Predictors of clinical features in early-onset severe systemic sclerosis: An analysis from a multicenter prospective observational Japanese cohort.

As the clinical course of systemic sclerosis (SSc) varies widely, prognostic indicators have been sought to predict the outcomes of individual patients. Racial differences in SSc render it necessary to validate prognostic indicators in different patient cohorts. In this study, we aimed to assess clinical and laboratory parameters in Japanese patients with early-stage SSc with diffuse cutaneous involvement and/or interstitial lung disease, and identify predictive factors for disease progression. We performed multivariate analyses of baseline clinical information to estimate symptoms 4 years later in Japanese patients with diffuse cutaneous SSc and/or SSc with interstitial lung disease. Patients were enrolled in the study within 5 years of disease onset at 10 Japanese SSc centers. Over 12 years, 115 patients followed up for 4 years were included in this study. The modified Rodnan skin score (mRSS) at 4 years correlated with the baseline mRSS and finger-to-palm distance, defined as the average length from the distal tip of the fourth finger to the distal palmar crease. The percentage predicted vital capacity (%VC) in year 4 positively and negatively correlated with initial %VC and the presence of anti-topoisomerase I antibodies, respectively. The Health Assessment Questionnaire Disability Index (HAQ-DI) at 4 years was positively and negatively associated with baseline HAQ-DI and %VC, respectively. The occurrence of digital ulcers within 4 years was associated with the initial presence of digital ulcers, finger-to-palm distance, and the presence of digital pitting scars and anti-topoisomerase I antibodies. This study identified several factors that may predict the progression of early-stage SSc in Japanese patients. Finger-to-palm distance may be a useful tool for predicting the progression of skin thickening and the development of digital ulcers in the early stages of severe SSc, but larger, long-term prospective studies are needed to confirm our findings.

Avoiding Photocyclized Degradation of Electrochromic Materials Based on Quantum Chemical Molecular Design.

Suppressing the photodegradation of organic electronic materials is crucial for their device applications. This study proposes a method to mitigate the photodegradation. With focus on the molecular design of triphenylamine derivatives commonly used in organic electronics, it was demonstrated that spin distributions of the derivatives would be a good quantum descriptor for predicting the photocyclization resistance to not give carbazole derivatives.

Improved hourly estimate of aerosol optical thickness over Asian land by fusing geostationary satellites Fengyun-4B and Himawari-9.

Asian over-land aerosols are complexities due to a mixture of anthropogenic air pollutants and natural dust. The accuracy of the aerosol optical thickness (AOT) retrieved from the satellite is crucial to their application in the aerosol data assimilation system. Fusion of AOTs with high spatiotemporal resolution from next-generation geostationary satellites such as Fengyun-4B (FY-4B) and Himawari-9, provides a new high-quality dataset capturing the aerosol spatiotemporal variability for data assimilation. This study develops a complete fusion algorithm to estimate the optimal AOT over-land in Asia from September 2022 to August 2023 at 10 km × 10 km resolution with high efficiency. The data fusion involves four steps: (1) investigating the spatiotemporal variability of FY-4B AOT within the past 1 h and 12 km radius calculation domain; (2) utilizing the aerosol spatiotemporal variability characteristics to estimate FY-4B pure and hourly merged AOTs; (3) performing bias corrections for FY-4B and Himwari-9 hourly merged AOT for different observation times and seasons considering pixel-level errors for each satellite; (4) fusing the bias-corrected FY-4B and Himawari-9 hourly merged AOT based on maximum-likelihood estimation (MLE) method. Compared to the original FY-4B AOT, validation with AERONET observation confirms that the root mean square error (RMSE) of hourly merged FY-4B AOT decreases by around 40.6 % and the correlation coefficient (CORR) increases by about 27.8 %. Compared to FY-4B and Himawari-9 merged AOT, the fused AOT significantly decreases (increases) RMSE (CORR) by around 24.7 % (7.3 %) and 20.2 % (5.6 %). In addition, fused AOT is double the number of single-sensor merged AOT. Fusion aerosol map accurately describes the spatial and temporal variations in Asian regions controlled by air pollution and dust storms. Further studies are required for other landscapes with different satellite combinations to promote the application in the data assimilation system.

