bluuebunny/crossref_metadata_2025 huggingface dataset:
Survival of bronchopulmonary cancers according to radon exposure
Authors: Dessemon Juliette , Perol Olivia , Chauvel Cécile , Noelle Hugo , Coudon Thomas , Grassot Lény , Foray Nicolas , Belladame Elodie , Fayette Jérôme , Fournie Françoise , Swalduz Aurélie , Neidhart Eve-Marie , Saintigny Pierre , Tabutin Mayeul , Boussageon Maxime , Gomez Frédéric , Avrillon Virginie , Perol Maurice , Charbotel Barbara , Fervers Béatrice
Published: January 2024

Introduction

Residential exposure is estimated to be responsible for nearly 10% of lung cancers in 2015 in France, making it the second leading cause, after tobacco. The Auvergne-Rhône-Alpes region, in the southwest of France, is particularly affected by this exposure as 30% of the population lives in areas with medium or high radon potential. This study aimed to investigate the impact of radon exposure on the survival of lung cancer patients.

Methods

In this single-center study, patients with a histologically confirmed diagnosis of lung cancer, and newly managed, were prospectively included between 2014 and 2020. Univariate and multivariate survival analyses were carried out using a non-proportional risk survival model to consider variations in risk over time.

Results

A total of 1,477 patients were included in the analysis. In the multivariate analysis and after adjustment for covariates, radon exposure was not statistically associated with survival of bronchopulmonary cancers (HR = 0.82 [0.54–1.23], HR = 0.92 [0.72–1.18], HR = 0.95 [0.76–1.19] at 1, 3, and 5 years, respectively, for patients residing in category 2 municipalities; HR = 0.87 [0.66–1.16], HR = 0.92 [0.76–1.10], and HR = 0.89 [0.75–1.06] at 1, 3, and 5 years, respectively, for patients residing in category 3 municipalities).

Discussion

Although radon exposure is known to increase the risk of lung cancer, in the present study, no significant association was found between radon exposure and survival of bronchopulmonary cancers.
Association between alcohol consumption and latent fasting blood glucose trajectories among midlife women
Authors: Wang Xingzhou , Lin Song , Wang Xiwei , Gao Pengxia , Chen Juan
Published: January 2024

Background

This investigation sought to elucidate the correlations between alcohol intake and trajectories of fasting blood glucose (FBG) among American women in midlife.

Methods

Our analysis was rooted in the foundational data from the Study of Women’s Health Across the Nation (SWAN), a comprehensive longitudinal study centered on US women during their midlife transition. We employed group-based trajectory modeling to chart the FBG trajectories spanning from 1996 to 2005. Employing logistic regression, we gauged the odds ratios (ORs) and 95% confidence intervals (CIs) to draw connections between initial alcohol consumption and FBG trajectory patterns, whilst controlling for predominant potential confounders.

Results

Our cohort comprised 2,578 women in midlife, ranging in age from 42 to 52, each having a minimum of three subsequent FPG assessments. We discerned two distinct FBG trajectories: a low-stable pattern (n = 2,467) and a high-decreasing pattern (n = 111). Contrasted with the low-stable group, our data showcased an inverse relationship between alcohol intake and the high-decreasing FBG trajectory in the fully adjusted model 3. The most pronounced reduction was evident in the highest tertile of daily servings of alcoholic beverages (OR: 0.23, 95% CI: 0.10–0.52, p < 0.001), percentage of kilocalories sourced from alcoholic beverages (OR: 0.30, 95% CI: 0.16–0.58, p < 0.001), and daily caloric intake from alcoholic beverages (OR: 0.31, 95% CI: 0.16–0.62, p < 0.001).

Conclusion

Moderate alcohol consumption may protect against high FPG trajectories in middle-aged women in a dose–response manner. Further researches are needed to investigate this causality in midlife women.
BK polyomavirus infection: more than 50 years and still a threat to kidney transplant recipients
Authors: Parajuli Sandesh , Aziz Fahad , Zhong Weixiong , Djamali Arjang
Published: January 2024

BK polyomavirus (BKPyV) is a ubiquitous human polyomavirus and a major infection after kidney transplantation, primarily due to immunosuppression. BKPyV reactivation can manifest as viruria in 30%–40%, viremia in 10%–20%, and BK polyomavirus-associated nephropathy (BKPyVAN) in 1%–10% of recipients. BKPyVAN is an important cause of kidney graft failure. Although the first case of BKPyV was identified in 1971, progress in its management has been limited. Specifically, there is no safe and effective antiviral agent or vaccine to treat or prevent the infection. Even in the current era, the mainstay approach to BKPyV is a reduction in immunosuppression, which is also limited by safety (risk of de novo donor specific antibody and rejection) and efficacy (graft failure). However, recently BKPyV has been getting more attention in the field, and some new treatment strategies including the utilization of viral-specific T-cell therapy are emerging. Given all these challenges, the primary focus of this article is complications associated with BKPyV, as well as strategies to mitigate negative outcomes.
Watching Out for Coral Reefs With Forams
Authors: Girard Elsa B. , Renema Willem
Published: January 2024

Lots of creatures live in coral reefs, including some tiny ones you might never have heard of. In this article, we will tell you about the importance of Foraminifera (also called forams), unicellular organisms with shells, that contribute to coral reefs in many ways. Just like corals, some forams living on the seafloor live closely together with microalgae. Some forams also thrive in similar environmental conditions (sunlight, temperature, salt) as corals. For this reason, forams can be used as reef “sensors”, to keep track of the overall health of coral reefs. They can even help to detect poor environmental conditions that might harm coral growth in the future. In this article, we will look at a study of an Indonesian reef ecosystem in which the foram communities living on the seafloor were monitored between 1997 and 2018.
Exploring the link between perceived physical literacy and academic performance outcomes: insights from the EHDLA study
Authors: Domínguez-Martín Gabriel , Tárraga-López Pedro J. , López-Gil José Francisco
Published: January 2024

Objective

The aim of this study was to verify the relationship between perceived physical literacy (PPL) and academic performance outcomes among Spanish adolescents aged 12–17 years.

