bluuebunny/crossref_metadata_2025 huggingface dataset:
Postoperative Reduction Quality May Be the Most Important Factor That Causes Worse Functional Outcomes in Open and Closed Pelvic Fractures
Authors: Lai Chih‐Yang , Lai Po‐Ju , Tseng I‐Chuan , Su Chun‐Yi , Hsu Yung‐Heng , Chou Ying‐Chao , Yu Yi‐Hsun
Published: January 2022

Background

Data on the functional outcomes of patients with open pelvic fractures after osteosynthesis are limited, and whether open fracture is a risk factor for worse outcomes, as compared with closed fracture, remains unclear. This study aimed to compare the functional outcomes of patients with open and closed pelvic fractures and evaluate potential factors that might affect outcomes.

Methods

Overall, 19 consecutive patients with open pelvic fractures and 78 patients with closed pelvic fractures between January 2014 and June 2018 were retrospectively reviewed. All fractures were surgically treated, with a minimal follow‐up period of three years. Patients’ demographic profile, associated injuries, management protocol, quality of reduction, and outcomes were recorded and analyzed.

Results

Patients with open pelvic fractures had higher new injury severity score, higher incidence of diverting colostomy, and longer length of stay. Both radiological and functional evaluations revealed no significant differences between the two groups at 1‐year and 3‐year evaluations. Multiple logistic regression analysis identified poor radiological outcomes (using Lefaivre criteria) and longer length of stay as risk factors for worse short‐term functional outcomes. At 3‐year evaluation, fair‐to‐poor radiological outcomes (using Matta/Tornetta and Lefaivre criteria) and the presence of diverting colostomy were potential risk factors.

Conclusions

Compared with closed pelvic fracture, open pelvic fracture was not an indicator of worse functional outcomes. Functional outcomes may be comparable between patients with open and closed pelvic fractures at different time points within three years postoperatively. Achieving anatomical reduction in a fracture is crucial, because it might affect patient satisfaction.
Relationship between platelet aggregation and stroke risk after percutaneous coronary intervention: a PENDULUM analysis
Authors: Matsumaru Yuji , Kitazono Takanari , Kadota Kazushige , Nakao Koichi , Nakagawa Yoshihisa , Shite Junya , Yokoi Hiroyoshi , Kozuma Ken , Tanabe Kengo , Akasaka Takashi , Shinke Toshiro , Ueno Takafumi , Hirayama Atsushi , Uemura Shiro , Kuroda Takeshi , Takita Atsushi , Harada Atsushi , Iijima Raisuke , Murakami Yoshitaka , Saito Shigeru , Nakamura Masato
Published: January 2022

In patients undergoing percutaneous coronary intervention (PCI) with a stent, high on-treatment platelet reactivity may be associated with an increased risk of stroke. This post hoc analysis of the PENDULUM registry compared the risk of post-PCI stroke according to on-treatment P2Y12 reaction unit (PRU) values. Patients aged ≥ 20 years who underwent PCI were stratified by baseline PRU (at 12 and 48 h post-PCI) as either high (HPR, > 208), optimal (OPR, > 85 to ≤ 208), or low on-treatment platelet reactivity (LPR, ≤ 85). The incidences of non-fatal ischemic and non-ischemic stroke through to 12 months post-PCI were recorded. Almost all enrolled patients (6102/6267 [97.4%]) had a risk factor for ischemic stroke, and most were receiving dual antiplatelet therapy. Of the 5906 patients with PRU data (HPR, n = 2227; OPR, n = 3002; LPR, n = 677), 47 had a non-fatal stroke post-PCI (cumulative incidence: 0.68%, ischemic; 0.18%, non-ischemic stroke). Patients with a non-fatal ischemic stroke event had statistically significantly higher post-PCI PRU values versus those without an event (P = 0.037). The incidence of non-fatal non-ischemic stroke was not related to PRU value. When the patients were stratified by PRU ≤ 153 versus > 153 at 12–48 h post-PCI, a significant difference was observed in the cumulative incidence of non-fatal stroke at 12 months (P = 0.044). We found that patients with ischemic stroke tended to have higher PRU values at 12–48 h after PCI versus those without ischemic stroke.

Clinical trial registration: UMIN000020332.
Contribution of voluntary fortified foods to micronutrient intake in The Netherlands
Authors: de Jong Marjolein H. , Nawijn Eline L. , Verkaik-Kloosterman Janneke
Published: January 2022

Purpose

In the Netherlands, voluntary fortification of foods with micronutrients is allowed under strict regulations. This study investigates the impact of voluntary food fortification practices in the Netherlands on the frequency and type of fortified food consumption and on the micronutrient intakes of the Dutch population.

Methods

Data of the Dutch National Food Consumption Survey (2012–2016; N = 4314; 1–79 year) and the Dutch Food Composition Database (NEVO version 2016) was used. To determine if voluntary fortified foods could be classified as healthy foods, criteria of the Dutch Wheel of Five were used. Habitual intakes of users and non-users of voluntary food fortification were calculated using Statistical Program to Assess Dietary Exposure (SPADE) and compared.

Results

Within the Dutch population, 75% could be classified as user of voluntary fortified foods. Consumed voluntary fortified foods were mostly within food groups ‘Fats and Oils’, ‘Non-alcoholic Beverages’ and ‘Dairy products and Substitutes’ and fell mostly outside the Wheel of Five. Voluntary foods contributed between 9 and 78% to total micronutrient intake of users. Users had up to 64% higher habitual micronutrient intakes, compared to non-users. These higher intakes resulted into lower risks on inadequate intakes, and did not contribute to increased risks of excessive intakes.

