bluuebunny/crossref_metadata_2025 huggingface dataset:
SARS-CoV-2 infection of intestinal epithelia cells sensed by RIG-I and DHX-15 evokes innate immune response and immune cross-talk
Authors: Zhang Lijuan , Zhang Yize , Wang Ruiqin , Liu Xiaoning , Zhao Jinmeng , Tsuda Masato , Li You
Published: February 2023

SARS-CoV-2 causes a spectrum of clinical symptoms from respiratory damage to gastrointestinal disorders. Intestinal infection of SARS-CoV-2 triggers immune response. However, the cellular mechanism that how SARS-CoV-2 initiates and induces intestinal immunity is not understood. Here, we exploited SARS-CoV-2-GFP/ΔN trVLP pseudo-virus system and demonstrated that RIG-I and DHX15 are required for sensing SARS-CoV-2 and inducing cellular immune response through MAVS signaling in intestinal epithelial cells (IECs) upon SARS-CoV-2 infection. NLRP6 also engages in the regulation of SARS-CoV-2 immunity by producing IL-18. Furthermore, primary cellular immune response provoked by SARS-CoV-2 in IECs further cascades activation of MAIT cells and produces cytotoxic cytokines including IFN-γ, granzyme B via an IL-18 dependent mechanism. These findings taken together unveil molecular basis of immune recognition in IECs in response to SARS-CoV-2, and provide insights that intestinal immune cross-talk with other immune cells triggers amplified immunity and probably contributes to immunopathogenesis of COVID-19.
Mucor indicus caused disseminated infection diagnosed by metagenomic next-generation sequencing in an acute myeloid leukemia patient: A case report
Authors: Shen Meixiao , Li Qian , Zeng Zhaocheng , Han Dongxu , Luo Xiansheng
Published: February 2023

Background

Mucormycosis commonly occurs in immunosuppressed patients with hematological diseases, which can be life-threatening. However, many cases are often misdiagnosed due to lack of specific clinical manifestations. Additionally, the traditional blood culture or serological testing, with a high false-negative rate, is time-consuming. Thus, precise and timely diagnosis of infections is essential for the clinical care of infected patients.

Case presentation

We report a 29-year-old Chinese man with acute myeloid leukemia (AML) who developed febrile neutropenia after the first course of induction chemotherapy. He received empirical antibiotics, which did not relieve his symptoms. No pathogen was detected by traditional microbiologic assays, while Mucor indicus was identified by metagenomic next-generation sequencing (mNGS) in the blood specimen. Liposomal amphotericin B (LAmB) was used, resulting in the patient’s temperature returning to normal. A few days later, abdominal computed tomography (CT) scan showed multiple liver abscesses; fluorescence staining, histopathology, and mNGS identified the causative agent—M. indicus. Posaconazole was combined with LAmB as long-term antifungal treatment. Finally, the patient received allogeneic hematopoietic stem cell transplantation successfully after controlled infection. During follow-up 1 year after transplantation, the number of liver abscesses was reduced to one and remained stable.

Conclusion

This report described the first case of an AML patient diagnosed with culture-negative disseminated infections caused by M. indicus leading to rare hepatic manifestations using mNGS of peripheral blood and liver biopsy. LAmB combined with posaconazole was given in time, resulting in a favorable outcome. mNGS is a new method that assists in detecting the probable pathogen and increases the accuracy of identifying an etiology.
Global Versus Local Lyapunov Approach Used in Disturbance Observer-Based Wind Turbine Control
Authors: Gauterin Eckhard , Pöschke Florian , Schulte Horst
Published: February 2023

This contribution presents a Lyapunov-based controller and observer design method to achieve an effective design process for more dedicated closed-loop dynamics, i.e., a maximal flexibility in an observer-based controller design with a large consistency in desired and achieved closed-loop system dynamics is intended. The proposed, pragmatic approach enhances the scope for controller and observer design by using local instead of global Lyapunov functions, beneficial for systems with widely spaced pole locations. Within this contribution, the proposed design approach is applied to the complex control design task of wind turbine control. As the mechanical loads that affect the wind turbine components are very sensitive to the closed-loop system dynamic, a maximum flexibility in the control design is necessary for an appropriate wind turbine controller performance. Therefore, the implication of the local Lyapunov approach for an effective control design in the Takagi-Sugeno framework is discussed based on the sensitivity of the closed-loop pole locations and resulting mechanical loads to a variation of the design parameters.
Additional improvement in regional myocardial ischemia after intracardiac injection of bone marrow cells during CABG surgery
Authors: Gowdak Luís Henrique Wolff , Schettert Isolmar Tadeu , Rochitte Carlos Eduardo , de Carvalho Leonardo P. , Vieira Marcelo Luiz Campos , Dallan Luís Alberto Oliveira , de Oliveira Sérgio Almeida , César Luiz Antonio Machado , Brito José Oscar Reis , Guarita-Souza Luiz César , de Carvalho Antonio Carlos Campos , Krieger Jose Eduardo
Published: February 2023

Background

Post-procedure residual ischemia is associated with worse prognosis in patients with coronary artery diasease (CAD).

Objective

We evaluated whether autologous bone marrow-derived cells (BMC) contribute to additional reduction in regional stress-induced myocardial ischemia (SIMI) in patients undergoing incomplete coronary artery bypass graft surgery (CABG).

