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Influenza viruses continually evolve new antigenic variants, through mutations in epitopes of their major surface proteins, hemagglutinin (HA) and neuraminidase (NA). Antigenic drift potentiates the reinfection of previously infected individuals, but the contribution of this process to variability in annual epidemics is not well understood. Here, we link influenza A(H3N2) virus evolution to regional epidemic dynamics in the United States during 1997-2019. We integrate phenotypic measures of HA antigenic drift and sequence-based measures of HA and NA fitness to infer antigenic and genetic distances between viruses circulating in successive seasons. We estimate the magnitude, severity, timing, transmission rate, age-specific patterns, and subtype dominance of each regional outbreak and find that genetic distance based on broad sets of epitope sites is the strongest evolutionary predictor of A(H3N2) virus epidemiology. Increased HA and NA epitope distance between seasons correlates with larger, more intense epidemics, higher transmission, greater A(H3N2) subtype dominance, and a greater proportion of cases in adults relative to children, consistent with increased population susceptibility. Based on random forest models, A(H1N1) incidence impacts A(H3N2) epidemics to a greater extent than viral evolution, suggesting that subtype interference is a major driver of influenza A virus infection ynamics, presumably via heterosubtypic cross-immunity.

This perspective encompasses a focused review of the literature leading to a tipping point in electroanalytical chemistry. We tie together the threads of a revolution quietly in the making for years through the work of many authors. Long-held misconceptions about the use of background subtraction in fast voltammetry are addressed. We lay out future advantages that accompany background-inclusive voltammetry, particularly when paired with modern machine-learning algorithms for data analysis.

The fundamental goal of a rare plant translocation is to create self-sustaining populations with the evolutionary resilience to persist in the long term. Yet, most plant translocation syntheses focus on a few factors influencing short-term benchmarks of success (e.g., survival and reproduction). Short-term benchmarks can be misleading when trying to infer future growth and viability because the factors that promote establishment may differ from those required for long-term persistence. We assembled a large (n = 275) and broadly representative data set of well-documented and monitored (7.9 years on average) at-risk plant translocations to identify the most important site attributes, management techniques, and species' traits for six life-cycle benchmarks and population metrics of translocation success. We used the random forest algorithm to quantify the relative importance of 29 predictor variables for each metric of success. Drivers of translocation outcomes varied across time frames and success metrics. Management techniques had the greatest relative influence on the attainment of life-cycle benchmarks and short-term population trends, whereas site attributes and species' traits were more important for population persistence and long-term trends. Specifically, large founder sizes increased the potential for reproduction and recruitment into the next generation, whereas declining habitat quality and the outplanting of species with low seed production led to increased extinction risks and a reduction in potential reproductive output in the long-term, respectively. We also detected novel interactions between some of the most important drivers, such as an increased probability of next-generation recruitment in species with greater seed production rates, but only when coupled with large founder sizes. Because most significant barriers to plant translocation success can be overcome by improving techniques or resolving site-level issues through early intervention and management, we suggest that by combining long-term monitoring with adaptive management, translocation programs can enhance the prospects of achieving long-term success.

The BAPS Hindu Mandir, recently constructed in Abu Dhabi, UAE, is a complex unreinforced stone masonry structure built from thousands of sculpted sandstone and marble pieces employing ancient Indian techniques called Shilp Shastra. The entire structure is substantially large with a footprint size of 5,100 m2 and unique so that it is not covered by modern seismic design standards. Its performance was verified by conducting dynamic field tests presented herein. The most vulnerable substructure was identified based on both engineering judgement and modal analysis of the entire structure employing a detailed 3D finite element model, which was validated via the field experiments. A “local” model was developed for the identified vulnerable substructure which significantly reduced model complexity and allowed to overcome computational limitations. Based on the response of the local model, the relative importance of the sensor locations was determined via a Displacement Index method in addition to a reduction of the total variance of spectral accelerations using conditional probability theory. Through this approach, a methodology for selecting the optimal sensor placement with application on the complex unreinforced stone masonry Hindu Mandir is proposed.

