bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding the impact of hydrodynamics on coastal erosion in Latin America: a systematic review
Authors: Vallarino Castillo Ruby , Negro Valdecantos Vicente , del Campo José María
Published: October 2023

Coastal zones in Latin America support a significant regional population and are vital for providing essential ecosystem services that underpin crucial socio economic activities. However, these zones face pressing challenges, with coastal erosion being a prominent concern. Coastal erosion not only jeopardizes coastal stability but also leads to occasional loss of natural habitats. This is particularly worrisome for sandy beaches due to the consistent shoreline retreat in specific regions. Short term adverse effects of coastal erosion are often attributed to human activities. Nonetheless, the influence of hydrodynamic processes, intensified by extreme events, is gaining prominence. This is due to the combined impact of tides, waves, currents, and other factors, resulting in accelerated shoreline retreat and significant losses of infrastructure and beach areas across Latin America. This article conducts a comprehensive analysis of case studies in Latin America related to coastal erosion due to hydrodynamic processes. Employing a systematic review approach, data is extracted from Scopus and Web of Science databases. From an initial dataset of 701 records, 62 records meet strict eligibility criteria. Case studies present evidence of how hydrodynamic processes interact with various factors, encompassing oceanic climatic conditions, atmospheric climatic conditions, anthropogenic influences, geomorphological and bathymetric characteristics, geological and tectonic factors, and climate change related aspects. These interactions have an immediate and significant impact on sandy beaches, emphasizing the necessity of comprehensively addressing these linkages when analyzing shoreline changes. This approach aids in identifying key erosion mechanisms and developing effective mitigation measures. Furthermore, the article provides a concise overview of data sources, tools, and methodologies identified in the case studies, spanning from field investigations to the utilization of geographic information systems and numerical models. Underscores the crucial role of international academic collaboration in coastal erosion research, facilitating the adoption of innovative methodologies from other regions, potentially offering a more comprehensive perspective in the formulation of mitigation and adaptation strategies. Finally, potential areas for future research in Latin America are explored, including the assessment of extreme event variability and its impacts on local and regional hydrodynamic processes. This aspect holds critical importance in steering future research towards scenarios that encompass economic and social considerations.
Misconceptions about quantifying animal encounter and interaction processes
Authors: Das Debraj , Kenkre V. M. , Nathan Ran , Giuggioli Luca
Published: October 2023

The ability to quantify when and where animals interact is key to the understanding of a plethora of ecological processes, from the structure of social communities and predator–prey relations to the spreading of pathogens and information. Despite the ubiquity of interaction processes among animals and the revolution in tracking technologies that now allows for the monitoring of multiple individuals simultaneously, a common theoretical framework with which to analyze movement data and extract interaction events is still lacking. Given the wide spectrum of mechanisms that governs how a biological organism detects the proximity of other organisms, most of the proposed theoretical approaches have been tailored to specific species or empirical situations and so far have been lacking a common currency with which to evaluate and compare findings across taxa. Here, we propose such general framework by borrowing techniques from statistical physics, specifically from the theory of reaction diffusion processes. Some of these techniques have already been employed to predict analytically pathogen transmission events between pairs of animals living within home ranges, but have not yet pervaded the movement ecology literature. Using both continuous and discrete variables, we present the mathematical framework and demonstrate its suitability to study interaction processes. By defining interactions whenever a token of information is transferred from one individual to another, we show that the probability of transferring information for the first time is equivalent to the first-passage probability of reacting in a multi-target environment. As interaction events reduce to encounter events when information transfer is perfectly efficient, we compare our formalism to a recently proposed approach to study encounters. Such approach takes the joint occupation probability of two animals over a region of interaction as a measure of the probability of encounter, rather than the first-encounter probability. We show the discrepancy of the two approaches by analytically comparing their predictions with continuous variables, while with discrete space–time variables, we quantify their difference over time. We conclude by pointing to some of the open problems that the reaction diffusion formalism, alternatively, the reaction motion formalism, as it should be more appropriately called, might be able to tackle.
Levodopa-induced dyskinesia: interplay between the N-methyl-D-aspartic acid receptor and neuroinflammation
Authors: Zhang Fanshi , Liu Mei , Tuo Jinmei , Zhang Li , Zhang Jun , Yu Changyin , Xu Zucai
Published: October 2023