Methods

This cross-sectional study is a secondary examination utilizing data derived from the Eating Healthy and Daily Life Activities (EHDLA) project. The Spanish Perceived Physical Literacy Instrument for Adolescents (S-PPLI) was used to evaluate the PPL of the participants. To determine academic performance, the numerical grades for each subject were added together and then divided by the total number of subjects.

Results

Overall, a positive trend in the association between S-PPLI scores and academic performance was observed. We identified two significant ranges within the S-PPLI scores. First, there was a significant range between 9 and 33 points on the S-PPLI, indicating an inverse association with academic performance. Second, another significant range was observed at scores of 34 points or higher on the S-PPLI, suggesting a positive association with academic performance. Participants with low PPL had the lowest academic performance (mean = 6.4; bias-corrected and accelerated (BCa) bootstrapped 95% confidence interval (CI): 6.2–6.6). Conversely, those adolescents with high PPL had the highest academic performance (mean = 6.9; BCa bootstrapped 95% CI: 6.6–7.1). Significant differences were found between low PPL and medium PPL (p-adjusted = 0.031) and between low PPL and high PPL (p-adjusted = 0.031).

Conclusions

Increased physical literacy could be a relevant factor for achieving greater academic performance in adolescents. This study has potential implications for physical education instructors, school leaders, and healthcare practitioners.
Hot spots and frontiers in bone-tendon interface research: a bibliometric analysis and visualization from 2000 to 2023
Authors: Xiao Hao , Wen Boyuan , Yan Dong , Li Quansi , Yang Yujie , Yin Xianye , Chen Deyu , Liu Jiachen
Published: January 2024

Objective

In this research, we investigated the current status, hotspots, frontiers, and trends of research in the field of bone-tendon interface (BTI) from 2000 to 2023, based on bibliometrics and visualization and analysis in CiteSpace, VOSviewer, and a bibliometric package in R software.

Methods

We collected and organized the papers in the Web of Science core collection (WoSCC) for the past 23 years (2000–2023), and extracted and analyzed the papers related to BTI. The extracted papers were bibliometrically analyzed using CiteSpace for overall publication trends, authors, countries/regions, journals, keywords, research hotspots, and frontiers.

Results

A total of 1,995 papers met the inclusion criteria. The number of papers published and the number of citations in the field of BTI have continued to grow steadily over the past 23 years. In terms of research contribution, the United States leads in terms of the number and quality of publications, number of citations, and collaborations with other countries, while the United Kingdom and the Netherlands lead in terms of the average number of citations. The University of Leeds publishes the largest number of papers, and among the institutions hosting the 100 most cited papers Hospital for Special Surgery takes the top spot. MCGONAGLE D has published the highest number of papers (73) in the last 10 years. The top three clusters include #0 “psoriatic arthritis”, #1 “rotator cuff repair”, and #2 “tissue engineering”. The structure and function of the BTI and its key mechanisms in the healing process are the key to research, while new therapies such as mechanical stimulation, platelet-rich plasma, mesenchymal stem cells, and biological scaffolds are hot topics and trends in research.

Conclusion

Over the past 23 years, global research on the BTI has expanded in both breadth and depth. The focus of research has shifted from studies concentrating on the structure of the BTI and the disease itself to new therapies such as biomaterial-based alternative treatments, mechanical stimulation, platelet-rich plasma, etc.
CMV Infection and Lymphopenia: Warning Markers of Pneumocystis Pneumonia in Kidney Transplant Recipients
Authors: Eberl Isabelle , Binquet Christine , Guilloteau Adrien , Legendre Mathieu , Dalle Frederic , Piroth Lionel , Tinel Claire , Blot Mathieu
Published: January 2024

Pneumocystis pneumonia (PcP) remains life-threatening in kidney transplant recipients (KTR). Our study investigated risk factors one-year before PcP. We conducted a monocentric, case-control study including all KTR at the Dijon University Hospital (France) with a diagnosis of PcP between 2005 and 2022 (cases), and matched control KTR with no history of PcP (3 controls/case). Among all 1,135 KTR, 57 cases (5%) and 169 matched-controls were included. PcP was associated with 18% mortality. Compared to controls, cases were older, with a higher immunological risk, and CMV infection was more frequent in the year preceding the occurrence of PcP (23% vs. 4%; p < 0.001). As early as 1 year before PcP, lymphocyte counts were lower and serum creatinine levels were higher in cases, but immunosuppressive regimens were not significantly different. Multivariable analysis identified lymphocyte count, serum creatinine level, being treated by immunosuppressive therapy other than anti-rejection drugs, and CMV infection in the year preceding the time PcP as independently associated with the occurrence of PcP. PcP was associated with an increased risk of subsequent chronic rejection (27% vs. 3%; p = 0.001) and return to dialysis (20% vs. 3%; p = 0.002). The occurrence of CMV infection and a low lymphocyte count could redefine the indications for continuation or reinitiation of anti-Pneumocystis prophylaxis.
Ludzki człowiek. O rzadkim, lecz interesującym użyciu polskiego przymiotnika w zestawieniu z angielskim human
Authors: Ciunovič Małgorzata
Published: January 2024