Methods

In a double-blind, randomized, placebo-controlled trial, we enrolled 143 patients (82% men, 58 ± 11 years) with stable CAD and not candidates for complete CABG. They received 100 million BMC (n = 77) or placebo (n = 66) injected into ischemic non-revascularized segments during CABG. The primary outcome was improvement on SIMI quantified as the area at risk in injected segments assessed by cardiovascular magnetic resonance (CMR) 1, 6, and 12 months after CABG.

Results

The reduction in global SIMI after CABG was comparable (p = 0.491) in both groups indicating sustained beneficial effects of the surgical procedure over 12 month period. In contrast, we observed additional improvement in regional SIMI in BMC treated group (p = 0.047). Baseline regional SIMI values were comparable [18.5 (16.2–21.0) vs. 18.5 (16.5–20.7)] and reached the lowest values at 1 month [9.74 (8.25; 11.49) vs. 12.69 (10.84; 14.85)] for BMC and placebo groups, respectively. The ischemia’s improvement from baseline represented a 50% difference in regional SIMI in favor of the BMC transplanted group at 30 days. We found no differences in clinical and LVEF% between groups during the 12 month follow-up period. The 1 month rate of major adverse cerebral and cardiovascular events (MACCE) (p = 0.34) and all-cause mortality (p = 0.08) did not differ between groups 1 month post intervention.

Conclusion

We provided evidence that BMC leads to additional reduction in regional SIMI in chronic ischemic patients when injected in segments not subjected to direct surgical revascularization. This adjuvant therapy deserves further assessment in patients with advanced CAD especially in those with microcirculation dysfunction.

Clinical trial registration

https://clinicaltrials.gov/, identifier NCT01727063
Is it time for class I recommendation for sodium-glucose cotransporter-2 inhibitors in heart failure with mildly reduced or preserved ejection fraction?: An updated systematic review and meta-analysis
Authors: Treewaree Sukrit , Kulthamrongsri Narathorn , Owattanapanich Weerapat , Krittayaphong Rungroj
Published: February 2023

Background

In heart failure with reduced ejection fraction (HFrEF), sodium-glucose cotransporter-2 (SGLT2) inhibitors were demonstrated to lower cardiovascular mortality (CV death) and hospitalization for heart failure (HHF); however, the advantages of SGLT2 inhibitors in heart failure with mildly reduced (HFmrEF) or preserved ejection fraction (HFpEF) are less clear. SGLT2 inhibitors were reported to enhance quality of life (QoL) in HFmrEF or HFpEF patients; however, the findings among studies are inconsistent.

Objective

To conduct an updated systematic review and meta-analysis of recent data to assess the effect of SGLT2 inhibitors on cardiovascular outcomes and QoL in patients with HFmrEF or HFpEF.

Method

Three databases were searched for studies that evaluated SGLT2 inhibitors and their effect on cardiovascular outcomes, including CV death, HHF, all-cause death, and the composite outcome of CV death, HHF, and urgent visit for heart failure (HF), and patient QoL (Kansas City Cardiomyopathy Questionnaire [KCCQ] score compared to baseline, and increase in KCCQ score ≥ 5 points) that were published during January 2000–August 2022. The meta-analysis was performed using the inverse variance method and random-effects model. INPLASY registration: INPLASY202290023.

Results

Sixteen studies (9 recent RCTs) were included, and a total of 16,710 HFmrEF or HFpEF patients were enrolled. SGLT2 inhibitors significantly reduced composite cardiovascular outcome (CV death/HHF/urgent visit for HF; pooled hazard ratio [HR]: 0.80, 95% confidence interval [95%CI]: 0.74–0.86) and HHF alone (HR: 0.74, 95%CI: 0.67–0.82), but there was no significant reduction in CV death alone (HR: 0.93, 95%CI: 0.82–1.05). Benefit of SGLT2 inhibitors for decreasing CV death/HHF was observed across all subgroups, including left ventricular ejection fraction (LVEF) range, diabetes status, New York Heart Association functional class, and baseline renal function. For total HHF, SGLT2 inhibitors conferred benefit in both LVEF 50–60% (HR: 0.64, 95%CI: 0.54–0.76), and LVEF >60% (HR: 0.84, 95%CI: 0.71–0.98). Significant change was observed in the KCCQ-clinical summary score compared to baseline (mean difference: 1.33, 95%CI: 1.31–1.35), and meaningful improvement in QoL was shown across all 3 types of increase in KCCQ score ≥ 5 points.

Conclusion

This study demonstrates the benefits of SGLT2 inhibitors for improving cardiovascular outcomes and QoL in HFmrEF or HFpEF patients.
Pulse-wave velocity assessments derived from a simple photoplethysmography device: Agreement with a referent device
Authors: Zieff Gabriel , Stone Keeron , Paterson Craig , Fryer Simon , Diana Jake , Blackwell Jade , Meyer Michelle L. , Stoner Lee
Published: February 2023

Objective

Pulse-wave velocity (PWV), a common measure of arterial stiffness, can be measured continuously and across multiple body sites using photoplethysmography (PPG). The objective was to determine whether a simple photoplethysmography PPG PWV method agrees with a referent device.