Conclusion

Although voluntary fortified foods increased micronutrient intakes, most of these foods cannot be classified as healthy foods. Future studies should study the association between higher micronutrient intakes and (potential) excessive intakes of e.g. saturated fat and sugar to better understand the role of voluntary fortified foods in a healthy food pattern.
Standardized fracture creation in the distal humerus and the olecranon for surgical training and biomechanical testing
Authors: Schmoelz Werner , Zierleyn Jan Philipp , Hoermann Romed , Arora Rohit
Published: January 2022

Introduction

Surgical training and biomechanical testing require models that realistically represent the in vivo injury condition. The aim of this work was to develop and test a method for the generation of distal humerus fractures and olecranon fractures in human specimens, while preserving the soft tissue envelope.

Methods

Twenty-one cadaveric upper extremity specimens (7 female, 14 male) were used. Two different experimental setups were developed, one to generate distal humerus fractures and one to generate olecranon fractures. Specimens were placed in a material testing machine and fractured with a predefined displacement. The force required for fracturing and the corresponding displacement were recorded and the induced energy was derived of the force–displacement graphs. After fracturing, CT imaging was performed and fractures were classified according to the AO classification.

Results

Eleven distal humerus fractures and 10 olecranon fractures with intact soft tissue envelope could be created. Distal humerus fractures were classified as AO type C (n = 9) and as type B (n = 2), all olecranon fractures were classified as AO type B (n = 10). Distal humerus fractures required significantly more load than olecranon fractures (6077 N ± 1583 vs 4136 N ± 2368, p = 0.038) and absorbed more energy until fracture than olecranon fractures (17.8 J ± 9.1 vs 11.7 J ± 7.6, p = 0.11), while the displacement at fracture was similar (5.8 mm ± 1.6 vs 5.9 mm ± 3.1, p = 0.89).

Conclusion

The experimental setups are suitable for generating olecranon fractures and distal humerus fractures with intact soft tissue mantle for surgical training and biomechanical testing.
A perspective on persistent toxicants in veterans and amyotrophic lateral sclerosis: identifying exposures determining higher ALS risk
Authors: Re Diane B. , Yan Beizhan , Calderón-Garcidueñas Lilian , Andrew Angeline S. , Tischbein Maeve , Stommel Elijah W.
Published: January 2022

Multiple studies indicate that United States veterans have an increased risk of developing amyotrophic lateral sclerosis (ALS) compared to civilians. However, the responsible etiological factors are unknown. In the general population, specific occupational (e.g. truck drivers, airline pilots) and environmental exposures (e.g. metals, pesticides) are associated with an increased ALS risk. As such, the increased prevalence of ALS in veterans strongly suggests that there are exposures experienced by military personnel that are disproportionate to civilians. During service, veterans may encounter numerous neurotoxic exposures (e.g. burn pits, engine exhaust, firing ranges). So far, however, there is a paucity of studies investigating environmental factors contributing to ALS in veterans and even fewer assessing their exposure using biomarkers. Herein, we discuss ALS pathogenesis in relation to a series of persistent neurotoxicants (often emitted as mixtures) including: chemical elements, nanoparticles and lipophilic toxicants such as dioxins, polycyclic aromatic hydrocarbons and polychlorinated biphenyls. We propose these toxicants should be directly measured in veteran central nervous system tissue, where they may have accumulated for decades. Specific toxicants (or mixtures thereof) may accelerate ALS development following a multistep hypothesis or act synergistically with other service-linked exposures (e.g. head trauma/concussions). Such possibilities could explain the lower age of onset observed in veterans compared to civilians. Identifying high-risk exposures within vulnerable populations is key to understanding ALS etiopathogenesis and is urgently needed to act upon modifiable risk factors for military personnel who deserve enhanced protection during their years of service, not only for their short-term, but also long-term health.
Carboplatin and nab-paclitaxel chemotherapy with or without atezolizumab as front-line management for treatment-naïve metastatic nonsquamous non-small cell lung cancer with PD-L1 staining: a retrospective study
Authors: Xu Bo , Cheng Huihui , Li Kunhong , Lv Yukai , Zeng Xianshang , Liu Tao , Yu Weiguang , Guo Wenbo
Published: January 2022

Purpose

The aim of this retrospective review was to compare the efficacy and safety of the atezolizumab plus carboplatin and nab-paclitaxel regimen versus the carboplatin and nab-paclitaxel regimen as front-line management for treatment-naïve, metastatic nonsquamous programmed death-ligand 1 (PD-L1)-positive non-small cell lung cancer (NSCLC) in a selected population.

Methods

Consecutive patients with untreated, metastatic nonsquamous PD-L1-positive NSCLC who initially received the atezolizumab plus carboplatin and nab-paclitaxel (ACN) regimen or carboplatin and nab-paclitaxel (CN) regimen were retrospectively identified in two medical institutions from 2017 to 2020. The co-primary end points were overall survival (OS) and progression-free survival (PFS); secondary end point was the rate of key adverse events (AEs).

Results

In sum, 171 patients were retrospectively analysed, 47 of whom were excluded according to the criteria used in this study, leaving 124 patients (ACN: n = 60, median age 64 years [range 46–75]; CN: n = 64, 63 years [47–72]). The median duration of follow-up was 27 months [range 1–37]. At the final follow-up, the median OS was 19.9 months (95% confidence interval [CI], 16.3–22.5) in the ACN group vs. 14.8 months (95% CI 12.5–17.2) in the CN group (hazard ratio [HR] 0.51, 95% CI 0.33–0.77; p = 0.001). A marked distinction in the median PFS was seen (8.5 months [95% CI 6.7–9.4] in the ACN group vs. in the CN group [5.1 months [95% CI 3.6–6.8; HR 0.60; 95% CI 0.38–0.95; p = 0.005]). The rates of the key AEs (neutropenia and anaemia) were greater in the ACN group than in the CN group (all p < 0.05), but these AEs were manageable.