Parkinson’s disease (PD) is a common neurodegenerative disorder of middle-aged and elderly people, clinically characterized by resting tremor, myotonia, reduced movement, and impaired postural balance. Clinically, patients with PD are often administered levodopa (L-DOPA) to improve their symptoms. However, after years of L-DOPA treatment, most patients experience complications of varying severity, including the “on-off phenomenon”, decreased efficacy, and levodopa-induced dyskinesia (LID). The development of LID can seriously affect the quality of life of patients, but its pathogenesis is unclear and effective treatments are lacking. Glutamic acid (Glu)-mediated changes in synaptic plasticity play a major role in LID. The N-methyl-D-aspartic acid receptor (NMDAR), an ionotropic glutamate receptor, is closely associated with synaptic plasticity, and neuroinflammation can modulate NMDAR activation or expression; in addition, neuroinflammation may be involved in the development of LID. However, it is not clear whether NMDA receptors are co-regulated with neuroinflammation during LID formation. Here we review how neuroinflammation mediates the development of LID through the regulation of NMDA receptors, and assess whether common anti-inflammatory drugs and NMDA receptor antagonists may be able to mitigate the development of LID through the regulation of central neuroinflammation, thereby providing a new theoretical basis for finding new therapeutic targets for LID.
Leveraging cryoablation and checkpoint inhibitors for high-risk triple negative breast cancer
Authors: Sardela de Miranda Flávia , Castro Maribel , Remmert Nicole , Singh Sharda P. , Layeequr Rahman Rakhshanda , Melkus Michael W.
Published: October 2023

Breast cancer is the second most common cancer among women in the United States in which the standard of care treatment is surgery with adjunctive therapy. Cryoablation, which destroys the tumor using extremely cold temperatures while preserving the potential tumor antigens, is a promising alternative to surgical resection. It is less invasive, cosmetically appeasing, cost-effective, and capable of contributing to the abscopal effect – the immune response targeting potential distant metastasis. However, to maximize the immunologic benefit of cryoablation in biologically high-risk breast cancers, combination with therapies that enhance immune activation, such as immune checkpoint inhibitors (ICIs) may be necessary. This mini review describes the fundamentals of cryoablation and treatment with ICIs, as well as discuss the caveats in both strategies and current clinical trials aimed to improve this approach to benefit patients.
Nivolumab adjuvant therapy for esophageal cancer: a review based on subgroup analysis of CheckMate 577 trial
Authors: Lin Yan , Liang Huan-Wei , Liu Yang , Pan Xin-Bin
Published: October 2023

Esophageal cancer is the sixth most common cancer worldwide. Approximately 50% of patients have locally advanced disease. The CROSS and NEOCRTEC5010 trials have demonstrated that neoadjuvant chemoradiotherapy followed by surgery is the standard treatment for patients with resectable disease. However, a pathological complete response is frequently not achieved, and most patients have a poor prognosis. The CheckMate 577 trial demonstrates that nivolumab adjuvant therapy improves disease-free survival in patents without a pathological complete response. However, there are still numerous clinical questions of concern that remain controversial based on the results of the subgroup analysis. In this review, we aim to offer constructive suggestions addressing the clinical concerns raised in the CheckMate 577 trial.
The role of inflammation in autoimmune disease: a therapeutic target
Authors: Xiang Yu , Zhang Mingxue , Jiang Die , Su Qian , Shi Jianyou
Published: October 2023

Autoimmune diseases (AIDs) are immune disorders whose incidence and prevalence are increasing year by year. AIDs are produced by the immune system’s misidentification of self-antigens, seemingly caused by excessive immune function, but in fact they are the result of reduced accuracy due to the decline in immune system function, which cannot clearly identify foreign invaders and self-antigens, thus issuing false attacks, and eventually leading to disease. The occurrence of AIDs is often accompanied by the emergence of inflammation, and inflammatory mediators (inflammatory factors, inflammasomes) play an important role in the pathogenesis of AIDs, which mediate the immune process by affecting innate cells (such as macrophages) and adaptive cells (such as T and B cells), and ultimately promote the occurrence of autoimmune responses, so targeting inflammatory mediators/pathways is one of emerging the treatment strategies of AIDs. This review will briefly describe the role of inflammation in the pathogenesis of different AIDs, and give a rough introduction to inhibitors targeting inflammatory factors, hoping to have reference significance for subsequent treatment options for AIDs.
Effect of Danhong injection on heart failure in rats evaluated by metabolomics
Authors: Li Lin , Zhong Senjie , Ye Jiahao , Hu Siyuan , Hu Zhixi
Published: October 2023

Background

Heart failure (HF) is characterized by reduced ventricular filling or ejection function due to organic or non-organic cardiovascular diseases. Danhong injection (DHI) is a medicinal material used clinically to treat HF for many years in China. Although prior research has shown that Danhong injection can improve cardiac function and structure, the biological mechanism has yet to be determined.

