bluuebunny/crossref_metadata_2025 huggingface dataset:
SmoGSI: smoothed multiscale iterative geostatistical seismic inversion
Authors: Kang Qiangqiang , Hou Jiagen , Hu Xun , Liu Yuming , Ren Quan , Hou Mingqiu , Yin Yanshu
Published: August 2024

Iterative geostatistical seismic inversion is a vital technique for estimating subsurface properties. However, a conventional single-scale strategy faces challenges in preserving large-scale geological features due to the limited restoration of the type of data template, and conventional multiscale strategies face the challenge in that it is easy to lose the large-scale structure that was previously preserved. This paper introduces a novel smoothed multiscale strategy aimed at overcoming these limitations, which comprises two components: Simulated annealing at the coarsest scale and smooth conversation between two scale grids. This approach offers a smoother way to simultaneously retain large-scale and small-scale structures, improving the overall accuracy of the subsurface property estimations. To validate the effectiveness of our approach, we apply it to both synthetic and real examples. The results show that the simulated annealing strategy at the coarsest scale grid explores the prior space and finds the best large structures to avoid the generated models trapping in the local minimal. Meanwhile, the smooth conversation strategy between two scale grids helps us avoid the damage of the coarser structure. It can be explained that a large weight is assigned to the coarse structure at the beginning of the conversation of two grid scale, reducing the likelihood of the replacing proposed local small-scale geological patterns, which prone to be accepted in the conventional multiscale strategies. The combination of the two strategies used in the proposed smoothed multiscale strategy displays a significant improvement in subsurface property estimation accuracy compared to traditional multiscale strategies. This innovation can have far-reaching implications, benefiting a wide range of geophysical applications and contributing to more accurate and informed decision-making in geological and hydrogeological assessments.
Numerical simulation of depressurization exploitation in class 1 hydrate reservoirs under different development factors in Shenhu area, South China sea
Authors: Wei Na , Li Cong , Zhao Xingxin , Li Haitao , Zhang Liehui , Zhao Jinzhou , Kvamme Bjørn , Coffin Richard B.
Published: August 2024

Most of the implemented marine gas hydrate test exploitation in the world adopt the depressurization method to break down the hydrate in the reservoir into natural gas and then extract it, but because the gas production results are still a certain distance away from the commercial exploitation, and it mainly stays in the stage of theoretical research and trial exploitation. Based on two trial productions in the Shenhu area of the South China Sea, this study established a model for hydrate exploitation and investigated the impact of different well types on the recovery rates of hydrates and free gas in different development layers during depressurization. For the Class 1 hydrate reservoirs, horizontal wells are the optimal solution to extract hydrate and free gas simultaneously when exploiting the hydrate three-phase layer. Meanwhile, the effect of different well spacing in vertical wells on the recovery rate of hydrate and free gas was studied. It is found that the best recovery efficiency is achieved when the spacing between two wells is 80 m. The lower the bottom flow pressure of the well, the higher the production capacity, but its influence is limited.
Research on optimization methods for large-flow coefficient centrifugal compressors
Authors: Yang Changzhu , Fan Liyun , Chen Shuo , Zhang Hanwen , Wu Yuelin
Published: August 2024

The present paper focuses on the optimization of large-flow coefficient centrifugal compressors, utilizing a mature centrifugal compressor impeller with a flow coefficient of 0.16 under design point condition in engineering as the research subject. Due to the more complex flow mechanism and more design parameters in the impeller with large flow coefficient, the traditional artificial optimization method is insufficient. In present paper, the impeller with a large flow coefficient is optimized using the concept of combining physical principles and artificial intelligence tools. Firstly, the impeller underwent a redesign based on the theory of maximum flow capacity, with the aim of reducing the Mach number at the impeller inlet to enhance the compressor’s performance. And the efficiency of the impeller at the design point has been increased from 88.6% to 89.9%. In order to further improve the performance of the impeller, an optimization algorithm grounded in gradient variation was employed to facilitate the automatic compressor optimization, and the flow losses at the impeller’s top under low-flow conditions has been mitigated. The results of three-dimensional numerical simulation showed that the operating range of the new impeller is 7% wider than that of the original impeller.
Severe mitochondrial encephalomyopathy caused by de novo variants in OPA1 gene
Authors: Di Nottia Michela , Rizza Teresa , Baruffini Enrico , Nesti Claudia , Torraco Alessandra , Diodato Daria , Martinelli Diego , Dal Canto Flavio , Gilea Alexandru Ionut , Zoccola Martina , Siri Barbara , Dionisi-Vici Carlo , Bertini Enrico , Santorelli Filippo Maria , Goffrini Paola , Carrozzo Rosalba
Published: August 2024

Background

Mitochondria adjust their shape in response to the different energetic and metabolic requirements of the cell, through extremely dynamic fusion and fission events. Several highly conserved dynamin-like GTPases are involved in these processes and, among those, the OPA1 protein is a key player in the fusion of inner mitochondrial membranes. Hundreds of monoallelic or biallelic pathogenic gene variants have been described in OPA1, all associated with a plethora of clinical phenotypes without a straightforward genotype-phenotype correlation.

Methods

Here we report two patients harboring novel de novo variants in OPA1. DNA of two patients was analyzed using NGS technology and the pathogenicity has been evaluated through biochemical and morphological studies in patient’s derived fibroblasts and in yeast model.