Conclusion

Among selected populations of individuals with treatment-naïve, metastatic nonsquamous PD-L1-positive NSCLC, atezolizumab combined with carboplatin and nab-paclitaxel chemotherapy might have encouraging anticancer activity, with a tolerable safety profile.
Segmental resection of splenic flexure colon cancers provides an adequate lymph node harvest and is a safe operative approach – an analysis of the ACS-NSQIP database
Authors: Pang Allison J. , Marinescu Daniel , Morin Nancy , Vasilevsky Carol-Ann , Boutros Marylise
Published: January 2022

Introduction

Fewer than 10% of colon cancers are found at the splenic flexure. A standard surgical approach to these cancers has not been defined. The goal of this study was to compare lymph node harvest and post-operative morbidity between segmental resection and formal left hemicolectomy for splenic flexure colon cancers.

Method

Patients diagnosed with a splenic flexure cancer were identified from the 2012–2018 ACS-NSQIP colectomy-targeted database. Patients were categorized based on type of surgical resection – left hemicolectomy with colorectal anastomosis or segmental colectomy with colocolonic anastomosis. Demographic, clinicopathologic, and post-operative outcomes were compared between groups. Factors independently associated with lymph node harvest, operative time, and post-operative morbidity were investigated by linear and binomial logistic regression models.

Results

A total of 3,049 patients underwent colectomy for a splenic flexure cancer. Of these, 83.6% had a segmental colectomy and 73% were performed by a minimally invasive approach. T- and N-stage did not differ between segmental and left hemicolectomy groups (p = 0.703 and p = 0.429, respectively). Inadequate nodal harvest (< 12 nodes) was infrequent and similar between the two procedures (7.4% vs. 9.1%, p = 0.13). Operative time was significantly shorter for segmental colectomy (213 ± 83.5 min vs. 193 ± 84.1 min, p < 0.0001) and major morbidity was similar between the two surgical techniques (8.4% vs. 8.9%, p = 0.75). After accounting for demographic, clinicopathologic, and operative factors, binomial logistic regression showed that type of procedure was not significantly associated with LN harvest (OR 0.80, 95%CI 0.54–1.17) or major morbidity (OR 1.17, 95%CI 0.36–3.81). However, on linear regression, segmental splenic flexure resection was associated with shorter operative time (estimate 20.29, 95%CI 12.61–27.97, p < 0.0001).

Conclusion

Splenic flexure resection for colon cancer is associated with an adequate lymph node harvest. Compared to a formal left hemicolectomy, a segmental resection also has a shorter operative time with equivalent post-operative morbidity.
Sexual dysfunction associated with prostate cancer treatment in Japanese men: a qualitative research
Authors: Hayashi Saeko , Oishi Fumiko , Sato Kazuki , Fukuda Hiromi , Ando Shoko
Published: January 2022

Purpose

We investigated the experiences of Japanese men with sexual dysfunction associated with various prostate cancer treatments.

Methods

We included 38 Japanese men who underwent the following initial treatments for prostate cancer: radical prostatectomy (n = 10), external beam radiotherapy (n = 12), brachytherapy (n = 5), and androgen deprivation therapy (n = 11). Semi-structured interviews were conducted regarding sexual dysfunction associated with prostate cancer treatment. Data were analyzed using a content analysis method. To obtain a unique experience for each treatment, we confirmed and organized the treatment method from which the code that constituted each category was derived. The category reliability was calculated based on Scott’s formula for the matching rate of the classification by three qualitative researchers. The criterion for good reliability was set at 70%.

Results

Japanese men with sexual dysfunction associated with prostate cancer treatments experienced the following: a desire to maintain sexual function and conflict in decision-making concerning the initial treatment for prostate cancer; a loss of values related to sexual dysfunction; an uncertainty regarding the consequences of sexual dysfunction; a sense of calm with fewer adverse effects of sexual dysfunction at the early treatment stage; an effort to accept sexual dysfunction; and management of their changed body at the later treatment stages. The concordance rates for the categories were 70% and 78%. Additionally, there were glimpses of experiences common to all treatments and trends in treatment-specific experiences.

Conclusion

It is necessary to provide care based on the experience of Japanese men with sexual dysfunction after prostate cancer treatment.
Classification of lower limb motor imagery based on iterative EEG source localization and feature fusion
Authors: Peng Xiaobo , Liu Junhong , Huang Ying , Mao Yanhao , Li Dong
Published: January 2022

Motor imagery (MI) brain–computer interface (BCI) systems have broad application prospects in rehabilitation and other fields. However, to achieve accurate and practical MI-BCI applications, there are still several critical issues, such as channel selection, electroencephalogram (EEG) feature extraction and EEG classification, needed to be better resolved. In this paper, these issues are studied for lower limb MI which is more difficult and less studied than upper limb MI. First, a novel iterative EEG source localization method is proposed for channel selection. Channels FC1, FC2, C1, C2 and Cz, instead of the commonly used traditional channel set (TCS) C3, C4 and Cz, are selected as the optimal channel set (OCS). Then, a multi-domain feature (MDF) extraction algorithm is presented to fuse single-domain features into multi-domain features. Finally, a particle swarm optimization based support vector machine (SVM) method is utilized to classify the EEG data collected by the lower limb MI experiment designed by us. The results show that the classification accuracy is 88.43%, 3.35–5.41% higher than those of using traditional SVM to classify single-domain features on the TCS, which proves that the combination of OCS and MDF can not only reduce the amount of data processing, but also retain more feature information to improve the accuracy of EEG classification.
Early pregnancy hyperglycaemia as a significant predictor of large for gestational age neonates
Authors: Jayasinghe Imasha Upulini , Koralegedara Iresha Sandamali , Agampodi Suneth Buddhika
Published: January 2022

Aims

We aimed to determine the effect of early pregnancy hyperglycaemia on having a large for gestational age (LGA) neonate.

