bluuebunny/crossref_metadata_2025 huggingface dataset:
Facial synthesis of V-doped α-MoO3 nanoparticles for potential ethanol/alcohol sensors
Authors: Jain Vishva , Doshi Yash , Raval Adhish V , Shah Dimple
Published: December 2022

The pure and vanadium doped α-MoO3 nanoparticles have been synthesized via a facile liquid state chemical reaction process. The annealed powder was then characterized by various analysis techniques. Thermal Gravimetric Analysis (TGA), x-ray diffraction (XRD), Scanning electron microscopy (SEM), Energy dispersive x-ray analysis (EDAX), Raman spectroscopy, UV visible spectroscopy, and Brunauer–Emmett–Teller (BET) analysis have been used to analyze the changes in thermal, structural, morphology, functional and optical property of prepared samples. The results from the structural characterization showed no distortions and phase change in the structure of α-MoO3 with an increase in doping concentration of V-element up to 8% and Raman confirms the result obtained from XRD. BET reveals that when vanadium doping increases, the surface area of the samples increases. It was also discovered that as the vanadium concentration in MoO3 increases, the optical band gap reduces. The impact of V-doping on MoO3’s gas sensing performance was investigated. The study concludes the response towards the gases increases with an increase in the concentration of V-doping. The measured response for ethanol and methanol is almost 10 times higher than other gases which show good selectivity towards alcohol. The response time decreases from 175 s to 37 s (100 ppm) whereas recovery time increases from 120 s to 326 s (100 ppm) with an increase in doping concentration in MoO3.
Design and verification of an all-dielectric metamaterial and its application in wide-spectrum measurement of clothing fabrics
Authors: Huang Ge , Su Nanguang , Zhong Min
Published: December 2022

The application of metamaterial sensors is a hot topic in the field of material measurement. However, the resonant absorption modes are difficult to be eliminated due to many metamaterial sensors containing metal arrays. In measurements of the clothing fabrics, absorption rate requires a smooth spectrum in a wide frequency range. Here, an all-dielectric metamaterial is proposed and measured, and a smooth absorption spectrum is achieved (average absorptivity of 25.2%). When this metamaterial is covered by a fabric sample (Polyester), the measured average absorptivity is 41.5%. When the thickness of the fabric sample Polyester is set to be 0.2 mm, 0.3 mm, 0.4 mm, and 0.5 mm, the measured average absorptivity of the Polyester is: 41.5%, 48.3, 57.6, 62.1, respectively. Moreover, four fabric samples are measured and the achieved absorptivity is: 41.5%, 25.1%, 34.3%, and 56.6%, respectively. The simulated results are close to the measurement results. This all-dielectric metamaterial demonstrates the feasibility of clothing fabric measurement.
Modeling the Vertical Distribution of the Milky Way’s Flat Subsystem Objects
Authors: Nikiforov Igor’ I. , Usik Vadim A. , Veselova Angelina V.
Published: December 2022

This paper is an initial stage of consideration of the general problem of joint modeling of the vertical structure of a Galactic flat subsystem and the average surface of the disk of the Galaxy, taking into account the natural and measurement dispersions. We approximate the average surface of the Galactic disk in the region covered by the data with a general (polynomial) model and determine its parameters by minimizing the squared deviations of objects along the normal to the model surface. The smoothness of the model, i.e., its order n, is optimized. An outlier elimination algorithm is applied. The developed method allows us to simultaneously identify significant details of the Galactic warping and estimate the offset z
☉ of the Sun relative to the average (in general, non-flat) surface of the Galactic disk and the vertical scale of the object system under consideration for an arbitrary area of the disk covered by data. The method is applied to data on classical Cepheids. Significant local extremes of the average disk surface model were found based on Cepheid data: the minimum in the first Galactic quadrant and the maximum in the second. A well-known warp (lowering of the disk surface) in the third quadrant has been confirmed. The optimal order of the model describing all these warping details was found to be n
o = 4. The local (for a small neighborhood of the Sun, n
o = 0) estimate of

z

⊙

=
28.1
±

6.1

stat

.

±
1.3

cal

.

pc is close to the non-local (taking into account warping, n
o = 4)

z

☉

=
27.1
±

8.8

stat
.

−
1.2

+
1.3

cal
.

pc (statistical and calibration uncertainties are indicated), which suggests that the proposed modeling method eliminates the influence of warping on the z
☉ estimate. However, the non-local estimate of the vertical standard deviation of Cepheids

σ

ρ

=
132.0
±

3.7

stat
.

−
5.9

+
6.3

cal
.

pc differs significantly from the local

σ

ρ

=

76.5
±
4.4

stat
.