Methods

Serum metabolic analysis was conducted via ultra-high-performance liquid chromatography-quadrupole time-of-flight/mass spectrometry (UHPLC-QE/MS) to explore underlying protective mechanisms of DHI in the transverse aortic constriction (TAC)-induced heart failure. Multivariate statistical techniques were used in the research, such as unsupervised principal component analysis (PCA) and orthogonal projection to latent structures discriminant analysis (OPLS-DA). MetaboAnalyst and Kyoto Encyclopedia of Genes and Genomes (KEGG) were employed to pinpoint pertinent metabolic pathways.

Results

After DHI treatment, cardiac morphology and function as well as the metabolism in model rats were improved. We identified 17 differential metabolites and six metabolic pathways. Two biomarkers, PC(18:3(6Z,9Z,12Z)/24:0) and L-Phenylalanine, were identified for the first time as strong indicators for the significant effect of DHI.

Conclusion

This study revealed that DHI could regulate potential biomarkers and correlated metabolic pathway, which highlighted therapeutic potential of DHI in managing HF.
Transcriptional profile reveals the physiological responses to prey availability in the mixotrophic chrysophyte Poterioochromonas malhamensis
Authors: Ma Mingyang , Yang Wentao , Chen Hong , Ke Wanwan , Gong Yingchun , Hu Qiang
Published: October 2023

Mixotrophic flagellates, which have diverse nutritional modes and play important roles in connecting the microbial loop with the classical food chain, are ideal models to study the mechanisms of adaptation between different nutritional modes in protists. In their natural ecosystems, mixotrophic flagellates may encounter microalgal prey of different digestibility, which may affect the carbon flow. To date, a molecular biological view of the metabolic processes in the mixotrophic flagellate Poterioochromonas malhamensis during nutritional adaptation and feeding on microalgal prey of different digestibility is still lacking. Accordingly, this study focused on the gene expression differences in P. malhamensis under autotrophy, being fed by the digestible microalga Chlorella sorokiniana GT-1, and being fed by the indigestible microalga C. sorokiniana CMBB-146. Results showed that the growth rate of P. malhamensis under autotrophy was much lower than that when fed by digestible microalgae. Addition of C. sorokiniana CMBB-146 could only increase the growth rate of P. malhamensis in the first 3 days, but the cell concentration of P. malhamensis started to decrease gradually after 4 days. Compared to autotrophic P. malhamensis, total 6,583 and 3,510 genes were significantly and differentially expressed in P. malhamensis fed by digestible microalgae and indigestible microalgae, respectively. Compared to autotrophic cells, genes related to the ribosome, lysosome, glycolysis, gluconeogenesis, TCA cycle, β-oxidation, duplication, and β-1,3-glucan in P. malhamensis grazing on digestible prey were up-regulated, while genes related to light harvesting and key enzymes referring to chlorophyll were down-regulated. Genes related to apoptosis and necrosis in P. malhamensis were up-regulated after grazing on indigestible microalgae compared to the autotrophic group, which we suggest is associated with the up-regulation of genes related to lysosome enzymes. This study provides abundant information on the potential intracellular physiological responses of P. malhamensis during the process of nutritional adaptation.
Exploring oxidative stress pathways in Geobacter sulfurreducens: the redox network between MacA peroxidase and triheme periplasmic cytochromes
Authors: Portela Pilar C. , Morgado Leonor , Silva Marta A. , Denkhaus Lukas , Einsle Oliver , Salgueiro Carlos A.
Published: October 2023

The recent reclassification of the strict anaerobe Geobacter sulfurreducens bacterium as aerotolerant brought attention for oxidative stress protection pathways. Although the electron transfer pathways for oxygen detoxification are not well established, evidence was obtained for the formation of a redox complex between the periplasmic triheme cytochrome PpcA and the diheme cytochrome peroxidase MacA. In the latter, the reduction of the high-potential heme triggers a conformational change that displaces the axial histidine of the low-potential heme with peroxidase activity. More recently, a possible involvement of the triheme periplasmic cytochrome family (PpcA-E) in the protection from oxidative stress in G. sulfurreducens was suggested. To evaluate this hypothesis, we investigated the electron transfer reaction and the biomolecular interaction between each PpcA-E cytochrome and MacA. Using a newly developed method that relies on the different NMR spectral signatures of the heme proteins, we directly monitored the electron transfer reaction from reduced PpcA-E cytochromes to oxidized MacA. The results obtained showed a complete electron transfer from the cytochromes to the high-potential heme of MacA. This highlights PpcA-E cytochromes’ efficient role in providing the necessary reducing power to mitigate oxidative stress situations, hence contributing to a better knowledge of oxidative stress protection pathways in G. sulfurreducens.
GTPase Era at the heart of ribosome assembly
Authors: Gruffaz Christelle , Smirnov Alexandre
Published: October 2023