Methods

A prospective cohort study was conducted among pregnant women in their first trimester. One-step plasma glucose (PG) evaluation procedure was performed to assess gestational diabetes mellitus (GDM) and diabetes mellitus (DM) in pregnancy as defined by the World Health Organization (WHO) criteria with International Association of Diabetes in Pregnancy Study Group (IADPSG) thresholds. The main outcome studied was large for gestational age neonates (LGA).

Results

A total of 2,709 participants were recruited with a mean age of 28 years (SD = 5.4) and a median gestational age (GA) of eight weeks (interquartile range [IQR] = 2). The prevalence of GDM in first trimester (T1) was 15.0% (95% confidence interval [CI] = 13.7–16.4). Previously undiagnosed DM was detected among 2.5% of the participants. Out of 2,285 live births with a median delivery GA of 38 weeks (IQR = 3), 7.0% were LGA neonates. The cumulative incidence of LGA neonates in women with GDM and DM was 11.1 and 15.5 per 100 women, respectively. The relative risk of having an LGA neonate among women with DM and GDM was 2.30 (95% CI = 1.23–4.28) and 1.80 (95% CI = 1.27–2.53), respectively. The attributable risk percentage of a LGA neonate for hyperglycaemia was 15.01%. T1 fasting PG was significantly correlated with both neonatal birth weight and birth weight centile.

Conclusions

The proposed WHO criteria for hyperglycaemia in pregnancy are valid, even in T1, for predicting LGA neonates. The use of IADPSG threshold for Fasting PG, for risk assessment in early pregnancy in high-risk populations is recommended.
Hospital admission risk stratification of patients with gout presenting to the emergency department
Authors: Han Wang , Allameen Nur Azizah , Ibrahim Irwani , Dhanasekaran Preeti , Mengling Feng , Lahiri Manjari
Published: January 2022

To characterise gout patients at high risk of hospitalisation and to develop a web-based prognostic model to predict the likelihood of gout-related hospital admissions.
This was a retrospective single-centre study of 1417 patients presenting to the emergency department (ED) with a gout flare between 2015 and 2017 with a 1-year look-back period. The dataset was randomly divided, with 80% forming the derivation and the remaining forming the validation cohort. A multivariable logistic regression model was used to determine the likelihood of hospitalisation from a gout flare in the derivation cohort. The coefficients for the variables with statistically significant adjusted odds ratios were used for the development of a web-based hospitalisation risk estimator. The performance of this risk estimator model was assessed via the area under the receiver operating characteristic curve (AUROC), calibration plot, and brier score. Patients who were hospitalised with gout tended to be older, less likely male, more likely to have had a previous hospital stay with an inpatient primary diagnosis of gout, or a previous ED visit for gout, less likely to have been prescribed standby acute gout therapy, and had a significant burden of comorbidities. In the multivariable-adjusted analyses, previous hospitalisation for gout was associated with the highest odds of gout-related admission. Early identification of patients with a high likelihood of gout-related hospitalisation using our web-based validated risk estimator model may assist to target resources to the highest risk individuals, reducing the frequency of gout-related admissions and improving the overall health-related quality of life in the long term.

Key points

• We reported the characteristics of gout patients visiting a tertiary hospital in Singapore.

• We developed a web-based prognostic model with non-invasive variables to predict the likelihood of gout-relatedhospital admissions.
Effect of dose adjustments on the efficacy and safety of tofacitinib in patients with rheumatoid arthritis: a post hoc analysis of an open-label, long-term extension study (ORAL Sequel)
Authors: Mueller Ruediger B. , Schulze-Koops Hendrik , Furst Daniel E. , Cohen Stanley B.  , Kwok Kenneth , Wang Lisy , Killeen Tim , von Kempis Johannes
Published: January 2022

Introduction/objectives

We assess the impact of switching versus staying on the same tofacitinib dose on efficacy and safety in patients with rheumatoid arthritis (RA).

Methods

ORAL Sequel was an open-label, long-term extension study of patients with RA receiving tofacitinib 5 or 10 mg BID for up to 9.5 years. Tofacitinib doses could be switched during the study at investigator discretion. In this post hoc analysis, data from ORAL Sequel were stratified into four groups: 5 → 10 mg BID (Dose-up); 5 mg BID (Stay-on 5); 10 → 5 mg BID (Dose-down); and 10 mg BID (Stay-on 10). Efficacy assessments over 12 months included: change from baseline in 4-component Disease Activity Score in 28 joints, erythrocyte sedimentation rate (DAS28), and DAS28 minimum clinically important difference, remission, and low disease activity (LDA) rates. Safety was assessed for the study duration.

Results

Generally, DAS28 improvements and minimum clinically important difference rates were significantly greater (p < 0.05) in Dose-up versus Stay-on 5 up to month 12. DAS28 remission rates were significantly greater in Dose-up versus Stay-on 5 at month 12. Change from baseline in DAS28 was similar in Dose-down and Stay-on 10. No significant differences in DAS28 LDA rates were observed between groups. Safety data were similar overall across the four groups.