−
3.4

+
3.6

cal
.

pc, which implies the need to introduce more complex models for the vertical distribution outside the Sun’s vicinity.
Strategic uses for ancillary bioenergy in a carbon-neutral and fossil-free 2050 European energy system
Authors: Wu Fei , Muller Adrian , Pfenninger Stefan
Published: December 2022

Biomass is a growing renewable energy source in Europe and is envisioned to play a role for realising carbon neutrality, predominantly using dedicated energy crops. However, dedicated biomass is controversial for reasons including its competition with food production or its land-use and emissions impacts. Here we examine the potential role of a land-free alternative: ancillary bioenergy (AB) from biomass sources not primarily grown for energy and without land/food/feed competition. We provide the first dataset of 2050 ancillary biomass potential using the agricultural system model SOLm, which encompasses untapped by-/co-products and detailed agricultural residues. Results show that there is a limited future potential for AB in Europe (2394–10 342 PJ, which is 3–6 times lower than other estimates including dedicated biomass). We design and investigate alternative scenarios where this bioenergy resource can be fully utilised, not utilised at all, or utilised optimally by the sector-coupled energy system model Euro-Calliope. We find that fully utilising ancillary biomass can help phase out controversial nuclear or land-intensive dedicated biomass, so might achieve higher societal acceptability. Using all ancillary biomass as a negative-emissions source at stationary bioenergy carbon capture and storage plants in a nuclear-free system provides additional climate benefits. It is also possible to leave the AB potential completely unused, which barely increases total system cost, but would preserve agricultural nutrients. We conclude that there are synergies and trade-offs among possible strategic uses of AB, which can provide guidelines for a more coherent European bioenergy strategy. Although the 2050 potential of AB is limited, our findings suggest that it could fill critical strategic niches for realising carbon-neutrality.
Democracy and the Novel in the US: An Introduction
Authors: Smith Rachel Greenwald , Hutner Gordon
Published: December 2022

This introduction outlines the rationale and some of the key concerns of this special issue on democracy and the novel in the US. Beginning with George Saunders’s experiment with democratic form in Lincoln in the Bardo (2017), we turn to some points of tension that emerge in taking up the question of US democracy now. As many contributors observe, US liberal democracy was built upon practices of settler colonialism, slavery, racial capitalism, and xenophobia. And yet the danger posed by antidemocratic right-wing movements today makes the question of the relationship between the novel and democracy newly relevant. How, then, does the novel critique the violence of liberal democratic institutions? How do novels imagine alternative democratic possibilities? What do different subgenres of the novel—experimental, literary, speculative, pulp, graphic—offer in their understanding of democracy? And how have novels throughout US history—from the immediate post-Revolutionary period through Reconstruction, modernism, and through the 1960s to the present—treated the specific democratic and antidemocratic currents of their time?Perhaps this belief that novels can give insights into the failures of US liberal democracy even as they may speculate as to what alternative democratic forms will look like is one explanation why so many of our contributions hold out hope for the novel to retain—in one form or another—its long-argued connection to democracy.
Heave reduction of payload through crane control based on deep reinforcement learning using dual offshore cranes
Authors: Bae Jun-Hyeok , Cha Ju-Hwan , Ha Sol
Published: December 2022

Offshore operation causes the dynamic motion of offshore cranes and payload by the ocean environment. The motion of the payload lowers the safety and efficiency of the work, which may increase the working time or cause accidents. Therefore, we design a control method for the crane using artificial intelligence to minimize the heave motion of the payload. Herein, reinforcement learning (RL), which calculates actions according to states, is applied. Furthermore, the deep deterministic policy gradient (DDPG) algorithm is used because the actions need to be determined in a continuous state. In the DDPG algorithm, the state is defined as the motion of the crane and speed of the wire rope, and the action is defined as the speed of the wire rope. In addition, the reward is calculated using the motion of the payload. In this study, the heave motion of the payload was reduced by developing an agent suitable for adjusting the length of the wire rope. The heave motion of the payload was compared in between the non-learning condition of the RL-based control and proportional integral differential (PID) control; and an average payload reduction rate of 30% was observed under RL-based control. The RL-based control performed better than the PID control under learned conditions.
Secondary meningioma after cranial irradiation: case series and comprehensive literature review
Authors: Maeda Yugo , Onishi Shumpei , Yamasaki Fumiyuki , Takayasu Takeshi , Yonezawa Ushio , Taguchi Akira , Horie Nobutaka
Published: December 2022

Background

Secondary meningioma after cranial irradiation, so-called radiation-induced meningioma, is one of the important late effects after cranial radiation therapy. In this report, we analyzed our case series of secondary meningioma after cranial irradiation and conducted a critical review of literature to reveal the characteristics of secondary meningioma.

Materials and methods

We performed a comprehensive literature review by using Pubmed, MEDLINE and Google scholar databases and investigated pathologically confirmed individual cases. In our institute, we found pathologically diagnosed seven cases with secondary meningioma between 2000 and 2018. Totally, 364 cases were analyzed based on gender, WHO grade, radiation dose, chemotherapy. The latency years from irradiation to development of secondary meningioma were analyzed with Kaplan–Meier analysis. Spearman’s correlation test was used to determine the relationship between age at irradiation and the latency years.

Results

The mean age at secondary meningioma development was 35.6 ± 15.7 years and the mean latency periods were 22.6 ± 12.1 years. The latency periods from irradiation to the development of secondary meningioma are significantly shorter in higher WHO grade group (P = 0.0026, generalized Wilcoxon test), higher radiation dose group (P < 0.0001) and concomitant systemic chemotherapy group (P = 0.0003). Age at irradiation was negatively associated with the latency periods (r = −0.23231, P < 0.0001, Spearman’s correlation test).

