaire, 670 doctors and nurses were interviewed face-to-face by the Infection Control Committee nurse. The questionnaire consisted of 22 questions, and the answers were recorded. The questions were on demographic data and injuries. The data of NSIs, whose active surveillance was made in our hospital since 2005 and in the last 1 year, were also analyzed retrospectively.

Results

A total of 119 (17%) people out of 670 people who participated in the study had at least one NSI; 43 (36%) people of the 119 people were doctors and 76 (63.9%) people were nurses. The most common injuries among doctors were found in assistant doctors (60%). No statistically significant differences were detected between the doctors and nurses in terms of injury status (P = 0.398). The most common injuries were found in surgical clinics, and a significant difference was detected here when compared to other clinics. The data that 20 (17%) people of the 118 people who were injured by the NSIs reported the injury were obtained from the Infection Control Committee database.

Conclusion

It is seen that injuries are high in surgical clinics and assistant doctors who have high work stress and workload. There were more injuries with sharp objects than the expected rates in our hospital although the reports were made very rarely. First of all, we should determine strategies, especially education, to reduce injuries, and then remove the obstacles to unreported injuries. The methods of clinics with a high rates of reporting needlestick and sharps injuries to the infection control committee should be examined and tried to be applied in our own clinics.
Forensic odontology: Assessing bite wounds to determine the role of teeth in piscivorous fishes
Authors: Muruga Pooventhran , Bellwood David R , Mihalitsis Michalis
Published: March 2022

Synopsis

Teeth facilitate the acquisition and processing of food in most vertebrates. However, relatively little is known about the functions of the diverse tooth morphologies observed in fishes. Piscivorous fishes (fish-eating fish) are crucial in shaping community structure and rely on their oral teeth to capture and/or process prey. However, how teeth are utilized in capturing and/or processing prey remains unclear. Most studies have determined the function of teeth by assessing morphological traits. The behavior during feeding, however, is seldom quantified. Here, we describe the function of teeth within piscivorous fishes by considering how morphological and behavioral traits interact during prey capture and processing. This was achieved through aquarium-based performance experiments, where prey fish were fed to 12 species of piscivorous fishes. Building on techniques in forensic odontology, we incorporate a novel approach to quantify and categorize bite damage on prey fish that were extracted from the piscivore’s stomachs immediately after being ingested. We then assess the significance of morphological and behavioral traits in determining the extent and severity of damage inflicted on prey fish. Results show that engulfing piscivores capture their prey whole and head-first. Grabbing piscivores capture prey tail-first using their teeth, process them using multiple headshakes and bites, before spitting them out, and then re-capturing prey head-first for ingestion. Prey from engulfers sustained minimal damage, whereas prey from grabbers sustained significant damage to the epaxial musculature. Within grabbers, headshakes were significantly associated with more severe damage categories. Headshaking behavior damages the locomotive muscles of prey, presumably to prevent escape. Compared to non-pharyngognaths, pharyngognath piscivores inflict significantly greater damage to prey. Overall, when present, oral jaw teeth appear to be crucial for both prey capture and processing (immobilization) in piscivorous fishes.
Anger and Apology, Recognition and Reconciliation: Managing Emotions in the Wake of Injustice
Authors: Friedrich Jasper
Published: March 2022

This article treats rituals of apology and reconciliation as responses to social discontent, specifically to expressions of anger and resentment. A standard account of social discontent, found both in the literature on transitional justice and in the social theory of Axel Honneth, has it that these emotional expressions are evidence of an underlying psychic need for recognition. In this framework, the appropriate response to expressions of anger and discontent is a recognitive one that includes victims of injustice in the political community by showing them that they are valued members. In the aftermath of injustices, such recognitive responses are thought to include acknowledgments of victim suffering, reconciliatory gestures, and rituals of contrition. I will argue, against this narrative, that treating victim anger as evidence of an underlying need for recognition threatens to depoliticize emotional responses to injustice by treating them as symptoms of psychic injuries instead of intelligible political claims. Discussing mainly the Canadian Truth and Reconciliation process set up to deal with the history of the Indian Residential School system, I show how rituals of reconciliation and apology, in the context of settler-colonial states and neoliberal politics, serve as a biopolitical management of “bad” emotions. This will serve as a critique both of the politics of reconciliation and of social–theoretic approaches that treat expressions of discontent exclusively through a lens of recognition. Instead, I argue, in politics as well as theory, we need to engage with emotional expressions as intelligible political claims that exceed the psychic need for recognition.
Charting a Path Towards Asian American Cancer Health Equity: A Way Forward
Authors: Chen Moon S , Lee Richard J , Madan Ravi A , Ta Park Van , Shinagawa Susan M , Sun Tracy , Gomez Scarlett L
Published: March 2022