Conclusion

In patients with RA receiving open-label tofacitinib, this analysis found that some benefited from increasing dose from 5 to 10 mg BID and did not find that reducing dose from 10 to 5 mg BID affected efficacy or that dose switching in either direction affected safety.

Study registration

ClinicalTrials.gov number NCT00413699. Registered December 20, 2006. https://clinicaltrials.gov/ct2/show/NCT00413699

Key Points• This post hoc analysis of data from the long-term extension study, ORAL Sequel, assessed the impact of dose switching between tofacitinib 5 and 10 mg twice daily (BID), at the investigator’s discretion, on efficacy and safety in patients with rheumatoid arthritis (RA).• Dosing up from tofacitinib 5 to 10 mg BID was associated with improved efficacy up to 12 months versus staying on 5 mg BID, and dosing down from 10 to 5 mg BID was not generally associated with a significant loss of efficacy.• Safety outcomes were generally consistent across dose groups and did not change markedly after switching dose in either direction.• These findings can help to inform physicians on what may be expected in terms of efficacy and safety when adjusting tofacitinib dose according to clinical need. The recommended tofacitinib dosage for the treatment of RA in most jurisdictions is 5 mg BID.
Avelumab first-line maintenance plus best supportive care (BSC) vs BSC alone for advanced urothelial carcinoma: JAVELIN Bladder 100 Japanese subgroup analysis
Authors: Tomita Yoshihiko , Yamamoto Yoshiaki , Tsuchiya Norihiko , Kanayama Hiroomi , Eto Masatoshi , Miyake Hideaki , Powles Thomas , Yoshida Mizuki , Koide Yuichiro , Umeyama Yoshiko , di Pietro Alessandra , Uemura Hirotsugu
Published: January 2022

Background

The phase 3 JAVELIN Bladder 100 trial showed significantly prolonged overall survival (OS) with avelumab as first-line (1L) maintenance therapy + best supportive care (BSC) vs BSC alone in patients with advanced urothelial carcinoma (UC) that had not progressed with 1L platinum-containing chemotherapy. Efficacy and safety were assessed in patients enrolled in Japan.

Methods

Patients with locally advanced or metastatic UC that had not progressed with 4–6 cycles of 1L platinum-containing chemotherapy were randomized to avelumab (10 mg/kg intravenously every 2 weeks) + BSC or BSC alone. The primary endpoint was OS, and secondary endpoints included progression-free survival (PFS) and safety.

Results

In Japanese patients (n = 73) randomized to avelumab + BSC (n = 36) or BSC alone (n = 37), median OS was 24.7 months (95% CI, 18.2-not estimable) vs 18.7 months (95% CI, 12.8–33.0), respectively (HR, 0.81 [95% CI, 0.41–1.58]), and median PFS was 5.6 months (95% CI, 1.9–9.4) vs 1.9 months (95% CI, 1.9–3.8), respectively (HR, 0.63 [95% CI, 0.36–1.11]). In the avelumab + BSC and BSC-alone arms, grade ≥ 3 treatment-emergent adverse events (AEs) occurred in 50.0% vs 8.1%, including grade ≥ 3 treatment-related AEs in 13.9% vs 0%, respectively. Efficacy and safety results in Japanese patients were generally consistent with findings in the overall trial population.

Conclusion

Avelumab 1L maintenance treatment showed a favorable benefit-risk balance in Japanese patients, supporting avelumab 1L maintenance as a new standard of care in Japanese patients with advanced UC that has not progressed with 1L platinum-containing chemotherapy.

Trial registration

Clinicaltrials.gov NCT02603432.
Validation of the estimated glomerular filtration rate equation for Japanese children younger than 2 years
Authors: Gotoh Yoshimitsu , Uemura Osamu , Fujita Naoya , Hamasaki Yuko , Honda Masataka , Ishikura Kenji ,   On behalf of the Pediatric CKD Study Group in Japan in conjunction with the Committee of Measures for Pediatric CKD of the Japanese Society of Pediatric Nephrology, Gotoh Yoshimitsu , Uemura Osamu , Fujita Naoya , Hamasaki Yuko , Honda Masataka , Ishikura Kenji
Published: January 2022

Background

We have developed a simple and easy method of estimating the glomerular filtration rate (eGFR) of serum creatinine in Japanese children (eGFRUemura). The eGFR equation is for children aged 2–18 years. Therefore Uemura et al. developed an equation for children younger than 2 years (eGFRunder 2). The aim of the present study was to validate this new equation.

Methods

We collected the data of 13 patients from previous studies and compared the results of eGFRunder 2, eGFRUemura, and updated eGFR developed by Schwartz (eGFRSchwartz) with measured GFR using mean error (ME), root mean square error (RMSE), P30 and Bland–Altman analysis.

Results

The ME of eGFRunder 2, eGFRUemura and eGFRSchwartz were 2.3 ± 15.9, 7.7 ± 14.5, and 16.0 ± 18.2 ml/min/1.73m2, respectively. The RMSEs were 15.5, 15.9, and 49.6, respectively. The P30 values were 76.9%, 76.9%, and 53.8%, respectively. The graph of Bland–Altman bias analysis showed fan-shape. The eGFRunder 2 equation was the most accurate in the three equations.

