bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamical characteristics of the surface plasmon-polariton wave supported by a thin metal film
Authors: Bekshaev A Y , Angelsky O V
Published: August 2022

We study the energy and momentum of the surface plasmon-polariton (SPP) excited in a symmetric three-layer ‘insulator–metal–insulator’ structure, which is known to support the symmetric (S) mode (which, under certain conditions, possesses the negative group velocity) as well as the antisymmetric (AS) mode with always positive energy flow. The electric and magnetic field vectors are calculated via both the phenomenological and the microscopic approach; the latter involves the hydrodynamic model accounting for the quantum statistical effects for the electron gas in metal. Explicit representation for the energy and momentum constituents in the dielectric and in the metal film are obtained, and the wavenumber dependences of the energy and momentum contributions for the whole SPP are analyzed numerically. The various energy and momentum constituents are classified with respect to their origin (‘field’ or ‘material’), and the physical nature (orbital (canonical) and spin (Belinfante) momentum contributions). The pictures characteristic for the S and AS modes are systematically compared. The results can be useful for the studies and applications of the SPP-induced thin-film effects, in particular, for the charge and spin dynamics in thin-film plasmonic systems.
Associations of time-dependent changes in phosphorus levels with cardiovascular diseases in patients undergoing hemodialysis: results from the Japan Dialysis Active Vitamin D (J-DAVID) randomized clinical trial
Authors: Koshi-Ito Eri , Inaguma Daijo , Ishii Haruka , Yuzawa Yukio , Kabata Daijiro , Shintani Ayumi , Inaba Masaaki , Emoto Masanori , Mori Katsuhito , Morioka Tomoaki , Nakatani Shinya , Shoji Tetsuo
Published: August 2022

Background

While the risk of exceeding the standard range of phosphorus levels has been investigated, the impact of the degree of fluctuations has not been investigated.

Methods

Data were derived from the Japan Dialysis Active Vitamin D trial, a 4-year prospective, randomized study involving 976 patients without secondary hyperparathyroidism undergoing hemodialysis in Japan. Laboratory data were collected every 6 months and the primary outcome was the time to the occurrence of cardiovascular events. The effect of time-dependent changes in phosphorus levels was assessed using a time-varying Cox proportional hazards regression model.

Results

The median serum phosphorus levels at baseline and at the final observation were 4.70 mg/dl [interquartile range (IQR) 3.90–5.30] and 5.00 mg/dl (IQR 4.20–5.80), respectively. Over each 6-month period, phosphorus changes ranged from −7.1 to +6.7 mg/dl, with a median value of −0.1 to +0.3 mg/dl. During follow-up, composite cardiovascular events occurred in 103 of 964 patients. Although the P-value for the interaction between serum phosphorus level fluctuations and baseline phosphorus levels was insignificant, the following trends were observed. First, patients with relatively high initial phosphorus levels over a 6-month period showed a trend towards a higher hazard, with greater changes in the phosphorus level over the 6-month period. Second, it was suggested that oral vitamin D receptor activators could contribute to the relationship between fluctuating phosphorus levels and cardiovascular events.

Conclusions

Our results suggest the importance of maintaining stable phosphorus levels, not only in the normal range, but also without fluctuations, in the risk of cardiovascular events among patients without secondary hyperparathyroidism undergoing maintenance hemodialysis.
Probability of chronic kidney disease and associated risk factors in Chinese adults: a cross-sectional study of 9 million Chinese adults in the Meinian Onehealth screening survey
Authors: Zhuang Zhenhuang , Tong Mingkun , Clarke Robert , Wang Bo , Huang Tao , Li Liming
Published: August 2022

Background

Chronic kidney disease (CKD) is an increasing global health problem, but little is known about the age- and sex-specific prevalence of CKD and the associated risk factors in low- and middle-income populations. We examined the age- and sex-specific prevalence of CKD and the associated risk factors in a population-based study of 9 million Chinese adults.

Methods

The study involved a cross-sectional survey of 9 461 631 adults, >18 years of age, who were recruited in 2017 from 31 provinces in the Meinian Onehealth screening survey. All participants had plasma creatinine measured by standard methods and CKD was defined if the estimated glomerular filtration rate (eGFR) was <60 ml/min/1.73 m2.

Results

Overall, among 9.5 million adults [mean age 41 years (standard deviation 13.1)], 88 271 (1.26%) had CKD. The prevalence rate of CKD was 1.20%, 0.04% and 0.02% for stage 3, 4 and 5, respectively. After adjustment for the proportion and prevalence of urban and rural areas, the overall prevalence rate of CKD was 1.07%, indicating that ∼14 million Chinese adults have CKD. The prevalence of CKD increased 3-fold for each 10-year increment in age (1.15%, 3.05% and 13.02% at age 50–59, 60–69 and >70 years, respectively) and was 1.8-fold higher in women than men. The prevalence of CKD was higher in the Southwest region {1.68% [95% confidence interval (CI) 1.12–2.24]} but lower in the Northwest region [0.84% (95% CI 0.61–1.07)] than other regions. If proteinuria is also used as a diagnostic criterion, the prevalence rate increased to 2.16%. Stepwise logistic regression analysis demonstrated that body mass index; history of hypertension, cardiovascular disease or diabetes; and levels of systolic blood pressure, triglycerides, fasting glucose and uric acid were independent risk factors for CKD.

