bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of prolyl hydroxylase/HIF-1 signaling in vascular calcification
Authors: Negri Armando Luis
Published: October 2022

Morbidity and mortality of chronic kidney disease (CKD) patients are largely associated with vascular calcification, an actively regulated process in which vascular smooth muscle cells (VSMCs) change into cells similar to osteocytes/chondrocytes, known as trans-differentiation. Cellular and systemic response to low oxygen (hypoxia) is regulated by the prolyl hydroxylase/hypoxia-inducible factor (HIF)-1 pathway. Recent studies highlighted that hypoxia-mediated activation of HIF-1 induces trans-differentiation of VSMCs into bone-forming type through an increase in osteo-/chondrogenic genes. Inhibition of the HIF-1 pathway abolished osteochondrogenic differentiation of VSMCs. Hypoxia strongly enhanced elevated phosphate-induced VSMC osteogenic trans-differentiation and calcification. HIF-1 was shown to be essential for phosphate enhanced VSMC calcification. O2-dependent degradation HIF-1 is triggered by the prolyl hydroxylase domain proteins (PHD). Prolyl hydroxylase inhibitors, daprodustat and roxadustat, increase high phosphate–induced VC in VSMCs, stabilizing HIF-1α and activating the HIF-1 pathway in these cells. Whether the use of these PHD inhibitors to treat anemia in CKD patients will favor the development and progression of vascular calcification remains to be explored.
Unmet needs in clinical trials in CKD: questions we have not answered and answers we have not questioned
Authors: Levin Adeera , Borkum Megan
Published: October 2022

Many advances have been made in the field of nephrology over the last decade. These include an increasing focus on patient-centred involvement in trials, exploration of innovative trial designs and methodology, the growth of personalized medicine and, most importantly, novel therapeutic agents that are disease-modifying for large groups of patients with and without diabetes and chronic kidney disease. Despite this progress, many questions remain unanswered and we have not critically evaluated some of our assumptions, practices and guidelines despite emerging evidence to challenge current paradigms and discrepant patient-preferred outcomes. How best to implement best practices, diagnose various conditions, examine better diagnostic tools, treat laboratory values versus patients and understand prediction equations in the clinical context remain unanswered. As we enter a new era in nephrology, there are extraordinary opportunities to change the culture and care. Rigorous research paradigms enabling both the generation and the use of new information should be explored. We identify here some key areas of interest and suggest renewed efforts to describe and address these gaps so that we can develop, design and execute trials of importance to all.
Donor liquid biopsy and outcomes in kidney transplantation
Authors: Anfaiha-Sanchez Miriam , Rodrigo Calabia Emilio , Ortiz Alberto , Martin-Lorenzo Marta , Alvarez-Llamas Gloria
Published: October 2022

Kidney transplantation is the treatment of choice for patients with kidney failure. Priority on the waiting list and optimal donor–recipient matching are guided by mathematical scores, clinical variables and macroscopic observation of the donated organ. Despite the increasing rates of successful kidney transplantation, maximizing the number of available organs while ensuring the optimum long-term performance of the transplanted kidney remains both key and challenging, and no unequivocal markers are available for clinical decision making. Moreover, the majority of studies performed thus far has focused on the risk of primary non-function and delayed graft function and subsequent survival and have mainly analysed recipients’ samples. Given the increasing use of donors with expanded criteria and/or cardiac death, predicting whether grafts will provide sufficient kidney function is increasingly more challenging. Here we compile the available tools for pre-transplant kidney evaluation and summarize the latest molecular data from donors that may predict short-term (immediate or delayed graft function), medium-term (6 months) and long-term (≥12 months) kidney function. The use of liquid biopsy (urine, serum, plasma) to overcome the limitations of the pre-transplant histological evaluation is proposed. Novel molecules and approaches such as the use of urinary extracellular vesicles are also reviewed and discussed, along with directions for future research.
Dynamic demand for differentiated products with fixed-effects unobserved heterogeneity
Authors: Aguirregabiria Victor
Published: October 2022

This paper studies identification and estimation of a dynamic discrete choice model of demand for differentiated product using consumer-level panel data with few purchase events per consumer (i.e., short panel). Consumers are forward-looking and their preferences incorporate two sources of dynamics: last choice dependence due to habits and switching costs, and duration dependence due to inventory, depreciation, or learning. A key distinguishing feature of the model is that consumer unobserved heterogeneity has a Fixed Effects structure; that is, its probability distribution conditional on the initial values of endogenous state variables is unrestricted. I apply and extend recent results to establish the identification of all the structural parameters as long as the dataset includes four or more purchase events per household. The parameters can be estimated using a sufficient statistic—conditional maximum likelihood (CML) method. An attractive feature of CML in this model is that the sufficient statistic controls for the forward-looking value of the consumer’s decision problem, such that the method does not require solving dynamic programming problems or calculating expected present values.
Fifteen-year secular changes in the care and outcomes of patients with out-of-hospital cardiac arrest in Japan: a nationwide, population-based study
Authors: Shibahashi Keita , Kato Taichi , Hikone Mayu , Sugiyama Kazuhiro
Published: October 2022

Aims

Countries have implemented initiatives to improve the outcomes of patients with out-of-hospital cardiac arrest (OHCA). However, secular changes in care and outcomes at the national level have not been extensively investigated. This study aimed to determine 15-year secular changes in the outcomes of such patients in Japan.