Conclusion

The eGFRunder 2 equation was useful for Japanese children younger than 2 years.
Aboveground biomass increments over 26 years (1993–2019) in an old-growth cool-temperate forest in northern Japan
Authors: Noguchi Mahoko , Hoshizaki Kazuhiko , Matsushita Michinari , Sugiura Daiki , Yagihashi Tsutomu , Saitoh Tomoyuki , Itabashi Tomohiro , Kazuhide Ohta , Shibata Mitsue , Hoshino Daisuke , Masaki Takashi , Osumi Katsuhiro , Takahashi Kazunori , Suzuki Wajirou
Published: January 2022

Assessing long-term changes in the biomass of old-growth forests with consideration of climate effects is essential for understanding forest ecosystem functions under a changing climate. Long-term biomass changes are the result of accumulated short-term changes, which can be affected by endogenous processes such as gap filling in small-scale canopy openings. Here, we used 26 years (1993–2019) of repeated tree census data in an old-growth, cool-temperate, mixed deciduous forest that contains three topographic units (riparian, denuded slope, and terrace) in northern Japan to document decadal changes in aboveground biomass (AGB) and their processes in relation to endogenous processes and climatic factors. AGB increased steadily over the 26 years in all topographic units, but different tree species contributed to the increase among the topographic units. AGB gain within each topographic unit exceeded AGB loss via tree mortality in most of the measurement periods despite substantial temporal variation in AGB loss. At the local scale, variations in AGB gain were partially explained by compensating growth of trees around canopy gaps. Climate affected the local-scale AGB gain: the gain was larger in the measurement periods with higher mean air temperature during the current summer but smaller in those with higher mean air temperature during the previous autumn, synchronously in all topographic units. The influences of decadal summer and autumn warming on AGB growth appeared to be counteracting, suggesting that the observed steady AGB increase in KRRF is not fully explained by the warming. Future studies should consider global and regional environmental factors such as elevated CO2 concentrations and nitrogen deposition, and include cool-temperate forests with a broader temperature range to improve our understanding on biomass accumulation in this type of forests under climate change.
Transgenic plants expressing immunosuppressive dsRNA improve entomopathogen efficacy against Spodoptera littoralis larvae
Authors: Di Lelio Ilaria , Barra Eleonora , Coppola Mariangela , Corrado Giandomenico , Rao Rosa , Caccia Silvia
Published: January 2022

Transgenic plants that express double-stranded RNA (dsRNA) targeting vital insect genes have recently emerged as a valuable new tool for pest control. In this study, tobacco plants were transformed to produce dsRNA targeting Sl 102 gene that is involved in the immune response of Spodoptera littoralis larvae, a serious lepidopteran pest of several crops. Experimental larvae reared on transgenic tobacco lines showed (1) a strongly reduced level of Sl 102 transcripts, which was positively associated with food consumption; (2) a substantial impairment of the encapsulation response mediated by hemocytes; and (3) a marked increase in the susceptibility to Xentari™, a Bacillus thuringiensis-based insecticide. Importantly, this approach may allow a reduction in the doses of B. thuringiensis used for field applications and enhance its killing activity on mature larvae. The results obtained thus support the use of immunosuppressive RNAi plants to enhance the performance of microbial insecticides on lepidopteran larvae.
Silvopastoral and conventional management of extensive livestock and the diversity of bats in fragments of tropical dry forest in Córdoba, Colombia
Authors: Ballesteros-Correa Jesús , Pérez-Torres Jairo
Published: January 2022

The establishment of extensive livestock systems in the Colombian Caribbean Region has historically generated a strong loss of the tropical dry forest (TDF) with negative effects on biodiversity. Currently, the implementation of silvopastoral systems (SPS) has been proposed with strategy to curb the loss of biodiversity caused by the conventional management system (CS). The objective was to evaluate the effect of SPS and CS of extensive livestock on the assemblage of bats associated with fragments of TDF. During a continuous year and a sampling effort of 30,240 h-net/night, the structure and composition of bat assemblage between SPS and CS were compared. 2788 bats belonging to six families, 23 genera, and 39 species were captured. ThePhyllostomidaefamily presented the highest species richness (S = 30), with the greatest abundance in theStenodermatinaesubfamily (n = 1543). Bat assemblage in the SPS fragments was more equitable; and the relative abundance per species, per genera, and per foraging guilds was also significantly higher. The capture success showed significant variations between the climatic seasons (dry and rainy). The rate of species turnover was higher in the CS fragments. The speciesArtibeus planirostris, Artibeus lituratus, Carollia perspicillata, Carollia castanea, Phyllostomus discolor, Dermanura phaeotis, Uroderma convexum, Glossophaga soricina, C. brevicauda,andSturnira liliumaccounted for 92% of the captures. In conclusion, frugivorous bats were more abundant in the SPS, type of extensive livestock management that can generate greater temporal stability of bat assemblage. This research provides the first scientific evidence of the positive effect of silvopastoral management on the diversity of bats in tropical dry forest areas of the Colombian Caribbean region.
Multiple graph fusion based on Riemannian geometry for motor imagery classification
Authors: Xie Xiaofeng , Zou Xiaokun , Yu Tianyou , Tang Rongnian , Hou Yao , Qi Feifei
Published: January 2022

In motor imagery-based brain-computer interfaces (BCIs), the spatial covariance features of electroencephalography (EEG) signals that lie on Riemannian manifolds are used to enhance the classification performance of motor imagery BCIs. However, the problem of subject-specific bandpass frequency selection frequently arises in Riemannian manifold-based methods. In this study, we propose a multiple Riemannian graph fusion (MRGF) model to optimize the subject-specific frequency band for a Riemannian manifold. After constructing multiple Riemannian graphs corresponding to multiple bandpass frequency bands, graph embedding based on bilinear mapping and graph fusion based on mutual information were applied to simultaneously extract the spatial and spectral features of the EEG signals from Riemannian graphs. Furthermore, with a support vector machine (SVM) classifier performed on learned features, we obtained an efficient algorithm, which achieves higher classification performance on various datasets, such as BCI competition IIa and in-house BCI datasets. The proposed methods can also be used in other classification problems with sample data in the form of covariance matrices.
Interaction Between Waves and Turbulence Within the Nocturnal Boundary Layer
Authors: Barbano Francesco , Brogno Luigi , Tampieri Francesco , Di Sabatino Silvana
Published: January 2022