Results

The two patients here reported manifest with neurological signs resembling Leigh syndrome, thus further expanding the clinical spectrum associated with variants in OPA1. In cultured skin fibroblasts we observed a reduced amount of mitochondrial DNA (mtDNA) and altered mitochondrial network characterized by more fragmented mitochondria. Modeling in yeast allowed to define the deleterious mechanism and the pathogenicity of the identified gene mutations.

Conclusion

We have described two novel-single OPA1 mutations in two patients characterized by early-onset neurological signs, never documented, thus expanding the clinical spectrum of this complex syndrome. Moreover, both yeast model and patients derived fibroblasts showed mitochondrial defects, including decreased mtDNA maintenance, correlating with patients’ clinical phenotypes.
Development and characterization of dendritic cell internalization and activation assays contributing to the immunogenicity risk evaluation of biotherapeutics
Authors: Siegel Michel , Padamsey Aman , Bolender Anna-Lena , Hargreaves Patrick , Fraidling Johannes , Ducret Axel , Hartman Katharina , Looney Cary M. , Bertinetti-Lapatki Cristina , Rohr Olivier , Hickling Timothy P. , Kraft Thomas E. , Marban-Doran Céline
Published: August 2024

Introduction

Immunogenicity refers to the ability of a substance, such as a therapeutic drug, to elicit an immune response. While beneficial in vaccine development, undesirable immunogenicity can compromise the safety and efficacy of therapeutic proteins by inducing anti-drug antibodies (ADAs). These ADAs can reduce drug bioavailability and alter pharmacokinetics, necessitating comprehensive immunogenicity risk assessments starting at early stages of drug development. Given the complexity of immunogenicity, an integrated approach is essential, as no single assay can universally recapitulate the immune response leading to the formation of anti-drug antibodies.

Methods

To better understand the Dendritic Cell (DC) contribution to immunogenicity, we developed two flow cytometry-based assays: the DC internalization assay and the DC activation assay. Monocyte-derived dendritic cells (moDCs) were generated from peripheral blood mononuclear cells (PBMCs) and differentiated over a five-day period. The internalization assay measured the accumulation rate of therapeutic antibodies within moDCs, while the activation assay assessed the expression of DC activation markers such as CD40, CD80, CD86, CD83, and DC-SIGN (CD209). To characterize these two assays further, we used a set of marketed therapeutic antibodies.

Results

The study highlights that moDCs differentiated for 5 days from freshly isolated monocytes were more prone to respond to external stimuli. The internalization assay has been shown to be highly sensitive to the molecule tested, allowing the use of only 4 donors to detect small but significant differences. We also demonstrated that therapeutic antibodies were efficiently taken up by moDCs, with a strong correlation with their peptide presentation on MHC-II. On the other hand, by monitoring DC activation through a limited set of activation markers including CD40, CD83, and DC-SIGN, the DC activation assay has the potential to compare a series of compounds. These two assays provide a more comprehensive understanding of DC function in the context of immunogenicity, highlighting the importance of both internalization and activation processes in ADA development.

Discussion

The DC internalization and activation assays described here address key gaps in existing immunogenicity assessment methods by providing specific and reliable measures of DC function. The assays enhance our ability to pre-clinically evaluate the immunogenic potential of biotherapeutics, thereby improving their safety and efficacy. Future work should focus on further validating these assays and integrating them into a holistic immunogenicity risk assessment framework.
The role of RNA modifications in hepatocellular carcinoma: functional mechanism and potential applications
Authors: Liu Jin-Xiu , Zhang Xiaoping , Xu Wen-Hua , Hao Xiao-Dan
Published: August 2024

Hepatocellular carcinoma (HCC) is a highly aggressive cancer with a poor prognosis. The molecular mechanisms underlying its development remain unclear. Recent studies have highlighted the crucial role of RNA modifications in HCC progression, which indicates their potential as therapeutic targets and biomarkers for managing HCC. In this review, we discuss the functional role and molecular mechanisms of RNA modifications in HCC through a review and summary of relevant literature, to explore the potential therapeutic agents and biomarkers for diagnostic and prognostic of HCC. This review indicates that specific RNA modification pathways, such as N6-methyladenosine, 5-methylcytosine, N7-methylguanosine, and N1-methyladenosine, are erroneously regulated and are involved in the proliferation, autophagy, innate immunity, invasion, metastasis, immune cell infiltration, and drug resistance of HCC. These findings provide a new perspective for understanding the molecular mechanisms of HCC, as well as potential targets for the diagnosis and treatment of HCC by targeting specific RNA-modifying enzymes or recognition proteins. More than ten RNA-modifying regulators showed the potential for use for the diagnosis, prognosis and treatment decision utility biomarkers of HCC. Their application value for HCC biomarkers necessitates extensive multi-center sample validation in the future. A growing number of RNA modifier inhibitors are being developed, but the lack of preclinical experiments and clinical studies targeting RNA modification in HCC poses a significant obstacle, and further research is needed to evaluate their application value in HCC treatment. In conclusion, this review provides an in-depth understanding of the complex interplay between RNA modifications and HCC while emphasizing the promising potential of RNA modifications as therapeutic targets and biomarkers for managing HCC.
IL6 receptor inhibitors: exploring the therapeutic potential across multiple diseases through drug target Mendelian randomization
Authors: Fu Chong , Wang Longquan , Cai Wenjiao
Published: August 2024

Background

High interleukin-6 levels correlate with diseases like cancer, autoimmune disorders, and infections. IL-6 receptor inhibitors (IL-6Ri), used for rheumatoid arthritis and COVID-19, may have wider uses. We apply drug-target Mendelian Randomization (MR) to study IL-6Ri’s effects.