Methods and results

Using population-based data of patients with OHCA, covering all populations in Japan (2005–19), patients for whom resuscitation was attempted were identified. The primary outcome was a favourable neurological outcome (Cerebral Performance Category 1 or 2: sufficient cerebral function for independent activities of daily life and work in a sheltered environment). Secular changes in outcomes were determined using a mixed-level multivariate logistic regression analysis. Overall, 1 764 440 patients (42.4% women; median age, 78 years) were examined. The incidence, median age, and proportion of patients who received bystander cardiopulmonary resuscitation (CPR) and dispatcher instructions for resuscitation increased significantly during the study period (P  < 0.001). A significant trend was noted toward improved outcomes over time (P for trend < 0.001); favourable neurological outcome proportions 1 month after arrest increased from 1.7–3.0% (odds ratio, 1.03 per 1-incremental year). A remarkable increase was noted in favourable neurological outcomes in younger patients and patients with initial shockable cardiac rhythm, while improvement varied among prefectures.

Conclusion

In Japan, collaborative efforts have yielded commendable achievements in the care and outcomes of patients with OHCA over 15 years through to 2019, while the improvement depended on patient characteristics. Further initiatives are needed to improve OHCA outcomes.
Data standards for atrial fibrillation/flutter and catheter ablation: the European Unified Registries for Heart Care Evaluation and Randomized Trials (EuroHeart)
Authors: Batra Gorav , Aktaa Suleman , Camm A John , Costa Francisco , Di Biase Luigi , Duncker David , Fauchier Laurent , Fragakis Nikolaos , Frost Lars , Hijazi Ziad , Juhlin Tord , Merino José L , Mont Lluis , Nielsen Jens C , Oldgren Jonas , Polewczyk Anna , Potpara Tatjana , Sacher Frederic , Sommer Philipp , Tilz Roland , Maggioni Aldo P , Wallentin Lars , Casadei Barbara , Gale Chris P
Published: October 2022

Aims

Standardized data definitions are essential for monitoring and assessment of care and outcomes in observational studies and randomized controlled trials (RCTs). The European Unified Registries for Heart Care Evaluation and Randomized Trials (EuroHeart) project of the European Society of Cardiology aimed to develop contemporary data standards for atrial fibrillation/flutter (AF/AFL) and catheter ablation.

Methods and results

We used the EuroHeart methodology for the development of data standards and formed a Working Group comprising 23 experts in AF/AFL and catheter ablation registries, as well as representatives from the European Heart Rhythm Association and EuroHeart. We conducted a systematic literature review of AF/AFL and catheter ablation registries and data standard documents to generate candidate variables. We used a modified Delphi method to reach a consensus on a final variable set. For each variable, the Working Group developed permissible values and definitions, and agreed as to whether the variable was mandatory (Level 1) or additional (Level 2). In total, 70 Level 1 and 92 Level 2 variables were selected and reviewed by a wider Reference Group of 42 experts from 24 countries. The Level 1 variables were implemented into the EuroHeart IT platform as the basis for continuous registration of individual patient data.

Conclusion

By means of a structured process and working with international stakeholders, harmonized data standards for AF/AFL and catheter ablation for AF/AFL were developed. In the context of the EuroHeart project, this will facilitate country-level quality of care improvement, international observational research, registry-based RCTs, and post-marketing surveillance of devices and pharmacotherapies.
Factor XI inhibitors: cardiovascular perspectives
Authors: De Caterina Raffaele , Prisco Domenico , Eikelboom John W
Published: October 2022

Anticoagulants are the cornerstone for prevention and treatment of thrombosis but are not completely effective, and concerns about the risk of bleeding continue to limit their uptake. Animal studies and experience from patients with genetic coagulation factor XI deficiency suggesting that this factor is more important for thrombosis than for haemostasis raises the potential for drugs that target factor XI to provide safer anticoagulation. Multiple factor XI inhibitors are currently under evaluation in clinical trials, including parenterally administered antisense oligonucleotides, monoclonal antibodies, and orally active small-molecule inhibitors. Promising results of phase 2 trials in patients undergoing major orthopaedic surgery, and in those with end-stage kidney disease, atrial fibrillation and acute coronary syndromes have led to large phase 3 trials that are currently ongoing. We here review premises for the use of these agents, results so far accrued, ongoing studies, and perspectives for future patient care.
Detection of pneumococcus during hospitalization for SARS-CoV-2
Authors: Stahlfeld Anne , Glick Laura R , Ott Isabel M , Craft Samuel B , Yolda-Carr Devyn , Harden Christina A , Nakahata Maura , Farhadian Shelli F , Grant Lindsay R , Alexander-Parrish Ronika , Arguedas Adriano , Gessner Bradford D , Weinberger Daniel M , Wyllie Anne L
Published: October 2022

Background

Infections with respiratory viruses [e.g. influenza and respiratory syncytial virus (RSV)] can increase the risk of severe pneumococcal infections. Likewise, pneumococcal coinfection is associated with poorer outcomes in viral respiratory infection. However, there are limited data describing the frequency of pneumococcus and SARS-CoV-2 coinfection and the role of coinfection in influencing COVID-19 severity. We, therefore, investigated the detection of pneumococcus in COVID-19 inpatients during the early pandemic period.

Methods

The study included patients aged 18 years and older, admitted to the Yale-New Haven Hospital who were symptomatic for respiratory infection and tested positive for SARS-CoV-2 during March–August 2020. Patients were tested for pneumococcus through culture-enrichment of saliva followed by RT-qPCR (to identify carriage) and serotype-specific urine antigen detection (UAD) assays (to identify presumed lower respiratory tract pneumococcal disease).