Conclusion

CKD is an important public health problem in Chinese adults and this study highlights the need for public health strategies to detect and reduce modifiable risk factors for prevention of CKD.
Standardization of serum creatinine is essential for accurate use of unbiased estimated GFR equations: evidence from three cohorts matched on renal function
Authors: Pottel Hans , Cavalier Etienne , Björk Jonas , Nyman Ulf , Grubb Anders , Ebert Natalie , Schaeffner Elke , Eriksen Björn O , Melsom Toralf , Lamb Edmund J , Mariat Christophe , Dubourg Laurence , Hansson Magnus , Littmann Karin , Sundin Per-Ola , Åkesson Anna , Larsson Anders , Rule Andrew , Delanaye Pierre
Published: August 2022

Background

Differences in the performance of estimated glomerular filtration rate (eGFR) equations have been attributed to the mathematical form of the equations and to differences between patient demographics and measurement methods. We evaluated differences in serum creatinine (SCr) and eGFR in cohorts matched for age, sex, body mass index (BMI) and measured GFR (mGFR).

Methods

White North Americans from Minnesota (n = 1093) and the Chronic Renal Insufficiency Cohort (CRIC) (n = 1548) and White subjects from the European Kidney Function Consortium (EKFC) cohort (n = 7727) were matched for demographic patient characteristics (sex, age ± 3 years, BMI ± 2.5 kg/m2) and renal function (mGFR ± 3 ml/min/1.73 m2). SCr was measured with isotope dilution mass spectrometry (IDMS)-traceable assays in the Minnesota and EKFC cohorts and with non-standardized SCr assays recalculated to IDMS in the CRIC. The Minnesota cohort and CRIC shared a common method to measure GFR (renal clearance of iothalamate), while the EKFC cohort used a variety of exogenous markers and methods, all with recognized sufficient accuracy. We compared the SCr levels and eGFR predictions [for Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and EKFC equations] of patients fulfilling these matching criteria.

Results

For 305 matched individuals, mean SCr (mg/dL) was not different between the Minnesota and EKFC cohorts (females 0.83 ± 0.20 versus 0.86 ± 0.23, males 1.06 ± 0.23 versus 1.12 ± 0.37; P > .05) but significantly different from the CRIC [females 1.13 ± 0.23 (P < .0001), males 1.42 ± 0.31 (P < .0001)]. The CKD-EPI equations performed better than the EKFC equation in the CRIC, while the opposite was true in the Minnesota and EKFC cohorts.

Conclusion

Significant differences in SCr concentrations between the Minnesota and EKFC cohorts versus CRIC were observed in subjects with the same level of mGFR and equal demographic characteristics and can be explained by the difference in SCr calibration.
Sophia’s double: photography, archaeology, and modern Greece
Authors: Stager Jennifer M S
Published: August 2022

In the context of the entangled productions of scientific archaeology, photographic technologies, and the Greek nation-state, this article analyses the ancient Greek idea of the eidōlon (image, phantom, double) as a paradigm for photography. Sophia Engastromenou Schliemann presented herself for the camera as Helen of Troy and mobilized an ancient textual debate about Helen and her double and the Trojan War. This image of Sophia adorned in Trojan gold is widely known and little studied and, as this essay will explore, it circulated far beyond Sophia’s control. Undergirding this article’s historical contingencies is an exploration of the photograph as eidōlon.
Right atrial function and fibrosis in relation to successful atrial fibrillation ablation
Authors: Hopman Luuk H G A , Visch Julia E , Bhagirath Pranav , van der Laan Anja M , Mulder Mark J , Razeghi Orod , Kemme Michiel J B , Niederer Steven A , Allaart Cornelis P , Götte Marco J W
Published: August 2022

Aims

Bi-atrial remodelling in patients with atrial fibrillation (AF) is rarely assessed and data on the presence of right atrial (RA) fibrosis, the relationship between RA and left atrial (LA) fibrosis, and possible association of RA remodelling with AF recurrence after ablation in patients with AF is limited.

Methods and results

A total of 110 patients with AF undergoing initial pulmonary vein isolation (PVI) were included in the present study. All patients were in sinus rhythm during cardiac magnetic resonance (CMR) imaging performed prior to ablation. LA and RA volumes and function (volumetric and feature tracking strain) were derived from cine CMR images. The extent of LA and RA fibrosis was assessed from 3D late gadolinium enhancement images. AF recurrence was followed up for 12 months after PVI using either 12-lead electrocardiograms or Holter monitoring. Arrhythmia recurrence was observed in 39 patients (36%) after the 90-day blanking period, occurring at a median of 181 (interquartile range: 122–286) days. RA remodelling parameters were not significantly different between patients with and without AF recurrence after ablation, whereas LA remodelling parameters were different (volume, emptying fraction, and strain indices). LA fibrosis had a strong correlation with RA fibrosis (r = 0.88, P < 0.001). Both LA and RA fibrosis were not different between patients with and without AF recurrence.