Accurately identifying neoantigens is crucial for developing effective cancer vaccines and improving tumor immunotherapy. Mass spectrometry-based immunopeptidomics has emerged as a promising approach to identifying human leukocyte antigen (HLA) peptides presented on the surface of cancer cells, but false-positive identifications remain a significant challenge. In this study, liquid chromatography-tandem mass spectrometry-based proteomics and next-generation sequencing were utilized to identify HLA-presenting neoantigenic peptides resulting from non-synonymous single nucleotide variations in tumor tissues from 18 patients with renal cell carcinoma or pancreatic cancer. Machine learning was utilized to evaluate Mascot identifications through the prediction of MS/MS spectral consistency, and four descriptors for each candidate sequence: the max Mascot ion score, predicted HLA binding affinity, aliphatic index and retention time deviation, were selected as important features in filtering out identifications with inadequate fragmentation consistency. This suggests that incorporating rescoring filters based on peptide physicochemical characteristics could enhance the identification rate of MS-based immunopeptidomics compared to the traditional Mascot approach predominantly used for proteomics, indicating the potential for optimizing neoantigen identification pipelines as well as clinical applications.

Abstract Background Diffusion-weighted magnetic resonance imaging (DWI) is essential for diagnosing Creutzfeldt–Jakob disease (CJD). Thalamic lesions are rarely detected by DWI in sporadic CJD (sCJD) cases with methionine homozygosity at polymorphic codon 129 (129MM) of the prion protein (PrP) gene. Here, we describe an unusual sCJD case, characterized by prolonged isolated thalamic diffusion hyperintensities and atypical brain pathology, in combination with the 129MM genotype. Case presentation A 72-year-old Japanese man developed a mild unsteady gait that had persisted for 1 year. DWI revealed isolated thalamic diffusion hyperintensities. Over the following 4 years, his condition progressed to include ataxia and cognitive decline. Repeated cerebrospinal fluid tests were negative for 14-3-3 protein, total tau protein, and real-time quaking-induced conversion assay. Electroencephalography did not show periodic sharp wave complexes or generalized periodic discharges. Despite these findings, thalamic DWI abnormalities persisted and evolved to include cortical lesions in the later stage of the disease. Genetic testing confirmed a 129MM genotype with no pathogenic PrP gene variants. Brain autopsy identified type 2 pathogenic PrP and the absence of the M2-thalamic prion strain, suggesting an MM2-cortical (MM2C)-subtype of sCJD. Histopathology revealed small vacuoles (sv) and patchy-perivacuolar PrP deposits without large vacuoles (lv). Patchy-perivacuolar deposits are a characteristic feature of the MM2C (lv) subtype and indicate MM2C (lv) pathology. Thus, this case was classified as a rare MM2C (sv + lv) subtype. No PrP protein staining was observed in the thalamus, despite spongiform changes with small vacuoles. Conclusions This case underscores the diagnostic challenges of atypical CJD with isolated thalamic abnormalities on DWI. Despite negative cerebrospinal fluid findings and clinical diagnostic criteria, persistent DWI abnormalities and evolving clinical symptoms continued to raise suspicion of CJD. A definitive diagnosis, being the MM2C (sv + lv) subtype of sCJD, was confirmed upon pathological examination. Even when atypical findings, such as isolated thalamic abnormalities, are observed and various tests are negative, if suspicion of CJD cannot be ruled out, it is important to confirm the diagnosis and pathological subtypes via postmortem analysis.

Abstract Background This case report presents the case of a patient with P369S and R408Q variants in the MEFV gene who exhibited clinical features of Kikuchi disease and Mollaret meningitis. Furthermore, it discusses colchicine as a new potential treatment option for Kikuchi disease-associated meningitis. Case presentation A 41-year-old Japanese woman presented with fever and headache. She had nuchal rigidity and bilateral cervical lymphadenopathies. Her past medical history included multiple episodes of aseptic meningitis and cervical lymphadenopathy for more than twenty years. Lumbar puncture showed increased lymphocytes and IL-6 level and pathognomonic Mollaret cells. Excisional lymph node biopsy revealed histiocytic necrotizing lymphadenitis, confirming the diagnosis of Kikuchi disease. Subsequently, her recurrent Kikuchi disease and meningitis were successfully treated with colchicine. Furthermore, genetic analysis of the MEFV gene revealed heterozygous P369S/R408Q variants in exon 3. Conclusion Mollaret meningitis can be associated with Kikuchi disease, and recurrence of both conditions may be suppressed by colchicine when these two coexist.