Ribosome biogenesis is a key process in all organisms. It relies on coordinated work of multiple proteins and RNAs, including an array of assembly factors. Among them, the GTPase Era stands out as an especially deeply conserved protein, critically required for the assembly of bacterial-type ribosomes from Escherichia coli to humans. In this review, we bring together and critically analyze a wealth of phylogenetic, biochemical, structural, genetic and physiological data about this extensively studied but still insufficiently understood factor. We do so using a comparative and, wherever possible, synthetic approach, by confronting observations from diverse groups of bacteria and eukaryotic organelles (mitochondria and chloroplasts). The emerging consensus posits that Era intervenes relatively early in the small subunit biogenesis and is essential for the proper shaping of the platform which, in its turn, is a prerequisite for efficient translation. The timing of Era action on the ribosome is defined by its interactions with guanosine nucleotides [GTP, GDP, (p)ppGpp], ribosomal RNA, and likely other factors that trigger or delay its GTPase activity. As a critical nexus of the small subunit biogenesis, Era is subject to sophisticated regulatory mechanisms at the transcriptional, post-transcriptional, and post-translational levels. Failure of these mechanisms or a deficiency in Era function entail dramatic generalized consequences for the protein synthesis and far-reaching, pleiotropic effects on the organism physiology, such as the Perrault syndrome in humans.
Changing trends of disease burden of stroke from 1990 to 2019 and its predictions among the Chinese population
Authors: Liang Dong , Guan Qing , Huang Minqing , He Yiyu , Ou Yangjiang , Chen Min , Zheng Xiaoxin , Lin Xiuquan
Published: October 2023

Objective

This study aimed to understand the temporal trends in the disease burden of stroke and its attributable risk factors in China, along with the future trends in the next 25 years, that is important for effective prevention strategies and improvement, and to provide new insights into the age- and sex-specific incidence, prevalence, mortality, disability-adjusted life-years (DALYs) and their trends from 1990 to 2019, and the prediction in the next 25 years.

Methods

The Global Burden of Disease Study (2019) was used to extract the data on age- and sex-specific incidence, mortality, and disability-adjusted life-years (DALYs) of stroke in China, 1990–2019. We estimated the estimated annual percentage change (EAPC) to access the temporal trends of the disease burden of stroke. The R package called Nordpred was used to perform an age-period-cohort analysis to predict the prevalence of stroke.

Results

The number of incidence cases, deaths, and DALYs of stroke increased from 1990 to 2019. Overall downward trends were observed in the age-standardized incidence rate (ASIR) from 1990 to 2019. Significant temporal trends in mortality and DALYs of stroke were observed. High systolic blood pressure, smoking, and high-sodium diet were the main driving forces for stroke. The DALYs lost attributable to smoking were different for male and female patients. In the next 25 years, the number of new cases and deaths from stroke should continue to increase. The ASIR and age-standardized mortality rate (ASMR) should show a downward trend among male and female patients.

Conclusion

Despite the overall rates of stroke declined over the period from 1990 to 2019, the absolute number of people affected by stroke has substantially increased. There has been a substantial increase in the burden of stroke due to risk factors and will continue to increase in the next 25 years.
Progression risk stratification with six-minute walk gait speed trajectory in multiple sclerosis
Authors: Goldman Myla D. , Chen Shanshan , Motl Robert , Pearsall Rylan , Oh Unsong , Brenton J. Nicholas
Published: October 2023

Background

Multiple Sclerosis (MS) disease progression has notable heterogeneity among patients and over time. There is no available single method to predict the risk of progression, which represents a significant and unmet need in MS.

Methods

MS and healthy control (HC) participants were recruited for a 2-year observational study. A latent-variable growth mixture model (GMM) was applied to cluster baseline 6-min walk gait speed trajectories (6MWGST). MS patients within different 6 MWGST clusters were identified and stratified. The group membership of these MS patients was compared against 2-year confirmed-disease progression (CDP). Clinical and patient-reported outcome (PRO) measures were compared between HC and MS subgroups over 2 years.