Conclusions

This study shows that RA remodelling parameters were not predictive of AF recurrence after AF ablation. Bi-atrial fibrotic remodelling is present in patients with AF and moreover, the amount of LA fibrosis had a strong correlation with the amount of RA fibrosis.
Can vaccines control bacterial virulence and pathogenicity? Bordetella pertussis: the advantage of fitness over virulence
Authors: Guiso Nicole , Soubeyrand Benoit , Macina Denis
Published: August 2022

Some vaccines, such as diphtheria toxoid and acellular pertussis vaccines (aPVs), may favor the emergence of less pathogenic strains of the respective bacteria they target. This review discusses the impact of the wide use of aPV on Bordetella pertussis phenotype evolutions and their beneficial consequences in the light of the diphtheria toxoid immunization program experience and structuring evidence review in a causal analysis following Bradford Hill’s causality criteria. All aPVs contain the pertussis toxin (PT), the main virulence factor of B.pertussis, alone or with one adhesin (filamentous hemagglutinin (FHA)), two adhesins (FHA and pertactin (PRN)) or four adhesins (FHA, PRN and two fimbriae (Fim 2/3)). In countries where the coverage of aPVs containing PRN is high, PRN negative B.pertussis isolates are increasing in prevalence, but isolates nonproducing the other antigens are rarely reported. We hypothesize that the selective pressure at play with PRN should exist against all aVP antigens, although detection biases may hinder its detection for other antigens, especially PT. PT being responsible for clinically frank cases of the disease, the opportunity to collect PT negative isolates is far lower than to collect PRN negative isolates which have a limited clinical impact. The replacement of the current B.pertussis by far less pathogenic isolates no longer producing the factors contained in aPVs should be expected as a consequence of the wide aPV use.
Comparative whole-genome sequence analysis of a BoNT/B5-producing Clostridium botulinum isolate from an infant botulism case of unknown source in Osaka, Japan
Authors: Umeda Kaoru , Hirai Yuji , Nakamura Hiromi , Amo Kiyoko
Published: August 2022

A case of infant botulism of unknown origin, not involved in honey consumption, occurred in Osaka, Japan in 2020. A Clostridium botulinum type B strain named Osaka2020 was isolated from a stool sample of the patient. To clarify the epidemiology of the case, we performed whole-genome sequencing (WGS) of the isolate and compared it with strains from other sources. WGS analysis revealed that isolate Osaka2020 was classified into ST133 of a new sequence type, B5 subtype, and its toxin gene was encoded in a ∼274 kb plasmid. This plasmid was closely related to the pCLJ plasmid from strain 657Ba in the USA, reported to be conjugatively transferable to other strains. Moreover, isolate Osaka2020 also possesses another smaller plasmid that was common with some type A(B) infant botulism isolates in Japan. The phylogenetic tree from whole-genome SNP analysis showed that isolate Osaka2020 was the most closely related to a type B infant botulism isolate that occurred in Japan 10 years ago. Although no epidemiological connection among the two cases was confirmed, there is possibility that the cases are attributed to common causes such as some environmental substance.
A yeast-based in vivo assay system for analyzing efflux of sugars mediated by glucose and xylose transporters
Authors: Tamayo Rojas Sebastian A , Boles Eckhard , Oreb Mislav
Published: August 2022

Sugar transporter research focuses on the sugar uptake into cells. Under certain physiological conditions, however, the intracellular accumulation and secretion of carbohydrates (efflux) are relevant processes in many cell types. Currently, no cell-based system is available for specifically investigating glucose efflux. Therefore, we designed a system based on a hexose transporter-deficient Saccharomyces cerevisiae strain, in which the disaccharide maltose is provided as a donor of intracellular glucose. By deleting the hexokinase genes, we prevented the metabolization of glucose, and thereby achieved the accumulation of growth-inhibitory glucose levels inside the cells. When a permease mediating glucose efflux is expressed in this system, the inhibitory effect is relieved proportionally to the capacity of the introduced transporter. The assay is thereby suitable for screening of transporters and quantitative analyses of their glucose efflux capacities. Moreover, by simultaneous provision of intracellular glucose and extracellular xylose, we investigated how each sugar influences the transport of the other one from the opposite side of the membrane. Thereby, we could show that the xylose transporter variant Gal2N376F is insensitive not only to extracellular but also to intracellular glucose. Considering the importance of sugar transporters in biotechnology, the assay could facilitate new developments in a variety of applications.
Disclosing complex mutational dynamics at a Y chromosome palindrome evolving through intra- and inter-chromosomal gene conversion
Authors: Bonito Maria , Ravasini Francesco , Novelletto Andrea , D’Atanasio Eugenia , Cruciani Fulvio , Trombetta Beniamino
Published: August 2022

The human MSY ampliconic region is mainly composed of large duplicated sequences that are organized in eight palindromes (termed P1–P8), and may undergo arm-to-arm gene conversion. Although the importance of these elements is widely recognized, their evolutionary dynamics are still nuanced. Here, we focused on the P8 palindrome, which shows a complex evolutionary history, being involved in intra- and inter-chromosomal gene conversion. To disclose its evolutionary complexity, we performed a high-depth (50×) targeted next-generation sequencing of this element in 157 subjects belonging to the most divergent lineages of the Y chromosome tree. We found a total of 72 polymorphic paralogous sequence variants that have been exploited to identify 41 Y-Y gene conversion events that occurred during recent human history. Through our analysis, we were able to categorize P8 arms into three portions, whose molecular diversity was modelled by different evolutionary forces. Notably, the outer region of the palindrome is not involved in any gene conversion event and evolves exclusively through the action of mutational pressure. The inner region is affected by Y-Y gene conversion occurring at a rate of 1.52 × 10−5 conversions/base/year, with no bias towards the retention of the ancestral state of the sequence. In this portion, GC-biased gene conversion is counterbalanced by a mutational bias towards AT bases. Finally, the middle region of the arms, in addition to intra-chromosomal gene conversion, is involved in X-to-Y gene conversion (at a rate of 6.013 × 10−8 conversions/base/year) thus being a major force in the evolution of the VCY/VCX gene family.
Comparative Efficacy of Infliximab vs Ustekinumab for Maintenance of Clinical Response in Biologic Naïve Crohn’s Disease
Authors: Wong Emily C L , Dulai Parambir S , Marshall John K , Jairath Vipul , Reinisch Walter , Narula Neeraj
Published: August 2022

Background

There is a need to better understand the positioning of biologic therapies for long-term outcomes in biologic-naïve Crohn’s disease (CD). We assessed the comparative effectiveness of infliximab and ustekinumab among induction responders for 1-year outcomes.