Abstract Background Patient trust plays a central role in the patient-physician relationship. This study aimed to determine whether the number of outpatient visits with a covering rheumatologist is associated with patient trust in their usual rheumatologist. Methods Japanese adults with systemic lupus erythematosus (SLE) who met the 1997 revised classification criteria of the American College of Rheumatology and had outpatient visits with a covering rheumatologist in the past year were included. We used the 11-item Japanese version of the modified Trust in Physician Scale (range 0–100) to assess patient trust. A general linear model with cluster-robust variance estimation was used to evaluate the association between the number of outpatient visits with covering rheumatologists and the patient’s trust in their usual rheumatologist. Results Of the 515 enrolled participants, 421 patients with SLE were included in our analyses. Patients were divided into groups according to the number of outpatient visits with a covering rheumatologist in the past year as follows: no visits (59.9%; reference group), one to three visits (24.2%; low-frequency group), and four or more visits (15.9%; high-frequency group). The median Trust in Physician Scale score was 81.8 (interquartile range: 72.7–93.2). Both the low-frequency group (mean difference: -3.03; 95% confidence interval [CI] -5.93 to -0.80) and high-frequency group (mean difference: -4.17; 95% CI -7.77 to -0.58) exhibited lower trust in their usual rheumatologist. Conclusion This study revealed that the number of outpatient visits with a covering rheumatologist was associated with lower trust in a patient’s usual rheumatologist.

To prevent damage from landslide disasters, traffic regulation based on records is implemented before disasters occur in Japan. Logistics and accordingly economic activities are halted once the traffic regulation is implemented. There are problems that the operation of the traffic regulation tends to be redundant in terms of temporal duration and spatial coverage. In this paper, to consider the effect of topography and land deformation and resolve the problems of redundant traffic regulation, we attempted to predict the land deformation using spatio-temporal statistical models whose objective variable was deformation estimated PSInSAR and explanatory variables were accumulated rainfall and maximum gradient angle. Three statistical models: low-rank GP model, separable covariance model, and product-sum covariance model were used. According to the results of experiments, three spatio-temporal models showed similar predictions; relatively small deformations were well fitted while relatively large deformations were poorly fitted. Since land deformation due to landslides is relatively large, it should be considered the measures to improve the prediction of larger deformations.

Abstract Background There have been several reports showing that heart-related deaths are common in long-term survivors of esophageal cancer after radiation therapy; however, radiotherapy technology is evolving year by year. This study was carried out using the SEER database to determine whether the frequency of mortality from heart disease after radiotherapy has improved over time in patients with esophageal cancer. Methods SEER*Stat statistical software version 8.3.9.2 (National Cancer Institute) was used to perform case listing and data extraction. We reviewed causes of death in 8,297 patients who were treated by radiotherapy without surgery between 2004 and 2015 (radiotherapy group). For comparison with this group, we also reviewed causes of death in 5,149 patients who were treated by surgery without radiotherapy (surgery group). Results In the radiotherapy group, the cumulative heart-related death rate in patients with carcinoma in the middle to abdominal esophagus, for which it was considered that the heart was irradiated with a higher dose, was significantly higher than that in patients with carcinoma in the cervical to upper thoracic esophagus (p = 0.017). However, in the surgery group, the cumulative heart-related death rate in patients with carcinoma in the middle to abdominal esophagus tended to be lower than that in patients with carcinoma in the cervical to upper thoracic esophagus (p = 0.063). The cumulative heart-related death rate in patients treated in 2010–2015 was significantly lower than that in patients treated in 2004–2009 in the radiotherapy group (p = 0.011), although the cumulative heart-related death rate was not significantly different between patients treated in 2010–2015 and patients treated in 2004–2009 in the surgery group (p = 0.90). Conclusions The results suggest that recent advances in radiotherapy have enabled a reduction in radiation-induced heart disease in patients with esophageal cancer.

This study investigated the clinical features and prognostic relevance of decreased serum complement levels in patients with idiopathic inflammatory myositis (IIM). The clinical information of IIM patients with less than normal serum complement levels (L-Com) and that of those with normal serum complement levels (N-Com) was compared. In patients with interstitial lung disease (ILD), regression analyses were used to investigate the implication of L-Com in their PaO2/FiO2 (P/F) ratio. Prognostic outcomes of ILD were evaluated using the log-rank test. Of 94 IIM patients, 26 with L-Com (median age, 56.0 years) and 68 with N-Com (56.5 years) were included. The prevalence of women was significantly higher in patients with L-Com (92.3%) than in those with N-Com (67.6%). ILD was observed in 17 (65.4%) patients with L-Com and in 46 (67.6%) with N-Com. Among patients with ILD, the P/F ratio was significantly lower in those with L-Com than in those with N-Com. Serum C3 levels were correlated with decreased P/F ratio. Inferior prognosis of ILD was significantly demonstrated in patients with L-Com, especially in those positive for anti-melanoma differentiation-associated protein 5 antibody. L-Com may be implicated in reduced arterial oxygen levels and a poorer prognosis in patients with IIM-related ILD.