Method

To simulate the effects of genetically blocking the IL-6R, we selected single nucleotide polymorphisms (SNPs) within or near the IL6R gene that show significant genome-wide associations with C-reactive protein. Using rheumatoid arthritis and COVID-19 as positive controls, our primary research outcomes included the risk of asthma, asthmatic pneumonia, cor pulmonale, non-small cell lung cancer, small cell lung cancer, Parkinson’s disease, Alzheimer’s disease, ulcerative colitis, Crohn’s disease, systemic lupus erythematosus, type 1 diabetes, and type 2 diabetes. The Inverse Variance Weighted (IVW) method served as our principal analytical approach, with the hypotheses of MR being evaluated through sensitivity and colocalization analyses. Additionally, we conducted Bayesian Mendelian Randomization analyses to minimize confounding and reverse causation biases to the greatest extent possible.

Results

IL-6 inhibitors significantly reduced the risk of idiopathic pulmonary fibrosis (OR= 0.278, 95% [CI], 0.138–0.558; P <0.001), Parkinson’s disease (OR = 0.354, 95% CI, 0.215–0.582; P <0.001), and positively influenced the causal relationship with Type 2 diabetes (OR = 0.759, 95% CI, 0.637–0.905; P = 0.002). However, these inhibitors increased the risk for asthma (OR = 1.327, 95% CI, 1.118–1.576; P = 0.001) and asthmatic pneumonia (OR = 1.823, 95% CI, 1.246–2.666; P = 0.002). The causal effect estimates obtained via the BWMR method are consistent with those based on the IVW approach. Similarly, sIL-6R also exerts a significant influence on these diseases.Diseases such as Alzheimer’s disease, Crohn’s disease, pulmonary heart disease, systemic lupus erythematosus, Type 1 diabetes, Non-small cell lung cancer and ulcerative colitis showed non-significant associations (p > 0.05) and were excluded from further analysis. Similarly, Small cell lung cancer were excluded due to inconsistent results. Notably, the colocalization evidence for asthmatic pneumonia (coloc.abf-PPH4 = 0.811) robustly supports its association with CRP. The colocalization evidence for Parkinson’s disease (coloc.abf-PPH4 = 0.725) moderately supports its association with CRP.

Conclusion

IL-6Ri may represent a promising therapeutic avenue for idiopathic pulmonary fibrosis, Parkinson’s disease, and Type 2 diabetes.
Managing technology-critical elements from electronic waste in Small Developing Island States: a burden or an opportunity?
Authors: Wosnick Natascha , Curtis Dorlan , Hauser-Davis Rachel Ann
Published: August 2024

Small Island Developing States (SIDS) face profound challenges from pollution, exacerbated by inadequate infrastructure and resource limitations. This paper examines the longstanding pollution issues plaguing SIDS, highlighting their vulnerability to environmental degradation due to underdeveloped waste management systems and unique oceanographic conditions. The case study of Eleuthera Island in The Bahamas illustrates these challenges vividly, showcasing the island’s struggle with e-waste management. This example reinforces the urgency of integrated strategies to enhance environmental resilience and sustainable development in SIDS. Emerging concerns include the proliferation of technology-critical elements (TCEs) in e-waste, driven by rapid urbanization and tourism growth. Despite their crucial role in technological advancement, TCEs pose significant recycling and management difficulties, particularly in the context of limited waste infrastructure. The paper also highlights the imperative for comprehensive regulatory frameworks and sustainable practices to mitigate pollution impacts and safeguard ocean and human health, particularly by shedding light on legislative gaps and opportunities for enhancing pollution control measures in The Bahamas.
Respiratory, cardio-metabolic and neurodevelopmental long-term outcomes of moderate to late preterm birth: not just a near term-population. A follow-up study
Authors: Alonso-Lopez Patricia , Arroyas Maria , Beato Maite , Ruiz-Gonzalez Sara , Olabarrieta Iciar , Garcia-Garcia Maria Luz
Published: August 2024

Introduction

Moderate-to-late preterm infants constitute the majority within the preterm infant population. Most research on preterm infants has focused on very preterm children, often treating moderate-to-late preterm infants as similar to full-term infants. Our objective was to compare clinical, respiratory, cardio-metabolic and neurodevelopmental outcomes in adolescents aged 12–15 years born moderate and late preterm with a control group of the same age born full-term.

Methods

Observational cross-sectional study, comparing moderate-to-late preterm (32–36+6 weeks’ gestational age) with full-term adolescents (37–41+6 weeks’ gestational age; 75 each group). Perinatal and neonatal history were collected as well as data on respiratory evolution (ISAAC questionnaire for asthma symptoms for adolescents 13–14 years), anthropometric values, learning difficulties, behavioral test (screening questionnaire for high-performance autism spectrum disorder and evaluation test for attention deficit hyperactivity disorder), skin prick test, pulmonary function test, echocardiogram and blood pressure. A blood test with metabolic profile was conducted.