Conclusion

Cranial irradiation at older ages, at higher doses and concomitant chemotherapy was associated with a shorter latency period to develop secondary meningiomas. However, even low-dose irradiation can cause secondary meningiomas after a long latency period. Long-term follow-up is necessary to minimize the morbidity and mortality caused by secondary meningioma after cranial irradiation.
Water availability and plant–herbivore interactions
Authors: Lin Po-An , Kansman Jessica , Chuang Wen-Po , Robert Christelle , Erb Matthias , Felton Gary W
Published: December 2022

Water is essential to plant growth and drives plant evolution and interactions with other organisms such as herbivores. However, water availability fluctuates, and these fluctuations are intensified by climate change. How plant water availability influences plant–herbivore interactions in the future is an important question in basic and applied ecology. Here we summarize and synthesize the recent discoveries on the impact of water availability on plant antiherbivore defense ecology and the underlying physiological processes. Water deficit tends to enhance plant resistance and escape traits (i.e. early phenology) against herbivory but negatively affects other defense strategies, including indirect defense and tolerance. However, exceptions are sometimes observed in specific plant–herbivore species pairs. We discuss the effect of water availability on species interactions associated with plants and herbivores from individual to community levels and how these interactions drive plant evolution. Although water stress and many other abiotic stresses are predicted to increase in intensity and frequency due to climate change, we identify a significant lack of study on the interactive impact of additional abiotic stressors on water–plant–herbivore interactions. This review summarizes critical knowledge gaps and informs possible future research directions in water–plant–herbivore interactions.
Formation of hub–filament structure triggered by a cloud–cloud collision in the W33 complex
Authors: Zhou Jian-Wen , Li Shanghuo , Liu Hong-Li , Peng Yaping , Zhang Siju , Xu Feng-Wei , Zhang Chao , Liu Tie , Li Jin-Zeng
Published: December 2022

Hub–filament systems are suggested to be the birth cradles of high-mass stars and clusters, but the formation of hub–filament structure is still unclear. Using FUGIN 13CO (1–0), C18O (1–0) and SEDIGISM 13CO (2–1) survey data, we investigate the formation of hub–filament structure in the W33 complex. The W33 complex consists of two colliding clouds, called W33-blue and W33-red. We decompose the velocity structures in W33-blue by fitting multiple velocity components and find a continuous and monotonic velocity field. Virial parameters of Dendrogram structures suggest the dominance of gravity in W33-blue. The strong positive correlation between velocity dispersion and column density indicates that the non-thermal motions in W33-blue may originate from gravitationally driven collapse. These signatures suggest that the filamentary structures in W33-blue result from the gravitational collapse of a compressed layer. However, the large-scale velocity gradient in W33-blue may originate mainly from cloud–cloud collision and feedback of active star formation, instead of filament-rooted longitudinal inflow. From the results observed above, we argue that cloud–cloud collision triggers the formation of hub–filament structures in the W33 complex. Meanwhile, the appearance of multiple-scale hub–filament structures in W33-blue is likely an imprint of the transition from a compressed layer to a hub–filament system.
The natural history of chronic widespread pain in patients with axial spondyloarthritis: a cohort study with clinical and self-tracking data
Authors: Soni Anushka , Nishtala Revathi , Ng Stanley , Barnett Rosemarie , Chyou Te-yuan , Cavill Charlotte , Sengupta Raj
Published: December 2022

Objectives

This study investigates longitudinal patterns, predictors and long-term impact of pain in axial spondyloarthritis (axSpA), using clinical and self-tracking data.

Methods

The presence of multisite pain (MSP), affecting at least six of nine body regions using a Margolis pain drawing, and subsequent chronic widespread pain (CWP), MSP at more than one timepoint, was assessed in a cohort of axSpA patients. Incident MSP (MSP at two consecutive visits or more), intermittent MSP (MSP at two or more non-consecutive visits) and persistent MSP (MSP at each visit) were described. Demographic, clinical and self-tracking measures were compared for the CWP vs non-CWP groups using Students t test, Wilcoxon–Mann–Whitney and χ2 test for normal, non-normal and categorical data, respectively. Predictors of CWP were evaluated using logistic regression modelling.

Results

A total of 136 patients, mean clinical study duration of 120 weeks (range 27–277 weeks) were included, with sufficient self-tracking data in 97 patients. Sixty-eight (50%) patients reported MSP during at least one clinical visit: eight (6%) incident MSP; 16 (12%) persistent MSP; and 44 (32%) intermittent MSP. Forty-six (34%) of the cohort had CWP. All baseline measures of disease activity, function, quality of life, sleep disturbance, fatigue and overall activity impairment were significant predictors of the development of CWP. BASDAI and BASFI scores were significantly higher in those with CWP and self-tracking data revealed significantly worse pain, fatigue, sleep quality and stress.