On July 29, 2021, the US Food and Drug Administration’s Oncology Center of Excellence convened Conversations on Cancer. This Conversation, the first ever by the US Food and Drug Administration, focused on Asian Americans and served as the platform for this Commentary. Panelists elaborated on topics ranging from heterogeneity in Asian American demographics to racism through a path to health equity and supplemented this Commentary with literature citations. Asian Americans are the fastest-growing US race group, yet data aggregation obscures distinctions and cancer disparities within the more than 24 million Asians living in the United States with harmful impacts on communities and patients, as illustrated by breast cancer survivor Susan Shinagawa’s patient-to-advocate journey. Bigotry against Asian Americans has been pervasive since the 19th century, but especially during the COVID-19 pandemic. Asian Americans are unique as the first US population to experience cancer as the leading cause of death. Asian Americans are disproportionately affected by cancers because of infectious origins and have the highest rates of lung cancer among never-smoking women. The infinitesimal proportion of the National Institutes of Health’s budget compared with experiencing the highest percentage increases of any US racial population more than 3 decades highlights the dearth of focused research among Asian Americans. Recognizing the heterogeneity of Asian Americans and that disaggregated data are critical for accurately characterizing distinct ethnic groups, focusing on the impact of racism and COVID-19 on cancer disparities, and focusing and prioritizing funding resources are necessary steps forward for achieving health equity for Asian Americans.
MtGSTF7, a TT19-like GST gene, is essential for accumulation of anthocyanins, but not proanthocyanins in Medicago truncatula
Authors: Wang Ruoruo , Lu Nan , Liu Chenggang , Dixon Richard A , Wu Qing , Mao Yawen , Yang Yating , Zheng Xiaoling , He Liangliang , Zhao Baolin , Zhang Fan , Yang Shengchao , Chen Haitao , Jun Ji Hyung , Li Ying , Liu Changning , Liu Yu , Chen Jianghua
Published: March 2022

Anthocyanins and proanthocyanins (PAs) are two end products of the flavonoid biosynthesis pathway. They are believed to be synthesized in the endoplasmic reticulum and then sequestered into the vacuole. In Arabidopsis thaliana, TRANSPARENT TESTA 19 (TT19) is necessary for both anthocyanin and PA accumulation. Here, we found that MtGSTF7, a homolog of AtTT19, is essential for anthocyanin accumulation but not required for PA accumulation in Medicago truncatula. MtGSTF7 was induced by the anthocyanin regulator LEGUME ANTHOCYANIN PRODUCTION 1 (LAP1), and its tissue expression pattern correlated with anthocyanin deposition in M. truncatula. Tnt1-insertional mutants of MtGSTF7 lost anthocyanin accumulation in vegetative organs, and introducing a genomic fragment of MtGSTF7 could complement the mutant phenotypes. Additionally, the accumulation of anthocyanins induced by LAP1 was significantly reduced in mtgstf7 mutants. Yeast-one-hybridization and dual-luciferase reporter assays revealed that LAP1 could bind to the MtGSTF7 promoter to activate its expression. Ectopic expression of MtGSTF7 in tt19 mutants could rescue their anthocyanin deficiency, but not their PA defect. Furthermore, PA accumulation was not affected in the mtgstf7 mutants. Taken together, our results show that the mechanism of anthocyanin and PA accumulation in M. truncatula is different from that in A. thaliana, and provide a new target gene for engineering anthocyanins in plants.
Real World Impact of Remdesivir and Dexamethasone on Clinical Outcomes of Severe Coronavirus Disease 2019 in a Community Hospital
Authors: Larson Derek T , Ewers Evan C , Gallagher Kia M , Mahoney Alexandra M , Paul Madison L , Weina Peter J
Published: March 2022

Background

Evidence has emerged showing potential benefit of Remdesivir and dexamethasone in severe coronavirus disease 2019 (COVID-19) but results from large randomized control trials are conflicting. While initial data for dexamethasone indicated a mortality benefit, the impact of Remdesivir was best demonstrated in decreased time to recovery. Despite extensive disease burden throughout the world efficacy data of individual interventions is lacking in part due to extensive concurrent use of confounding investigational therapeutics.