The lexemes ludzki and human are treated (e.g. in didactics and translation studies) as equivalents, which is refl ected in the dictionary descriptions of the meanings of these words. At the same time, the analysis of the contexts where the expression ludzki człowiek is used leads to other conclusions: not all contents of the Polish adjective are present in its English equivalent. Ludzki is also ‘one who suspends the operation of principles for the sake of another human being’. This component of a more general meaning (‘consistent with the human nature, conceived as good; hence: characterised by favourable disposition, understanding for other people; humane, merciful, gentle, kind’, SJPDor) seems to be absent from English (adjectives human and humane).This article applies the methodology based on the pragmatic analysis of the communication situation and consideration for the context of the utterance/statement (after Grzegorczykowa 1990). The language material used was derived from the following corpora: NKJP (National Corpus of Polish), BNC (British National Corpus), and COCA (Corpus of Contemporary American English).
Poetyckie sposoby wyrażania ocen. Wartościująca funkcja formy metrycznej w wierszu Juliana Tuwima Ruch
Authors: Dobrzyńska Teresa
Published: January 2024

This aticle discusses briefly the evaluation devices encoded in language (axiological vocabulary) and more complex ways of expressing evaluaƟtions used in utterances and statements and based on the employment of connotations and conversational implicatures (comparisons, metaphors, irony). The subject of a closer analysis is the use of the verse form in the evaluative function. The combined applicaƟtion of a variety of evaluative devices, including versological ones, is illustrated by Ruch (Movement) by Julian Tuwim. The metrical structure of this poem, i.e. the 4-accent tonic verse, which is rarely used in Poland, functions as a sound metaphor that contributes to the grotesque image of the movement of passers-by hurrying without a clear purpose along the streets of the city, and hence the tonic rhythm becomes an important factor in the satirical approach to the work’s theme
Aktorska i amatorska: dwie interpretacje głosowe tego samego wiersza
Authors: Bańko Mirosław
Published: January 2024

This article concerns two vocal interpretations of the poem Dwa wiatry (Two Winds) by Julian Tuwim: one comes from an actor, the other from an amateur publishing educational materials on the Internet. The aim is to explain why the actor’s interpretation seems more suggestive than the amateur one. The subject of the study is the prosodic features of both performances of the poem (tempo, sound intensity, and tone changes), treated as an iconic indicator of its cognitive and emotional content. This article is a continuation of an earlier publication in which Tuwim’s Lokomotywa (Locomotive) was examined in a similar way. In both studies, the Praat programme for acoustic analysis of sound was used for research.
Emerging Technologies Revolutionising Public Procurement: Insights from Comprehensive Bibliometric Analysis
Authors: Mavidis Aristotelis , Folinas Dimitris , Skiadas Dimitrios , Xanthopoulos Alexandros
Published: January 2024

This study aims to deepen our understanding of the evolving landscape of public procurement (PP) and emerging technologies (ET). It addresses the critical gap in scholarly production analysis, author collaborations, and thematic trends in PP and ET, providing valuable insights for researchers, policymakers, and practitioners. Employing a methodology inspired by prior research, this study leveraged advanced bibliometric tools, including Studio R and the Biblioshiny app, for data retrieval, processing, and visualization. This approach facilitated co-citation, source coupling, and network collaboration analyses. Thematic maps and correspondence analysis were used to explore research themes in depth. The findings highlight a significant surge in research interest in the integration of ET in PP since 2018, underlining the growing importance of technology-driven advancements in the field. These insights are vital for shaping policy decisions, spurring innovation, and enhancing PP processes’ efficiency, transparency, and sustainability, which are crucial for effective governance and economic growth.
Towards Artificial Intelligence Applications in Precision and Sustainable Agriculture
Authors: Son Nguyenthanh , Chen Cheng-Ru , Syu Chien-Hui
Published: January 2024

Agriculture is the backbone of many economies across the globe [...]
ESG-YOLO: A Method for Detecting Male Tassels and Assessing Density of Maize in the Field
Authors: Wu Wendi , Zhang Jianhua , Zhou Guomin , Zhang Yuhang , Wang Jian , Hu Lin
Published: January 2024

The intelligent acquisition of phenotypic information on male tassels is critical for maize growth and yield assessment. In order to realize accurate detection and density assessment of maize male tassels in complex field environments, this study used a UAV to collect images of maize male tassels under different environmental factors in the experimental field and then constructed and formed the ESG-YOLO detection model based on the YOLOv7 model by using GELU as the activation function instead of the original SiLU and by adding a dual ECA attention mechanism and an SPD-Conv module. And then, through the model to identify and detect the male tassel, the model’s average accuracy reached a mean value (mAP) of 93.1%; compared with the YOLOv7 model, its average accuracy mean value (mAP) is 2.3 percentage points higher. Its low-resolution image and small object target detection is excellent, and it can be more intuitive and fast to obtain the maize male tassel density from automatic identification surveys. It provides an effective method for high-precision and high-efficiency identification of maize male tassel phenotypes in the field, and it has certain application value for maize growth potential, yield, and density assessment.
Commercial Cultivation of Edible Halophytes: The Issue of Oxalates and Potential Mitigation Options
Authors: Barkla Bronwyn J. , Farzana Tania , Rose Terry J.
Published: January 2024