Conclusions

The development of CWP is predicted by higher levels of disease activity and burden at baseline. It also impacts future disease activity and wellbeing.
Genome Resource for the Verticillium Wilt Resistant Gossypium hirsutum Cultivar Zhongzhimian No. 2
Authors: Li Ran , Zhang Yong-Jun , Ma Xi-Yue , Li Song-Ke , Klosterman Steven J. , Chen Jie-Yin , Subbarao Krishna V. , Dai Xiao-Feng
Published: December 2022

Verticillium wilt, caused by the fungal pathogen Verticillium dahliae, is the major cause of disease-related yield losses in cotton ( Gossypium hirsutum). Despite these losses, the major cultivars of G. hirsutum remain highly susceptible to Verticillium wilt. The lack of understanding on the genetic basis for Verticillium wilt resistance may further hinder progress in deploying elite cultivars with proven resistance, such as the wilt resistant G. hirsutum cultivar Zhongzhimian No. 2. To help remedy this knowledge gap, we sequenced the whole genome of Zhongzhimian No. 2 and assembled it from a combination of PacBio long reads, Illumina short reads, and high-throughput chromosome conformation capture technologies. The final assembly of the genome was 2.33 Gb, encoding 95,327 predicted coding sequences. The GC content was 34.39% with 99.2% of the bases anchored to 26 pseudo-chromosomes that ranged from 53.8 to 127.7 Mb. This resource will help gain a detailed understanding of the genomic features governing high yield and Verticillium wilt resistance in this cultivar. Comparative genomics will be particularly helpful, since there are several published genomes of other Gossypium species.

[Formula: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .
Increased insulin resistance due to Long COVID is associated with depressive symptoms and partly predicted by the inflammatory response during acute infection
Authors: Al-Hakeim Hussein Kadhem , Al-Rubaye Haneen Tahseen , Jubran Abdulsahib S. , Almulla Abbas F. , Moustafa Shatha Rouf , Maes Michael
Published: December 2022

Background

Some months after the remission of acute COVID-19 infection, some people show depressive symptoms, which are predicted by increased peak body temperature (PBT) and lowered blood oxygen saturation (SpO2). Nevertheless, no data indicate whether Long COVID is associated with increased insulin resistance (IR) in association with depressive symptoms and immune, oxidative, and nitrosative (IO&NS) processes.

Methods

We used the homeostasis Model Assessment 2 (HOMA2) calculator©to compute β-cell function, insulin sensitivity and resistance (HOMA2-IR) and measured the Beck Depression Inventory (BDI) and the Hamilton Depression Rating Scale (HAMD) in 86 Long COVID patients and 39 controls. We examined the associations between the HOMA2 indices and PBT and SpO2 during acute infection, and depression, IO&NS biomarkers (C-reactive protein, NLRP3 activation, myeloperoxidase, and advanced oxidation protein products) 3-4 months after the acute infection.

Results

Long COVID is accompanied by increased HOMA2-IR, fasting blood glucose, and insulin levels. We found that 33.7% of the patients versus 0% of the controls had HOMA2-IR values >1.8, suggesting IR. PBT, but not SpO2, during acute infection significantly predicted IR, albeit with a small effect size. Increased IR was significantly associated with depressive symptoms as assessed with the BDI and HAMD above and beyond the effects of IO&NS pathways. There were no significant associations between increased IR and the activated IO&NS pathways during Long COVID.

Conclusion

Long COVID is associated with new-onset IR in a subset of patients. Increased IR may contribute to the onset of depressive symptoms due to Long COVID by enhancing overall neurotoxicity.
Durability of immune responses to the booster mRNA vaccination against COVID-19
Authors: Arunachalam Prabhu S. , Lai Lilin , Samaha Hady , Feng Yupeng , Hu Mengyun , Hui Harold Sai-yin , Wali Bushra , Ellis Madison , Huerta Christopher , Bechnack Kareem , Bechnack Sarah , Lee Matthew , Litvack Matthew , Losada Cecilia , Grifoni Alba , Sette Alessandro , Zarnitsyna Veronika I. , Rouphael Nadine , Suthar Mehul S. , Pulendran Bali
Published: December 2022

Waning immunity to vaccination represents a major challenge in vaccinology. Whether booster vaccination improves the durability of immune responses is unknown. Here we show, using a cohort of 55 adult vaccinees who received the BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccine against SARS-CoV-2, that a booster (i.e., 3rdimmunization) dose at 6 - 10 months increased the half-life of serum neutralizing antibody (nAb) titers to 76 days from 56 - 66 days estimated after the primary two-dose vaccination series. A second booster dose (i.e., 4thimmunization) more than a year after the primary vaccination increased the half-life further to 88 days. However, despite this modestly improved durability in nAb responses against the Wuhan strain, there was a loss in neutralization capacity against Omicron subvariants, especially the recently emerged variants, BA.2.75.2 and BQ.1.1 (35 and 50-fold drop in titers respectively, relative to the ancestral (WA.1) strain. While only 55 – 65% of participants demonstrated a detectable nAb titer against the newer variants after the booster (3rddose), the response declined to below the detection limit in almost all individuals by 6 months. Notably, even against BA.1 and BA.5, the titers declined rapidly in a third of the vaccinees and were below the detection limit at 6 months. In contrast, booster vaccination induced antigen-specific memory B and T cells that persisted for at least 6 months. Collectively, our data show that the durability of immune responses improves following subsequent booster immunizations; however, the emergence of immune evasive variants reduces the effectiveness of booster doses in preventing infection.
A retrospective case - control study for assessing the risk factors for development of Diabetic Kidney Disease among people with Type 2 Diabetes in Tamil Nadu and Puducherry
Authors: Saji Sneha , Suresh Srividya , MC Deepak , Krishnaswamy Sampath Kumar , Asirvatham Arthur Joseph , Kumar Manoj , George Melvin , Kumaraswamy Subramaniyan , Krishnamoorthy Narayanan , Raman Gopinath , Kannan Arun , Mehta Ratnesh Bhai
Published: December 2022

Objective

To understand the associated risk factors in the progression of Diabetic Kidney Disease among the Type 2 Diabetes individuals living in the state of Tamil Nadu and Puducherry.