Methods

This post hoc analysis included data from 220 biologic-naïve CD participants with response to induction therapy from 2 clinical trial programs. Participants achieving 1-year clinical remission (CR) (Crohn’s disease activity index <150), corticosteroid-free CR, normalization of fecal calprotectin (FC), endoscopic response (Simple Endoscopic Score for CD decrease ≥50% from baseline), and endoscopic remission (ER) (Simple Endoscopic Score for CD <3) were compared. Multivariate logistic regression evaluated the likelihood of achieving the outcomes adjusted for confounders. Propensity score matching created a cohort with similar distribution of baseline covariates.

Results

One-year CR and corticosteroid-free CR rates were similar between infliximab-treated and ustekinumab-treated patients (CR, 66 of 110 [60.0%] vs 63 of 110 [57.3%]; adjusted odds ratio [aOR], 1.15; 95% CI, 0.67-1.98; P = .681; corticosteroid-free CR, 11 of 28 (39.3%) vs 27 of 51 [52.9%]; aOR, 0.58; 95% CI, 0.23-1.47; P = .251). Compared with ustekinumab-treated patients, infliximab-treated participants were more likely to achieve 1-year endoscopic response (43 of 92 [46.7%] vs 6 of 30 [20.0%], aOR, 3.59; 95% CI, 1.34-9.66; P = .011) and ER (31 of 92 [33.7%] vs 4 of 30 [13.3%]; aOR, 3.35; 95% CI, 1.07-10.49; P = .038). Among patients with FC ≥250 mg/kg at baseline, normalization (<250 mg/kg) at 1-year was similar between groups. Similar results were observed within the propensity matched population for all analyses.

Conclusions

Treatment with infliximab and ustekinumab among induction responders achieved 1-year CR with similar efficacy, but infliximab may confer greater benefit for endoscopic outcomes. Findings should be interpreted with caution as our analyses were unpowered.
Scalability and robustness of spectral embedding: landmark diffusion is all you need
Authors: Shen Chao , Wu Hau-Tieng
Published: August 2022

Although spectral embedding is a widely applied dimension reduction technique in various fields, so far it is still challenging to make it scalable to handle ’big data’. On the other hand, the robustness property is less explored and there exists only limited theoretical results. Motivated by the need of handling such data, recently we proposed a novel spectral embedding algorithm, which we coined Robust and Scalable Embedding via Landmark Diffusion (ROSELAND). In short, we measure the affinity between two points via a set of landmarks, which is composed of a small number of points, and ’diffuse’ on the dataset via the landmark set to achieve a spectral embedding. Roseland can be viewed as a generalization of the commonly applied spectral embedding algorithm, the diffusion map (DM), in the sense that it shares various properties of DM. In this paper, we show that Roseland is not only numerically scalable, but also preserves the geometric properties via its diffusion nature under the manifold setup; that is, we theoretically explore the asymptotic behavior of Roseland under the manifold setup, including handling the U-statistics-like quantities, and provide a $L^\infty $ spectral convergence with a rate. Moreover, we offer a high dimensional noise analysis, and show that Roseland is robust to noise. We also compare Roseland with other existing algorithms with numerical simulations.
Solvability of discrete Helmholtz equations
Authors: Bernkopf Maximilian , Sauter Stefan , Torres Céline , Veit Alexander
Published: August 2022

We study the unique solvability of the discretized Helmholtz problem with Robin boundary conditions using a conforming Galerkin finite element method. Well-posedness of the discrete equations is typically investigated by applying a compact perturbation argument to the continuous Helmholtz problem so that a `sufficiently rich' discretization results in a `sufficiently small' perturbation of the continuous problem and well-posedness is inherited via Fredholm’s alternative. The qualitative notion `sufficiently rich', however, involves unknown constants and is only of asymptotic nature. Our paper is focussed on a fully discrete approach by mimicking the tools for proving well-posedness of the continuous problem directly on the discrete level. In this way, a computable criterion is derived, which certifies discrete well-posedness without relying on an asymptotic perturbation argument. By using this novel approach we obtain (a) new existence and uniqueness results for the $hp$-FEM for the Helmholtz problem, (b) examples for meshes such that the discretization becomes unstable (Galerkin matrix is singular) and (c) a simple checking Algorithm MOTZ `marching-of-the-zeros', which guarantees in an a posteriori way that a given mesh is certified for a well-posed Helmholtz discretization.
Coronavirus Disease 2019 Vaccine Effectiveness Against Severe Acute Respiratory Syndrome Coronavirus 2 Infection in the United States Before the Delta- and Omicron-Associated Surges: A Retrospective Cohort Study of Repeat Blood Donors
Authors: Grebe Eduard , Yu Elaine A , Bravo Marjorie D , Welte Alex , Bruhn Roberta L , Stone Mars , Green Valerie , Williamson Phillip C , Feldstein Leora R , Jones Jefferson M , Busch Michael P , Custer Brian
Published: August 2022

Background

To inform public health policy, it is critical to monitor coronavirus disease 2019 vaccine effectiveness (VE), including against acquiring infection.

Methods

We estimated VE using self-reported vaccination in a retrospective cohort of repeat blood donors who donated during the first half of 2021, and we demonstrated a viable approach for monitoring VE via serological surveillance.