Saline agriculture, including the commercial cultivation of edible halophytes, is expanding rapidly to address the increase in salinised soil due to natural and man-made causes, the decline in availability of fresh water, the increased use of poor-quality water, and increasing food insecurity. Halophytes, as food crops, offer an innovative new opportunity in agriculture, many being highly nutritious and containing bioactive compounds. However, the commercial production of edible halophytes to meet emerging consumer demands faces several challenges. This review examines the market potential for the expansion of edible halophyte crops and the challenges of consumer acceptance and production capacity beyond wild harvest. In addition to beneficial compounds, halophytes are known to contain several anti-nutrient compounds, which can have negative health consequences. In edible halophytes, oxalates are of particular concern. However, research has shown that there are ways to mitigate the accumulation of oxalate through processing, agronomic practice, and genetic engineering. These approaches are presented as potential strategies that can be used in commercial farming systems to reduce the levels of this compound.
Functional Analysis of MoMyb13, a Myb Transcription Factor Involved in Regulating Growth, Conidiation, Hydrophobicity, and Pathogenicity of Magnaporthe oryzae
Authors: Li Ya , Zheng Xiuxia , Pei Mengtian , Chen Mengting , Zhang Shengnan , Liang Chenyu , Gao Luyao , Huang Pin , Olsson Stefan
Published: January 2024

The Myb family of transcription factors (TFs) is a large and functionally diverse group found in all eukaryotes. Its role in fungi remains poorly studied, despite the fact that it is thought to play a role in the pathogenicity of fungal pathogens. In this study, we have characterized the functional role of a Myb family TF called MoMyb13 in the rice blast fungus, Magnaporthe oryzae. MoMyb13 has orthologues only in ascomycete fungi, making it of special interest. Localization experiments confirmed that MoMyb13 is located in the nuclei, as expected for a TF. Phenotypic analysis showed that MoMyb13 mutants exhibited reduced growth, white instead of dark colonies, formed no conidia and, consequently, no conidial appressoria. The mutants completely lost pathogenicity, despite being able to form dark hyphal appressoria at their hyphae ends. Furthermore, the mutant colonies lost hydrophobicity and had significantly reduced expression of the hydrophobin MPG1 that MoMyb13 appears to regulate. However, overexpression of MPG1 in the mutants restored hydrophobicity, but not pathogenicity. Stress assay showed that the mutants were more sensitive to SDS, CR, and H2O2, but more tolerant to NaCl and SOR. In summary, our study revealed the crucial function of MoMyb13 in the growth, conidiation, hydrophobicity, stress response, and pathogenicity of M. oryzae. MoMyb13 is thus needed in the late and very early stages of infection for the spreading of the fungus to other plants and the early establishment of infection in other plants.
Mitochonic Acid 5 Increases Ram Sperm Quality by Improving Mitochondrial Function during Storage at 4 °C
Authors: Wang Ruyuan , Liu Luwei , Min Lingjiang , Adetunji Adedeji O. , Kou Xin , Zhou Kaifeng , Zhu Zhendong
Published: January 2024

Semen preservation involves lengthening sperm’s fertile lifespan without any detrimental effects on its biochemical, functional, and ultrastructural properties. Liquid storage at 4 °C is a ram sperm preservation method. However, this method of storage causes irreversible damage due to cold shocks, osmotic stresses, oxidative stresses, and reductions in sperm metabolism. The present study aims to investigate whether the supplementation of mitochonic acid 5 (MA-5) in a sperm extender could improve chilled ram sperm quality and elucidate its mechanism of action. Ram sperm were diluted with a tris-citrate-glucose extender containing different concentrations of MA-5 (0, 0.1, 1, 10, and 100 nM) and stored at 4 °C for up to 48 h. Sperm motility, membrane integrity, acrosome integrity, mitochondrial membrane potential, reactive oxygen species (ROS) level, ATP content, and the expression of NADPH dehydrogenase subunits 1 (MT-ND1) and NADPH dehydrogenase subunits 6 (MT-ND6) were evaluated. It was observed that compared to the control, the 10 nM MA-5 treatment significantly (p < 0.05) increased total motility (82 ± 3.5% vs. 76 ± 5.9%), progressive motility (67.6 ± 8.2% vs. 51 ± 8.3%), and other parameters (straight-line velocity (VSL), average path velocity (VAP), and curvilinear velocity (VCL)). In addition, 10 nM MA-5 supplementation also improved ram sperm membrane integrity and acrosomal integrity as well increased mitochondrial membrane potential (51.1 ± 0.7% vs. 37.7 ± 1.3%), reduced ROS levels, and elevated adenosine triphosphate (ATP) contents. Furthermore, a Western blot analysis demonstrated that the addition of MA-5 significantly (p < 0.05) increased the expression of MT-ND1 and MT-ND6 proteins in ram sperm, with the 10 nM MA-5 treatment resulting in the highest expression level. These results suggest that MA-5 improves ram sperm quality by maintaining high sperm mitochondrial function during liquid storage at 4 °C.
3D Morphological Scanning and Environmental Correlates of Bufo gargarizans in the Yellow River Basin
Authors: Li Zihan , Guo Xuecheng , Guo Zeguang , Shi Xiaoqin , Zhou Jin , Liu Zhidong , Xiao Qi , Chen Youhua
Published: January 2024