Research design and methods

Clinical and socio-demographic data was collected, digitized, and analyzed for 482 participants diagnosed either with Diabetic Kidney Disease (DKD) or Type 2 Diabetes (T2D). The study was analyzed by using descriptive statistical analysis SAS version 9.4.

Results

Out of 482 participants, 422 fulfilled the eligibility criteria. Gender, age, T2D duration, and comorbidity are the major risk factors that are found to be associated with DKD in population understudy. We also found inclination towards usage of insulin among DKD participants rather than oral diabetic medications. Metformin (Biguanides) was the most used oral diabetic medication among the T2D participants followed by DPP-4 inhibitors and Sulphonylureas.

Conclusion

Together, these data describe the risk pattern among participants diagnosed with DKD at regional level that is integral in early and proper management of the disease.
Multicenter analysis of immunosuppressive medications on the subsequent risk of malignancy in solid organ transplant recipients
Authors: Shaw Reid , Haque Ali R. , Fitzsimons Jack , Hamidi Adam , O’Connor Timothy E. , Roloff Gregory W. , Bemiss Bradford C. , Kallwitz Eric R. , Hagen Patrick A. , Berg Stephanie
Published: December 2022

Solid organ transplant is a curative treatment for end organ disease. However, the immunosuppressive therapy required to prevent graft rejection increases the likelihood of developing a subsequent malignancy. This retrospective cohort study from a multi-center academic hospital system investigated solid organ transplantation, immunosuppression, and the risk of subsequent malignancy. Of the 5,591 patients and 6,142 transplanted organs studied, there were 517 subsequent malignancies identified. Skin cancer was the most common type of malignancy to be diagnosed, whereas liver cancer was the first malignancy to present at a median time of one-year post-transplant. Subsequent malignancy was proportionally more often diagnosed in non-Hispanic White transplant recipients compared to other racial groups. Heart and lung transplant recipients had relatively higher rates of subsequent malignancy than liver and kidney transplant recipients, but this finding was not significant upon adjusting for immunosuppressive medications. Multivariate cox proportional hazard analysis and random forest variable importance calculations identified statistically significant correlations with sirolimus and azathioprine and high rates of malignancy after transplant, while tacrolimus was associated with low rates of post-transplant neoplasia.
Are fewer cases of diabetes mellitus diagnosed in the months after SARS-CoV-2 infection?
Authors: Reddy Neha V , Yeh Hsin-Chieh , Tronieri Jena S , Stürmer Til , Buse John B , Reusch Jane E , Johnson Steven G , Wong Rachel , Moffitt Richard , Wilkins Kenneth J , Harper Jeremy , Bramante Carolyn T ,   the N3C and RECOVER Consortiums
Published: December 2022

Long-term sequelae of severe acute respiratory coronavirus-2 (SARS-CoV-2) infection may include an increased incidence of diabetes. Our objective was to describe the temporal relationship between new diagnoses of diabetes mellitus and SARS-CoV-2 infection in a nationally representative database. There appears to be a sharp increase in diabetes diagnoses in the 30 days surrounding SARS-CoV-2 infection, followed by a decrease in new diagnoses in the post-acute period, up to 360 days after infection. These results underscore the need for further investigation, as understanding the timing of new diabetes onset after COVID-19 has implications regarding potential etiology and screening and treatment strategies.
Decreased Viral Load, Symptom Reduction, and Prevention of Respiratory Syncytial Virus Infection with MVA-BN-RSV Vaccine
Authors: Jordan Elke , Kabir Golam , Schultz Stephanie , Silbernagl Günter , Schmidt Darja , Jenkins Victoria A. , Weidenthaler Heinz , Stroukova Daria , Martin Barbara K. , De Moerlooze Laurence
Published: December 2022

Background

Respiratory syncytial virus (RSV) causes significant disease burden in infants and older adults. Most vaccines in development focus on the virus’s F protein. MVA-BN-RSV is a novel vectored vaccine encoding internal and external proteins from both RSV subtypes.

Methods

In a phase 2a trial, participants aged 18 to 50 years selected for low RSV titers were randomized to receive MVA-BN-RSV or placebo, then challenged 4 weeks later with RSV-A Memphis 37b. Viral load was assessed from nasal washes and virus cultivation, and RSV symptoms were collected throughout quarantine. Antibody titers and cellular markers were assessed before and after vaccination and challenge.

Results

Of 74 participants randomized, 36 received MVA-BN-RSV and 37 received placebo; 31 and 32, respectively, were challenged. Viral load areas under the curve from nasal washes were lower (p=0.017) for MVA-BN-RSV (median=0.00) compared to placebo (median=49.05). Total symptom scores also were lower with MVA-BN-RSV. Vaccine efficacy in preventing infection confirmed by viral culture was 88.5% (CI: 14.8%; 98.5%). Immunoglobulin A and G in serum increased about 4-fold after MVA-BN-RSV vaccination, which was greater than the placebo response to challenge, and neutralizing antibody titer increased about 2-fold. Cellular responses were robust, particularly to the internal RSV proteins. Injection site pain occurred more frequently with MVA-BN-RSV. No serious adverse events were attributed to vaccination.