Real-world use of first-line pembrolizumab + platinum + taxane combination regimens in recurrent / metastatic head and neck squamous cell carcinoma.

Introduction: The programmed death-1 (PD-1) immune checkpoint inhibitor pembrolizumab is currently approved in the US for the first-line (1L) treatment of recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC), either alone or in combination with platinum and 5-fluorouracil (5-FU). However, the toxicity of 5-FU has motivated the study of alternate combinations that replace 5-FU with a taxane. The objective of the current study was to describe the baseline characteristics, treatment patterns and sequences, and real-world outcomes of individuals receiving pembrolizumab + platinum + taxane as 1L treatment for R/M HNSCC in the US. Methods: This was a retrospective study of US adults ≥18 years of age receiving pembrolizumab + platinum + taxane as 1L treatment for R/M HNSCC, using electronic health record data from a nationwide de-identified database. Real-world overall survival (rwOS), time on treatment (rwToT), and time to next treatment (rwTTNT) outcomes were assessed using Kaplan-Meier analysis. Results: The study population comprised 83 individuals (80.7% male) with a median age of 64 years. The most common tumor site was the oropharynx (48.2%); 70.0% of these tumors were HPV-positive. A total of 71.1% of the study population had an Eastern Cooperative Oncology Group performance status of 0-1 at index date, 71.8% had a combined positive score for programmed death ligand-1 (PD-L1) expression of ≥1, and 30.8% had a score of ≥20. The median (95% CI) rwOS was 14.9 (8.8-23.3) months, rwToT was 5.3 (4.0-8.2) months, and rwTTNT was 8.7 (6.8-12.3) months. Among the 24 individuals who received a subsequent therapy, the most common second-line therapies were cetuximab-based (n = 9) or pembrolizumab-containing (n = 8) regimens. Conclusions: The rwOS and other real-world outcomes observed for this study population further support pembrolizumab + platinum + taxane combination therapy as a potential 1L treatment option for R/M HNSCC.

Prognostic Factors for Severe-to-Fatal Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis: A Multicenter Prospective Cohort Study.

The prognostic factors associated with severe-to-fatal post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) remain unclear despite the extensive number of studies on PEP. In total, 3739 ERCP patients with biliary disease with an intact papilla and indicated for ERCP were prospectively enrolled at 36 centers from April 2017 to March 2018. Those with acute pancreatitis diagnosed before ERCP, altered gastrointestinal anatomy, and an American Society of Anesthesiologists (ASA) physical status > 4 were excluded. Univariate and multivariate logistic regression analyses were performed on patient-related factors, operator-related factors, procedure-related factors, and preventive measures to identify potential prognostic factors for severe-to-fatal PEP. Multivariate analyses revealed pancreatic guidewire-assisted biliary cannulation (OR 13.59, 95% CI 4.21-43.83, p < 0.001), post-ERCP non-steroidal anti-inflammatory drug (NSAID) administration (OR 11.54, 95% CI 3.83-34.81, p < 0.001), and previous pancreatitis (OR 6.94, 95% CI 1.45-33.33, p = 0.015) as significant risk factors for severe-to-fatal PEP. Preventive measures included endoscopic biliary sphincterotomy (EST; OR 0.29, 95% CI, 0.11-0.79, p = 0.015) and prophylactic pancreatic stents (PPSs; OR 0.11, 95% CI, 0.01-0.87, p = 0.036). In biliary ERCP, pancreatic guidewire-assisted biliary cannulation, NSAID administration after ERCP, and previous pancreatitis were risk factors for severe-to-fatal PEP, whereas EST and PPS were significant preventive measures for severe-to-fatal PEP.

GWAS for systemic sclerosis identifies six novel susceptibility loci including one in the Fcγ receptor region.

Here we report the largest Asian genome-wide association study (GWAS) for systemic sclerosis performed to date, based on data from Japanese subjects and comprising of 1428 cases and 112,599 controls. The lead SNP is in the FCGR/FCRL region, which shows a penetrating association in the Asian population, while a complete linkage disequilibrium SNP, rs10917688, is found in a cis-regulatory element for IRF8. IRF8 is also a significant locus in European GWAS for systemic sclerosis, but rs10917688 only shows an association in the presence of the risk allele of IRF8 in the Japanese population. Further analysis shows that rs10917688 is marked with H3K4me1 in primary B cells. A meta-analysis with a European GWAS detects 30 additional significant loci. Polygenic risk scores constructed with the effect sizes of the meta-analysis suggest the potential portability of genetic associations beyond populations. Prioritizing the top 5% of SNPs of IRF8 binding sites in B cells improves the fitting of the polygenic risk scores, underscoring the roles of B cells and IRF8 in the development of systemic sclerosis. The results also suggest that systemic sclerosis shares a common genetic architecture across populations.