Morphology plays a crucial role in understanding the intricacies of biological forms. Traditional morphometric methods, focusing on one- or two-dimensional geometric levels, often fall short of accurately capturing the three-dimensional (3D) structure of organisms. The advent of 3D scanning techniques has revolutionized the study of organismal morphology, enabling comprehensive and accurate measurements. This study employs a 3D structured light scanning system to analyze the morphological variations in the Chinese toad (Bufo gargarizans Cantor, 1842) along the Yellow River Basin. The 3D digital model obtained from the scan was used to calculate various morphological parameters including body surface area, volume, fractal dimensions, and limb size. The research explores geographic variability patterns and identifies environmental drivers affecting the 3D phenotypic variation of B. gargarizans. Results reveal a bimodal pattern of variation in the toad population, with higher elevations exhibiting smaller body sizes, greater appendage proportions, and more complex body structures. Linear regression analyses highlight the influence of elevation and annual mean temperature on the morphological variation of B. gargarizans, with elevation playing a significant role. This study underscores the significance of 3D morphometric analysis in unraveling the intricacies of organismal morphology and understanding the adaptive strategies of species in diverse environments.
A Precision Assessment of a Point-of-Care Immunological Analyzer for Swift Progesterone Measurement and Guidance for Determining the Optimal Breeding Time in Bitches
Authors: Suwannachote Thanikran , Wutthiwitthayaphong Supphathat , Arayatham Saengtawan , Prasitsuwan Wisut , Ruenphet Sakchai
Published: January 2024

The measurement of serum progesterone often varies due to different laboratory methodologies and individual canine characteristics. In this investigation, serum progesterone outcomes obtained from a commercial point-of-care immunological analyzer, designed for efficient serum progesterone assessment in bitches, were compared with results derived from chemiluminescent microparticle immunoassay from reference laboratories in Thailand. Our thorough documentation encompassed various parameters: mean, standard deviation, 95% confidence interval, and minimum and maximum serum progesterone concentration values. Additionally, we meticulously recorded the Pearson’s correlation coefficient, Lin’s concordance correlation coefficient, and the bias correction factor. Interestingly, there was no significant difference (p > 0.05) in the means obtained by the point-of-care immunological analyzer and chemiluminescent microparticle immunoassay. The Pearson’s correlation coefficient between the point-of-care immunological analyzer and chemiluminescent microparticle immunoassay stood at 0.957, with Lin’s concordance correlation coefficient for point-of-care immunological analyzer recorded as 0.949. Furthermore, the bias correction factor was established at 0.991. This investigation followed established chemiluminescent microparticle immunoassay guidelines, modified to incorporate the mean and 95% confidence interval as criteria for optimal breeding time using the point-of-care immunological analyzer. In conclusion, the commercial point-of-care immunological analyzer emerges as a valuable tool, aiding in precisely determining the optimal timing for natural mating or artificial insemination in bitches.
Exploring Novel Frontiers: Leveraging STAT3 Signaling for Advanced Cancer Therapeutics
Authors: Adesoye Taiwo , Tripathy Debasish , Hunt Kelly K. , Keyomarsi Khandan
Published: January 2024

Signal Transducer and Activator of Transcription 3 (STAT3) plays a significant role in diverse physiologic processes, including cell proliferation, differentiation, angiogenesis, and survival. STAT3 activation via phosphorylation of tyrosine and serine residues is a complex and tightly regulated process initiated by upstream signaling pathways with ligand binding to receptor and non-receptor-linked kinases. Through downstream deregulation of target genes, aberrations in STAT3 activation are implicated in tumorigenesis, metastasis, and recurrence in multiple cancers. While there have been extensive efforts to develop direct and indirect STAT3 inhibitors using novel drugs as a therapeutic strategy, direct clinical application remains in evolution. In this review, we outline the mechanisms of STAT3 activation, the resulting downstream effects in physiologic and malignant settings, and therapeutic strategies for targeting STAT3. We also summarize the pre-clinical and clinical evidence of novel drug therapies targeting STAT3 and discuss the challenges of establishing their therapeutic efficacy in the current clinical landscape.
Nivolumab Plus 5-Azacitidine in Pediatric Relapsed/Refractory Acute Myeloid Leukemia (AML): Phase I/II Trial Results from the Therapeutic Advances in Childhood Leukemia and Lymphoma (TACL) Consortium
Authors: Verma Anupam , Chi Yueh-Yun , Malvar Jemily , Lamble Adam , Chaudhury Sonali , Agarwal Archana , Li Hong-Tao , Liang Gangning , Leong Roy , Brown Patrick A. , Kaplan Joel , Schafer Eric S. , Slone Tamra , Pauly Melinda , Chang Bill H. , Stieglitz Elliot , Wayne Alan S. , Hijiya Nobuko , Bhojwani Deepa
Published: January 2024

Improvements in survival have been made over the past two decades for childhood acute myeloid leukemia (AML), but the approximately 40% of patients who relapse continue to have poor outcomes. A combination of checkpoint-inhibitor nivolumab and azacitidine has demonstrated improvements in median survival in adults with AML. This phase I/II study with nivolumab and azacitidine in children with relapsed/refractory AML (NCT03825367) was conducted through the Therapeutic Advances in Childhood Leukemia & Lymphoma consortium. Thirteen patients, median age 13.7 years, were enrolled. Patients had refractory disease with multiple reinduction attempts. Twelve evaluable patients were treated at the recommended phase II dose (established at dose level 1, 3 mg/kg/dose). Four patients (33%) maintained stable disease. This combination was well tolerated, with no dose-limiting toxicities observed. Grade 3–4 adverse events (AEs) were primarily hematological. Febrile neutropenia was the most common AE ≥ grade 3. A trend to improved quality of life was noted. Increases in CD8+ T cells and reductions in CD4+/CD8+ T cells and demethylation were observed. The combination was well tolerated and had an acceptable safety profile in pediatric patients with relapsed/refractory AML. Future studies might explore this combination for the maintenance of remission in children with AML at high risk of relapse.
Novel LIPA-Targeted Therapy for Treating Ovarian Cancer
Authors: Collier Alexia B. , Viswanadhapalli Suryavathi , Gopalam Rahul , Lee Tae-Kyung , Kassees Kara , Parra Karla , Sharma Gaurav , Reese Tanner C. , Liu Xihui , Yang Xue , Ebrahimi Behnam , Pratap Uday P. , Mahajan Megharani , Arnold William C. , Baker Adriana , Chen Chia-Yuan , Elmore Scott Terry , Subbarayalu Panneerdoss , Sareddy Gangadhara R. , Valente Philip T. , Kost Edward R. , Ahn Jung-Mo , Vadlamudi Ratna K.
Published: January 2024