Results

62 MS and 41 HC participants completed the 2-year study. Within the MS cohort, 90% were relapsing MS. Two distinct patterns of baseline 6 MWGST emerged, with one cluster displaying a faster gait speed and a typical “U” shape, and the other showing a slower gait speed and a “flattened” 6 MWGST curve. We stratified MS participants in each cluster as low- and high-risk progressors (LRP and HRP, respectively). When compared against 2-year CDP, our 6 MWGST approach had 71% accuracy and 60% positive predictive value. Compared to the LRP group, those MS participants stratified as HRP (15 out of 62 MS participants), were on average 3.8 years older, had longer MS disease duration and poorer baseline performance on clinical outcomes and PROs scores. Over the subsequent 2 years, only the HRP subgroup showed a significant worsened performance on 6 MW, clinical measures and PROs from baseline.

Conclusion

Baseline 6 MWGST was useful for stratifying MS participants with high or low risks for progression over the subsequent 2 years. Findings represent the first reported single measure to predict MS disease progression with important potential applications in both clinical trials and care in MS.
Neurocognitive function in children with cochlear implants and hearing aids: a systematic review
Authors: Lima Jefferson Vilela da Silva , de Morais Caroline Favaretto Martins , Zamberlan-Amorim Nelma Ellen , Mandrá Patricia Pupin , Reis Ana Cláudia Mirândola Barbosa
Published: October 2023

Purpose

To systematically review the existing literature that examines the relationship between cognition, hearing, and language in children using cochlear implants and hearing aids.

Method

The review has been registered in Prospero (Registration: CRD 42020203974). The review was based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis and examined the scientific literature in VHL, MEDLINE, CINAHL, Scopus, WOS, and Embase. It included original observational studies in children using hearing aids and/or cochlear implants who underwent cognitive and auditory and/or language tests. Data were extracted from the studies and their level of evidence was graded with the Oxford Center for Evidence-Based Medicine: Levels of Evidence. Meta-analysis could not be performed due to data heterogeneity. Outcomes are described in narrative and tables synthesis.

Results

The systematic search and subsequent full-text evaluation identified 21 studies, conducted in 10 different countries. Altogether, their samples comprised 1,098 individuals, aged 0.16–12.6 years. The studies assessed the following cognitive domains: memory, nonverbal cognition, reasoning, attention, executive functions, language, perceptual-motor function, visuoconstructive ability, processing speed, and phonological processing/phonological memory. Children with hearing loss using cochlear implants and hearing aids scored significantly lower in many cognitive functions than normal hearing (NH) children. Neurocognitive functions were correlated with hearing and language outcomes.

Conclusion

Many cognitive tools were used to assess cognitive function in children with hearing devices. Results suggest that children with cochlear implants and hearing aids have cognitive deficits; these outcomes are mainly correlated with vocabulary. This study highlights the need to understand children’s cognitive function and increase the knowledge of the relationship between cognition, language, and hearing in children using cochlear implants and hearing aids.
Memantine increases the dendritic complexity of hippocampal young neurons in the juvenile brain after cranial irradiation
Authors: Zisiadis Georgios Alkis , Alevyzaki Androniki , Nicola Elene , Rodrigues Carlos F. D. , Blomgren Klas , Osman Ahmed M.
Published: October 2023

Introduction

Cranial irradiation (IR) negatively regulates hippocampal neurogenesis and causes cognitive dysfunctions in cancer survivors, especially in pediatric patients. IR decreases proliferation of neural stem/progenitor cells (NSPC) and consequently diminishes production of new hippocampal neurons. Memantine, an NMDA receptor antagonist, used clinically to improve cognition in patients suffering from Alzheimer’s disease and dementia. In animal models, memantine acts as a potent enhancer of hippocampal neurogenesis. Memantine was recently proposed as an intervention to improve cognitive impairments occurring after radiotherapy and is currently under investigation in a number of clinical trials, including pediatric patients. To date, preclinical studies investigating the mechanisms underpinning how memantine improves cognition after IR remain limited, especially in the young, developing brain. Here, we investigated whether memantine could restore proliferation in the subgranular zone (SGZ) or rescue the reduction in the number of hippocampal young neurons after IR in the juvenile mouse brain.

Methods

Mice were whole-brain irradiated with 6 Gy on postnatal day 20 (P20) and subjected to acute or long-term treatment with memantine. Proliferation in the SGZ and the number of young neurons were further evaluated after the treatment. We also measured the levels of neurotrophins associated with memantine improved neural plasticity, brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF).