The presence of waves is proven to be ubiquitous within nocturnal stable boundary layers over complex terrain, where turbulence is in a continuous, although weak, state of activity. The typical approach based on Reynolds decomposition is unable to disaggregate waves from turbulence contributions, thus hiding any information about the production/destruction of turbulence energy injected/subtracted by the wave motion. We adopt a triple-decomposition approach to disaggregate the mean, wave, and turbulence contributions within near-surface boundary-layer flows, with the aim of unveiling the role of wave motion as a source and/or sink of turbulence kinetic and potential energies in the respective explicit budgets. By exploring the balance between buoyancy (driving waves) and shear (driving turbulence), a simple interpretation paradigm is introduced to distinguish two layers, namely the near-ground and far-ground sublayer, estimating where the turbulence kinetic energy can significantly feed or be fed by the wave. To prove this paradigm, a nocturnal valley flow is used as a case study to detail the role of wave motions on the kinetic and potential energy budgets within the two sublayers. From this dataset, the explicit kinetic and potential energy budgets are calculated, relying on a variance–covariance analysis to further comprehend the balance of energy production/destruction in each sublayer. With this investigation, we propose a simple interpretation scheme to capture and interpret the extent of the complex interaction between waves and turbulence in nocturnal stable boundary layers.
The Selective NLRP3-inflammasome inhibitor MCC950 Mitigates Post-resuscitation Myocardial Dysfunction and Improves Survival in a Rat Model of Cardiac Arrest and Resuscitation
Authors: Zheng Guanghui , He Fenglian , Xu Jing , Hu Juntao , Ge Weiwei , Ji Xianfei , Wang Changsheng , Bradley Jennifer L. , Peberdy Mary Ann , Ornato Joseph P. , Jiang Longyuan , Toldo Stefano , Wang Tong , Tang Wanchun
Published: January 2022

Purpose

To investigate the effects of the selective NLRP3 inflammasome inhibitor MCC950 on post-resuscitation myocardial function and survival in a rat model of cardiopulmonary resuscitation (CPR).

Methods

Thirty-six Sprague Dawley rats were randomized into three groups: (1) MCC950, (2) control, and (3) sham. Each group consisted of a 6 h non-survival subgroup (n = 6) and a 48 h survival subgroup (n = 6). Ventricular fibrillation (VF) was induced and untreated for 6 min. CPR was initiated and continued for 8 min. Resuscitation was attempted with a 4 J defibrillation. MCC950 (10 mg/kg) or vehicle was administered via intraperitoneal injection immediately after the return of spontaneous circulation (ROSC). Myocardial function and sublingual microcirculation were measured after ROSC in the non-survival subgroups. Plasma levels of interleukin Iβ (IL-1β) and cardiac troponin I (cTnI) were measured at baseline and 6 h in the non-survival subgroups. Heart tissue was harvested to measure the NLRP3 inflammasome constituents, including NLRP3, apoptosis-associated speck-like protein (ASC), Caspase-1, and IL-1β. Survival duration and neurologic deficit score (NDS) were recorded and evaluated among survival groups.

Results

Post-resuscitation myocardial function and sublingual microcirculation were improved in MCC950 compared with control (p < 0.05). IL-1β and cTnI were decreased in MCC950 compared to control (p < 0.01). The MCC950 treated groups showed significantly reduced ASC, caspase-1, and IL-1β compared with the control group (p < 0.05). Survival at 48 h after ROSC was greater in MCC950 (p < 0.05) with improved NDS (p < 0.05).

Conclusion

Administration of MCC950 following ROSC mitigates post-resuscitation myocardial dysfunction and improves survival.
Genome-wide DNA methylome and transcriptome changes induced by inorganic nanoparticles in human kidney cells after chronic exposure
Authors: Soltysova Andrea , Begerova Patricia , Jakic Kristina , Kozics Katarina , Sramkova Monika , Meese Eckart , Smolkova Bozena , Gabelova Alena
Published: January 2022

The unique physicochemical properties make inorganic nanoparticles (INPs) an exciting tool in diagnosis and disease management. However, as INPs are relatively difficult to fully degrade and excrete, their unintended accumulation in the tissue might result in adverse health effects. Herein, we provide a methylome–transcriptome framework for chronic effects of INPs, commonly used in biomedical applications, in human kidney TH-1 cells. Renal clearance is one of the most important routes of nanoparticle excretion; therefore, a detailed evaluation of nanoparticle-mediated nephrotoxicity is an important task. Integrated analysis of methylome and transcriptome changes induced by INPs (PEG-AuNPs, Fe3O4NPs, SiO2NPs, and TiO2NPs) revealed significantly deregulated genes with functional classification in immune response, DNA damage, and cancer-related pathways. Although most deregulated genes were unique to individual INPs, a relatively high proportion of them encoded the transcription factors. Interestingly, FOS hypermethylation inversely correlating with gene expression was associated with all INPs exposures. Our study emphasizes the need for a more comprehensive investigation of INPs’ biological safety, especially after chronic exposure.