Approach

Photoplethysmography heart-finger PWV (hfPWV) and heart-toe PWV (htPWV) were compared to oscillometric carotid-wrist PWV (cwPWV) and carotid-ankle PWV (caPWV) referent measurements, respectively. In 30 adults (24.6 ± 4.8 years, body mass index 25.2 ± 5.9 kg/m2, 18 female), three measurements were made: two supine baseline measurements (Base 1, Base 2) and one measurement (Tilt) 5 min after a modified head-up tilt test (mHUTT). Overall agreement and repeated measures agreement (change in PPG PWV from Base to Tilt vs. change in referent PWV from Base to Tilt) were calculated using linear mixed models. Agreement estimates were expressed as intra-class correlation coefficients (ICC).

Main results

For hfPWV there was strong overall agreement (ICC: 0.77, 95%CI: 0.67–0.85), but negligible and non-significant repeated measures agreement (ICC: 0.10, 95%CI: −0.18 to 0.36). For htPWV, there was moderate overall agreement (ICC:0.50, 95%CI: 0.31–0.65) and strong repeated measures agreement (ICC: 0.81, 95%CI: 0.69–0.89).

Significance

Photoplethysmography can continuously measure PWV at multiple arterial segments with moderate-strong overall agreement. While further work with upper-limb PPG PWV is needed, PPG can adequately capture acute changes in lower-limb PWV.
Deep learning-based end-to-end automated stenosis classification and localization on catheter coronary angiography
Authors: Cong Chao , Kato Yoko , Vasconcellos Henrique Doria De , Ostovaneh Mohammad R. , Lima Joao A. C. , Ambale-Venkatesh Bharath
Published: February 2023

Background

Automatic coronary angiography (CAG) assessment may help in faster screening and diagnosis of stenosis in patients with atherosclerotic disease. We aimed to provide an end-to-end workflow that separates cases with normal or mild stenoses from those with higher stenosis severities to facilitate safety screening of a large volume of the CAG images.

Methods

A deep learning-based end-to-end workflow was employed as follows: (1) Candidate frame selection from CAG videograms with Convolutional Neural Network (CNN) + Long Short Term Memory (LSTM) network, (2) Stenosis classification with Inception-v3 using 2 or 3 categories (<25%, >25%, and/or total occlusion) with and without redundancy training, and (3) Stenosis localization with two methods of class activation map (CAM) and anchor-based feature pyramid network (FPN). Overall 13,744 frames from 230 studies were used for the stenosis classification training and fourfold cross-validation for image-, artery-, and per-patient-level. For the stenosis localization training and fourfold cross-validation, 690 images with > 25% stenosis were used.

Results

Our model achieved an accuracy of 0.85, sensitivity of 0.96, and AUC of 0.86 in per-patient level stenosis classification. Redundancy training was effective to improve classification performance. Stenosis position localization was adequate with better quantitative results in anchor-based FPN model, achieving global-sensitivity for left coronary artery (LCA) and right coronary artery (RCA) of 0.68 and 0.70.

Conclusion

We demonstrated a fully automatic end-to-end deep learning-based workflow that eliminates the vessel extraction and segmentation step in coronary artery stenosis classification and localization on CAG images. This tool may be useful to facilitate safety screening in high-volume centers and in clinical trial settings.
Density structure beneath the Rungwe volcanic province and surroundings, East Africa from shear-wave velocity perturbations constrained inversion of gravity data
Authors: Njinju Emmanuel A. , Moorkamp Max , Stamps D. Sarah
Published: February 2023

Density perturbations in the subsurface are the main driver of mantle convection and can contribute to lithospheric deformation. However, in many places the density structure in the subsurface is poorly constrained. Most geodynamic models rely on simplified equations of state or use linear seismic velocity perturbations to density conversions. In this study, we investigate the density structure beneath the Rungwe Volcanic Province (RVP), which is the southernmost volcanic center in the Western Branch of the East African Rift (EAR). We use shear-wave velocity perturbations (dlnvs) as a reference model to perform constrained inversions of satellite gravity data centered on the RVP. We use the code jif3D with a dlnvs-density coupling criterion based on mutual information to generate a 3D density model beneath the RVP up to a depth of 660 km. Our results reveal a conspicuous negative density anomaly (∼−200 kg/m3) in the sublithospheric mantle (at depths ranging from ∼100 km to ∼250 km) beneath the central part of the Malawi Rift extending to the west, beneath the Niassa Craton, coincident with locations with positive shear-wave velocity perturbations (+7%). We calculate a 3D model of the velocity-to-density conversion factor (f) and find negative f-values beneath the Niassa Craton which suggests the observed negative density anomaly is mostly due to compositional variations. Apart from the Niassa Craton, there are generally positive f-values in the study area, which suggest dominance of temperature control on the density structure. Although the RVP generally shows negative density anomalies and positive f-values, at shallow depths (<120 km), f≈ 0, which suggests important contributions of both temperature and composition on the density structure possibly due to the presence of plume material. The negative buoyancy of the Niassa Craton contributes to its long stability, while constituting a barrier to the southward flow of plume material, thus restricting the southward continuation of magmatism in the Western Branch of the EAR. The presence of a negative-density anomaly where dlnvs are positive is incompatible with models based on the use of simple dlnvs to density conversion factors. These results have implications on how dlnvs models are converted to density perturbations.
Inquiring children and elementary school teachers to diagnose their conceptions about islands
Authors: Vasconcelos Clara , Paz Marta
Published: February 2023