Conclusion

MVA-BN-RSV vaccination resulted in lower viral load and was effective against laboratory-confirmed symptomatic infection. Humoral and cellular responses support broad immunogenicity of the vaccine. No safety issues were identified with vaccination.

Clinical Trial Registry Number

NCT04752644
Echocardiographic progression of calcific aortic valve disease in patients with preexisting aortic valve sclerosis
Authors: Shamekhi Jasmin , Uehre Carina , Al-Kassou Baravan , Weber Marcel , Sedaghat Alexander , Sugiura Atsushi , Wilde Nihal , Adam Matti , Veulemans Verena , Kelm Malte , Baldus Stephan , Nickenig Georg , Zimmer Sebastian
Published: December 2022

Objective

We aimed to evaluate echocardiographic parameters to predict CAVD progression.

Background

Calcific aortic valve disease (CAVD) ranges from aortic valve sclerosis (ASc) with no functional impairment of the aortic valve to severe aortic stenosis (AS). It remains uncertain, which patients with ASc are at particular high risk of developing AS.

Methods

We included a total of 153 patients with visual signs of ASc and peak flow velocity (Vmax.) below 2.5m/s at baseline echocardiography. Progression of CAVD to AS was defined as an increase of the Vmax. ≥ 2.5m/s with a delta of ≥ 0.1m/s; stable ASc complied with a Vmax. below 2.5m/s and a delta < 0.1m/s. Finally, we compared clinical and echocardiographic parameters between these two groups.

Results

The mean age at baseline was 73.5 (± 8.2) years and 66.7% were of male gender. After a mean follow-up of 1463 days, 57 patients developed AS, while 96 patients remained in the ASc group. The AS group showed significantly more calcification (p < 0.001) and thickening (p < 0.001) of the aortic valve cusps at baseline, although hemodynamics showed no evidence of AS in both groups (ASc group: Vmax. 1.6 ± 0.3 m/s versus AS group: Vmax. 1.9 ± 0.3 m/s; p < 0.001). Advanced calcification (OR (95% CI): 4.8 (1.5 − 15.9); p = 0.009) and a cusp thickness > 0.26cm (OR (95% CI): 16.6 (5.4 – 50.7); p < 0.001) were independent predictors for the development of AS.

Conclusion

The acquisition of simple echocardiographic parameter may help to identify patients at particular high risk of developing AS.
BLM overexpression as a predictive biomarker for CHK1 inhibitor response in PARP inhibitor–resistant BRCA-mutant ovarian cancer
Authors: Gupta Nitasha , Huang Tzu-Ting , Nair Jayakumar R. , An Daniel , Zurcher Grant , Lampert Erika J. , McCoy Ann , Cimino-Mathews Ashley , Swisher Elizabeth M. , Radke Marc R. , Lockwood Christina M , Reichel Jonathan B. , Chiang Chih-Yuan , Wilson Kelli M. , Cheng Ken Chih-Chien , Nousome Darryl , Lee Jung-Min
Published: December 2022

PARP inhibitors (PARPis) have changed the treatment paradigm inBRCA-mutant high-grade serous ovarian carcinoma (HGSC). However, most patients eventually develop resistance to PARPis, highlighting an unmet need for novel therapeutic strategies. Using high-throughput drug screens, we identified ATR/CHK1 pathway inhibitors as cytotoxic, and further validated monotherapy activity of the CHK1 inhibitor (CHK1i), prexasertib, in PARPi-resistantBRCA-mutant HGSC cells and animal models. As a proof-of-concept trial, we conducted a phase II study of prexasertib inBRCA-mutant HGSC patients. The treatment was well-tolerated but yielded an objective response rate of 6% (1/17; 1 PR) in patients with prior PARPi treatment. Exploratory biomarker analyses revealed that replication stress and fork stabilization were associated with clinical benefit to CHK1i. In particular, overexpression ofBLM, andCCNE1overexpression or copy number gain/amplification were seen in patients deriving durable benefit from CHK1i. Our findings suggest replication fork–related biomarkers should be further evaluated for CHK1i sensitivity in HGSC.

One Sentence Summary

Overexpression of RecQ helicase BLM is a predictive biomarker for CHK1 inhibitor response in PARP inhibitor–resistantBRCA-mutant ovarian cancer.
A systematic review of low-dose interleukin-2 for the treatment of systemic lupus erythematosus
Authors: Bader Lara , Boyman Onur , Raeber Miro E.
Published: December 2022

Background

Low-dose interleukin-2 (IL-2) shows promise as a treatment for restoring functional and numerical deficits of regulatory T (Treg) cells in patients with various autoimmune diseases. Several clinical trials testing low-dose IL-2 in systemic lupus erythematosus (SLE) have been completed, with a comprehensive review of these trials currently lacking.

Objective

We aimed to conduct a systematic synthesis of findings from clinical trials regarding the clinical efficacy and safety of using low-dose IL-2 in patients with SLE. Furthermore, we intended to determine the sensitivity of different responder indices for IL-2-induced clinical improvement in SLE.

Methods

Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, we searched the Scopus and MEDLINE databases for articles reporting trials testing low-dose IL-2 in patients with SLE published between January 2010 and September 2022. To evaluate the risk of bias, we applied a modified version of the Downs and Black assessment tool.