Materials and Methods

We performed a retrospective analysis of the impact of Remdesivir and dexamethasone on real-world outcomes in severe COVID-19. All patients admitted to our community hospital between March 2020 and December 31, 2020 were included, and all patients admitted before national guidelines endorsed Remdesivir and dexamethasone outside of clinical trials were treated with only supportive care and used as historical controls. No other investigational therapeutics were utilized. This study was reviewed and approved by the Fort Belvoir Community Hospital IRB.

Results

58 hospitalized patients met criteria for severe COVID-19 as confirmed by RT-PCR, and 14 (25%) were used as historical controls. Baseline demographics and overall mortality rate (7.1%) did not significantly differ between the groups. The median length of stay was 7 days and 6 days in the historical control group and interventional group, respectively (P = 0.55).

Conclusions

We did not observe an appreciable impact on the duration of hospitalization when Remdesivir and dexamethasone were added to supportive care in a community hospital. This study was not sufficiently powered to detect the previously described mortality benefit of dexamethasone.
Timing and evolution of PSR B0950+08
Authors: Huang Hai-tao , Zhou Xia , Yuan Jian-ping , Zheng Xiao-Ping
Published: March 2022

We present timing solutions of PSR B0950+08, using 14 years of observations from the Nanshan 26-m Radio Telescope of Xinjiang Astronomical Observatory. The braking index of PSR B0950+08 varies from –367 392 to 168 883, which shows an oscillation with large amplitude (∼105) and uncertainty. Considering the variation of braking indices and the most probable kinematic age of PSR B0950+08, a model with long-term magnetic field decay modulated by short-term oscillations is proposed to explain the timing data. With this magnetic field decay model, we discuss the spin and thermal evolution of PSR B0950+08. The uncertainties of its age are also considered. The results show that three-component oscillations are the more reasonable for the spin-frequency derivative distributions of PSR B0950+08, and the initial spin period of PSR B0950+08 must be shorter than $97\rm \ ms$ when the age is equal to the lower bound of its kinematic age. The standard cooling model could explain the surface temperature of PSR B0950+08 with its most probable kinematic age. Vortex creep heating with a long-term magnetic field decay could maintain a relatively high temperature at the later stages of evolution and explain the thermal emission data of old and warm pulsars. Coupling with the long-term magnetic field decay, an explanation of the temperature of PSR B0950+08 with roto-chemical heating needs an implausibly short initial rotation period ($P_0 \lesssim 17\rm { ms}$). The spin and thermal evolution of pulsars should be studied simultaneously. Future timing, ultraviolet or X-ray observations are essential for studying the evolution and interior properties of pulsars.
Follow the water: finding water, snow, and clouds on terrestrial exoplanets with photometry and machine learning
Authors: Pham Dang , Kaltenegger Lisa
Published: March 2022

All life on Earth needs water. NASA’s quest to follow the water links water to the search for life in the cosmos. Telescopes like the James Webb Space Telescope and mission concepts like HabEx, LUVOIR, and Origins are designed to characterize rocky exoplanets spectroscopically. However, spectroscopy remains time-intensive, and therefore, initial characterization is critical to prioritization of targets. Here, we study machine learning as a tool to assess water’s existence through broad-band filter reflected photometric flux on Earth-like exoplanets in three forms: seawater, water-clouds, and snow; based on 53 130 spectra of cold, Earth-like planets with six major surfaces. XGBoost, a well-known machine-learning algorithm, achieves over 90 per cent balanced accuracy in detecting the existence of snow or clouds for S/N ≳ 20, and 70 per cent for liquid seawater for S/N ≳ 30. Finally, we perform mock Bayesian analysis with Markov chain Monte Carlo with five filters identified to derive exact surface compositions to test for retrieval feasibility. The results show that the use of machine learning to identify water on the surface of exoplanets from broad-band filter photometry provides a promising initial characterization tool of water in different forms. Planned small and large telescope missions could use this to aid their prioritization of targets for time-intense follow-up observations.
Geography-Dependent Horizontal Gene Transfer from Vertebrate Predators to Their Prey
Authors: Kambayashi Chiaki , Kakehashi Ryosuke , Sato Yusuke , Mizuno Hideaki , Tanabe Hideyuki , Rakotoarison Andolalao , Künzel Sven , Furuno Nobuaki , Ohshima Kazuhiko , Kumazawa Yoshinori , Nagy Zoltán T. , Mori Akira , Allison Allen , Donnellan Stephen C. , Ota Hidetoshi , Hoso Masaki , Yanagida Tetsuya , Sato Hiroshi , Vences Miguel , Kurabayashi Atsushi
Published: March 2022