Current challenges faced by modern societies assign larger importance to geological knowledge, particularly in the youngest, as geoscience education is an important path toward a more comprehensive understanding of the Earth’s processes and, therefore, to achieve a more sustainable world. The present investigation aims to deepen the knowledge regarding the conceptions related to islands and island formation. Children’s diagrams and drawings are prototypical representations of how they view and understand their world and can also illustrate misunderstandings in their knowledge. This study focuses on the conceptions of islands in elementary school children (K-9) and elementary school teachers. For that purpose, the investigation resorted to a small survey based on a drawing task. The sample consisted of 118 elementary school students (n = 118), whose ages ranged from 6 to 10 years, and their four elementary school teachers (n = 4), whose ages ranged from 43 to 49 years. In line with prior studies that acknowledged the existence of many misconceptions regarding geology topics, this investigation found unscientific ideas about islands, both in students and teachers. The study results also show that students and teachers share misconceptions about the formation of islands and their relation with the seafloor. The implications of our findings for science education are discussed, namely, the development of an Earth sciences education for elementary schooling and the construction of educational resources better adapted to the teaching and learning of the topic.
Unequal literacy development and access to online education in public versus private Panamanian schools during COVID-19 pandemic
Authors: Cubilla-Bonnetier Daniel , Grajales-Barrios María , Ortega-Espinosa Anis , Puertas Luz , De León Sautú Nadia
Published: February 2023

National and international tests have yielded low reading comprehension results for education in Panama, although there is limited information regarding literacy development and performance. There are wide gaps in social inequality, access to technology, and public versus private school achievement. Considering this, after a year off from regular face-to-face classes and a partial transition to online education due to the COVID-19 pandemic, the present study utilizes existing data to carry out a pre-post comparison of the reading performance of fourth (n = 167) and sixth (n = 164) grade students in the province of Panama employing a subsample stratified by educational system for comparability (Mann–WhitneyUtest,α = 0.05). The pre-post comparison was also carried out independently in both the public (n = 235) and private (n = 106) systems, as well as an additional comparison of the average weekly hours of online academic engagement in both systems during the pandemic in fourth (n = 117) and sixth grade (n = 109). The results support a significant decrease in reading performance. Based on the comparative analysis, findings indicate that public school students interacted online with their teachers significantly less than their private schools’ counterparts; and that, in the same sample, only the public-school students exhibited a significant decrease in reading speed by phonological and lexical route with a medium effect size compared to pre-pandemic standards, greater than those reported in other contexts. This highlights the need to develop effective strategies to narrow the existing educational gaps in the country, which seem to have widened due to the pandemic, with particular emphasis on reading performance in primary school.
Update on the surgical management of Graves’ orbitopathy
Authors: Baeg Joonyoung , Choi Han Sol , Kim Charm , Kim Hyuna , Jang Sun Young
Published: February 2023

Graves’ orbitopathy (GO) is a complex autoimmune disorder of the orbit that causes the eye to appear disfigured. GO is typically associated with Graves’ disease, an inflammatory autoimmune condition that is caused by thyrotropin receptor autoantibodies. Although our knowledge of the pathophysiology of GO has improved, its exact pathogenesis remains unclear. Some patients suffer from disfigurement, double vision, and even vision loss rather than hyperthyroidism. The disease severity and activity prompt different treatments, as the signs of GO are heterogeneous, so their management can be very complex. Despite medical advances, the first-line treatment for moderate-to-severe active GO is still glucocorticoids, while surgery can be critical for the treatment of chronic inactive GO. Surgery is sometimes required in the acute phase of the disease when there is an immediate risk to vision, such as in dysthyroid optic neuropathy. Most surgeries for GO are rehabilitative and subdivided into three categories: decompression, strabismus repair, and lid surgery. This review is a basic overview of the field, with up-to-date knowledge of the surgical techniques for GO. We review and summarize recent literature on the advances in surgery for GO to provide up-to-date insights on the optimal surgical treatment for GO.
Effects of precipitation changes and land-use alteration on streamflow: A comparative analysis from two adjacent catchments in the Qilian Mountains, arid northwestern China
Authors: Bai Xuelian , Zhao Wenzhi , Liu Hu , Zhang Yongyong , Yang Qiyue , Liu Jintao , Chang Xueli
Published: February 2023

Comparative analysis of the impacts of precipitation and land use on streamflow from adjacent catchments is critical to exploring pathways toward water security and sustainable development. In this work, two adjacent catchments (the Mayinghe and Xidahe, abbreviated as MYC and XDC, respectively) in northwestern China were selected to compare the impacts of precipitation change and land use alteration on streamflow change during 1956–2019 using field observation streamflow data and satellite data. An opposite trend of streamflow was found for the two catchments from 1956 to 2019: the streamflow decreased significantly in the MYC (-0.63 × 107m3/10a, p < 0.05), while it increased in the XDC (0.71 × 107m3/10a, p < 0.05). Land conversion dominated the streamflow reduction in the MYC, with a contribution of about 68.3%. In the XDC, precipitation was confirmed to be the major factor driving the increase in streamflow. The streamflow for farmland irrigation reached 27.97 × 104 m3/km2 in the MYC, which was the leading factor of streamflow reduction in the basin. The findings obtained from this work can shed light on the quantitative understanding of streamflow changes in small catchments and offer a scientific basis for sustainable water management in other inland river basins.
Integrated genomic analysis defines molecular subgroups in dilated cardiomyopathy and identifies novel biomarkers based on machine learning methods
Authors: Ye Ling-Fang , Weng Jia-Yi , Wu Li-Da
Published: February 2023

Aim: As the most common cardiomyopathy, dilated cardiomyopathy (DCM) often leads to progressive heart failure and sudden cardiac death. This study was designed to investigate the molecular subgroups of DCM.