Results

We retrieved 1,018 articles, six of which we analyzed including four open-label studies and two randomized controlled trials following a detailed review process. The studies included a total of 230 patients, of which 150 received low dose IL-2 and 80 received placebo. Although the open-label studies demonstrated an expansion of Treg cells that coincided with a clinical response, the predefined primary endpoints for clinical efficacy were not achieved in the randomized controlled trials. In general, treatment with low-dose IL-2 appears to be safe and tolerated well.

Conclusion

Low-dose IL-2 therapy appears to be a promising strategy for treating SLE; however, larger trials are still necessary to assess clinical responses in patients with such a heterogeneous disease.
Death, Inequality, and the Pandemic in the Nation’s Capital
Authors: Alva Maria L. , Illa Srujana S. , Haber Jaren
Published: December 2022

Abrupt changes in mortality rates and life expectancy allow us to understand how shocks like COVID-19 can exacerbate health inequalities across groups. We look at Washington, D.C., a major city with a diverse population and long-standing socio-economic divisions, to describe the all-cause mortality trends from 2015 to 2021 by age, sex, race, and ward of residence. We report differences in cause-specific mortality pre- and post-COVID-19 outbreak and estimate the Years of Life Lost (YLL) attributable to COVID-19. We compute death rates using information from death certificates and the Census, and we calculate YLL using the life table approach, comparing the life expectancy of people with and without COVID-19. We find that in 2020 and 2021, there were respectively 1,128 and 629 excess deaths (158 per 100K and 94 per 100K) compared to the annual average over the previous five years, and 689 and 363 deaths in 2020 and 2021, respectively (97 per 100K and 54 per 100K) listing COVID-19 as a cause of death. Death rates in 2020 and 2021, compared to the five previous years, were higher for men than women by about 12pp and 5pp and occurred almost entirely among residents 45 and older. Excess deaths between 2020 and 2021 were higher for Black and Hispanic residents by about 286 and 97 per 100K, respectively—with the highest proportional increase (almost twofold) for Hispanics in 2020. YLL was highest for Hispanic males and lowest for White females.

Significance Statement

The leading causes of death in DC were historically heart disease and cancer. In 2020, the leading cause of death was COVID. Accidental and violent deaths increased dramatically and disproportionately by race. Racial disparities in COVID and non-COVID deaths indicate that these correlate with socioeconomic conditions.

Life expectancy in the United States decreased for the first time in 2020 due to COVID-19. In the nation’s capital, the decline in life expectancy was more significant for Hispanic and non-Hispanic Black than White people, widening the already large difference in life expectancy among these groups.
Evaluating primary and booster vaccination prioritization strategies for COVID-19 by age and high-contact employment status using data from contact surveys
Authors: Roubenoff Ethan , Feehan Dennis , Mahmud Ayesha S.
Published: December 2022

The debate around vaccine prioritization for COVID-19 has revolved around balancing the benefits from: (1) the direct protection conferred by the vaccine amongst those at highest risk of severe disease outcomes, and (2) the indirect protection through vaccinating those that are at highest risk of being infected and of transmitting the virus. While adults aged 65+ are at highest risk for severe disease and death from COVID-19, essential service and other in-person workers with greater rates of contact may be at higher risk of acquiring and transmitting SARS-CoV-2. Unfortunately, there have been relatively little data available to understand heterogeneity in contact rates and risk across these demographic groups. Here, we retrospectively analyze and evaluate vaccination prioritization strategies by age and worker status. We use a mathematical model of SARS-CoV-2 transmission and uniquely detailed contact data collected as part of the Berkeley Interpersonal Contact Survey to evaluate five vaccination prioritization strategies: (1) prioritizing only adults over age 65, (2) prioritizing only high-contact workers, (3) splitting prioritization between adults 65+ and high-contact workers, (4) tiered prioritization of adults over age 65 followed by high-contact workers, and (5) tiered prioritization of high-contact workers followed by adults. We find that for the primary two-dose vaccination schedule, assuming 70% uptake, a tiered roll-out that first prioritizes adults 65+ averts the most deaths (31% fewer deaths compared to a no-vaccination scenario) while a tiered roll-out that prioritizes high contact workers averts the most number of clinical infections (14% fewer clinical infections compared to a no-vaccination scenario). We also consider prioritization strategies for booster doses during a subsequent outbreak of a hypothetical new SARS-CoV-2 variant. We find that a tiered roll-out that prioritizes adults 65+ for booster doses consistently averts the most deaths, and it may also avert the most number of clinical cases depending on the epidemiology of the SARS-CoV-2 variant and the vaccine efficacy.
A systematic review of interleukin-2-based immunotherapies in clinical trials for cancer and autoimmune diseases
Authors: Raeber Miro E. , Sahin Dilara , Karakus Ufuk , Boyman Onur
Published: December 2022

Background

The cytokine interleukin-2 (IL-2) can stimulate both effector immune cells and regulatory T (Treg) cells. The ability of selectively engaging either of these effects has spurred interest in using IL-2 for immunotherapy of cancer and autoimmune diseases. Thus, numerous IL-2-based biologic agents with improved bias or delivery toward effector immune cells or Treg cells have been developed. These improved IL-2-based compounds recently entered clinical trials.