Horizontal transfer (HT) of genes between multicellular animals, once thought to be extremely rare, is being more commonly detected, but its global geographic trend and transfer mechanism have not been investigated. We discovered a unique HT pattern of Bovine-B (BovB) LINE retrotransposons in vertebrates, with a bizarre transfer direction from predators (snakes) to their prey (frogs). At least 54 instances of BovB HT were detected, which we estimate to have occurred across time between 85 and 1.3 Ma. Using comprehensive transcontinental sampling, our study demonstrates that BovB HT is highly prevalent in one geographical region, Madagascar, suggesting important regional differences in the occurrence of HTs. We discovered parasite vectors that may plausibly transmit BovB and found that the proportion of BovB-positive parasites is also high in Madagascar where BovB thus might be physically transported by parasites to diverse vertebrates, potentially including humans. Remarkably, in two frog lineages, BovB HT occurred after migration from a non-HT area (Africa) to the HT hotspot (Madagascar). These results provide a novel perspective on how the prevalence of parasites influences the occurrence of HT in a region, similar to pathogens and their vectors in some endemic diseases.
Baseline distribution of stable copper isotope compositions of the brain and other organs in mice
Authors: Moynier Frédéric , Merland Ariane , Rigoussen Dimitri , Moureau Julien , Paquet Marine , Mahan Brandon , Le Borgne Marie
Published: March 2022

Copper (Cu) stable isotopes are useful for understanding pathways and tracing changes in Cu homeostasis, such as those induced by various diseases (e.g. liver cirrhosis, numerous forms of cancer, and neurodegenerative diseases). However, this utility relies on a baseline understanding of the natural distribution of Cu isotopes between organs of healthy organisms, which is not well-known at present. Here, the distribution of natural Cu isotopes in the brain, liver, red blood cells, plasma, kidneys, and muscle of 14 mice (7 males and 7 females) from three different genetic backgrounds is assessed. We show that the Cu isotopic composition of most mouse organs is isotopically distinct from one another. The most striking feature is the heavy isotope enrichment of the kidney (δ65Cu = 1.65 ± 0.06‰, 2SE), brain (δ65Cu = 0.87 ± 0.03‰, 2SE) and liver (δ65Cu = 0.71 ± 0.24‰, 2SE) compared to blood components, i.e. red blood cells (RBCs) (δ65Cu = 0.30 ± 0.06‰, 2SE), and plasma (δ65Cu = –0.61 ± 0.08‰, 2SE), with δ65Cu being the per mil deviation of the 65Cu/63Cu ratio from the NIST SRM 976 standard. Differences in genetic background do not appear to affect the isotopic distribution of Cu. Interestingly, male and female mice appear to have different Cu concentrations and isotopic compositions in their brain, plasma, muscle, and RBC.

By demonstrating that organs have distinct isotopic compositions, our study reinforces the notion that Cu stable isotopes can be used to trace changes in homeostasis in diseases affecting Cu distribution, such as Alzheimer's disease, liver cancer, and possible chronic kidney failure.
Tamarisk biocontrol alters bird community composition in the absence of cottonwood and willow vegetation
Authors: Mahoney Sean M , Johnson Matthew J , Holmes Jennifer A , Dudley Tom L , Kuehn Michael J , Theimer Tad C
Published: March 2022