Wet scavenging of multi-mode 137Cs aerosols following the Fukushima accident: Size-resolved microphysics modeling with observed diameters.

Wet scavenging was critical in the atmospheric transport of 137Cs aerosols following the Fukushima accident. The aerosol size diversity and related microphysical processes produce complex behaviors during wet scavenging. Such behaviors are difficult to investigate using traditional simplified size distributions, resulting in inaccurate modeling. This study establishes an improved size-resolved wet scavenging model that considers the activation process. Using this model, five monodisperse simulations with five representative observed diameters with realistic solubility setting are performed to investigate the spatiotemporal wet scavenging behaviors of 137Cs aerosols. One polydisperse simulation with an empirical size distribution is also validated against the observation. The results reveal that 137Cs aerosols with diameters of 0.6 and 2.0 µm are mainly subject to below-cloud scavenging, which makes a significant contribution to low-deposition areas (<300 kBq/m2). For 137Cs aerosols with diameters of 6.4, 15, and 30 µm, in-cloud scavenging dominates, and the resulting depositions make significant contributions in high-deposition areas. The polydisperse results satisfy the criteria for good performance and better agree with the size, and deposition observations than the five monodisperse simulations, whereas for the concentration, the results show a similar RANK2 with the best mono1 and mono2 cases and reach the satisfactory criteria. These findings reveal the complex behavior and wet scavenging process of multi-mode 137Cs aerosols, improving our understanding and modeling.

Transient demographic dynamics of recovering fish populations shaped by past climate variability, harvest, and management.

Large-scale commercial harvesting and climate-induced fluctuations in ocean properties shape the dynamics of marine populations as interdependent drivers at varied timescales. Persistent selective removals of larger, older members of a population can distort its demographic structure, eroding resilience to fluctuations in habitat conditions and thus amplifying volatility in transient dynamics. Many historically depleted marine fish stocks have begun showing signs of recovery in recent decades following the implementation of stricter management measures. But these interventions coincide with accelerated changes in the oceans triggered by increasingly warmer, more variable climates. Applying multilevel models to annual estimates of demographic metrics of 38 stocks comprising 11 species across seven northeast Atlantic ecoregions, this study explores how time-varying local and regional climates contributed to the transient dynamics of recovering populations exposed to variable fishing pressures moderated by management actions. Analyses reveal that progressive reductions in fishing pressure and shifting climate conditions discontinuously shaped rebuilding patterns of the stocks through restorations of maternal demographic structure (reversing age truncation) and reproductive capacity. As the survival rate and demographic structure of reproductive fish improved, transient growth became less sensitive to variability in recruitment and juvenile survival and more to that in adult survival. As the biomass of reproductive fish rose, recruitment success also became increasingly regulated by density-dependent processes involving higher numbers of older fish. When reductions in fishing pressure were insufficient or delayed, however, stocks became further depleted, with more eroded demographic structures. Although warmer local climates in spawning seasons promoted recruitment success in some ecoregions, changing climates in recent decades began adversely affecting reproductive performances overall, amplifying sensitivities to recruitment variability. These shared patterns underscore the value of demographic transients in developing robust strategies for managing marine resources. Such strategies could form the foundation for effective applications of adaptive measures resilient to future environmental change.

Corrigendum: Real-world treatment patterns and outcomes among individuals receiving first-line pembrolizumab therapy for recurrent/metastatic head and neck squamous cell carcinoma.

[This corrects the article DOI: 10.3389/fonc.2023.1160144.].

Real-world treatment patterns and outcomes among individuals receiving first-line pembrolizumab therapy for recurrent/metastatic head and neck squamous cell carcinoma.