Results

Using Poisson regression, we estimated an overall VE of 88.8% (95% confidence interval, 86.2–91.1), adjusted for demographic covariates and variable baseline risk.

Conclusions

The time since first reporting vaccination, age, race and/or ethnicity, region, and calendar time were statistically significant predictors of incident infection.
Potent Neutralizing Activity of Polyclonal Equine Antibodies Against Severe Acute Respiratory Syndrome Coronavirus 2 Variants of Concern
Authors: Luczkowiak Joanna , Radreau Pauline , Nguyen Ludovic , Labiod Nuria , Lasala Fátima , Veas Francisco , Herbreteau Cécile Hélène , Delgado Rafael
Published: August 2022

Several anti–severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) monoclonal antibodies (mAbs) have received emergency authorization for coronavirus disease 2019 (COVID-19) treatment. However, most of these mAbs are not active against the highly mutated Omicron SARS-CoV-2 subvariants. We have tested a polyclonal approach of equine anti-SARS-CoV-2 F(ab’)2 antibodies that achieved a high level of neutralizing potency against all SARS-CoV-2 variants of concern tested including Omicron BA.1, BA.2, BA.2.12 and BA.4/5. A repertoire of antibodies targeting conserved epitopes in different regions of the spike protein could plausibly account for this remarkable breadth of neutralization. These results warrant the clinical investigation of equine polyclonal F(ab’)2 antibodies as a novel therapeutic strategy against COVID-19.
Demographic inference provides insights into the extirpation and ecological dominance of eusocial snapping shrimps
Authors: Chak Solomon T C , Harris Stephen E , Hultgren Kristin M , Duffy J Emmett , Rubenstein Dustin R
Published: August 2022

Although eusocial animals often achieve ecological dominance in the ecosystems where they occur, many populations are unstable, resulting in local extinction. Both patterns may be linked to the characteristic demography of eusocial species—high reproductive skew and reproductive division of labor support stable effective population sizes that make eusocial groups more competitive in some species, but also lower effective population sizes that increase susceptibility to population collapse in others. Here, we examine the relationship between demography and social organization in Synalpheus snapping shrimps, a group in which eusociality has evolved recently and repeatedly. We show using coalescent demographic modeling that eusocial species have had lower but more stable effective population sizes across 100,000 generations. Our results are consistent with the idea that stable population sizes may enable competitive dominance in eusocial shrimps, but they also suggest that recent population declines are likely caused by eusocial shrimps’ heightened sensitivity to environmental changes, perhaps as a result of their low effective population sizes and localized dispersal. Thus, although the unique life histories and demography of eusocial shrimps have likely contributed to their persistence and ecological dominance over evolutionary time scales, these social traits may also make them vulnerable to contemporary environmental change.
Immunohistochemical Phenotype of T Cells Invading Muscle in Inclusion Body Myositis
Authors: Matsubara Shiro , Suzuki Shigeaki , Komori Takashi
Published: August 2022

Inclusion body myositis (IBM) is an inflammatory myopathy of aged people with poor response to therapy. To characterize muscle-invading inflammatory cells, we performed immunohistochemical and ultrastructural studies on muscle biopsies from 10 patients with IBM with durations of illness from 3 to 84 months. At the surface of muscle fibers, 79% and 48% of CD8+ cells were positive for killer cell lectin-like receptor subfamily G, member 1 (KLRG1) and CD57, respectively. CD8+KLRG1+ cells are highly differentiated cytotoxic cells. On an average, 27% of CD8−CD57+KLRG1+ cells at the surface were CD4+. Proportions of CD28+ cells among KLRG1+ cells showed a negative correlation with duration of illness (r = −0.68). These changes indicated progressive differentiation of CD8+ T cells. Moreover, PD-1 expression on CD57+ and CD8+ cells increased early, then fluctuated, and reincreased in later stages. PD ligand-1 (PD-L1) and PD-L2 were expressed on adjacent cells including muscle fibers. T cell large granular lymphocytes (LGLs) are potent effector cells and cells with ultrastructure indistinguishable from LGLs were seen in the sarcoplasm along with lymphocytes undergoing degeneration. Together, along the course of IBM, some inflammatory cells retained the potential for cytotoxicity whereas others indicated suppression by exhaustion, senescence, or through the PD-1 pathway.
Social Stratification and Career Choice Anxieties in Nineteenth-Century Central Europe
Authors: Beilinson Orel
Published: August 2022

Central Europe around 1900 was marred with anxiety around the choice of career. This article weaves histories of education, labor, bureaucracy, and the social sciences to show how families reacted to changes in the labor market, including the opening of careers to talent and the mechanization of handicrafts. Parents found themselves unable to guide their children to a safe profession. Whereas previously, career choices were limited, changes in education and the labor market offered adolescents more options. Simultaneously, however, some occupations became endangered and others overcrowded. The erosion of labor stratification gave families the hope of social mobility but also upended their ontological security, as traditional roads to adulthood became impossible to follow. This article uses the discourse on career choice to write a history of this crisis. The discourse was born in early modern Europe to stop parents from forcing their children into a profession against the children’s wishes. In nineteenth-century Europe, however, parents and schools weaponized this discourse against each other to widen or narrow access to advanced education. Social scientists concerned with the industrial labor force joined the conversation by turning career choice into a matter of scientific expertise. Finally, the article shows how voluntary associations pioneered the provision of vocational guidance before state intervention after World War I. Thus, the article traces a significant transformation in the transition to adulthood and offers a prehistory of vocational guidance.
Enhanced proteostasis, lipid remodeling, and nitrogen remobilization define barley flag leaf senescence
Authors: Cohen Maja , Hertweck Kendra , Itkin Maxim , Malitsky Sergey , Dassa Bareket , Fischer Andreas M , Fluhr Robert
Published: August 2022