Graphical abstract
ERK inhibitor ASN007 effectively overcomes acquired resistance to EGFR inhibitor in non‐small cell lung cancer
Authors: Ku Bo Mi , Heo Jae Yeong , Kim Jinchul , sun Jong-Mu , Lee Se-Hoon , Ahn Jin Seok , Park Keunchil , Ahn Myung-Ju
Published: January 2022

The emergence of acquired resistance limits the long-term efficacy of EGFR tyrosine kinase inhibitors (EGFR TKIs). Thus, development of effective strategies to overcome resistance to EGFR TKI is urgently needed. Multiple mechanisms to reactivate ERK signaling have been successfully demonstrated in acquired resistance models. We found that in EGFR mutant non-small cell lung cancer (NSCLC) patients, acquired resistance to EGFR TKIs was accompanied by increased activation of ERK. Increased ERK activation was also found in in vitro models of acquired EGFR TKI resistance. ASN007 is a potent selective ERK1/2 inhibitor with promising antitumor activity in cancers with BRAF and RAS mutations. ASN007 treatment impeded tumor cell growth and the cell cycle in EGFR TKI-resistant cells. In addition, combination treatment with ASN007 and EGFR TKIs significantly decreased the survival of resistant cells, enhanced induction of apoptosis, and effectively inhibited the growth of erlotinib-resistant xenografts, providing the preclinical rationale for testing combinations of ASN007 and EGFR TKIs in EGFR-mutated NSCLC patients. This study emphasizes the importance of targeting ERK signaling in maintaining the long-term benefits of EGFR TKIs by overcoming acquired resistance.
Enhancement of growth, antioxidative status, nonspecific immunity, and disease resistance in gibel carp (Carassius auratus) in response to dietary Flos populi extract
Authors: Zhang Xuhui , Sun Zhiyuan , Wang Yuheng , Cao Yindi , Wang Guibin , Cao Fuliang
Published: January 2022

This study investigated the effects of dietary Flos populi extract (FPE) on the growth, antioxidation capability, innate immune response, and disease resistance in gibel carp. A total of 480 fish were fed with five different diets containing 0, 0.5, 1.0, 1.5, or 2.0 g kg−1 FPE (designated as control, D0.5, D1.0, D1.5, or D2.0 groups) for 45 days. The fish were challenged with A. hydrophila after the feeding trial. Compared with the control, the feed efficiency (FE), weight gain (WG), final body weight (FBW), and specific growth rate (SGR) were significantly improved in groups D1.0 and D1.5. Dietary FPE significantly increased serum superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) activities, as well as glutathione (GSH) content. The contents of protein carbonyl (PCC) and malondialdehyde (MDA) in serum decreased significantly. Additionally, FPE supplementation in diets resulted in significant improvement in serum lysozyme (LZM) and myeloperoxidase (MPO) activities, as well as immunoglobulin M (IgM) and complement 3 (C3) concentrations. The hepatic antioxidant enzymes (CAT and SOD) activities increased, whereas content of MDA decreased in fish treated with dietary FPE than those of control both pre- and post-challenged. After 12 h-challenge, an obvious downregulation of hepatic Kelch-like-ECH-associated protein 1 (Keap1), splenic tumor necrosis factor-α (TNF-α), interleukin (IL)-8, IL-1β, and toll-like receptor 2 (TLR2) mRNA levels was observed in fish treated with dietary FPE, whereas hepatic Nrf2 transcription level was upregulated compared to the control. Furthermore, compared to group D0.5, higher relative percent survival (RPS) was observed in gibel carp fed dietary 1.0–2.0 g/kg FPE. Our results reveal that FPE supplemented diet has a stimulatory effect on antioxidant capacity and nonspecific immune response, along with improved growth performance and enhanced resistance against A. hydrophila infection in juvenile gibel carp.
Spectacles of Settler Colonial Memory: Archaeological Findings from an Early Twentieth-Century “First” Settlement Pageant and Other Commemorative Terrain in New England
Authors: Howey Meghan C.L. , DeLucia Christine M.
Published: January 2022

In 1923, rural New England mill town Dover, New Hampshire, staged a Tercentenary pageant of extraordinary proportions to celebrate its “first” settlement. This public spectacle memorialized a specific, and deeply exclusionary, narrative of English settler colonialism, shaped by social anxieties of the post-First World War United States. Recent archaeological research has found possible remnants from this spectacle on a seventeenth-century site. In disturbing this site, the Tercentenary pageant appears to have disregarded actual significant material traces from the very era it aimed to memorialize--traces that offer distinct, fuller understandings of deeply nuanced Native-settler interactions in the Piscataqua River region. Dover’s pageant is situated in a regional analysis of Native and Euro-colonial commemorative place-making of the early twentieth century, exploring how different communities pursued multivocal, monovocal, or other approaches in their performative engagements with the seventeenth century.
A relational tsetlin machine with applications to natural language understanding
Authors: Saha Rupsa , Granmo Ole-Christoffer , Zadorozhny Vladimir I. , Goodwin Morten
Published: January 2022

Tsetlin machines (TMs) are a pattern recognition approach that uses finite state machines for learning and propositional logic to represent patterns. In addition to being natively interpretable, they have provided competitive accuracy for various tasks. In this paper, we increase the computing power of TMs by proposing a first-order logic-based framework with Herbrand semantics. The resulting TM isrelationaland can take advantage of logical structures appearing in natural language, to learn rules that represent how actions and consequences are related in the real world. The outcome is a logic program of Horn clauses, bringing in a structured view of unstructured data. In closed-domain question-answering, the first-order representation produces 10 × more compact KBs, along with an increase in answering accuracy from 94.83%to 99.48%. The approach is further robust towards erroneous, missing, and superfluous information, distilling the aspects of a text that are important for real-world understanding