Objective

This study systematically reviews clinical results of improved IL-2-based compounds for the treatment of cancer or autoimmune diseases.

Methods

We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), searched theClinicalTrials.govdatabase for registered IL-2 trials using improved IL-2-based agents and different databases for available results of these studies.

Results

We identified 547 registered clinical trials, of which we extracted 36 studies on improved IL-2-based compounds. Moreover, we assessed another 9 agents reported in two recent literature reviews and based on our knowledge, totaling in 45 improved IL-2-based compounds. A secondary search for registered clinical trials of each of these improved 45 compounds resulted in 139 clinical trials included in this systematic review, with 29 trials reporting clinical results.

Conclusions

As of yet, none of the improved IL-2-based compounds gained regulatory approval for the treatment of cancer or autoimmune diseases. Three compounds treating cancer have entered phase 3 trials with two studies still ongoing. NKTR-214 is the only compound that has completed phase 3 studies. The PIVOT IO-001 study testing the combination of NKTR-214 plus Pembrolizumab compared to Pembrolizumab monotherapy in metastatic melanoma missed its primary endpoint of superior objective response rate and progression-free survival. The PIVOT-09 study, combining NKTR-214 with Nivolumab compared to Sunitinib or Cabozantinib in advanced renal cell carcinoma, missed its primary endpoint of improved objective response rate. Trials in autoimmune diseases are currently in early stages, thus not allowing conclusions on efficacy. Results of ongoing trials will provide insight into which improved IL-2-based compounds will be beneficial for cancer and autoimmune diseases.
The Societal Value of Vaccines: Expert-Based Conceptual Framework and Methods Using COVID-19 Vaccines as A Case Study
Authors: Fusco Manuela Di , Mendes Diana , Steuten Lotte , Bloom David E , Drummond Michael , Hauck Katharina , Pearson-Stuttard Jonathan , Power Rachel , Salisbury David , Towse Adrian , Roiz Julie , Szabo Gabor , Yang Jingyan , Marczell Kinga
Published: December 2022

Health technology assessments (HTAs) of vaccines typically focus on the direct health benefits to individuals and healthcare systems. COVID-19 highlighted the widespread societal impact of infectious diseases and the value of vaccines in averting adverse clinical consequences and in maintaining or resuming social and economic activities. Using COVID-19 as a case study, this research work aimed to set forth a conceptual framework capturing the broader value elements of vaccines and to identify appropriate methods to quantify value elements not routinely considered in HTAs. A two-step approach was adopted combining a targeted literature review and three rounds of expert elicitation based on a modified Delphi method, leading to a conceptual framework of 30 value elements related to broader health effects, societal and economic impact, public finances, and uncertainty value. When applying the framework to COVID-19 vaccines in post-pandemic settings, 13 value elements were consensually rated highly important by the experts for consideration in HTAs. The experts reviewed over 10 methods that could be leveraged to quantify broader value elements and provided technical forward-looking recommendations. Limitations of the framework and the identified methods were discussed. This study supplements on-going efforts aimed towards a broader recognition of the full societal value of vaccines.
Danger changes the way the brain consolidates neutral information; and does so by interacting with processes involved in the encoding of that information
Authors: Qureshi Omar A. , Leake Jessica , Delaney Andrew J. , Killcross Simon , Westbrook R. Frederick , Holmes Nathan M.
Published: December 2022

This study examined the effect of danger on consolidation of neutral information in two regions of the rat (male and female) medial temporal lobe: the perirhinal cortex (PRh) and basolateral amygdala complex (BLA). The neutral information was the association that forms between an auditory stimulus and a visual stimulus (labelled S2 and S1) across their pairings in sensory preconditioning. We show that, when the sensory preconditioning session is followed by a shocked context exposure, the danger shifts consolidation of the S2-S1 association from the PRh to the BLA; and does so by interacting with processes involved in encoding of the S2-S1 pairings. Specifically, we show that the initial S2-S1 pairing in sensory preconditioning is encoded in the BLA and not the PRh; whereas the later S2-S1 pairings are encoded in the PRh and not the BLA. When the sensory preconditioning session is followed by a context alone exposure, the BLA-dependent trace of the early S2-S1 pairings decays and the PRh-dependent trace of the later S2-S1 pairings is consolidated in memory. However, when the sensory preconditioning session is followed by a shocked context exposure, the PRh-dependent trace of the later S2-S1 pairings is suppressed and the BLA-dependent trace of the initial S2-S1 pairing is consolidated in memory. These findings are discussed with respect to mutually inhibitory interactions between the PRh and BLA, and the way that these regions support memory in other protocols, including recognition memory in people.

Significance Statement

The perirhinal cortex (PRh) and basolateral amygdala complex (BLA) process the pairings of neutral auditory and visual stimuli in sensory preconditioning. The involvement of each region in this processing is determined by the novelty/familiarity of the stimuli as well as events that occur immediately after the preconditioning session. Novel stimuli are represented in the BLA; however, as these stimuli are repeatedly presented without consequence, they come to be represented in the PRh. Whether the BLA- or PRh-dependent representation is consolidated in memory depends on what happens next. When nothing of significance occurs, the PRh-dependent representation is consolidated and the BLA-dependent representation decays; but when danger is encountered, the PRh-dependent representation is inhibited and the BLA-dependent representation is selected for consolidation.