Ovarian cancer (OCa) is the most lethal form of gynecologic cancer, and the tumor heterogeneities at the molecular, cellular, and tissue levels fuel tumor resistance to standard therapies and pose a substantial clinical challenge. Here, we tested the hypothesis that the heightened basal endoplasmic reticulum stress (ERS) observed in OCa represents an exploitable vulnerability and may overcome tumor heterogeneity. Our recent studies identified LIPA as a novel target to induce ERS in cancer cells using the small molecule ERX-41. However, the role of LIPA and theutility of ERX-41 to treat OCa remain unknown. Expression analysis using the TNMplot web tool, TCGA data sets, and immunohistochemistry analysis using a tumor tissue array showed that LIPA is highly expressed in OCa tissues, compared to normal tissues. ERX-41 treatment significantly reduced the cell viability and colony formation ability and promoted the apoptosis of OCa cells. Mechanistic studies revealed a robust and consistent induction of ERS markers, including CHOP, elF2α, PERK, and ATF4, upon ERX-41 treatment. In xenograft and PDX studies, ERX-41 treatment resulted in a significant reduction in tumor growth. Collectively, our results suggest that ERX-41 is a novel therapeutic agent that targets the LIPA with a unique mechanism of ERS induction, which could be exploited to treat heterogeneity in OCa.
Sargramostim for Prophylactic Management of Gastrointestinal Immune-Related Adverse Events of Immune Checkpoint Inhibitor Therapy for Cancer
Authors: Dougan Michael , Nguyen Long , Buchbinder Elizabeth , Lazarus Hillard
Published: January 2024

Immune checkpoint inhibitor (ICI) therapy improves outcomes in several cancers. Unfortunately, many patients experience grade 3–4 treatment-related adverse events, including gastrointestinal (GI) toxicities which are common. These GI immune-related adverse events (irAEs) induced by ICIs present significant clinical challenges, require prompt intervention, and result in treatment delays or discontinuations. The treatment for these potentially severe and even fatal GI irAEs which include enterocolitis, severe diarrhea, and hepatitis may interfere with the anti-cancer approach. Sargramostim (glycosylated, yeast-derived, recombinant human GM-CSF) is an agent that has been used in clinical practice for more than 30 years with a well-recognized safety profile and has been studied in many therapeutic areas. The mechanism of action of sargramostim may treat moderate-to-severe GI irAEs without impairing the anti-cancer therapy. Some early data also suggest a potential survival benefit. Through the differentiation/maturation of monocytes, macrophages, and neutrophils and induction of anti-inflammatory T cell responses, GM-CSF aids in GI homeostasis, mucosal healing, and mucosal immunity. GM-CSF knockout mice are susceptible to severe colitis which was prevented with murine GM-CSF administration. For some patients with GI mucosa and immune cell function impairment, e.g., Crohn’s disease, sargramostim reduces disease severity. In a prospective, randomized study (ECOG 1608), advanced melanoma patients had a reduction in grade 3–5 GI irAEs and less frequent colonic perforation in the sargramostim plus ipilimumab arm compared to ipilimumab alone. Sargramostim continues to be studied with ICIs for the prophylactic management of irAEs while also potentially providing a survival benefit.
Correction: Antón-García et al. TGFβ1-Induced EMT in the MCF10A Mammary Epithelial Cell Line Model Is Executed Independently of SNAIL1 and ZEB1 but Relies on JUNB-Coordinated Transcriptional Regulation. Cancers 2023, 15, 588
Authors: Antón-García Pablo , Haghighi Elham Bavafaye , Rose Katja , Vladimirov Georg , Boerries Melanie , Hecht Andreas
Published: January 2024

In the original publication [...]
Single-Cell Transcriptional Response of the Placenta to the Ablation of Caveolin-1: Insights into the Adaptive Regulation of Brain–Placental Axis in Mice
Authors: Islam Maliha , Behura Susanta K.
Published: January 2024