Leaf senescence is a developmental process allowing nutrient remobilization to sink organs. We characterized flag leaf senescence at 7, 14, and 21 d past anthesis in two near-isogenic barley lines varying in the allelic state of the HvNAM1 transcription factor gene, which influences senescence timing. Metabolomics and microscopy indicated that, as senescence progressed, thylakoid lipids were transiently converted to neutral lipids accumulating in lipid droplets. Senescing leaves also exhibited an accumulation of sugars including glucose, while nitrogen compounds (nucleobases, nucleotides, and amino acids) decreased. RNA-Seq analysis suggested lipid catabolism via β-oxidation and the glyoxylate cycle, producing carbon skeletons and feeding respiration as a replacement of the diminished carbon supply from photosynthesis. Comparison of the two barley lines highlighted a more prominent up-regulation of heat stress transcription factor- and chaperone-encoding genes in the late-senescing line, suggesting a role for these genes in the control of leaf longevity. While numerous genes with putative roles in nitrogen remobilization were up-regulated in both lines, several peptidases, nucleases, and nitrogen transporters were more highly induced in the early-senescing line; this finding identifies processes and specific candidates which may affect nitrogen remobilization from senescing barley leaves, downstream of the HvNAM1 transcription factor.
Two periods instead of one in a single 6.7 GHz methanol maser feature in G9.62+0.20E
Authors: MacLeod G C , Yonekura Y , Tanabe Y , Baan W A , Brogan C L , Burns R A , Chibueze J O , Houde M , Hunter T R , Kurtz S E , Rajabi F , Smits D P , Stecklum B , Sugiyama K
Published: August 2022

The source G9.62+0.20E surprises yet again! Analysis of the associated methanol maser feature at vlsr = +8.8 km s−1 revealed a second period of P = 52.1 ± 0.3 d, along with the previously reported period P = 243 d for this source. Various explanations, harmonic flaring, Dicke’s superradiance, a secondary pulsation, or two different periodically varying radio sources in the field of view with associated methanol masers are presented. The latter two hypotheses appear more plausible but it is not clear which, if any, best describe these observations.
Phylogenomic Evidence for the Origin of Obligate Anaerobic Anammox Bacteria Around the Great Oxidation Event
Authors: Liao Tianhua , Wang Sishuo , Stüeken Eva E , Luo Haiwei
Published: August 2022

The anaerobic ammonium oxidation (anammox) bacteria can transform ammonium and nitrite to dinitrogen gas, and this obligate anaerobic process accounts for up to half of the global nitrogen loss in surface environments. Yet its origin and evolution, which may give important insights into the biogeochemistry of early Earth, remain enigmatic. Here, we performed a comprehensive phylogenomic and molecular clock analysis of anammox bacteria within the phylum Planctomycetes. After accommodating the uncertainties and factors influencing time estimates, which include implementing both a traditional cyanobacteria-based and a recently developed mitochondria-based molecular dating approach, we estimated a consistent origin of anammox bacteria at early Proterozoic and most likely around the so-called Great Oxidation Event (GOE; 2.32–2.5 Ga) which fundamentally changed global biogeochemical cycles. We further showed that during the origin of anammox bacteria, genes involved in oxidative stress adaptation, bioenergetics, and anammox granules formation were recruited, which might have contributed to their survival on an increasingly oxic Earth. Our findings suggest the rising levels of atmospheric oxygen, which made nitrite increasingly available, was a potential driving force for the emergence of anammox bacteria. This is one of the first studies that link the GOE to the evolution of obligate anaerobic bacteria.
Lower bone mineral density can be a risk for an enlarging bone marrow lesion: A longitudinal cohort study of Japanese women without radiographic knee osteoarthritis
Authors: Chiba Daisuke , Sasaki Eiji , Ota Seiya , Oyama Tetsushi , Ishibashi Hikaru , Kimura Yuka , Nakaji Shigeyuki , Ishibashi Yasuyuki
Published: August 2022

Objectives

The aim is to elucidate the relationship between bone mineral density (BMD) at baseline and the change of bone marrow lesion (BML) during a 2-year follow-up (2YFU) period.

Methods

Seventy-eight female participants (mean age: 54.9 ± 9.6 years) without radiographic knee osteoarthritis were eligible. Based on right-knee magnetic resonance imaging, maximum BML area (BMLa) was calculated by tracing the BML border. The change in BMLa was defined using the following formula: [2YFU] – [Baseline] = ΔBMLa. Positive ΔBMLa was defined as enlarged; negative ΔBMLa was defined as regressed. Dual-energy X-ray absorptiometry was performed to measure the BMD of distal radius. Young adult mean [YAM (%)] of the BMD was used for statistical analysis. Linear regression analysis was conducted with ΔBMLa as the dependent variable and YAM as the independent variable. Receiver operating characteristic curve and logistic regression analyses were conducted for YAM to predict the prevalence of BML enlargement or regression.

Results

Twenty-six (33.3%) patients had enlarged BMLa, 12 (15.4%) participants showed regressing BMLa, and 40 (51.3%) patients remained stable. YAM was negatively associated with ΔBMLa (β: − 0.375, P = 0.046). The best predictor of BML enlargement risk was 85% (odds ratio: 8.383, P = 0.025).