Background: Pembrolizumab, a PD-1 immune checkpoint inhibitor, is approved as first-line (1L) treatment for recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) as monotherapy or in combination with platinum and 5-fluorouracil chemotherapy. Limited data exist on the use of these regimens in real-world settings. Objective: Our primary objectives were to describe baseline characteristics and real-world overall survival (rwOS), time on treatment (rwToT), and time to next treatment (rwTTNT) among individuals with R/M HNSCC receiving approved 1L pembrolizumab therapies. We also aimed to identify baseline factors associated with choice of 1L pembrolizumab therapy and with rwOS. Methods: This was a retrospective cohort study of adults with R/M HNSCC receiving 1L pembrolizumab monotherapy or pembrolizumab plus chemotherapy. We used Kaplan-Meier analyses to assess real-world outcomes, logistic regression modeling to identify factors associated with choice of 1L pembrolizumab therapy, and Cox proportional hazards models to identify factors associated with rwOS. Results: The study population included 431 individuals receiving 1L pembrolizumab monotherapy and 215 receiving 1L pembrolizumab plus chemotherapy. The use of 1L pembrolizumab monotherapy was associated with higher baseline combined positive score for PD-L1 expression, older age, higher Eastern Cooperative Oncology Group performance status (ECOG PS), laryngeal tumor site, and human papillomavirus (HPV)-positive tumor status. The pembrolizumab monotherapy group had a median (95% CI) rwOS of 12.1 (9.2-15.1) months, rwToT of 4.2 (3.5-4.6) months, and rwTTNT of 6.5 (5.4-7.4) months. Among this group, HPV-positive tumor status and lower ECOG PS were associated with longer rwOS, and oral cavity tumor site with shorter rwOS. The pembrolizumab plus chemotherapy cohort had a median (95% CI) rwOS of 11.9 (9.0-16.0) months, rwToT of 4.9 (3.8-5.6) months, and rwTTNT of 6.6 (5.8-8.3) months. In this group, HPV-positive tumor status was associated with longer rwOS. Conclusions: This study adds to clinical trial data by summarizing real-world treatment outcomes with 1L pembrolizumab-containing therapies in a more heterogeneous population. Overall survival outcomes in both treatment groups were similar to those observed in the registration clinical trial. These findings support the use of pembrolizumab as standard of care for R/M HNSCC.

Model behavior regarding in- and below-cloud 137Cs wet scavenging following the Fukushima accident using 1-km-resolution meteorological field data.

Wet deposition remains an important source of uncertainty in modeling of the atmospheric transport of 137Cs following the Fukushima Daiichi Nuclear Power Plant accident. Its behavior is often difficult to investigate owing to the limited resolution of meteorological field data and inconsistent model implementations. This study investigated the detailed behavior of 25 combinations of in- and below-cloud wet scavenging models using high-resolution (1 km × 1 km) meteorological input. These combinations were all implemented in the Weather Research and Forecasting-Chemistry model, thereby enabling consistent evaluation. The 1-km-resolution simulations were compared with simulations obtained previously using 3-km-resolution meteorological field data. Results revealed that rainfall of <1 mm/h is critical for simulation accuracy. The 1-km results revealed better representation of rainfall than that revealed by the 3-km results, but with spatiotemporal variability in accuracy. Owing to their sensitivity to rainfall, single-parameter wet deposition models showed improvements in performance in the 1-km simulations relative to that in the 3-km simulations. The multiparameter models showed more robust performance in terms of both simulations, and the Roselle-Mircea model presented the best performance among the 25 models considered. Wind transport showed substantial influence on the removal of atmospheric 137Cs, and it was nonnegligible even during periods in which wet deposition was dominant. The 1-km-resolution simulations effectively reproduced local-scale 137Cs concentrations but with deviations in timing, mainly because of biased wind direction. These findings indicate the necessity for a refined wind and dispersion model for local-scale simulation of 137Cs concentration.

Bending Angle Sensor Based on Double-Layer Capacitance Suitable for Human Joint.