Results

Among 148 subjects, the median age was 65 years; 54.7% were male; 50.7% had an ICU stay; 64.9% received antibiotics; and 14.9% died while admitted. Pneumococcal carriage was detected in 3/96 (3.1%) individuals tested by saliva RT-qPCR. Additionally, pneumococcus was detected in 14/127 (11.0%) individuals tested by UAD, and more commonly in severe than moderate COVID-19 [OR: 2.20; 95% CI: (0.72, 7.48)]; however, the numbers were small with a high degree of uncertainty. None of the UAD-positive individuals died.

Conclusions

Pneumococcal lower respiratory tract infection (LRTI), as detected by positive UAD, occurred in patients hospitalized with COVID-19. Moreover, pneumococcal LRTI was more common in those with more serious COVID-19 outcomes. Future studies should assess how pneumococcus and SARS-CoV-2 interact to influence COVID-19 severity in hospitalized patients.
The efficacy and safety of thalidomide in the treatment of refractory Crohn's disease in adults: a double-center, double-blind, randomized–controlled trial
Authors: Peng Xiang , Lin Zi-Wen , Zhang Min , Yao Jia-Yin , Zhao Jun-Zhang , Hu Pin-Jin , Cao Qian , Zhi Min
Published: October 2022

Background

Thalidomide is applied in therapy for refractory Crohn's disease (CD) in adults, but systematic and rigorous clinical evidence is scant. The aim was to provide theoretical references for the efficacy of thalidomide in the therapy for refractory CD in adults.

Methods

A double-center, double-blind, placebo-controlled, randomized clinical trial of refractory CD in adults in two inflammatory bowel disease centers in China. In the double-blind trial, patients were randomly assigned to 100 mg of thalidomide or placebo daily for 8 weeks. The primary outcome was considered as the clinical remission rate calculated based on the Crohn's disease activity index at the eighth week following thalidomide or placebo treatment. In open label, non-response to placebo was additionally treated with 8 weeks of thalidomide; all responders were continuously treated with thalidomide until the 48th week.

Results

Twenty-five patients were randomly assigned to each group. At the eighth week, the clinical remission rate in the thalidomide group was significantly higher than that in the placebo group (68.0% [17/25] vs 16.0% [4/25]; relative risk, 4.2; 95% confidence interval, 1.8–10.9, P < 0.001). After a 48-week follow-up, the continuous treatment rate of thalidomide was 46.3% (19/41). Adverse events during the whole process were reported in 58.5% of patients, mainly involving drowsiness, rash, and peripheral neuropathy that were mild and tolerable.

Conclusion

Thalidomide can be used in the induction and maintenance therapy of refractory CD in adults. And it could be one of the treatment options for refractory CD.
Sample2Sample: an improved self-supervised denoising framework for random noise suppression in distributed acoustic sensing vertical seismic profile data
Authors: Zhao Y X , Li Y , Wu N , Wang S N
Published: October 2022

The performance of supervised deep learning-based denoising methods relies on massive amounts of high-quality training data set with labels. However, data labelling is a time-consuming and tedious process, and the lack of labelled data set has become a major bottleneck affecting the development of supervised deep learning-based denoising methods. In recent years, denoising methods that only use unlabelled noisy data set for training have received more and more attention. Although these methods get rid of the dependence on labels, they usually have some specific requirements on the training data set. For example, the paired training data are required to be multiple noisy observations for each scene or obey a specific noise distribution, etc., which are often very challenging to meet in practical applications. In this study, we propose an improved self-supervised denoising framework based on Noise2Noise that only uses noisy seismic data set for training, and we name it sample2sample. The proposed denoising framework does not require multiple repeated acquisitions of seismic data to obtain multiple independent noisy observations for each scene used for training, and has no specific requirement for the noise distribution prior. Specifically, we introduce a random sampler to generate paired subsamples from some individual noisy seismic data for training. The corresponding elements in the two paired subsamples are adjacent in the original seismic data and approximately meet the training premise of Noise2Noise, that is the paired training data have the same signal. In addition, considering that there are some subtle differences in the signals of the paired subsamples generated by sampling, we also introduce a regularization loss to compensate for this. We conducted a qualitative and quantitative analysis of the denoising performance of the proposed method through further experiments, including synthetic data experiments and field data experiments.
Simulation of thermoelastic wave propagation in 3-D multilayered half-space media
Authors: Yang Bo , Li Zhengbo , Zeng Ling , Chen Xiaofei
Published: October 2022

Thermal phenomena are common in both the generation and propagation of seismic waves. To investigate the propagation characteristics of thermoelastic waves generated by point sources in a 3-D multilayered half-space, herein, we develop a method that can solve problems involving coupled mechanical and thermal motions. The method first transforms the governing equations into two sets of first-order ordinary differential equations with a unified form in the frequency–wavenumber domain and then solves them by a generalized reflection and transmission coefficient method. To verify the correctness of our method and the corresponding computer program, we compare our solutions with analytical solutions. We further apply the method to different multilayered models, and the numerical results clearly demonstrate the reflection and transmission phenomena of thermoelastic waves within the interlayer. Furthermore, the generated thermal and seismic signals are synchronous, and the two P waves predicted by generalized thermoelastic theory can be converted into each other. The records on the ground show that thermal motions influence our observation of direct waves, especially in the presence of high thermal conductivity subsurface media, it can significantly impact the propagation of both body and surface waves, making surface seismic observations more complex than those predicted by elastic theory.
New insights into the Rhône–Simplon fault system (Swiss Alps) from a consistent earthquake catalogue covering 35 yr
Authors: Lee Timothy , Diehl Tobias , Kissling Edi , Wiemer Stefan
Published: October 2022