Conclusions

Lower BMD could predict BML enlargement during a 2YFU period.
Trends in risks of malignancies in Japanese patients with rheumatoid arthritis: Analyses from a 14-year observation of the IORRA cohort
Authors: Sugimoto Naoki , Tanaka Eiichi , Inoue Eisuke , Abe Mai , Sugano Eri , Sugitani Naohiro , Saka Kumiko , Ochiai Moeko , Higuchi Yoko , Yamaguchi Rei , Ikari Katsunori , Nakajima Ayako , Yamanaka Hisashi , Harigai Masayoshi
Published: August 2022

Objectives

The aim is to investigate the trends in risks of overall and site-specific malignancies in patients with rheumatoid arthritis (RA).

Methods

Among Japanese patients with RA enrolled in the Institute of Rheumatology, Rheumatoid Arthritis cohort, all malignancies that occurred from 2000 to 2013 were extracted. The standardized incidence ratios and 95% confidence intervals for overall and site-specific malignancies were calculated during three periods: pre-biologics, 2000–04; early biologics, 2005–09; and recent biologics, 2010–13. Risk factors for overall and specific malignancies were analysed using time-dependent Cox regression models.

Results

Among 11,299 patients with RA (68,483 person-years), 507 malignancies were confirmed. Similar risks were observed versus the general Japanese population for overall malignancies throughout the three periods, with standardized incidence ratios (95% confidence intervals) of 0.96 (0.80–1.14) in the pre-biologics period, 0.95 (0.82–1.09) in the early biologics period, and 0.87 (0.75–1.01) in the recent biologics period. A significantly increased risk for malignant lymphoma was observed throughout the observation period (standardized incidence ratio 4.61, 95% confidence interval 3.58–5.85). The disease activity was a significant risk factor for overall malignancies and lung cancer.

Conclusions

Despite the expanding use of methotrexate and biologics, there were no increases in malignancy risk in Japanese patients with RA.
Drug-survival profiling of second-line biologic therapy in rheumatoid arthritis: Choice of another tumour necrosis factor inhibitor or a biologic of different mode of action?
Authors: Shipa Muhammad R A , Di Cicco Maria , Balogh Emese , Nitu Naila A , Mainuddin M D , Bhadauria Naveen , Mukerjee Dev , Roussou Euthalia
Published: August 2022

Objectives

To assess the best choice of second-line therapy between tumour necrosis factor-inhibitor (TNFi) and biologics of different-mode-of-action (BDMA-rituximab/tocilizumab/abatacept) in rheumatoid arthritis (RA) by evaluating drug-survival following discontinuation of the first-line TNFi.

Methods

This retrospective drug-survival study was performed across two different hospitals by conventional-statistics and machine-learning approach.

Results

From a total of 435 patients, 213 (48.9%; TNFi = 122, BDMA = 91) discontinued their second-line biologic {median drug-survival: TNFi, 27 months [95% confidence interval (95%CI) 22–32] vs BDMA, 37 months (95%CI 32–52)}. As a second-line biologic, BDMA was likely to reduce the risk of treatment-discontinuation [hazard-ratio (HR) 0.63, 95%CI 0.48–0.83] compared to TNFi, but only in seropositive-patients (HR 0.52, 95%CI 0.38–0.73), not in seronegative-RA. Drug-survival benefit of BDMA over TNFi was not observed if the seropositive-patients were previously exposed to monoclonal-TNFi (HR 0.77, 95%CI 0.49–1.22) versus soluble-TNFi (etanercept/biosimilars) or if the first-line TNFi was terminated within 23.9 months of initiation (HR 0.97, 95%CI 0.56–1.68).

Conclusions

BDMA, as a second-line biologic, is more likely to be sustained in seropositive-patients, particularly without prior exposure to monoclonal-TNFi. The drug-survival benefit of BDMA was not observed in seronegative-patients or if the first-line TNFi was stopped within 2 years.
FOXL2 and FOXA1 cooperatively assemble on the TP53 promoter in alternative dimer configurations
Authors: Choi Yuri , Luo Yongyang , Lee Seunghwa , Jin Hanyong , Yoon Hye-Jin , Hahn Yoonsoo , Bae Jeehyeon , Lee Hyung Ho
Published: August 2022

Although both the p53 and forkhead box (FOX) family proteins are key transcription factors associated with cancer progression, their direct relationship is unknown. Here, we found that FOX family proteins bind to the non-canonical homotypic cluster of the p53 promoter region (TP53). Analysis of crystal structures of FOX proteins (FOXL2 and FOXA1) bound to the p53 homotypic cluster indicated that they interact with a 2:1 stoichiometry accommodated by FOX-induced DNA allostery. In particular, FOX proteins exhibited distinct dimerization patterns in recognition of the same p53-DNA; dimer formation of FOXA1 involved protein–protein interaction, but FOXL2 did not. Biochemical and biological functional analyses confirmed the cooperative binding of FOX proteins to the TP53 promoter for the transcriptional activation of TP53. In addition, up-regulation of TP53 was necessary for FOX proteins to exhibit anti-proliferative activity in cancer cells. These analyses reveal the presence of a discrete characteristic within FOX family proteins in which FOX proteins regulate the transcription activity of the p53 tumor suppressor via cooperative binding to the TP53 promoter in alternative dimer configurations.
Artificial intelligence (AI)-based decision support improves reproducibility of tumor response assessment in neuro-oncology: An international multi-reader study
Authors: Vollmuth Philipp , Foltyn Martha , Huang Raymond Y , Galldiks Norbert , Petersen Jens , Isensee Fabian , van den Bent Martin J , Barkhof Frederik , Park Ji Eun , Park Yae Won , Ahn Sung Soo , Brugnara Gianluca , Meredig Hagen , Jain Rajan , Smits Marion , Pope Whitney B , Maier-Hein Klaus , Weller Michael , Wen Patrick Y , Wick Wolfgang , Bendszus Martin
Published: August 2022

Background

To assess whether artificial intelligence (AI)-based decision support allows more reproducible and standardized assessment of treatment response on MRI in neuro-oncology as compared to manual 2-dimensional measurements of tumor burden using the Response Assessment in Neuro-Oncology (RANO) criteria.