Methods: Three datasets of DCM were downloaded from GEO database (GSE17800, GSE79962 and GSE3585). After log2-transformation and background correction with “limma” package in R software, the three datasets were merged into a metadata cohort. The consensus clustering was conducted by the “Consensus Cluster Plus” package to uncover the molecular subgroups of DCM. Moreover, clinical characteristics of different molecular subgroups were compared in detail. We also adopted Weighted gene co-expression network analysis (WGCNA) analysis based on subgroup‐specific signatures of gene expression profiles to further explore the specific gene modules of each molecular subgroup and its biological function. Two machine learning methods of LASSO regression algorithm and SVM-RFE algorithm was used to screen out the genetic biomarkers, of which the discriminative ability of molecular subgroups was evaluated by receiver operating characteristic (ROC) curve.

Results: Based on the gene expression profiles, heart tissue samples from patients with DCM were clustered into three molecular subgroups. No statistical difference was found in age, body mass index (BMI) and left ventricular internal diameter at end-diastole (LVIDD) among three molecular subgroups. However, the results of left ventricular ejection fraction (LVEF) statistics showed that patients from subgroup 2 had a worse condition than the other group. We found that some of the gene modules (pink, black and grey) in WGCNA analysis were significantly related to cardiac function, and each molecular subgroup had its specific gene modules functions in modulating occurrence and progression of DCM. LASSO regression algorithm and SVM-RFE algorithm was used to further screen out genetic biomarkers of molecular subgroup 2, including TCEAL4, ISG15, RWDD1, ALG5, MRPL20, JTB and LITAF. The results of ROC curves showed that all of the genetic biomarkers had favorable discriminative effectiveness.

Conclusion: Patients from different molecular subgroups have their unique gene expression patterns and different clinical characteristics. More personalized treatment under the guidance of gene expression patterns should be realized.
Transcriptome sequencing of Cocos nucifera leaves in response to Rhynchophorus ferrugineus infestation
Authors: Liu Li , Yan Wei , Liu Bo
Published: February 2023

Red palm weevil (RPW, Rhynchophorus ferrugineus) is an invasive pest of palms. In China, coconut (Cocos nucifera) production is being significantly affected by the RPW attack. To develop a long-term RPW control strategy, host-plant resistance is the most sustainable option. In this regard, the availability of transcriptome sequencing data from RPW-infected coconut plants can be highly useful. Therefore, the present study assessed coconut leaf physiological responses and transcriptional changes after different days of RPW attack i.e., 5, 10, 15, 20, and 25 days after infestation (DAI). A comparison of physiological data indicated that populations with the higher number of RPW insects i.e., population C (15 males +21 females) and D (20 males +28 females) triggered higher antioxidant enzyme activities. We used this data to study the transcriptomic responses on 5 and 20 DAI. Of the 38,432 detected transcripts, 3,984, 1,981, 3,925, and 2,257 were differentially expressed in CK (control/no RPW)_vs._C (5 DAI), CK_vs._D (5 DAI), CK_vs._C (20 DAI), and CK_vs._D (20 DAI), respectively. These transcripts were enriched in plant-pathogen interaction, phenylpropanoid/flavonoid biosynthesis, amino sugar and nucleotide sugar metabolism, plant hormone signal transduction, mitogen-activated protein kinase, and reactive oxygen scavenging pathway. We discuss these results and present several candidate genes to be manipulated for developing a sustainable strategy to control RPW attack regarding host-plant resistance. Furthermore, these findings provide a basis for developing effective early and late RPW attack detection strategies.
Identification of subspecies-divergent genetic loci responsible for mineral accumulation in rice grains
Authors: Huang Zijian , Li Sai , Lv Zhaokun , Tian Yan , Chen Yibo , Zhu Yuxing , Wang Jiurong , Deng Huabing , Sun Liang , Tang Wenbang
Published: February 2023

Rice (Oryza sativa L.) is a major staple food that provides not only dietary calories but also trace elements for the global inhabitants. The insufficiency of mineral nutrients and the potential accumulation of excessive toxic elements in grains pose risks to human health. The substantial natural variations in mineral accumulation in rice grains presents potentials for genetic improvements of rice via biofortifications of essential mineral nutrients and eliminations of toxic elements in grains. However, the genetic mechanisms underlying the natural variations in mineral accumulation have not been fully explored to date owing to unstable phenotypic variations, which are attributed to poor genetic performance and strong environmental effects. In this study, we first compared the genetic performance of different normalization approaches in determining the grain-Cd, grain-Mn, and grain-Zn variations in rice in different genetic populations. Then through quantitative trait loci (QTLs) identification in two rice inter-ectype populations, three QTLs, including qCd7, qMn3, and qZn7, were identified and the QTLs were found to exhibit allelic differentiation in the different ecotypes. Our results were expected to broaden our understanding for mineral accumulation in rice and propose the potential functional alleles that can be explored for further genetic improvement of rice.
Intimate partner violence against women of reproductive age and associated factors during COVID-19 pandemic in Northern Ethiopia, 2021: A community-based cross-sectional study
Authors: Demeke Mekasha Getnet , Shibeshi Ehtemariam Tefera
Published: February 2023

Background

Intimate partner violence (IPV) is a major public health concern that affects more than one-third of all women globally. Assessing the prevalence of intimate partner violence and associated factors during the COVID-19 pandemic in various localities is crucial for intervention actions. So far, a few studies have been done in Ethiopia during the current COVID-19 pandemic.