Caveolin-1 (Cav1) is a major plasma membrane protein that plays important functions in cellular metabolism, proliferation, and senescence. Mice lacking Cav1 show abnormal gene expression in the fetal brain. Though evidence for placental influence on brain development is emerging, whether the ablation of Cav1 affects the regulation of the brain–placental axis remains unexamined. The current study tests the hypothesis that gene expression changes in specific cells of the placenta and the fetal brain are linked to the deregulation of the brain–placental axis in Cav1-null mice. By performing single-nuclei RNA sequencing (snRNA-seq) analyses, we show that the abundance of the extravillious trophoblast (EVT) and stromal cells, but not the cytotrophoblast (CTB) or syncytiotrophoblast (STB), are significantly impacted due to Cav1 ablation in mice. Interestingly, specific genes related to brain development and neurogenesis were significantly differentially expressed in trophoblast cells due to Cav1 deletion. Comparison of single-cell gene expression between the placenta and the fetal brain further showed that specific genes such as plexin A1 (Plxna1), phosphatase and actin regulator 1 (Phactr1) and amyloid precursor-like protein 2 (Aplp2) were differentially expressed between the EVT and STB cells of the placenta, and also, between the radial glia and ependymal cells of the fetal brain. Bulk RNA-seq analysis of the whole placenta and the fetal brain further identified genes differentially expressed in a similar manner between the placenta and the fetal brain due to the absence of Cav1. The deconvolution of reference cell types from the bulk RNA-seq data further showed that the loss of Cav1 impacted the abundance of EVT cells relative to the stromal cells in the placenta, and that of the glia cells relative to the neuronal cells in the fetal brain. Together, the results of this study suggest that the ablation of Cav1 causes deregulated gene expression in specific cell types of the placenta and the fetal brain in mice.
Genetic Predisposition for White Matter Hyperintensities and Risk of Mild Cognitive Impairment and Alzheimer’s Disease: Results from the HELIAD Study
Authors: Sampatakakis Stefanos N. , Mourtzi Niki , Charisis Sokratis , Mamalaki Eirini , Ntanasi Eva , Hatzimanolis Alexandros , Ramirez Alfredo , Lambert Jean-Charles , Yannakoulia Mary , Kosmidis Mary H. , Dardiotis Efthimios , Hadjigeorgiou Georgios , Sakka Paraskevi , Scarmeas Nikolaos
Published: January 2024

The present study investigated the association of genetic predisposition for white matter hyperintensities (WMHs) with incident amnestic mild cognitive impairment (aMCI) or Alzheimer’s disease (AD), as well as whether such an association was influenced by age, sex, and cognitive reserve. Overall, 537 individuals without aMCI or dementia at baseline were included. Among them, 62 individuals developed aMCI/AD at follow up. Genetic propensity to WMH was estimated using a polygenic risk score for WMHs (PRS WMH). The association of PRS WMH with aMCI/AD incidence was examined using COX models. A higher PRS WMH was associated with a 47.2% higher aMCI/AD incidence (p = 0.015) in the fully adjusted model. Subgroup analyses showed significant results in the older age group, in which individuals with a higher genetic predisposition for WMHs had a 3.4-fold higher risk for developing aMCI/AD at follow up (p < 0.001), as well as in the lower cognitive reserve (CR, proxied by education years) group, in which individuals with a higher genetic predisposition for WMHs had an over 2-fold higher risk (p = 0.013). Genetic predisposition for WMHs was associated with aMCI/AD incidence, particularly in the group of participants with a low CR. Thus, CR might be a modifier in the relationship between genetic predisposition for WMHs and incident aMCI/AD.
Ghrelin in Focus: Dissecting Its Critical Roles in Gastrointestinal Pathologies and Therapies
Authors: Wu Wei , Zhu Lei , Dou Zhimin , Hou Qiliang , Wang Sen , Yuan Ziqian , Li Bin
Published: January 2024

This review elucidates the critical role of ghrelin, a peptide hormone mainly synthesized in the stomach in various gastrointestinal (GI) diseases. Ghrelin participates in diverse biological functions ranging from appetite regulation to impacting autophagy and apoptosis. In sepsis, it reduces intestinal barrier damage by inhibiting inflammatory responses, enhancing GI blood flow, and modulating cellular processes like autophagy and apoptosis. Notably, in inflammatory bowel disease (IBD), serum ghrelin levels serve as markers for distinguishing between active and remission phases, underscoring its potential in IBD treatment. In gastric cancer, ghrelin acts as an early risk marker, and due to its significant role in increasing the proliferation and migration of gastric cancer cells, the ghrelin–GHS-R axis is poised to become a target for gastric cancer treatment. The role of ghrelin in colorectal cancer (CRC) remains controversial; however, ghrelin analogs have demonstrated substantial benefits in treating cachexia associated with CRC, highlighting the therapeutic potential of ghrelin. Nonetheless, the complex interplay between ghrelin’s protective and potential tumorigenic effects necessitates a cautious approach to its therapeutic application. In post-GI surgery scenarios, ghrelin and its analogs could be instrumental in enhancing recovery and reducing complications. This article accentuates ghrelin’s multifunctionality, shedding light on its influence on disease mechanisms, including inflammatory responses and cancer progression, and examines its therapeutic potential in GI surgeries and disorders, advocating for continued research in this evolving field.
Marine Bioactive Peptides: Anti-Photoaging Mechanisms and Potential Skin Protective Effects
Authors: Zhang Xiaoliang , Zhuang Hong , Wu Sijia , Mao Chen , Dai Yaxi , Yan Haiyang
Published: January 2024

Skin photoaging, resulting from prolonged exposure to ultraviolet radiation, is a form of exogenous aging that not only impacts the aesthetic aspect of the skin but also exhibits a strong correlation with the onset of skin cancer. Nonetheless, the safety profile of non-natural anti-photoaging medications and the underlying physiological alterations during the process of photoaging remain inadequately elucidated. Consequently, there exists a pressing necessity to devise more secure interventions involving anti-photoaging drugs. Multiple studies have demonstrated the noteworthy significance of marine biomolecules in addressing safety concerns related to anti-photoaging and safeguarding the skin. Notably, bioactive peptides have gained considerable attention in anti-photoaging research due to their capacity to mitigate the physiological alterations associated with photoaging, including oxidative stress; inflammatory response; the abnormal expression of matrix metalloproteinase, hyaluronidase, and elastase; and excessive melanin synthesis. This review provides a systematic description of the research progress on the anti-photoaging and skin protection mechanism of marine bioactive peptides. The focus is on the utilization of marine bioactive peptides as anti-photoaging agents, aiming to offer theoretical references for the development of novel anti-photoaging drugs and methodologies. Additionally, the future prospects of anti-aging drugs are discussed, providing an initial reference for further research in this field.
Effect of TiO2 on the Microstructure and Flexural Strength of Lunar Regolith Simulant
Authors: Chen Junhao , Chen Haoming , Zhao Zhe , Zong Xiao
Published: January 2024