Seismotectonic interpretations in regions characterized by low to moderate seismicity require consistent earthquake catalogues covering periods of several decades. Inevitable changes in network configuration and analysing procedures, however, introduce significant bias to the hypocentre parameters and uncertainty estimates reported in such catalogues. To overcome these limitations, we developed a procedure using coupled hypocentre-velocity inversions to compute consistent hypocentre locations covering time periods of several decades while accounting for changes in network geometry. We apply these procedures to 35 yr of instrumentally recorded seismicity along the Rhône–Simplon fault system in southwest Switzerland, which is at the transition between the Central and Western Alps. The entire catalogue is relocated using a probabilistic location algorithm in combination with the derived minimum 1-D velocity models. A combination of location parameters is used to define consistent location-quality classes allowing for reliable interpretation of epicentres and focal depths. The relocated catalogue is interpreted together with a recent 3-D P-wave tomographic model and available 2-D reflection seismic profiles. The relocated hypocentres indicate that the major band of seismicity north of the Rhône valley is associated with a 30–40 km long, steeply north-dipping shear zone, which roots in the crystalline basement of the Aar Massif and extends to the shallowest levels of the sedimentary cover of the Helvetic nappes in the Rawil Depression. Seismicity towards the southwest indicates the existence of a similar shear zone within the Aiguille Rouge Massif. This zone possibly extends to the northeast and joins the Rawil fault zone. To the south of the Rhône valley, seismicity is scattered within the Penninic nappes, but limited to the hanging wall of the Pennine Basal Thrust (PBT). The Penninic nappes are characterized by a relatively higher VP of about 5 per cent compared to the Aar Massif, indicating differences in composition or metamorphic grade across the PBT.
How China lost its wolf pack: the fracturing of the emerging-power alliance at the WTO
Authors: Hopewell Kristen
Published: October 2022

There has been considerable debate about the capacity of emerging powers, such as the BRICS (Brazil, India, China, South Africa), to act as a unified and coherent force in global economic governance. In the case of the World Trade Organization (WTO), strategic cooperation and alliance-building among the emerging powers—specifically Brazil, India and China (BIC)—were essential to counterbalancing the US and other traditional powers and enabling the rising powers to defend their interests. However, as this article shows, the BIC alliance at the WTO has collapsed. The core issue that historically united the emerging powers and provided the foundation for their alliance was ‘special and differential treatment’ (SDT) for developing countries. Yet both Brazil and India have now defected from the alliance, abandoning China. Brazil was the first to defect, switching sides and realigning itself with the US; the change in its alliance calculations reflected shifting economic priorities and a fundamental reorientation of its foreign policy strategy away from its earlier Third Worldism. India then defected when its alliance with China, once an important source of strength in WTO negotiations, instead became a liability. As a result, having lost its key allies at the WTO, China is increasingly isolated in multilateral trade negotiations.
Localizing refugeehood: norms and the US resettlement of Afghan allies
Authors: Coen Alise
Published: October 2022

A central challenge for the study of norms in International Relations entails understanding how meaning is enacted through use and local context. Amid trends towards governments reducing pathways of humanitarian migration, local constructions of meaning around refugeehood and the obligations owed to people fleeing persecution can influence global trajectories of containment and responsibility-sharing. As a means of advancing our understanding of norm localization and contestation, this article provides an account of how obligations around refugee protection are configured and contested among national and subnational authorities. Using a case study of discourses (re)produced among United States' federal, state and municipal leaders, it explores the multiple, complex layers of meaning which emerged around duties of care owed to foreign civilian ‘allies’ in the context of the 2021 Taliban takeover of Afghanistan. Beyond illustrating dynamics of localization and contestation, the article shows how domestic resistance to norm implementation can operate as a surrogate for wider visions of resisting liberal international principles. The case study more broadly contributes to understanding the conflicting logics associated with duties of care in the aftermath of military interventions.
Bone Density Variation in Rattails (Macrouridae, Gadiformes): Buoyancy, Depth, Body Size, and Feeding
Authors: Martin Rene P , Dias Abigail S , Summers Adam P , Gerringer Mackenzie E
Published: October 2022

Synopsis

Extreme abiotic factors in deep-sea environments, such as near-freezing temperatures, low light, and high hydrostatic pressure, drive the evolution of adaptations that allow organisms to survive under these conditions. Pelagic and benthopelagic fishes that have invaded the deep sea face physiological challenges from increased compression of gasses at depth, which limits the use of gas cavities as a buoyancy aid. One adaptation observed in deep-sea fishes to increase buoyancy is a decrease of high-density tissues. In this study, we analyze mineralization of high-density skeletal tissue in rattails (family Macrouridae), a group of widespread benthopelagic fishes that occur from surface waters to greater than 7000 m depth. We test the hypothesis that rattail species decrease bone density with increasing habitat depth as an adaptation to maintaining buoyancy while living under high hydrostatic pressures. We performed micro-computed tomography (micro-CT) scans on 15 species and 20 specimens of rattails and included two standards of known hydroxyapatite concentration (phantoms) to approximate voxel brightness to bone density. Bone density was compared across four bones (eleventh vertebra, lower jaw, pelvic girdle, and first dorsal-fin pterygiophore). On average, the lower jaw was significantly denser than the other bones. We found no correlation between bone density and depth or between bone density and phylogenetic relationships. Instead, we observed that bone density increases with increasing specimen length within and between species. This study adds to the growing body of work that suggests bone density can increase with growth in fishes, and that bone density does not vary in a straightforward way with depth.
Symptomatic Profile and Cognitive Performance in Autopsy-Confirmed Limbic-Predominant Age-Related TDP-43 Encephalopathy With Comorbid Alzheimer Disease
Authors: Gauthreaux Kathryn , Mock Charles , Teylan Merilee A , Culhane Jessica E , Chen Yen-Chi , Chan Kwun C G , Katsumata Yuriko , Nelson Peter T , Kukull Walter A
Published: October 2022