Results

We show that acute intraperitoneal treatment with a high, non-clinically used, dose of memantine (50 mg/kg) increased the number of proliferating cells in the intact brain by 72% and prevented 23% of IR-induced decrease in proliferation. Long-term treatment with 10 mg/kg/day of memantine, equivalent to the clinically used dose, did not impact proliferation, neither in the intact brain, nor after IR, but significantly increased the number of young neurons (doublecortin expressing cells) with radial dendrites (29% in sham controls and 156% after IR) and enhanced their dendritic arborization. Finally, we found that long-term treatment with 10 mg/kg/day memantine did not affect the levels of BDNF, but significantly reduced the levels of NGF by 40%.

Conclusion

These data suggest that the enhanced dendritic complexity of the hippocampal young neurons after treatment with memantine may contribute to the observed improved cognition in patients treated with cranial radiotherapy.
Association of plasma iron with the risk of incident cancer in Chinese adults with hypertension: a nested case-control study
Authors: Zhu Hehao , Wei Yaping , He Qiangqiang , Song Yun , Liu Lishun , Sun Yong , Zhang Hao , Guo Huiyuan , Xu Xiping , Wang Binyan
Published: October 2023

Background

Iron is an essential element for organismal health but excessive iron is potentially toxic. However, few observational studies link plasma iron (PI) concentrations and cancer risk, and the results are inconsistent.

Objective

This study aimed to explore the associations of PI concentrations with cancer risk in Chinese adults with hypertension.

Methods

We conducted a nested, case-control study, including 223 pairs of incident cancer cases and matched controls from the China Stroke Primary Prevention Trial. The median time between blood sample collection and subsequent cancer event occurrence was 2.13 years. The odds ratio (OR) and 95% confidence interval (CI) for the risk of cancer by PI were estimated from multivariable conditional logistic regression models.

Results

There was a nonlinear association between PI concentrations and total cancer risk. When compared with participants in tertile 2 of PI, the ORs of total cancer were 2.17 (95%CI: 1.25-3.85) and 1.29 (95%CI: 0.77-2.19) in participants in PI tertiles 3 and 1, respectively. Furthermore, higher PI was associated with increased digestive system cancer risk (OR=3.25, 95%CI:1.29-8.90), while lower PI was associated with increased risk of non-digestive system cancer (OR=3.32, 95%CI: 1.39-8.71). In a sensitivity analysis, the increases in total cancer risk or digestive system cancer risk were still observed with higher PI after excluding cancer cases occurring within the first year.

Conclusion

Our results showed an increased risk of cancer related to higher PI or lower PI in Chinese adults with hypertension. Higher iron levels were linked to an increased risk of digestive system cancers, whereas lower iron levels were linked to an increased risk of non-digestive system cancers.
Questionnaire study of application about sentinel lymph node biopsy surgery in locally advanced breast cancer patients who received neoadjuvant chemotherapy
Authors: Lee Eun-Gyeong , Lee Minjung , Jung So-Youn , Han Jai Hong , Kim Seok-Ki , Lee Seeyoun
Published: October 2023

Background

Nodal staging from sentinel lymph node (SLN) biopsy has become the standard procedure for early-stage breast cancer patients. SLN biopsy implementation after chemotherapy has previously been evaluated. This questionnaire study aimed to investigate the current trend of SLN biopsy after neoadjuvant chemotherapy (NAC) for locally advanced breast cancer.

Methods and materials

We conducted a web-based survey among breast surgeons who are members of the Korean Breast Cancer Society. The survey comprised 14 questions about axillary surgery after NAC.

Results

Of 135 respondents, 48.1% used a combined method of dye and radioactive isotope (RI). In the absence of SLN metastasis, 67.7% would perform only SLN biopsy, while 3% would perform ALN dissection. In case of SLN metastasis, the proportions of surgeons who would proceed with ALN dissection were 60.2% and 67.2% for less than two and more than three positive SLNs, respectively.

Conclusion

The present study confirmed the increasing tendency to adopt SLN biopsy for axillary staging in patients who achieved complete response with initial nodal metastasis. It could be expected that the mapping methods for patients receiving NAC have become diverse, including RI, vital dye, and indocyanine green fluorescence. The implementation of SLN biopsy after NAC will grow in the coming years due to an increasing demand of minimally invasive surgery.
Location, location, location: mapping the lymphoma tumor microenvironment using spatial transcriptomics
Authors: Pickard Keir , Stephenson Emily , Mitchell Alex , Jardine Laura , Bacon Chris M.
Published: October 2023