Results

Moderate-to-late preterm adolescents had more current asthma [p = 0.008, OR3 (95% CI 1.26–7.14)] and longer duration of combined treatments to control asthma (inhaled corticosteroids and anti-leukotrienes; p = 0.048). Forced vital capacity <80% was detected more often in moderate-to-late preterm patients (p = 0.013). When assessing right ventricle, moderate-to-late preterm adolescents showed better tricuspid annular plane systolic excursion z-score (p = 0.003), shortening fraction (p < 0.001) and E/A ratio z-score (p = 0.002). Regarding left ventricular assessment, moderate-to-late preterm group had smaller ventricle diastolic diameter (p = 0.04) and lower posterior wall z-score values (p = 0.037). They also showed a better S’wave z-score (p = 0.027), E wave (p = 0.005), E/A ratio (p = 0.003) and a higher septal myocardial performance index z-score (p = 0.025). Moderate-to-late preterm adolescents presented lower weight z-score (p = 0.039), body mass index z-score (p = 0.013), Waterlow weight index (p = 0.006) and higher undernutrition index [p = 0.04; OR 1.4 (95% CI 1–1.9)]. Although there were no differences in neurodevelopmental survey or behavioral tests.

Conclusion

Our findings underscore the importance of extended follow-up for this predominant group of premature infants to identify potential respiratory, cardiac and anthropometric issues that may emerge in the future.
Association between liver fibrosis scores and short-term clinical outcomes in hospitalized chronic kidney disease patients: a prospective observational study
Authors: Das Dhriti Sundar , Anupam Anurag , Saharia Gautom Kumar
Published: August 2024

Introduction

In resource-constrained countries, inadequate access to healthcare and prognostic tools can be the Achilles’ heel in effectively managing chronic kidney disease (CKD). There is a significant similarity in the pathogenesis of CKD and liver fibrosis. The role of liver fibrosis (LF) scores in predicting short-term clinical outcomes in hospitalized patients with CKD is unknown. Our study aimed at calculating LF scores and studying the association of liver fibrosis with short-term mortality and morbidity in CKD patients.

Methods

Patients aged above 15 years diagnosed with CKD as per the KDIGO criteria were enrolled. LF scores, namely, NFS, GPRI, and FIB-4 scores were calculated. Patients were followed up for a period of 28 days for good and poor composite outcomes, namely, the requirement of hemodialysis, non-invasive ventilation, prolonged hospital stay, and neurological and cardiovascular outcomes including death.

Results

Among 163 patients, 70.5% were below 60 years of age, 82.2% were male and 35% were diabetic. At 28-day follow up, 52.1% had poor composite outcome. The AUROC for GPRI and FIB-4 in predicting poor outcomes was 0.783 (95% CI: 0.71–0.855) (p < 0.001) and 0.62 (95% CI: 0.534–0.706) (p = 0.008), respectively. The AUROC for GPRI and NFS in predicting all-cause mortality was 0.735 (95% CI: 0.627–0.843) (p = 0.001) and 0.876 (95% CI, 0.8–0.952) (p < 0.001), respectively.

Conclusion

We found a positive association between LF scores and CKD outcomes in hospitalized patients. The LF scores significantly predicted poor outcomes in patients with CKD. Among the scores, GPRI was found to be a stronger predictor in predicting outcomes in both diabetic and non-diabetic patients with CKD. A high GPRI score was also associated with poor outcomes and increased mortality in both diabetics and non-diabetics.
Cocaine amphetamine-regulated transcription peptide inhibits apoptosis in oxygen–glucose deprived neural stem cells
Authors: Zhang Lu , Chen Shan , Zou Renfang , Shu Xin , Zhang Jingxuan , He Xuan , Su Moxi , Wang Luna , Wang Bin , Sha Dujuan
Published: August 2024

Background

Apoptosis has been recognized as a critical pathophysiological process during cerebral ischemia. The neuroprotective effect of CART on ischemic brain injury is determined. However, there is little research on the protective effect of CART on neural stem cells (NSCs).

Methods

Primary cultured rat NSCs were utilized as the research subject. In vitro oxygen glucose deprivation (OGD) treatment was employed, and NSCs were extracted from SD pregnant rats following previous experimental protocols and identified through cell immunofluorescence staining. The appropriate concentration of CART affecting OGD NSCs was initially screened using Cell Counting Kit-8 (CCK-8) and Lactate Dehydrogenase (LDH) assays. EdU staining and Western blotting (WB) techniques were employed to assess the impact of the suitable CART concentration on the proliferation and apoptosis of OGD NSCs. Finally, Western blot analysis was conducted to investigate the cAMP-response element binding protein (CREB) pathway and expression levels of related proteins after KG-501 treatment in order to elucidate the mechanism underlying apoptosis and proliferation regulation in OGD NSCs.

Results

CCK-8 and LDH assays indicated that a concentration of 0.8 nM CART may be the optimal concentration for modulating the proliferation of OGD NSCs. Subsequently, cellular immunofluorescence and EdU detection experiments further confirmed the findings obtained from CCK-8 analysis. Western blot analysis of apoptosis-related protein expression also demonstrated that an appropriate concentration of CART could suppress the apoptosis of OGD NSCs. Finally, Western blotting was conducted to examine the CREB pathway and related protein expression after treatment with KG-501, revealing that an appropriate concentration of CART regulated both apoptosis and proliferation in OGD NSCs through CREB signaling.