Transactive response DNA-binding protein 43 kDa (TDP-43) proteinopathy is the hallmark of limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC). LATE-NC is a common copathology with Alzheimer disease neuropathologic change (ADNC). Data from the National Alzheimer’s Coordinating Center were analyzed to compare clinical features and copathologies of autopsy-confirmed ADNC with versus without comorbid LATE-NC. A total of 735 participants with ADNC alone and 365 with ADNC with LATE-NC were included. Consistent with prior work, brains with LATE-NC had more severe ADNC, more hippocampal sclerosis, and more brain arteriolosclerosis copathologies. Behavioral symptoms and cognitive performance on neuropsychological tests were compared, stratified by ADNC severity (low/intermediate vs high). Participants with ADNC and LATE-NC were older, had higher ADNC burden, and had worse cognitive performance than participants with ADNC alone. In the low/intermediate ADNC strata, participants with comorbid LATE-NC had higher prevalence of behavioral symptoms (apathy, disinhibition, agitation, personality change). They also had worsened performance in episodic memory and language/semantic memory. Differences narrowed in the high ADNC strata, with worsened performance in only episodic memory in the comorbid LATE-NC group. The co-occurrence of LATE-NC with ADNC is associated with a different pattern of behavioral and cognitive performance than ADNC alone, particularly in people with low/intermediate ADNC burden.
Aβ Deposits in the Neocortex of Adult and Infant Hypoxic Brains, Including in Cases of COVID-19
Authors: Priemer David S , Rhodes Charles Harker , Karlovich Esma , Perl Daniel P , Goldman James E
Published: October 2022

The brain of a 58-year-old woman was included as a civilian control in an ongoing autopsy study of military traumatic brain injury (TBI). The woman died due to a polysubstance drug overdose, with Coronavirus Disease 2019 (COVID-19) serving as a contributing factor. Immunohistochemical stains for β-amyloid (Aβ), routinely performed for the TBI study, revealed numerous, unusual neocortical Aβ deposits. We investigated the autopsied brains of 10 additional young patients (<60 years old) who died of COVID-19, and found similar Aβ deposits in all, using two different Aβ antibodies across three different medical centers. The deposits failed to stain with Thioflavin-S. To investigate whether or not these deposits formed uniquely to COVID-19, we applied Aβ immunostains to the autopsied brains of COVID-19-negative adults who died with acute respiratory distress syndrome and infants with severe cardiac anomalies, and also biopsy samples from patients with subacute cerebral infarcts. Cortical Aβ deposits were also found in these cases, suggesting a link to hypoxia. The fate of these deposits and their effects on function are unknown, but it is possible that they contribute to the neurocognitive sequelae observed in some COVID-19 patients. Our findings may also have broader implications concerning hypoxia and its role in Aβ deposition in the brain.
Is standby therapy for Covid-19 a practical option for travellers?
Authors: Chen Lin H , Connor Bradley A
Published: October 2022

International travel has resumed while the risk of SARS-CoV-2 persists, leading to consideration of medications that can treat or prevent Covid-19 when travellers become ill abroad. Nirmatrelvir-ritonavir, molnupiravir and tixagevimab-cilgavimab are available under Emergency Use Authorization or conditional approval. We discuss the potential application of these medications to protect travellers.
Effectiveness of BNT162b2 and CoronaVac vaccinations against SARS-CoV-2 omicron infection in people aged 60 years or above: a case–control study
Authors: Wan Eric Yuk Fai , Mok Anna Hoi Ying , Yan Vincent Ka Chun , Chan Cheyenne I Ying , Wang Boyuan , Lai Francisco Tsz Tsun , Chui Celine Sze Ling , Li Xue , Wong Carlos King Ho , Lau Chak Sing , Wong Ian Chi Kei , Chan Esther Wai Yin
Published: October 2022

Background

In view of limited evidence that specifically addresses vaccine effectiveness (VE) in the older population, this study aims to evaluate the real-world effectiveness of BNT162b2 and CoronaVac in older adults during the Omicron BA.2 outbreak.

Methods

This case–control study analyzed data available between January and March 2022 from the electronic health databases in Hong Kong and enrolled individuals aged 60 or above. Each case was matched with up to 10 controls by age, sex, index date and Charlson Comorbidity Index for the four outcomes (COVID-19 infection, COVID-19-related hospitalization, severe complications, and all-cause mortality) independently. Conditional logistic regression was conducted to evaluate VE of BNT162b2 and CoronaVac against COVID-19-related outcomes within 28 days after COVID-19 infection among participants stratified by age groups (60–79, ≥80 years old).