Lunar regolith is the preferred material for lunar base construction using in situ resource utilization technology. The TiO2 variations in lunar regolith collected from different locations significantly impact its suitability as a construction material. Therefore, it is crucial to investigate the effects of TiO2 on the properties of lunar regolith. This study aims to evaluate the influence of TiO2 content and sintering temperature on phase transformation, microstructure, and macroscopic properties (e.g., the shrinkage rate, mechanical properties, and relative density) of lunar regolith simulant samples (CUG-1A). The flexural strength and relative density of the sample with a TiO2 content of 6 wt% sintered at 1100 °C reached 136.66 ± 4.92 MPa and 91.06%, which were 65% and 12.28% higher than those of the sample not doped with TiO2, respectively. The experiment demonstrated that the doped TiO2 not only reacted with Fe to form pseudobrookite (Fe2TiO5) but also effectively reduced the viscosity of the glass phase during heat treatment. As the sintering temperature increased, the particles underwent a gradual melting process, leading to a higher proportion of the liquid phase. The higher liquid-phase content had a positive impact on the diffusion of mass transfer, causing the voids and gaps between particles to shrink. This shrinkage resulted in greater density and, ultimately, improved the mechanical properties of the material.
Relative Cooperative Effects of Non-Covalent Interactions on Hydrogen Bonds in Model Y…HCN/HNC…XF Trimers (Y = FB, OC, N2, CO, BF; XF = HF, LiF, BeF2, BF3, ClF, PH2F, SF2, SiH3F)
Authors: McDowell Sean A. C. , Edwards Kodi A.
Published: January 2024

A computational study of model Y…HCN/HNC (Y = FB, OC, N2, CO, BF) dimers was undertaken to assess the effect on the Y…H hydrogen bond when the Lewis base Y is systematically varied, while another model study of HCN/HNC…XF (XF = HF, LiF, BeF2, BF3, ClF, PH2F, SF2, SiH3F) dimers was undertaken to compare the relative binding strengths of the various types of noncovalent interactions between HCN/HNC and the fluorinated Lewis acid XF. The X atoms represent elements that span Groups 1–2 and 13–17 of the periodic table. The optimized trimers Y…HCN/HNC…XF that result from the combined dimer pairs were then studied in order to assess the relative strengths of the cooperative effects of the noncovalent N…X or C…X interactions on the Y…H hydrogen bond. The properties computed for the dimers and trimers include interaction energies, intermolecular separations, bond length changes, vibrational frequencies and their infrared intensity enhancements.
Health and Comorbidities in Minority Ethnic Adults Living with Visual Impairment in the UK
Authors: Hussain Syeda F. , Heinze Nikki , Gomes Renata S. M.
Published: January 2024

Visual impairment has been associated with mental and physical comorbidities in older adults. Research into comorbidities within minority ethnic communities (MEC) with visual impairment is yet to be explored, despite the increase in numbers. A secondary analysis of survey data collected by UK-based sight loss charities provides the first insight into comorbid conditions in a matched control sample of 77 MEC and 77 White adults aged 18–85 years. Participants were matched based on age, gender, UK region, and urban/rural setting. Group differences were explored, and subgroup analysis was also carried out for the two largest subgroups within the MEC group: Asian (n = 46) and Black (n = 22). Response frequencies (n) and proportions (%) were calculated for all variables including eye conditions, vision difficulties, comorbid conditions, and exercise. The sample was predominantly young, and few significant differences were found. Sub-group analysis showed that Asian participants were more likely to report not doing any exercise, having bad health, and comorbidities including high blood pressure, dexterity, hearing and communication difficulties, and a recent emotional/psychological/mental health condition. Black participants, however, were more likely to report comorbidity, in particular physical conditions and mobility difficulties.
Aspen and Spruce Densities Affect Tree Size, Future Stand Volume, and Aboveground Carbon Following Precommercial Thinning
Authors: Comeau Philip G. , Bokalo Mike
Published: January 2024

Data collected over a 30-year period from an experiment replicated across 21 locations in western Canada are used to explore the effects of precommercial thinning of trembling aspen to a range of densities in combination with three initial white spruce densities on tree growth and stand dynamics. Increasing differentiation amongst the 15 treatments was observed with age after thinning for both spruce and aspen responses. Spruce height and diameter declined with increasing aspen density. At age 10 spruce diameter with no aspen was 1.5× that of spruce in unthinned while it was 2.6× that of spruce in unthinned at age 28. Following thinning aspen DBH and crown width declined with increasing density of retained aspen while slenderness and height to crown base of aspen increased. Thinning to 1500 aspen·ha−1 resulted in aspen DBH that was 22% larger relative to the unthinned at age 28. Spruce volume and stemwood biomass at age 90, estimated using the Mixedwood Growth Model (MGM21), declined with increasing initial aspen density, with the complete removal of aspen resulting in nearly double the spruce volume of unthinned plots. However, total stand volume, total stand biomass, and stemwood carbon at age 90 are predicted to be largest in mixed stands with aspen densities of 1500 stems·ha−1 or higher.