Objective

This study aimed to assess the prevalence of intimate partner violence in women of reproductive age and associated factors during the COVID-19 pandemic in Debre Berhan town, Ethiopia, 2021.

Methodology

A community-based cross-sectional study was done. A total of 809 ever-partnered women of reproductive age were selected randomly via a multistage sampling method. Crude and adjusted odds ratios (AOR) with the resulting 95% confidence interval (CI) were used to verify the strength of associations. Significant associations were declared at p-values <0.05.

Result

Among the 796 women who successfully participated in the study, 337 (42.3%) experienced at least one type of intimate partner violence. Prevalence of psychological, physical, and sexual violence was 35.3% (281), 15.3% (122), and 15.2% (121), respectively. Multivariate analysis revealed that women with no formal education [AOR (95% CI): 3.66 (1.91–6.98)], having no own income [AOR (95% CI): 1.78 (1.24–2.56)], and attitude of IPV were acceptable [AOR (95% CI): 4.02 (1.33–12.14)]; a male partner with no formal education [AOR (95% CI): 3.06 (1.53–6.14)], with “level of religious beliefs” [weak—AOR (95% CI): 4.17 (1.45–12.03); and medium—AOR (95% CI): 1.64 (1.13–2.39)], who is alcoholic [AOR (95% CI): 5.91 (4.03–8.67)], and with smoking habits [AOR (95% CI): 2.04 (1.10–3.77)] and >5 [AOR (95% CI): 1.83 (1.01–3.39)] was significantly associated with the presence of intimate partner violence.

Conclusion and recommendation

This study revealed a high prevalence of IPV in the study participants. The high intimate partner violence prevalence was due to multiple factors, thus demanding empowering women and tailored health education for male partners.
Digital expression profile of immune checkpoint genes in medulloblastomas identifies CD24 and CD276 as putative immunotherapy targets
Authors: Marques Rui Ferreira , Moreno Daniel Antunes , da Silva Luciane , Leal Leticia Ferro , de Paula Flávia Escremim , Santana Iara , Teixeira Gustavo , Saggioro Fabiano , Neder Luciano , Junior Carlos Almeida , Mançano Bruna , Reis Rui Manuel
Published: February 2023

Introduction

Medulloblastoma is the most common and lethal pediatric malignant brain tumor. It comprises four main molecular subgroups: WNT-activated, SHH-activated, Group 3, and Group 4. Medulloblastoma treatment is surgical resection, craniospinal radiation, and chemotherapy. However, many patients do not respond to therapy, and most suffer severe side effects. Cancer immunotherapy targeting immune checkpoints (IC) (PD-1, PD-L1, and CTLA4) has been getting disappointing outcomes in brain tumors. Nevertheless, other less explored immune checkpoints may be promising candidates for medulloblastoma therapy.

Objectives

In the present study, we aimed to characterize the expression profile of 19 immune checkpoints in medulloblastoma.

Methods

We analyzed 88 formalin-fixed paraffin-embedded medulloblastomas previously classified for each molecular subgroup and three non-tumoral brain tissue. mRNA levels of 19 immune checkpoint-related genes were quantified using the nCounter (PanCancer Immune Profiling Panel) assay. Further in silico analysis was performed in two larger public microarray datasets, one of which enabled comparisons between tumoral and non-tumoral tissues. Immunohistochemistry of PD-L1 was performed in a subset of cases. Microsatellite instability was also molecularly analyzed.

Results

We observed an absence of expression of the canonic ICs, namely PDCD1 (PD-1), CD274 (PD-L1), and CTLA4, as well as CD80, CD86, BTLA, IDO1, CD48, TNFSF14, CD160, CEACAM1, and CD244. PD-L1 protein expression was also practically absent. We found higher mRNA levels of CD24, CD47, CD276 (B7-H3), and PVR, and lower mRNA levels of HAVCR2, LAG3, and TIGIT genes, with significant differences across the four molecular subgroups. Compared to the non-tumor tissues, the expression levels of CD276 in all subgroups and CD24 in SHH, Group 3, and Group 4 subgroups are significantly higher. The in silico analysis confirmed the expression profile found in the Brazilian cohort, including the lower/absent expression of the canonic ICs. Moreover, it confirmed the overexpression of CD24 and CD276 in medulloblastomas compared with the non-tumor tissue. Additionally, CD276 and CD24 high levels were associated with worse survival.