Results

A dose–response relationship between the number of vaccine doses received and protection against severe or fatal disease was observed. Highest VE (95% CI) against COVID-19 infection was observed in individuals aged ≥80 who received three doses of BNT162b2 [75.5% (73.1–77.7%)] or three doses of CoronaVac [53.9% (51.0–56.5%)] compared to those in the younger age group who received three doses of BNT162b2 [51.1% (49.9–52.4%)] or three doses of CoronaVac [2.0% (−0.1–4.1%)]. VE (95% CI) was higher for other outcomes, reaching 91.9% (89.4–93.8%) and 86.7% (84.3–88.8%) against COVID-19-related hospitalization; 85.8% (61.2–94.8%) and 89.8% (72.4–96.3%) against COVID-19-related severe complications; and 96.4% (92.9–98.2%) and 95.0% (92.1–96.8%) against COVID-19-related mortality after three doses of BNT162b2 and CoronaVac in older vaccine recipients, respectively. A similar dose–response relationship was established in younger vaccine recipients and after stratification by sex and Charlson Comorbidity Index.

Conclusion

Both BNT162b2 and CoronaVac vaccination were effective in protecting older adults against COVID-19 infection and COVID-19-related severe outcomes amidst the Omicron BA.2 pandemic, and VE increased further with the third dose.
A ‘wiring diagram’ for source strength traits impacting wheat yield potential
Authors: Murchie Erik H , Reynolds Matthew , Slafer Gustavo A , Foulkes M John , Acevedo-Siaca Liana , McAusland Lorna , Sharwood Robert , Griffiths Simon , Flavell Richard B , Gwyn Jeff , Sawkins Mark , Carmo-Silva Elizabete
Published: October 2022

Source traits are currently of great interest for the enhancement of yield potential; for example, much effort is being expended to find ways of modifying photosynthesis. However, photosynthesis is but one component of crop regulation, so sink activities and the coordination of diverse processes throughout the crop must be considered in an integrated, systems approach. A set of ‘wiring diagrams’ has been devised as a visual tool to integrate the interactions of component processes at different stages of wheat development. They enable the roles of chloroplast, leaf, and whole-canopy processes to be seen in the context of sink development and crop growth as a whole. In this review, we dissect source traits both anatomically (foliar and non-foliar) and temporally (pre- and post-anthesis), and consider the evidence for their regulation at local and whole-plant/crop levels. We consider how the formation of a canopy creates challenges (self-occlusion) and opportunities (dynamic photosynthesis) for components of photosynthesis. Lastly, we discuss the regulation of source activity by feedback regulation. The review is written in the framework of the wiring diagrams which, as integrated descriptors of traits underpinning grain yield, are designed to provide a potential workspace for breeders and other crop scientists that, along with high-throughput and precision phenotyping data, genetics, and bioinformatics, will help build future dynamic models of trait and gene interactions to achieve yield gains in wheat and other field crops.
Proteomic perspective of azole resistance in Aspergillus fumigatus biofilm extracellular matrix in response to itraconazole
Authors: Wei Tianqi , Zheng Nan , Zheng Hailin , Chen Yuping , Hong Pianpian , Liu Weida , Liu Musang
Published: October 2022

Azole-resistant Aspergillus fumigatus makes a major challenge to the chemotherapy for invasive aspergillosis, whereas cyp51A gene mutation is the most dominant mechanism for azole resistance. Moreover, biofilm contributes to drug resistance for A. fumigatus, and extracellular matrix (ECM) is essential to protect live cells from antifungal drugs. Therefore, we performed a comparative proteomic study on the biofilm ECM of both the wild-type and azole-resistant strains of A. fumigatus under azole pressure. In total, 2377 proteins were identified, of which 480 and 604 proteins with differential expression were obtained from the wild-type and azole-resistant A. fumigatus in exposure to itraconazole respectively (fold change > 2 or < 0.5, P-value < .05). We found that a high proportion of regulated proteins were located in the cytoplasm, nucleus, and mitochondria. Meanwhile, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that the metabolic process and ribosome pathway were significantly enriched. Particularly, differentially expressed proteins in response to azole pressure of both the wild-type and resistant strains were further analyzed. Our results indicated that these changes in biofilm ECM proteins were related to ergosterol synthesis, oxidative stress, efflux pumps, DNA repair, DNA replication, and transcription.
Trinity I: self-consistently modelling the dark matter halo–galaxy–supermassive black hole connection from z = 0–10
Authors: Zhang (张昊文) Haowen , Behroozi Peter , Volonteri Marta , Silk Joseph , Fan Xiaohui , Hopkins Philip F , Yang (杨锦怡) Jinyi , Aird James
Published: October 2022