Conclusion

The concentration of CART at 0.8 nM may be deemed appropriate for inhibiting apoptosis and promoting proliferation in OGD NSCs in vitro. The mechanism maybe through activating the CREB pathway.
Diet and physical exercise as key players to tackle MASLD through improvement of insulin resistance and metabolic flexibility
Authors: Mambrini Sara Paola , Grillo Antonio , Colosimo Santo , Zarpellon Francesco , Pozzi Giorgia , Furlan Davide , Amodeo Gabriele , Bertoli Simona
Published: August 2024

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) has emerged as a prevalent health concern, encompassing a wide spectrum of liver-related disorders. Insulin resistance, a key pathophysiological feature of MASLD, can be effectively ameliorated through dietary interventions. The Mediterranean diet, rich in whole grains, fruits, vegetables, legumes, and healthy fats, has shown promising results in improving insulin sensitivity. Several components of the Mediterranean diet, such as monounsaturated fats and polyphenols, exert anti-inflammatory and antioxidant effects, thereby reducing hepatic steatosis and inflammation. Furthermore, this dietary pattern has been associated with a higher likelihood of achieving MASLD remission. In addition to dietary modifications, physical exercise, particularly resistance exercise, plays a crucial role in enhancing metabolic flexibility. Resistance exercise training promotes the utilization of fatty acids as an energy source. It enhances muscle glucose uptake and glycogen storage, thus reducing the burden on the liver to uptake excess blood glucose. Furthermore, resistance exercise stimulates muscle protein synthesis, contributing to an improved muscle-to-fat ratio and overall metabolic health. When implemented synergistically, the Mediterranean diet and resistance exercise can elicit complementary effects in combating MASLD. Combined interventions have demonstrated additive benefits, including greater improvements in insulin resistance, increased metabolic flexibility, and enhanced potential for MASLD remission. This underscores the importance of adopting a multifaceted approach encompassing dietary modifications and regular physical exercise to effectively manage MASLD. This narrative review explores the biological mechanisms of diet and physical exercise in addressing MASLD by targeting insulin resistance and decreased metabolic flexibility.
Trisomy 8 presentation by inflammatory manifestations and its response to thalidomide: two case reports and narrative review
Authors: Zhang Xiaohua , Zhao Yan , Pan Yuting , Jin Jing , Fan Zhidan , Yu Haiguo
Published: August 2024

Objective

It has been recognized that there is a nexus among Trisomy 8 (T8), Behcet's disease (BD), and myelodysplastic syndrome (MDS). We reported a series of inflammatory features in 2 children with T8 without hematological involvement.

Methods

2 children with trisomy 8 who were excluded from MDS were retrospectively collected from the Department of Rheumatology and Immunology, Children's Hospital of Nanjing Medical University, Nanjing.

Results

Patients developed a range of inflammatory manifestations before a diagnosis of T8. The clinical manifestations of T8 patients vary from normal to severely disabled. Glucocorticoids and thalidomide can effectively relieve inflammation in patients with T8.

Conclusion

The early clinical manifestations of T8 in children lack specificity, and the diagnosis is mainly based on karyotype analysis, gastrointestinal endoscopy and bone marrow aspiration findings. Active and effective immunoregulatory therapy and long-term follow-up can improve the prognosis of patients with T8.
Radiological evaluation of response in patients with locally advanced/metastatic soft tissue sarcoma treated with trabectedin
Authors: Ceddia S. , Onesti C. E. , Vari S. , Torchia A. , Cosimati A. , Riva F. , Maccallini M. T. , Cerro M. , Benvenuti G. , Russillo M. , Anelli V. , Sperduti I. , Biagini R. , Ferraresi V.
Published: August 2024

Background: Trabectedin is an antineoplastic drug approved for patients (pts) with advanced soft tissue sarcomas (STS). Interestingly, the radiological evaluation of response during trabectedin therapy is peculiar.

Methods: The aim of this single-center retrospective study is to analyze the concordance of response assessment according to RECIST compared with Choi criteria in patients with STS treated with trabectedin between 2009 and 2020 at Regina Elena National Cancer Institute in Rome.

Results: We present the preliminary data collected in the last 2 months (mos) on 37 pts who received the diagnosis between 2015 and 2020, with a median age of 52.5 years (range 32–78). The median number of trabectedin cycles administered was four (range 2–50) for a median follow up of 5.83 months (range 1–60). Histological subtypes of STS were five (13.5%) leiomyosarcoma, 14 (37.8%) liposarcoma, nine (24.3%) undifferentiated pleomorphic sarcoma, three (8.1%) synovial sarcoma, and six (16.2%) other rare histological subtypes. Eight pts (21.6%) received trabectedin in the first line setting, 21 (56.8%) in the second line, and seven (18.9%) received it in subsequent lines. One pt received trabectedin as neoadjuvant therapy in a clinical trial (ISG-STS 1001). Median progression-free survival was 3.6 months (CI95% 2.7–4.6); median overall survival was 34.3 months (CI95% 0–75.4). The radiological responses were evaluated with both RECIST and Choi criteria; responses matched in 33 pts (89.2%) but not in four (10.8%). The best responses obtained according to RECIST criteria were two (5.4%) partial response (PR), 13 (35.1%) stable disease (SD), and 22 (59.5%) progressive disease (PD). Instead, two (5.4%), 13 (35.1%), and 22 (59.5%) pts obtained PR, SD, and PD respectively, according to Choi criteria. Cohen’s kappa coefficient of concordance was 0.792 (p-value <0.002). A specialized radiologist performed all imaging examinations using a dedicated workstation in the same center.

Conclusion: In this first analysis, the concordance between RECIST and Choi assessments demonstrates no statistically significant difference. Responses did not match for four pts. We are expanding the analysis to all pts included in the original cohort to confirm or deny these initial results.
Ocular adverse events associated with antibody-drug conjugates in oncology: a pharmacovigilance study based on FDA adverse event reporting system (FAERS)
Authors: Mao KaiLi , Chen Ping , Sun HuaYu , Zhong SongYang , Zheng HongLiang , Xu LuYao
Published: August 2024

Background

Antibody-drug conjugates (ADCs) have emerged as the focus and hotspots in the cancer field, yet the accompanying ocular toxicity has often been underestimated. We aimed to comprehensively and comparatively analyze the risk of ocular toxicity associated with various ADCs using the FDA Adverse Event Reporting System (FAERS) database.