Goal: To develop bending angle sensors based on double-layer capacitance for monitoring joint angles during cycling exercises. Methods: We develop a bending angle sensor based on double-layer capacitive and conducted three stretching, bending, and cycling tests to evaluate its validity. Results: We demonstrate that the bending angle sensor based on double-layer capacitance minimizes the change in the capacitance difference in the stretching test. The hysteresis and root mean square error (RMSE) compared with the optical motion capture show hysteresis: 8.0% RMSE and 3.1° in the bending test. Moreover, a cycling experiment for human joint angle measurements confirm the changes in accuracy. The RMSEs ranged from 4.7° to 7.0°, even when a human wears leggings fixed with the developed bending-angle sensor in the cycling test. Conclusion: The developed bending angle sensor provides a practical application of the quantitative and observational evaluation tool for knee joint angles.

Vaccine financing in the Middle East and Africa: An overview from 2010 to 2019.

BACKGROUND: Vaccination is a cost-effective disease prevention measure. Sustainable financing is critical to successful implementation of vaccination programs. Countries in the Middle East and Africa (MEA) have vaccination programs that remain highly vulnerable to budget limitations. OBJECTIVES: The objectives of this study were to understand the current vaccine financing landscape in MEA; to assess the availability and variability of data on vaccination budgets, expenditure and schedules including introductions of new vaccines; and to identify and describe key trends. METHOD: A targeted literature review was conducted for 69 MEA countries for data between 2010 and 2019. Descriptive analysis of the collected data was conducted. RESULTS: Data on vaccination expenditure were available for 96% of the countries. However, data on vaccination budget were limited, and the variability was high. The median vaccination expenditure per capita was between US$0.57 and US$1.02. High-income countries spent the most on vaccination per capita (median US$3.41) compared to low-income countries (median US$0.69). The highest vaccination expenditure per capita was in countries that receive 100% government funding of vaccination programs (US$0.87) compared to those where government pays for > 0% to < 50% of vaccination expenditure (US$0.74). Vaccination expenditure as a proportion of gross domestic product was the highest (0.10%) in low-income countries and the lowest in high-income countries (0.01%). Vaccination expenditure as proportion of healthcare expenditure was the highest (1.76%) in low-income countries and the lowest in high-income countries (0.33%). Statistically significant trends in median expenditure per capita were identified for 27% of the countries. During this period, an average of 4.4 vaccines were introduced. CONCLUSION: Data on vaccination expenditure in MEA was available for detailed analysis, and it was useful to understand the characteristics of vaccination funding in the region. It is important to secure adequate financing to sustain current vaccination programs and to introduce new vaccines.

Coupled modeling of in- and below-cloud wet deposition for atmospheric 137Cs transport following the Fukushima Daiichi accident using WRF-Chem: A self-consistent evaluation of 25 scheme combinations.

Wet deposition, including both in- and below-cloud scavenging, is critical for the atmospheric transport modeling of 137Cs following the Fukushima Daiichi Nuclear power plant (FDNPP) accident. Although intensively investigated, wet deposition simulation is still subject to uncertainties of meteorological inputs and wet scavenging modeling, leading to biased 137Cs transport prediction. To reduce the dual uncertainties, in- and below-cloud wet scavenging schemes of 137Cs were simultaneously integrated into Weather Research and Forecasting-Chemistry (WRF-Chem), yielding online coupled modeling of meteorology and the two wet scavenging processes. The integration was performed using 25 combinations of different in- and below-cloud schemes, covering most schemes in the literature. Two microphysics schemes were also tested to better reproduce the precipitation. The 25 models and the ensemble mean of 9 representative models were systematically compared with the below-cloud-only WRF-Chem model, using the cumulative deposition and atmospheric concentrations of 137Cs measurements. The results reveal that, with the Morrison's double moment cloud microphysics scheme, the developed models could better reproduce the rainfall and substantially improve the cumulative deposition simulation. The in-cloud scheme is influential to the model behaviors and those schemes considering cloud parameters also improve the atmospheric concentration simulations, whereas the others solely dependent on the rain intensity are sensitive to meteorology. The ensemble mean achieves satisfactory performance except one plume event, but still outperforms most models.

Tradeoffs of managing cod as a sustainable resource in fluctuating environments.