We present Trinity, a flexible empirical model that self-consistently infers the statistical connection between dark matter haloes, galaxies, and supermassive black holes (SMBHs). Trinity is constrained by galaxy observables from 0 < z < 10 [galaxies’ stellar mass functions, specific and cosmic star formation rates (SFRs), quenched fractions, and UV luminosity functions] and SMBH observables from 0 < z < 6.5 (quasar luminosity functions, quasar probability distribution functions, active black hole mass functions, local SMBH mass–bulge mass relations, and the observed SMBH mass distributions of high-redshift bright quasars). The model includes full treatment of observational systematics [e.g. active galactic nucleus (AGN) obscuration and errors in stellar masses]. From these data, Trinity infers the average SMBH mass, SMBH accretion rate, merger rate, and Eddington ratio distribution as functions of halo mass, galaxy stellar mass, and redshift. Key findings include: (1) the normalization and the slope of the SMBH mass–bulge mass relation increases mildly from z = 0 to z = 10; (2) The best-fitting AGN radiative+kinetic efficiency is ∼0.05–0.06, but can be in the range ∼0.035–0.07 with alternative input assumptions; (3) AGNs show downsizing, i.e. the Eddington ratios of more massive SMBHs start to decrease earlier than those of lower mass objects; (4) The average ratio between average SMBH accretion rate and SFR is ∼10−3 for low-mass galaxies, which are primarily star-forming. This ratio increases to ∼10−1 for the most massive haloes below z ∼ 1, where star formation is quenched but SMBHs continue to accrete.
On the use of field RR Lyrae as galactic probes – VI. Mixed mode RR Lyrae variables in Fornax and in nearby dwarf galaxies
Authors: Braga V F , Fiorentino G , Bono G , Stetson P B , Martínez-Vázquez C E , Kwak S , Tantalo M , Dall’Ora M , Di Criscienzo M , Fabrizio M , Marengo M , Marinoni S , Marrese P M , Monelli M
Published: October 2022

We investigate the properties of the mixed-mode (RRd) RR Lyrae (RRL) variables in the Fornax dwarf spheroidal (dSph) galaxy by using B- and V-band time series collected over 24 yr. We compare the properties of the RRds in Fornax with those in the Magellanic Clouds and in nearby dSphs, with special focus on Sculptor. We found that the ratio of RRds over the total number of RRLs decreases with metallicity. Typically, dSphs have very few RRds with 0.49≲ P0 ≲0.53 d, but Fornax fills this period gap in the Petersen diagram (ratio between first overtone over fundamental period versus fundamental period). We also found that the distribution in the Petersen diagram of Fornax RRds is similar to Small Magellanic Cloud (SMC) RRds, thus suggesting that their old stars have a similar metallicity distribution. We introduce the Period–Amplitude RatioS diagram, a new pulsation diagnostics independent of distance and reddening. We found that Large Magellanic Cloud (LMC) RRds in this plane are distributed along a short- and a long-period sequence that we identified as the metal-rich and the metal-poor component. These two groups are also clearly separated in the Petersen and Bailey (luminosity amplitude versus logarithmic period) diagrams. This circumstantial evidence indicates that the two groups have different evolutionary properties. All the pulsation diagnostics adopted in this investigation suggest that old stellar populations in Fornax and Sculptor dSphs underwent different chemical enrichment histories. Fornax RRds are similar to SMC RRds, while Sculptor RRds are more similar to the metal-rich component of the LMC RRds.
Constraints on the contributions to the observed binary black hole population from individual evolutionary pathways in isolated binary evolution
Authors: Stevenson Simon , Clarke Teagan A
Published: October 2022

Gravitational waves from merging binary black holes can be used to shed light on poorly understood aspects of massive binary stellar evolution, such as the evolution of massive stars (including their mass-loss rates), the common envelope phase, and the rate at which massive stars form throughout the cosmic history of the Universe. In this paper, we explore the correlated impact of these phases on predictions for the merger rate and chirp mass distribution of merging binary black holes, aiming to identify possible degeneracies between model parameters. In many of our models, a large fraction (more than 70 per cent of detectable binary black holes) arise from the chemically homogeneous evolution scenario; these models tend to overpredict the binary black hole merger rate and produce systems that are on average too massive. Our preferred models favour enhanced mass-loss rates for helium rich Wolf–Rayet stars, in tension with recent theoretical and observational developments. We identify correlations between the impact of the mass-loss rates of Wolf–Rayet stars and the metallicity evolution of the Universe on the rates and properties of merging binary black holes. Based on the observed mass distribution, we argue that the $\sim 10{{\ \rm per\ cent}}$ of binary black holes with chirp masses greater than 40 M⊙ (the maximum predicted by our models) are unlikely to have formed through isolated binary evolution, implying a significant contribution (>10 per cent) from other formation channels such as dense star clusters or active galactic nuclei. Our models will enable inference on the uncertain parameters governing binary evolution in the near future.
Consistent lensing and clustering in a low-S8 Universe with BOSS, DES Year 3, HSC Year 1, and KiDS-1000
Authors: Amon A , Robertson N C , Miyatake H , Heymans C , White M , DeRose J , Yuan S , Wechsler R H , Varga T N , Bocquet S , Dvornik A , More S , Ross A J , Hoekstra H , Alarcon A , Asgari M , Blazek J , Campos A , Chen R , Choi A , Crocce M , Diehl H T , Doux C , Eckert K , Elvin-Poole J , Everett S , Ferté A , Gatti M , Giannini G , Gruen D , Gruendl R A , Hartley W G , Herner K , Hildebrandt H , Huang S , Huff E M , Joachimi B , Lee S , MacCrann N , Myles J , Navarro-Alsina A , Nishimichi T , Prat J , Secco L F , Sevilla-Noarbe I , Sheldon E , Shin T , Tröster T , Troxel M A , Tutusaus I , Wright A H , Yin B , Aguena M , Allam S , Annis J , Bacon D , Bilicki M , Brooks D , Burke D L , Carnero Rosell A , Carretero J , Castander F J , Cawthon R , Costanzi M , da Costa L N , Pereira M E S , de Jong J , De Vicente J , Desai S , Dietrich J P , Doel P , Ferrero I , Frieman J , García-Bellido J , Gerdes D W , Gschwend J , Gutierrez G , Hinton S R , Hollowood D L , Honscheid K , Huterer D , Kannawadi A , Kuehn K , Kuropatkin N , Lahav O , Lima M , Maia M A G , Marshall J L , Menanteau F , Miquel R , Mohr J J , Morgan R , Muir J , Paz-Chinchón F , Pieres A , Plazas Malagón A A , Porredon A , Rodriguez-Monroy M , Roodman A , Sanchez E , Serrano S , Shan H , Suchyta E , Swanson M E C , Tarle G , Thomas D , To C , Zhang Y
Published: October 2022