Methods

Data were extracted from the FAERS database from Q3 2011 to Q3 2023. We analyzed the clinical characteristics of ADCs-related ocular adverse events (AEs). These data were further mined by proportional analysis and Bayesian approach to detect signals of ADCs-induced ocular AEs. Moreover, the time to onset of ocular toxicity was also evaluated.

Results

A total of 1,246 cases of ocular AEs were attributed to ADCs. Ocular toxicity signals were observed in patients treated with belantamab mafodotin, brentuximab vedotin, enfortumab vedotin, mirvetuximab soravtansine, sacituzumab govitecan, trastuzumab deruxtecan, and trastuzumab emtansine. Of these, belantamab mafodotin, trastuzumab emtansine, and mirvetuximab soravtansine, whose payloads are microtubule polymerization inhibitors, were more susceptible to ocular toxicity. The ten most common ADCs-related ocular AEs signals are keratopathy [ROR = 1,273.52, 95% CI (1,129.26–1,436.21)], visual acuity reduced [ROR = 22.83, 95% CI (21.2–24.58)], dry eye [ROR = 9.69, 95% CI (8.81–10.66)], night blindness [ROR = 259.87, 95% CI (228.23–295.89)], vision blurred [ROR = 1.78, 95% CI (1.57–2.02)], photophobia [ROR = 10.45, 95% CI (9.07–12.05)], foreign body sensation in eyes [ROR = 23.35, 95% CI (19.88–27.42)], ocular toxicity [ROR = 144.62, 95% CI (117.3–178.32)], punctate keratitis [ROR = 126.21, 95% CI (101.66–156.69)], eye disorder [ROR = 2.71, 95% CI (2.21–3.32)]. In terms of onset time, sacituzumab govitecan displayed an earlier onset of 21 days, while trastuzumab deruxtecan exhibited the latest onset of 223 days.

Conclusion

ADCs may increase the risk of ocular toxicity in cancer patients, leading to serious mortality. With the widespread application of newly launched ADCs, combining the FAERS data with other data sources is crucial for monitoring the ocular toxicity of ADCs. In addition, novel ocular toxicity signals not documented in product labeling were detected. Further research will be necessary to validate our findings in the future.
Nanoscale temperature sensors based on MIM waveguide coupling and ring-embedded nanostructures
Authors: Chen Hongfu , Yan Shubin , Cao Yuhao , Jiang Wen , Yan Xiaoran , Wang Chong , Liu Guang , Xu Aiwei , Wu Taiquan , Li Yuntang
Published: August 2024

This study presents a novel refractive index sensor based on Fano resonance, incorporating a metal-insulator-metal (MIM) waveguide coupled with a circular ring structure (CRC). Using finite element method analysis, we investigated the propagation properties of the sensor. To evaluate their influence on sensor performance, we systematically varied the parameters of each Circular Resonant Cavity structure component, including the refractive index, employing a controlled variable approach. At its optimal configuration, the sensor achieves a maximum sensitivity of 3,240 nm/RIU and a figure of merit (FOM) of 57.9. With its high sensitivity, straightforward design, and suitability for temperature detection, the refractive index sensor holds promise for diverse applications.
Calcium lignosulfonate-induced modification of soil chemical properties improves physiological traits and grain quality of maize (Zea mays) under salinity stress
Authors: Alhaj Hamoud Yousef , Shaghaleh Hiba , Zhang Ke , Okla Mohammad K. , Alaraidh Ibrahim A. , AbdElgawad Hamada , Sheteiwy Mohamed S.
Published: August 2024

Introduction

Salinity negatively affects maize productivity. However, calcium lignosulfonate (CLS) could improve soil properties and maize productivity.

Methods

In this study, we evaluated the effects of CLS application on soil chemical properties, plant physiology and grain quality of maize under salinity stress. Thus, this experiment was conducted using three CLS application rates, CLS0, CLS5, and CLS10, corresponding to 0%, 5%, and 10% of soil mass, for three irrigation water salinity (WS) levels WS0.5, WS2.5, and WS5.5 corresponding to 0.5 and 2.5 and 5.5 dS/m, respectively.