Conclusion

These results highlight the low or absence of mRNA levels of the canonic targetable ICs in medulloblastomas. Importantly, the analysis revealed overexpression of CD24 and CD276, which can constitute prognostic biomarkers and attractive immunotherapy targets for medulloblastomas.
Treatment of extranodal NK/T-cell lymphoma: From past to future
Authors: Yan Zheng , Yao Shuna , Wang Zhizhong , Zhou Wenping , Yao Zhihua , Liu Yanyan
Published: February 2023

Extranodal NK/T-cell lymphoma (ENKTCL) is the most common subtype of T/NK-cell lymphoma in Asia and Latin America, but very rare in North American and Europe. Patient survival has improved significantly over the past two decades. However, standard treatment has not yet been established, although dozens of prospective trials have been conducted. To help understand how the treatment of ENKTCL has evolved in the past and what trends lie ahead, we have comprehensively reviewed the treatment of this aggressive malignancy, with a particular focus on neglected or unanswered issues, such as the optimal staging method, the best partner of asparaginase (Asp), the individualized administration of Asp, the preferred sequence of CT and RT and so on. Overall, the 5-year overall survival (OS) of patients with Ann Arbor stage I/II disease increased from < 50% in the early 20th century to > 80% in recent years, and the median OS of patients with Ann Arbor stage III/IV disease increased from < 1 year to more than 3 years. The improvement in patient survival is largely attributable to advances in radiation technology and the introduction of Asp and anti-PD-1/PD-L1 immunotherapy into practice. Radiotherapy is essential for patients with early-stage disease, while Asp-based chemotherapy (CT) and PD-1/PD-L1 inhibitors significantly improved the prognosis of patients with advanced-stage disease. ENKTCL management is trending toward simpler regimens, less toxicity, and higher efficacy. Novel drugs, such as manufactured T cells, monoclonal antibodies, and small molecule inhibitors, are being intensively investigated. Based on the fact that ENKTCL is highly resistant to cytotoxic drugs except Asp, and aggressive CT leads to higher toxicity rather than better outcomes, we recommend it is unnecessary to expend additional resources to compare different combinations of Asp with cytotoxic agents. Instead, more efforts should be made to optimize the use of Asp and immunotherapy to maximize efficacy and minimize toxicity, explore ways to overcome resistance to Asp and immunotherapy, identify novel treatment targets, and define subpopulations who may benefit more from specific treatments.
Hematopoietic stem cell transplantation for inborn errors of immunity: 30-year single-center experience
Authors: Dell’Orso Gianluca , Bagnasco Francesca , Giardino Stefano , Pierri Filomena , Ferrando Giulia , Di Martino Daniela , Micalizzi Concetta , Guardo Daniela , Volpi Stefano , Sabatini Federica , Miano Maurizio , Gattorno Marco , Dufour Carlo , Faraci Maura
Published: February 2023

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) represents an effective treatment for a variety of inborn errors of immunity (IEI). We report the experience of children affected by IEI who received allo-HSCT over a period of 32 years at IRCCS Istituto Giannina Gaslini, Genoa, Italy. HSCTs were performed in 67 children with IEI. Kaplan–Meier estimates of overall survival (OS) rate at 5 years in the whole group of patients was 83.4% after a median follow-up of 4 years. Median age at transplant was 2.5 years. Eight allo-HSCTs were complicated by either primary or secondary graft failure (GF), the overall incidence of this complication being 10.9%. Incidence of grade 3–4 acute GvHD (aGvHD) was 18.7%, significantly lower in the haploidentical transplant cohort (p = 0.005). Year of transplant (≤2006 vs. >2006) was the main factor influencing the outcome. In fact, a significant improvement in 5-year OS was demonstrated (92.5% >2006 vs. 65% ≤2006, p = 0.049). Frequency of severe aGvHD was significantly reduced in recent years (≤2006 61.5%, vs. >2006 20%, p = 0.027). A significant progress has been the introduction of the TCR αβ/CD19-depleted haploidentical platform, which was associated with the absence of severe aGvHD. However, it was associated with 23.5% incidence of GF. All but one patient experiencing GF in the this specific cohort were successfully retransplanted. In summary, allo-HSCT is confirmed to be an effective treatment for children with IEI, even in the absence of an HLA-matched donor.
High Temperature Composites From Renewable Resources: A Perspective on Current Technological Challenges for the Manufacturing of Non-Oil Based High Char Yield Matrices and Carbon Fibers
Authors: Natali Maurizio , Rallini Marco , Torre Luigi , Puglia Debora
Published: February 2023

During last decades a plethora of high temperature materials have been developed to work as a Thermal Protection System (TPS). Carbon based materials such as graphite, which possesses low density, high heat capacity and high energy of vaporization, have been used as TPS material. However, graphite has relatively poor mechanical properties, but exhibits low resistance to the thermal shocks. Accordingly, to bypass the limitation of graphite, carbon fibers are typically introduced in a carbon matrix to produce Carbon/Carbon Composites (CCCs). Among the different families of TPS solutions, Polymeric Ablative Materials (PAMs), produced combining high char yield matrices - mainly phenolic resins - and Carbon Fibers (CFs) are used to manufacture Carbon/Phenolic Composites (CPCs) i.e. the most important class of fiber reinforced PAM. Carbon fibers are traditionally produced from Polyacrylonitrile (PAN), Rayon and Pitch. Some limited researches also aimed to use cyanate-esters, bismaleimides, benzoxazines matrices in combination with ex-PAN-CFs, ex-Rayon-CFs, and ex-Pitch-CFs. In our paper, after covering the science and technology of these state-of-the-art fiber reinforced TPS materials, a review of current challenges behind the manufacturing of new, high char yield matrices and carbon fibers derived from alternative precursors will be provided to the reader. In particular, the possibility to produce CFs from precursors different from PAN, Rayon and Pitch will be reported and similarly, the technology of non-oil based phenolics, bismaleimides, cyanate-esters and benzoxazines will be discussed. The effect of the use of nanosized fillers on these matrices will also be reported. More in detail, after a preliminary section in which the state of the art of technologies behind carbon/phenolic composites will be covered, a second part of this review paper will be focused on the most recent development related to non-oil based phenolics and biomass derived carbon fibers. Finally, an outlook focused on the maturity of the lab-scale protocols behind the researches at the base of these non-traditional raw materials from an industrial point of view will conclude this review paper.
Tuning microstructure and mechanical and wear resistance of ZrNbTiMo refractory high-entropy alloy films via sputtering power
Authors: Liu Xinyu , Cai Wumin , Zhang Yan , Wang Linqing , Wang Junjun
Published: February 2023