We evaluate the consistency between lensing and clustering based on measurements from Baryon Oscillation Spectroscopic Survey combined with galaxy–galaxy lensing from Dark Energy Survey (DES) Year 3, Hyper Suprime-Cam Subaru Strategic Program (HSC) Year 1, and Kilo-Degree Survey (KiDS)-1000. We find good agreement between these lensing data sets. We model the observations using the Dark Emulator and fit the data at two fixed cosmologies: Planck (S8 = 0.83), and a Lensing cosmology (S8 = 0.76). For a joint analysis limited to large scales, we find that both cosmologies provide an acceptable fit to the data. Full utilization of the higher signal-to-noise small-scale measurements is hindered by uncertainty in the impact of baryon feedback and assembly bias, which we account for with a reasoned theoretical error budget. We incorporate a systematic inconsistency parameter for each redshift bin, A, that decouples the lensing and clustering. With a wide range of scales, we find different results for the consistency between the two cosmologies. Limiting the analysis to the bins for which the impact of the lens sample selection is expected to be minimal, for the Lensing cosmology, the measurements are consistent with A = 1; A = 0.91 ± 0.04 (A = 0.97 ± 0.06) using DES+KiDS (HSC). For the Planck case, we find a discrepancy: A = 0.79 ± 0.03 (A = 0.84 ± 0.05) using DES+KiDS (HSC). We demonstrate that a kinematic Sunyaev–Zeldovich-based estimate for baryonic effects alleviates some of the discrepancy in the Planck cosmology. This analysis demonstrates the statistical power of small-scale measurements; however, caution is still warranted given modelling uncertainties and foreground sample selection effects.
Unveiling the nitrogen-rich massive star in the metal-poor galaxy NGC 4068
Authors: Yarovova Anastasiya D , Egorov Oleg V , Moiseev Alexei V , Maryeva Olga V
Published: October 2022

We report the identification of the unusual emission-line stellar-like object in the nearby low-metallicity ($Z \sim 0.1 \, \mathrm{Z_{\odot }}$) dwarf galaxy NGC 4068. Our observations performed with long-slit spectrograph and Fabry–Perot interferometer demonstrate high velocity dispersion in H α line, presence of He ii λ4686Å line and peculiarly low [S ii]/[N ii] fluxes ratio for this object. From observational data, we derived that the object represents a single star of high bolometric luminosity (L* ∼ 1.5 × 106 L⊙) surrounded by an expanding nebula with kinematical age of t ∼ 0.5 Myr. The nebula exhibits significant nitrogen overabundance [log (N/O) ∼ −0.05, that is by ∼1.4 dex higher than expected for low-metallicity galaxies]. We suggested that this is a massive blue supergiant (BSG) or Wolf–Rayet (WR) star surrounded by its ejecta interacting with the interstellar medium. We calculated the models of the nebula using cloudy photoionization code, applying cmfgen-modelled BSG and WR stars as ionization sources. We found a best agreement between the modelled and observed spectra for the model assuming ionization by low-metallicity WR star of mass $M_*\approx 80\, \rm M_\odot$, ionizing the nebula through the strong wind and enriching the interstellar medium with nitrogen.
Gamma-ray spectral variability of HBL 1ES 1959+650 during MJD 57400–58000 and its consequence on leptonic blazar emission model
Authors: Ghosal B , Tolamatti A , Bhattacharyya S , Bhatt N , Yadav K K , Chandra P , Das M P , Tickoo A K , Rannot R C , Gaur K K , Goyal A , Kumar N , Marandi P , Agarwal N K , Kothari M , Sarkar D , Sharma M , Chouhan N , Borwankar C , Dhar V K , Koul M K , Venugopal K , Kotwal S V , Godiyal S , Godambe S , Mankuzhiyil N
Published: October 2022

1ES 1959+650, a high-energy peaked BL Lac object (HBL) with redshift z = 0.047, is known to exhibit flux and spectral variability in different energy bands. In this work, we primarily considered the simultaneous Fermi-LAT and Swift-XRT data of 1ES 1959+650 to study the flux and spectral variability in the energy ranges (0.1–300 GeV) and (0.6–10 keV), respectively. Using the Fermi-LAT light curve, a stretch of quiescent state and three high flux states of the source were identified. The flux and the spectral variability were studied using flare profiles and flux-index loops. In the γ-ray energies, 1ES 1959+650 clearly showed the evolution ‘softer-when-brighter’ whereas in the X-rays it showed the trend ‘harder-when-brighter’. 1ES 1959+650 also showed quick changes in spectral shape in the γ-ray band when the γ-ray flux was changing during the flares. The spectral energy distributions (SEDs) of the source were constructed using simultaneous data from Fermi-LAT, Swift-XRT, Swift-UVOT during its evolution. The TeV data from TACTIC imaging telescope were also used to construct the SED in the quiescent state. The spectral modelling of the SEDs revealed that due to the spectral variability of 1ES 1959+650, the standard leptonic one zone model cannot be used to explain the emission from this source. Instead a two zone leptonic model is needed to explain the observed SEDs from this blazar.