Results and discussion

Results show that the WS0.5 × CLS10 combination increased potassium (K 0.167 g/kg), and calcium (Ca, 0.39 g/kg) values while reducing the sodium (Na, 0.23 g/kg) content in soil. However, the treatment WS5.5 × CLS0 decreased K (0.120 g/kg), and Ca (0.15 g/kg) values while increasing Na (0.75 g/kg) content in soil. The root activity was larger in WS0.5 × CLS10 than in WS5.5 × CLS0, as the former combination enlarged K and Ca contents in the root while the latter decreased their values. The leaf glutamine synthetase (953.9 µmol/(g.h)) and nitrate reductase (40.39 µg/(g.h)) were higher in WS0.5 × CLS10 than in WS5.5 × CLS0 at 573.4 µmol/(g.h) and 20.76 µg/(g.h), leading to the improvement in cell progression cycle, as revealed by lower malonaldehyde level (6.57 µmol/g). The K and Ca contents in the leaf (881, 278 mg/plant), stem (1314, 731 mg/plant), and grains (1330, 1117 mg/plant) were greater in WS0.5 × CLS10 than in WS5.5 × CLS0 at (146, 21 mg/plant), (201, 159 mg/plant) and (206, 157 mg/plant), respectively. Therefore, the maize was more resistance to salt stress under the CLS10 level, as a 7.34% decline in yield was noticed when salinity surpassed the threshold value (5.96 dS/m). The protein (13.6 %) and starch (89.2 %) contents were greater in WS0.5 × CLS10 than in WS5.5 × CLS0 (6.1 %) and (67.0 %), respectively. This study reveals that CLS addition can alleviate the adverse impacts of salinity on soil quality and maize productivity. Thus, CLS application could be used as an effective soil amendment when irrigating with saline water for sustainable maize production.
Genetic dissection of value-added quality traits and agronomic parameters through genome-wide association mapping in bread wheat (T. aestivum L.)
Authors: Vishwakarma Manish K. , Bhati Pradeep K. , Kumar Uttam , Singh Ravi P. , Kumar Sundeep , Govindan Velu , Mavi Gurvinder Singh , Thiyagarajan Karthikeyan , Dhar Narain , Joshi Arun K.
Published: August 2024

Bread wheat (T. aestivum) is one of the world’s most widely consumed cereals. Since micronutrient deficiencies are becoming more common among people who primarily depend upon cereal-based diets, a need for better-quality wheat varieties has been felt. An association panel of 154 T. aestivum lines was evaluated for the following quality traits: grain appearance (GA) score, grain hardness (GH), phenol reaction (PR) score, protein percent, sodium dodecyl sulfate (SDS) sedimentation value, and test weight (TWt). In addition, the panel was also phenotyped for grain yield and related traits such as days to heading, days to maturity, plant height, and thousand kernel weight for the year 2017–18 at the Borlaug Institute for South Asia (BISA) Ludhiana and Jabalpur sites. We performed a genome-wide association analysis on this panel using 18,351 genotyping-by-sequencing (GBS) markers to find marker-trait associations for quality and grain yield-related traits. We detected 55 single nucleotide polymorphism (SNP) marker trait associations (MTAs) for quality-related traits on chromosomes 7B (10), 1A (9), 2A (8), 3B (6), 2B (5), 7A (4), and 1B (3), with 3A, 4A, and 6D, having two and the rest, 4B, 5A, 5B, and 1D, having one each. Additionally, 20 SNP MTAs were detected for yield-related traits based on a field experiment conducted in Ludhiana on 7D (4) and 4D (3) chromosomes, while 44 SNP MTAs were reported for Jabalpur on chromosomes 2D (6), 7A (5), 2A (4), and 4A (4). Utilizing these loci in marker-assisted selection will benefit from further validation studies for these loci to improve hexaploid wheat for better yield and grain quality.
Acceptance and commitment coaching for music performance anxiety in adolescent singers
Authors: Paul Anupa Elizabeth , Juncos David G. , Winter Debbie
Published: August 2024

Introduction

Most of the anxiety disorders, particularly social anxiety, seem to develop either during childhood or adolescence. Adolescent singers who experience physical, mental and emotional changes along with voice change are particularly prone to the development of MPA. However, adolescence also seems to be an opportune time to instil healthy behaviours in singing students as they are more likely to remember these coping strategies, owing to the release of dopamine and the ‘reminiscence bump’. As this period of a singer’s life is wrought with inevitable anxiety development, the additional aim of the study was to develop a coaching framework which can be used by singing teachers in their practice. Mindset training for adolescents seems crucial to help them continue singing through puberty so they do not drop out of singing lessons or choir during voice change and identity development.

Methods

The study aimed to determine if Acceptance and Commitment coaching could be used with adolescent singers with MPA and to record and analyse rich qualitative data in the form of semi-structured participant interviews and questionnaires.

Results

When their perception of MPA symptoms and physiological and psychological arousal before a performance changed, their behaviour and reactions changed accordingly. The change took place over a period of time, which was characterised by discoveries about themselves, confusion in understanding new concepts and letting go of old habits. Interestingly, by the end of the coaching sessions, their preoccupation with pleasing the audience and appearing perfect on stage was replaced by a new-found delight in pursuing values and goals related to their singing. Along with this came the acceptance of themselves and others as individuals with the potential for growth and change and the capacity to learn from mistakes.

Discussion

This study marks the first investigation into the effectiveness of using of ACC as an intervention for MPA in adolescent singers undergoing puberty by a singing teacher. The results are promising and suggest that ACC is an effective MPA intervention for adolescent singers to cope with inevitable development-related anxieties and keep them engaged in the activity of singing during their pubertal years.
Questioning evidence-based practice in physiotherapy: a philosophical reflection. The example of physiotherapy with musicians
Authors: Rousseau Céleste , Stiegler Barbara
Published: August 2024

Introduction

In the late 1990s, evidence-based medicine (EBM) emerged, emphasizing the conscientious use of current best evidence in medicine and ensuring the best care for each individual. Thus, applying evidence-based practice (EBP) in physiotherapy is complex due to sparse research, distinct challenges, and unsuitable tools. This is particularly relevant considering musicians’ health since the literature is very limited.

Part I

The first part advocates for EBP and explain how it ensures both the best care and adherence to ethical principles (beneficence, non-maleficence, respect for autonomy, and justice), for both caregivers and patients.