Lymphomas are a heterogenous group of lymphoid neoplasms with a wide variety of clinical presentations. Response to treatment and prognosis differs both between and within lymphoma subtypes. Improved molecular and genetic profiling has increased our understanding of the factors which drive these clinical dynamics. Immune and non-immune cells within the lymphoma tumor microenvironment (TME) can both play a key role in antitumor immune responses and conversely also support lymphoma growth and survival. A deeper understanding of the lymphoma TME would identify key lymphoma and immune cell interactions which could be disrupted for therapeutic benefit. Single cell RNA sequencing studies have provided a more comprehensive description of the TME, however these studies are limited in that they lack spatial context. Spatial transcriptomics provides a comprehensive analysis of gene expression within tissue and is an attractive technique in lymphoma to both disentangle the complex interactions between lymphoma and TME cells and improve understanding of how lymphoma cells evade the host immune response. This article summarizes current spatial transcriptomic technologies and their use in lymphoma research to date. The resulting data has already enriched our knowledge of the mechanisms and clinical impact of an immunosuppressive TME in lymphoma and the accrual of further studies will provide a fundamental step in the march towards personalized medicine.
Macrophage metallothioneins participate in the antileishmanial activity of antimonials
Authors: Vargas Deninson Alejandro , Gregory David J. , Koren Roni Nitzan , Zilberstein Dan , Belew Ashton Trey , El-Sayed Najib M. , Gómez María Adelaida
Published: October 2023

Host cell functions that participate in the pharmacokinetics and pharmacodynamics (PK/PD) of drugs against intracellular pathogen infections are critical for drug efficacy. In this study, we investigated whether macrophage mechanisms of xenobiotic detoxification contribute to the elimination of intracellular Leishmania upon exposure to pentavalent antimonials (SbV). Primary macrophages from patients with cutaneous leishmaniasis (CL) (n=6) were exposed ex vivo to L. V. panamensis infection and SbV, and transcriptomes were generated. Seven metallothionein (MT) genes, potent scavengers of heavy metals and central elements of the mammalian cell machinery for xenobiotic detoxification, were within the top 20 up-regulated genes. To functionally validate the participation of MTs in drug-mediated killing of intracellular Leishmania, tandem knockdown (KD) of MT2-A and MT1-E, MT1-F, and MT1-X was performed using a pan-MT shRNA approach in THP-1 cells. Parasite survival was unaffected in tandem-KD cells, as a consequence of strong transcriptional upregulation of MTs by infection and SbV, overcoming the KD effect. Gene silencing of the metal transcription factor-1 (MTF-1) abrogated expression of MT1 and MT2-A genes, but not ZnT-1. Upon exposure to SbV, intracellular survival of Leishmania in MTF-1KD cells was significantly enhanced. Results from this study highlight the participation of macrophage MTs in Sb-dependent parasite killing.
Clinical hypoxemia score for outpatient child pneumonia care lacking pulse oximetry in Africa and South Asia
Authors: Schuh Holly B. , Hooli Shubhada , Ahmed Salahuddin , King Carina , Roy Arunangshu D. , Lufesi Norman , Islam ASMD Ashraful , Mvalo Tisungane , Chowdhury Nabidul H. , Ginsburg Amy Sarah , Colbourn Tim , Checkley William , Baqui Abdullah H. , McCollum Eric D.
Published: October 2023

Background

Pulse oximeters are not routinely available in outpatient clinics in low- and middle-income countries. We derived clinical scores to identify hypoxemic child pneumonia.

Methods

This was a retrospective pooled analysis of two outpatient datasets of 3–35 month olds with World Health Organization (WHO)-defined pneumonia in Bangladesh and Malawi. We constructed, internally validated, and compared fit & discrimination of four models predicting SpO2 < 93% and <90%: (1) Integrated Management of Childhood Illness guidelines, (2) WHO-composite guidelines, (3) Independent variable least absolute shrinkage and selection operator (LASSO); (4) Composite variable LASSO.

Results

12,712 observations were included. The independent and composite LASSO models discriminated moderately (both C-statistic 0.77) between children with a SpO2 < 93% and ≥94%; model predictive capacities remained moderate after adjusting for potential overfitting (C-statistic 0.74 and 0.75). The IMCI and WHO-composite models had poorer discrimination (C-statistic 0.56 and 0.68) and identified 20.6% and 56.8% of SpO2 < 93% cases. The highest score stratum of the independent and composite LASSO models identified 46.7% and 49.0% of SpO2 < 93% cases. Both LASSO models had similar performance for a SpO2 < 90%.