Invasive plants threaten biodiversity worldwide, but control of non-native species may affect native species in complex ways. Non-native tamarisk (Tamarix spp.) is widespread in western U.S. riparian environments, and tamarisk beetles (Diorhabda spp.), a tamarisk-specific herbivore, were subsequently introduced as biocontrol. The primary effect of biocontrol is defoliation and branch dieback, with repeated defoliation killing the plant. We investigated the initial stages of site recovery after biocontrol and how tamarisk decline affected birds, their arthropod prey, and microclimate. We compared avian community diversity and composition, arthropod abundance, humidity, and temperature at sites along the Virgin River in Nevada and Arizona, USA characterized as either mixed native vegetation, tamarisk-dominated, or tamarisk-dominated where the majority of tamarisk died from biocontrol. We compared avian communities sampled after biocontrol to counts at the same locations before biocontrol. Prior to biocontrol, community compositions of all but one site grouped together using unbiased clustering algorithms. Following biocontrol, tamarisk-dominated sites grouped separately, and mixed sites grouped with the pre-biocontrol cluster. Comparison of pre- and post-biocontrol communities showed 7 common species declined by ≥30% in dead tamarisk sites, while one species did so at mixed sites and 3 at tamarisk-dominated sites. Individual census points in dead tamarisk had significantly lower Simpson diversity than the same points censused before biocontrol, unless native vegetation was present, suggesting tamarisk death was the cause of dominant species abundance changes. Tamarisk-dominated sites were hotter and drier than sites with native vegetation and supported fewer non-tamarisk-obligate arthropods, consistent with the hypothesis that bird reductions were driven by changes in microclimate and prey abundance. How long these effects last will depend upon the rate of native vegetation recovery after biocontrol, therefore we recommend monitoring sites to determine the trajectory of vegetative recovery and considering the need and feasibility of active restoration in those sites with slow or no native regeneration.
Pleiotropic and nonredundant effects of an auxin importer in Setaria and maize
Authors: Zhu Chuanmei , Box Mathew S , Thiruppathi Dhineshkumar , Hu Hao , Yu Yunqing , Martin Callista , Doust Andrew N , McSteen Paula , Kellogg Elizabeth A
Published: March 2022

Directional transport of auxin is critical for inflorescence and floral development in flowering plants, but the role of auxin influx carriers (AUX1 proteins) has been largely overlooked. Taking advantage of available AUX1 mutants in green millet (Setaria viridis) and maize (Zea mays), we uncover previously unreported aspects of plant development that are affected by auxin influx, including higher order branches in the inflorescence, stigma branch number, glume (floral bract) development, and plant fertility. However, disruption of auxin flux does not affect all parts of the plant, with little obvious effect on inflorescence meristem size, time to flowering, and anther morphology. In double mutant studies in maize, disruptions of ZmAUX1 also affect vegetative development. A green fluorescent protein (GFP)-tagged construct of the Setaria AUX1 protein Sparse Panicle1 (SPP1) under its native promoter showed that SPP1 localizes to the plasma membrane of outer tissue layers in both roots and inflorescences, and accumulates specifically in inflorescence branch meristems, consistent with the mutant phenotype and expected auxin maxima. RNA-seq analysis indicated that most gene expression modules are conserved between mutant and wild-type plants, with only a few hundred genes differentially expressed in spp1 inflorescences. Using clustered regularly interspaced short palindromic repeats (CRISPR)–Cas9 technology, we disrupted SPP1 and the other four AUX1 homologs in S. viridis. SPP1 has a larger effect on inflorescence development than the others, although all contribute to plant height, tiller formation, and leaf and root development. The AUX1 importers are thus not fully redundant in S. viridis. Our detailed phenotypic characterization plus a stable GFP-tagged line offer tools for future dissection of the function of auxin influx proteins.
Nailfold microvascular abnormalities are associated with a higher prevalence of pulmonary arterial hypertension in patients with MCTD
Authors: Todoroki Yasuyuki , Kubo Satoshi , Nakano Kazuhisa , Miyazaki Yusuke , Ueno Masanobu , Satoh-Kanda Yurie , Kanda Ryuichiro , Miyagawa Ippei , Hanami Kentaro , Nakatsuka Keisuke , Saito Kazuyoshi , Nakayamada Shingo , Tanaka Yoshiya
Published: March 2022

Objective

MCTD manifests with microvasculopathy and overlapping clinical features of SLE, SSc and idiopathic inflammatory myopathies (IIM). The aim of this study was to investigate the clinical significance of microvasculopathy in patients with MCTD using nailfold videocapillaroscopy (NVC).

Methods

Fifty patients with newly diagnosed and untreated MCTD were enrolled in this multicentre, prospective and observational study. Clinical features and NVC findings were assessed at baseline and after 1 year post-intervention, along with disease controls [SLE (n = 40), SSc (n = 70) and IIM (n = 50)].