Methods

A series of 30 patients (15 lower-grade gliomas, 15 glioblastoma) with availability of consecutive MRI scans was selected. The time to progression (TTP) on MRI was separately evaluated for each patient by 15 investigators over two rounds. In the first round the TTP was evaluated based on the RANO criteria, whereas in the second round the TTP was evaluated by incorporating additional information from AI-enhanced MRI sequences depicting the longitudinal changes in tumor volumes. The agreement of the TTP measurements between investigators was evaluated using concordance correlation coefficients (CCC) with confidence intervals (CI) and P-values obtained using bootstrap resampling.

Results

The CCC of TTP-measurements between investigators was 0.77 (95% CI = 0.69,0.88) with RANO alone and increased to 0.91 (95% CI = 0.82,0.95) with AI-based decision support (P = .005). This effect was significantly greater (P = .008) for patients with lower-grade gliomas (CCC = 0.70 [95% CI = 0.56,0.85] without vs. 0.90 [95% CI = 0.76,0.95] with AI-based decision support) as compared to glioblastoma (CCC = 0.83 [95% CI = 0.75,0.92] without vs. 0.86 [95% CI = 0.78,0.93] with AI-based decision support). Investigators with less years of experience judged the AI-based decision as more helpful (P = .02).

Conclusions

AI-based decision support has the potential to yield more reproducible and standardized assessment of treatment response in neuro-oncology as compared to manual 2-dimensional measurements of tumor burden, particularly in patients with lower-grade gliomas. A fully-functional version of this AI-based processing pipeline is provided as open-source (https://github.com/NeuroAI-HD/HD-GLIO-XNAT).
Five-Year Prospective Observational Study of African-American Men on Active Surveillance for Prostate Cancer Demonstrates Race Is Not Predictive of Oncologic Outcomes
Authors: Pincus Joshua , Greenberg Jacob W , Natale Caleb , Koller Christopher R , Miller Stephanie , Silberstein Jonathan L , Krane L Spencer
Published: August 2022

Introduction

This study aimed to evaluate if race impacted outcomes or risk of disease progression in men on active surveillance (AS) for prostate cancer. We present the results from our majority African-American cohort of men in an equal access setting over a 5-year follow-up period.

Patients and Methods

All patients who elected AS for prostate cancer at the Southeast Louisiana Veterans Health Care System are entered into a prospectively managed observational database. Patients were divided into groups based on self-reported race. Grade group progression was defined as pathologic upgrading above International Society of Urological Pathology Grade Group 1 disease on subsequent biopsies following diagnostic biopsy. All tests were 2 sided using a significance of .05.

Results

A total of 228 men met inclusion criteria in the study, including 154 non-Hispanic African American and 74 non-Hispanic Caucasian American men, with a median follow-up of 5 years from the initiation of AS. Race was not predictive of Gleason grade progression, AS discontinuation, or biochemical recurrence on Cox multivariate analysis (HR = 1.01, 0.94, 0.85, P = .96, .79, .81, respectively). On Kaplan-Meier analysis at 5 years, African-American progression-free, AS discontinuation free, and overall survival probability was comparable to their Caucasian American counterparts (P > .05 for all).

Conclusions

Active surveillance is a safe treatment option for low and very low risk prostate cancer, regardless of race. African-American and Caucasian-American men did not have any significant difference in Gleason grade group progression in our cohort with 5-year follow-up.
POPEYE intercellular localization mediates cell-specific iron deficiency responses
Authors: Muhammad DurreShahwar , Clark Natalie M , Haque Samiul , Williams Cranos M , Sozzani Rosangela , Long Terri A
Published: August 2022

Plants must tightly regulate iron (Fe) sensing, acquisition, transport, mobilization, and storage to ensure sufficient levels of this essential micronutrient. POPEYE (PYE) is an iron responsive transcription factor that positively regulates the iron deficiency response, while also repressing genes essential for maintaining iron homeostasis. However, little is known about how PYE plays such contradictory roles. Under iron-deficient conditions, pPYE:GFP accumulates in the root pericycle while pPYE:PYE–GFP is localized to the nucleus in all Arabidopsis (Arabidopsis thaliana) root cells, suggesting that PYE may have cell-specific dynamics and functions. Using scanning fluorescence correlation spectroscopy and cell-specific promoters, we found that PYE–GFP moves between different cells and that the tendency for movement corresponds with transcript abundance. While localization to the cortex, endodermis, and vasculature is required to manage changes in iron availability, vasculature and endodermis localization of PYE–GFP protein exacerbated pye-1 defects and elicited a host of transcriptional changes that are detrimental to iron mobilization. Our findings indicate that PYE acts as a positive regulator of iron deficiency response by regulating iron bioavailability differentially across cells, which may trigger iron uptake from the surrounding rhizosphere and impact root energy metabolism.