Sustainable human exploitation of living marine resources stems from a delicate balance between yield stability and population persistence to achieve socioeconomic and conservation goals. But our imperfect knowledge of how oceanic oscillations regulate temporal variation in an exploited species can obscure the risk of missing management targets. We illustrate how applying a management policy to suppress fluctuations in fishery yield in variable environments (prey density and regional climate) can present unintended outcomes in harvested predators and the sustainability of harvesting. Using Atlantic cod (Gadus morhua, an apex predatory fish) in the Barents Sea as a case study we simulate age-structured population and harvest dynamics through time-varying, density-dependent and density-independent processes with a stochastic, process-based model informed by 27-year monitoring data. In this model, capelin (Mallotus villosus, a pelagic forage fish), a primary prey of cod, fluctuations modulate the strength of density-dependent regulation primarily through cannibalistic pressure on juvenile cod survival; sea temperature fluctuations modulate thermal regulation of cod feeding, growth, maturation, and reproduction. We first explore how capelin and temperature fluctuations filtered through cod intrinsic dynamics modify catch stability and then evaluate how management to suppress short-term variability in catch targets alters overharvest risk. Analyses revealed that suppressing year-to-year catch variability impedes management responses to adjust fishing pressure, which becomes progressively out of sync with variations in cod abundance. This asynchrony becomes amplified in fluctuating environments, magnifying the amplitudes of both fishing pressure and cod abundance and then intensifying the density-dependent regulation of juvenile survival through cannibalism. Although these transient dynamics theoretically give higher average catches, emergent, quasicyclic behaviors of the population would increase long-term yield variability and elevate overharvest risk. Management strategies that overlook the interplay of extrinsic (fishing and environment) and intrinsic (life history and demography) fluctuations thus can inadvertently destabilize fish stocks, thereby jeopardizing the sustainability of harvesting. These policy implications underscore the value of ecosystem approaches to designing management measures to sustainably harvest ecologically connected resources while achieving socioeconomic security.

Movement Coordination during Forward and Backward Rope Jumping: A Relative Phase Study.

Rope jumping is a popular training method in athletic programs, fitness, and physical education. Forward and backward rope jumping has been used for evaluating athlete's performance. Both of these two jumps require coordination in the upper and lower limbs. However, no study has focused on movement coordination during forward and backward rope jumping. Relative phase (RP) analysis was widely known as an innovative method for evaluating human movement coordination. Thus we aimed to investigate the movement coordination during forward and backward rope jumping by using RP analysis. 78 elementary and junior high school students participated in this study. 30 seconds rope jumping was recorded for both forward and backward by using iPhone video. Pose estimation software was used for jump motion tacking. Movement coordination was analyzed through RP analysis, absolute maximum value, mean absolute RP, and deviation phase were calculated for evaluating movement coordination, the trend of in or out-of-phase, as well as movement stability. As a result, 3994 forward and 3961 backward jumps were analyzed. There was a significant difference in movement coordination between forward and backward rope jumping. Compared to forward, backward jumps showed worse movement coordination, a trend to be out-of-phase, and less stability. It was the first time that movement coordination during rope jumping was studied. We considered that further research on coordination during rope jumping can provide new insight into athlete performance management, fitness guidance, and physical education.

Clinical course of Japanese patients with early systemic sclerosis: A multicenter, prospective, observational study.

OBJECTIVES: To investigate the clinical course of Japanese patients with early diffuse cutaneous systemic sclerosis (dcSSc) and early SSc with interstitial lung disease (ILD). METHODS: We prospectively analyzed the clinical features of 207 Japanese patients with early dcSSc (n = 150) and limited cutaneous SSc (lcSSc) with ILD (n = 57) in 10 medical centers every year for 7 consecutive years. RESULTS: Mean modified Rodnan total skin thickness score (mRSS) was 18.3 and 67.4% of the cohort had ILD. Most patients started immunosuppressive therapy and vasodilators during 7 years (83.4% and 87.9%, respectively). Mean value of mRSS of total patients was significantly reduced from the initial registration after the first year. However, other parameters for physical function associated with skin sclerosis including fist closure, hand extension, and oral aperture were not so ameliorated during the study period. Health Assessment Questionnaire-disability index and serum KL-6 levels were constant throughout the course. Percent vital capacity and the presence of ILD, clinically suspected pulmonary arterial hypertension, and digital ulcers were gradually exacerbated during the period. CONCLUSION: In Japanese early dcSSc patients and SSc patients with ILD, mRSS was continuously reduced during 7 years of follow-up, but there was little improvement of physical disability and organ involvement.