Results

All MCTD patients presented Raynaud’s phenomenon and were positive for anti-U1 RNP antibodies, and 22.0% (11/50) had pulmonary arterial hypertension (PAH). The prevalence of NVC scleroderma patterns in MCTD was 38.0%, which was lower than SSc (88.6%) but higher than SLE (10.0%). In addition, when we divided MCTD patients into two groups by presence or absence of NVC scleroderma patterns, we found a higher prevalence of PAH in patients with NVC scleroderma patterns. Namely, NVC scleroderma patterns were observed in all MCTD patients with PAH, and in 21.0% of those without PAH. After intensive immunosuppressive therapy, NVC scleroderma patterns disappeared in half of the MCTD patients but were not changed in SSc patients.

Conclusions

MCTD differed from SLE, SSc and IIM in terms of the prevalence and responsiveness of NVC scleroderma patterns to immunosuppressive therapy. Detection of nailfold microvascular abnormalities in MCTD could contribute to predicting PAH and help us to understand further aspects of the pathogenesis of MCTD.
Conceptual limits of performativity: assessing the feasibility of market design blueprints
Authors: Rilinger Georg
Published: March 2022

Market designers work as social engineers. They create institutional structures to enforce the assumptions of theoretical market mechanisms. Despite much work on performative effects of economics, sociology has not analyzed the feasibility of designers’ theoretical blueprints. This article suggests that this may be done by identifying assumptions that derail the mechanism if they are not enforced. Sociologists then need to trace obstacles to their realization in practices of implementation. Blueprints are infeasible if the assumptions cannot be enforced either by themselves or jointly. To illustrate the approach, the article identifies one such assumption and traces its impact on a historical experiment of market design: the creation of markets for transmission capacity in California’s electricity markets. To realize the design’s explicit assumptions, designers built institutions that violated an implicit uniformity assumption and created opportunities for manipulations. Since the design’s assumptions could not be realized simultaneously, it was infeasible.
Bringing the market in: an expanded framework for understanding popular responses to economic inequality
Authors: Lindh Arvid , McCall Leslie
Published: March 2022

There has been an upsurge in research on the politics of economic inequality in the 21st century. Discussions of popular responses to rising inequality have expanded in turn yet remain centered on support for explicit government redistribution of income from the rich to the poor. We argue that this focus may downwardly bias measurement of preferences for less inequality and propose an expanded framework that incorporates preferences regarding market institutions and policies that reduce labor market inequalities, which together can shed light on the public’s adherence to free market ideology. Empirically, we use original data to examine the US case, with a comparison to Sweden and Denmark. The results offer initial evidence of (1) the need for an expanded framework and research agenda in this field and (2) potentially broad-based support for policies that address economic inequality directly in the market sphere, contrary to key tenets of free market ideology.
In search of a laundry receipt
Authors: Au-Yeung Bennett , Leung Samuel Yee Ching
Published: March 2022

There are, in general, three widely considered theoretical bases for a knowing receipt claim: unconscionability, a subsisting proprietary interest and unjust enrichment. In Byers v Saudi National Bank, the English Court of Appeal seemed to have settled for the first two bases. In this article, we first question why unconscionability alone cannot serve as the basis for a knowing receipt claim. We also bring to light the practical consequence that the Court’s decision may have in encouraging unscrupulous third parties to launder clean assets obtained in breach of trust by transferring them to safe-haven jurisdictions where the trust regime is not recognised.
The impact of Loa loa microfilaraemia on research subject retention during a whole sporozoite malaria vaccine trial in Equatorial Guinea
Authors: Manock Stephen R , Nsue Vicente Urbano , Olotu Ally , Mpina Maximillian , Nyakarungu Elizabeth , Raso José , Mtoro Ali , Ondo Mangue Martín Eka , Ntutumu Pasialo Beltrán Ekua , Nguema Rufino , Riyahi Pouria , Schindler Tobias , Daubenberger Claudia , Church L W Preston , Billingsley Peter F , Richie Thomas L , Abdulla Salim , Hoffman Stephen L
Published: March 2022

Loa loa microfilariae were found on thick blood smears (TBSs) from 8 of 300 (2.7%) residents of Bioko Island, Equatorial Guinea, during a Plasmodium falciparum sporozoite malaria vaccine clinical trial. Only one subject was found to have microfilaraemia on his first exam; parasites were not discovered in the other seven until subsequent TBSs were performed, at times many weeks into the study. All infected individuals were asymptomatic, and were offered treatment with diethylcarbamazine, per national guidelines. L. loa microfilaraemia complicated the enrolment or continued participation of these eight trial subjects, and only one was able to complete all study procedures. If ruling out loiasis is deemed to be important during clinical trials, tests that are more sensitive than TBSs should be performed.