Part II

The second part discusses the common pitfalls often encountered by healthcare professionals, and especially as physiotherapists for musicians, when applying evidence at the patient’s bedside, again from both perspectives, healthcare professionals and patients.

Part III

Finally, this third part aims to open the discussion by considering various perspectives, such as values-based practice or the importance of qualitative research, to reshape EBP in physiotherapy.

Conclusion

This work highlights the prevalent existence of grey zones encountered by healthcare practitioners with musicians. While conducting more research to help understand them, physiotherapists must learn to navigate these waters.
The impact of family factors and digital technologies on mental health in university students
Authors: Gandarillas Miguel Ángel , Elvira-Zorzo María Natividad , Pica-Miranda Gabriela Alicia , Correa-Concha Bernardita
Published: August 2024

Introduction

A substantial body of research indicates an increasing prevalence of mental health issues among university students in a range of countries. A number of psychosocial factors have been put forward in the research literature as possible explanations for this persistent decline in psychological wellbeing in higher education. The present study focused on the role of family factors and the use of digital technologies by students.

Methods

A replication study was conducted at the University of the Americas (Chile) based on a previous study on psychosocial factors of academic learning patterns and mental health of university students at the Complutense University of Madrid (UCM), Spain. A cross-sectional design was employed, using the same questionnaire, plus indicators of most frequently used digital technologies by the students. The questionnaire was administered online at the same time to all incoming students, gathering a sample of 4,523 students. A series of multiple regressions and ANOVAs was conducted to ascertain the extent to which family and digital factors could be identified as predictors of mental health indicators.

Results

The most significant findings indicate that high levels of parental protection and control/discipline, and especially the high use of social media and smartphones, are particularly salient factors contributing to mental health problems in the learning process of higher education students.

Discussion

The results suggest strategies to promote wellbeing, with a focus on the psychosocial diversity within an inclusive university community. Social and digital innovation, collective entrepreneurship, and participatory place-building may facilitate networks of artistic, cultural, ecological, and sports spaces to promote the sense of university community. A longitudinal follow-up on the same sample across academic years will reveal the extent to which these wellbeing initiatives are fruitful.
Comparison of executive functions in Russian and Japanese preschoolers
Authors: Veraksa Aleksander , Hasegawa Mari , Bukhalenkova Daria , Almazova Olga , Aslanova Margarita , Matsumoto Emi
Published: August 2024

This study analyzed differences in level of main executive function (EF) components (such as inhibition, working memory, and cognitive flexibility) among Russian and Japanese preschoolers. The study involved 102 children of 5–6.9 years old: 51 child from Russia and 51 child from Japan. Out of 102 children 48 were boys and 54 girls. It was found that the cognitive flexibility level in Russian children is higher and inhibition level is lower than in Japanese children. The results of the boys’ EF comparison showed that boys from Russia have lower cognitive and physical inhibition levels than boys from Japan. Also it was shown that cognitive flexibility in Russian girls is significantly higher and cognitive inhibition is lower than in Japanese girls. The results obtained are discussed from the point of view of possible cultural differences in the two countries studied, which are manifested in the expectations of adults from children.
The genetic association between bipolar disorder and dementia: a qualitative review
Authors: Hirakawa Hirofumi , Terao Takeshi
Published: August 2024

Bipolar disorder is a chronic disorder characterized by fluctuations in mood state and energy and recurrent episodes of mania/hypomania and depression. Bipolar disorder may be regarded as a neuro-progressive disorder in which repeated mood episodes may lead to cognitive decline and dementia development. In the current review, we employed genome-wide association studies to comprehensively investigate the genetic variants associated with bipolar disorder and dementia. Thirty-nine published manuscripts were identified: 20 on bipolar disorder and 19 on dementia. The results showed that the genes CACNA1C, GABBR2, SCN2A, CTSH, MSRA, and SH3PXD2A were overlapping between patients with bipolar disorder and dementia. In conclusion, the genes CACNA1C, GABBR2, SCN2A, CTSH, MSRA, and SH3PXD2A may be associated with the neuro-progression of bipolar disorder to dementia. Further genetic studies are needed to comprehensively clarify the role of genes in cognitive decline and the development of dementia in patients with bipolar disorder.
How is parental psychological control associated with adolescent mental health in economically disadvantaged areas? The serial mediating role of psychological reactance and problematic smartphone use
Authors: Li Qiangqiang , Wei Shuwen , Liu Zixiao
Published: August 2024

Introduction

Adolescent mental health has been an issue of global concern, and the mental health of adolescents in economically disadvantaged areas may require additional research. The research delves into factors associated with economically disadvantaged areas’ adolescent mental health, employing family systems theory, self-determination theory, and psychological reactance theory. Specifically, the present study which was done in Jingzhou country, an economically disadvantaged area of Hunan Province, China, aimed to examine the link between parental psychological control and adolescent mental health, as well as the mediating roles of psychological reactance and problematic smartphone use in this relationship.

Methods

A sample of 1300 Chinese middle school students (620 girls, mean age = 14.22 ± 1.29) completed self-reported measures of parental psychological control, psychological reactance, problematic smartphone use, and adolescent mental health.

Results

Results showed that parental psychological control was negatively associated with adolescent mental health. Psychological reactance and problematic smartphone use mediated the association between parental psychological control and adolescent mental health, separately and serially.

Discussion

The findings of the present study enrich the literature on parenting styles and adolescent mental health in economically disadvantaged areas, and this provides an intervention perspective to reduce the negative impact of poor parenting on adolescent mental health in economically disadvantaged areas.