Introduction: Recently, great efforts have been dedicated to tailoring the microstructure of the RHEA films to further optimize the performance of the films. However, there is still a lack of in-depth study on their wear mechanism and microstructure evolution.

Methods: In this work, the novel ZrNbTiMo RHEA films were prepared by DC magnetron sputtering and splicing target techniques. The effects of sputtering power on the microstructure, hardness, toughness, and wear resistance of ZrNbTiMo RHEA films were investigated in detail.

Results: The ZrNbTiMo films possess the nanocomposite structure, the bcc nanocrystal is wrapped in an amorphous phase. The wear resistance of the film is expected to be improved by finding an appropriate ratio between the amorphous phase and the nanocrystal phase. The nanocrystal structure ensures the high hardness (6.547 ∼ 7.560 GPa) of the ZrNbTiMo film. In addition, the nanocrystals hinder crack propagation, this toughness mechanism effectively improves the toughness of the film. The ZrNbTiMo film prepared at 150 W possesses excellent mechanical properties, hardness of 7.240 GPa and toughness of 0.437 ± 0.040 MPa × m1/2, exhibits better wear resistance (wear rate: 5.223 × 10−7 mm3/N m).

Discussion: The wear resistance of ZrNbTiMo film is controlled by both hardness and toughness. The nanocomposite structure makes the ZrNbTiMo films possess a composite fracture which could improve the toughness of the ZrNbTiMo film. The wear-resistant ZrNbTiMo RHEA films with wear rates of the order of 10−6 mm3/N m have been prepared by tuning the sputtering power, this film can be used as a potential candidate for wear-resistant coatings.
Delayed Infliximab Treatment Affects the Outcomes of Patients With Crohn's Disease During the COVID-19 Epidemic in China: A Propensity Score-Matched Analysis
Authors: Li Yong , Chen Lulu , Chen Shuijiao , Liu Xiaowei
Published: February 2023

Background: The coronavirus disease 2019 (COVID-19) has swept the world and led to delays in the treatment of Crohn's disease patients treated with biologics. This study aims to investigate the risk factors for delayed treatment during the epidemic and to observe the short- and long-term influences of such delays among them to provide some reference on treatments.

Methods: This study retrospectively enrolled patients diagnosed with Crohn's disease who received infliximab treatment between January 23, 2020 and April 30, 2020. Univariate and multivariate logistic regression were used to analyze the risk factors for delayed treatment. Propensity score matching was utilized to compare the effects of delayed treatment on the short- and long-term outcomes.

Result: Our cohort identified a total of 53 patients with a delay rate of 71.7%. Of these patients, 38 were in the delayed group, and 15 were in the non-delayed group. Logistic regression analysis showed that the baseline levels of C-reactive protein were an influence factor for delaying treatment (OR = 0.967, 95% CI = 0.935–1.000, p = 0.047). Regarding short-term effects, the delayed group had a lower decrease in the Crohn's Disease Activity Index than the non-delayed group [−43.3 (−92.7, −9.7) vs. −17.3 (−29.0, 79.9), p = 0.038] and significantly higher long-term readmission rates (33.3% vs. 0%, p = 0.014).

Conclusion: Delayed infliximab treatment could affect the short- and long-term outcomes in patients with Crohn's disease. Our study suggested that the regulated course of treatment with biological agents should be performed effectively and that education should be enhanced to minimize delays in treatment.
Civil society and medical product access in Africa: Lessons from COVID-19
Authors: Wale Janet L. , Sehmi Kawaldip , Kamoga Regina , Ssekubugu Robert
Published: February 2023

Understanding health as a human right creates a legal obligation on countries to ensure access to timely, acceptable, and affordable health care. We highlight the importance of a meaningful role for civil society in improving access to well-regulated quality medical products in Africa; to support and be part of a regional social contract approach following the access issues that have been particularly evident during the COVID-19 pandemic. We argue that African communities have a clear participatory role as important stakeholders in the regulatory lifecycle. Solidarity is important for a cohesive approach as formal government healthcare infrastructure may be minimal for some countries, with little training of communities available for disease management and insufficient money to fund people to organise and deliver health care. Some of the issues for civil society engagement with multi-stakeholders, and possible mitigating strategies, are tabulated to initiate discussion on facilitators and concerns of governments and other stakeholders for meaningful participation by patients, communities and civil society within a regional regulatory lifecycle approach. Solidarity is called for to address issues of equity, ethics and morality, stigmatisation and mutual empowerment – to sustainably support the region and national governments to develop greater self-sufficiency throughout the regulatory lifecycle. By creating a participatory space, patients, communities and civil society can be invited in with clear missions and supported by well-defined guidance to create a true sense of solidarity and social cohesion. Strong leadership coupled with the political will to share responsibilities in all aspects of this work is key.