Conclusions

In the absence of pulse oximeters, both LASSO models better identified outpatient hypoxemic pneumonia cases than the WHO guidelines. Score external validation and implementation are needed.
COVID-19 vaccination for children with pulmonary hypertension: efficacy, safety and reasons for opting against vaccination
Authors: Zhang Zeying , Wang Dan , Zuo Wanyun , Wang Xun , Yang Fan , Luo Haiyan , Xiao Zhenghui , Liu Qiming , Xiao Yunbin
Published: October 2023

Objective

To determine the reasons why pulmonary hypertension (PH) children refused vaccination against COVID-19, evaluate the safety and efficacy of COVID-19 vaccine in PH children.

Study design

This retrospective cohort study included congenital heart disease-associated pulmonary arterial hypertension (CHD-PAH) and bronchopulmonary dysplasia associated PH (BPD-PH) children who were divided into vaccinated group and non-vaccinated group. Univariate logistic regression analysis and multivariate logistic regression analysis were conducted to explore the reasons why PH children refused COVID-19 vaccine. Then, the prevalence, the number of symptoms, and the severity of COVID-19 disease were compared between the vaccinated and unvaccinated groups.

Result

We included 73 children and 61 children (83.6%) were unvaccinated. The main reasons for not being vaccinated were fear of worsening of existing diseases (31%). Age < 36 months (RR: 0.012; P < 0.001) and the presence of comorbidities (RR = 0.06; P = 0.023) were risk factors influencing willingness to vaccinate. The most common adverse events (AEs) were injection site pain (29.6%). COVID-19 vaccines are safe for PH children. The prevalence of COVID-19 disease decreased in PH children after vaccination (RR = 0.51; P = 0.009). 1 month after negative nucleic acid test or negative antigen test, PH children in the vaccinated group had fewer symptoms (P = 0.049).

Conclusions

The vaccination rate of COVID-19 vaccine is low in CHD-PAH and BPD-PH children while COVID-19 vaccines are safe. Vaccination can reduce the prevalence of COVID-19 disease and the number of symptoms 1 month after negative nucleic acid or antigen tests.
An overview of the past decade of bufalin in the treatment of refractory and drug-resistant cancers: current status, challenges, and future perspectives
Authors: Ye Qingmei , Zhou Xin , Ren Han , Han Fangxuan , Lin Rong , Li Juan
Published: October 2023

Profound progress has been made in cancer treatment in the past three decades. However, drug resistance remains prevalent and a critical challenge. Drug resistance can be attributed to oncogenes mutations, activated defensive mechanisms, ATP-bind cassette transporters overexpression, cancer stem cells, etc. Chinese traditional medicine toad venom has been used for centuries for different diseases, including resistant cancers. Bufalin is one of the bufadienolides in toad venom that has been extensively studied for its potential in refractory and drug-resistant cancer treatments in vitro and in vivo. In this work, we would like to critically review the progress made in the past decade (2013–2022) of bufalin in overcoming drug resistance in cancers. Generally, bufalin shows high potential in killing certain refractory and resistant cancer cells via multiple mechanisms. More importantly, bufalin can work as a chemo-sensitizer that enhances the sensitivity of certain conventional and targeted therapies at low concentrations. In addition, the development of bufalin derivatives was also briefly summarized and discussed. We also analyzed the obstacles and challenges and provided possible solutions for future perspectives. We hope that the collective information may help evoke more effort for more in-depth studies and evaluation of bufalin in both lab and possible clinical trials.
Sex-determining region complements traditionally used in phylogenetic studies nuclear and chloroplast sequences in investigation of Aigeiros Duby and Tacamahaca Spach poplars (genus Populus L., Salicaceae)
Authors: Borkhert Elena V. , Pushkova Elena N. , Nasimovich Yuri A. , Kostina Marina V. , Vasilieva Natalia V. , Murataev Ramil A. , Novakovskiy Roman O. , Dvorianinova Ekaterina M. , Povkhova Liubov V. , Zhernova Daiana A. , Turba Anastasia A. , Sigova Elizaveta A. , Snezhkina Anastasiya V. , Kudryavtseva Anna V. , Bolsheva Nadezhda L. , Krasnov George S. , Dmitriev Alexey A. , Melnikova Nataliya V.
Published: October 2023

Members of the genus Populus L. play an important role in the formation of forests in the northern hemisphere and are used in urban landscaping and timber production. Populus species of closely related sections show extensive hybridization. Therefore, the systematics of the genus is rather complicated, especially for poplars of hybrid origin. We aimed to assess the efficiency of application of the sex-determining region (SDR) in addition to the nuclear and chloroplast genome loci traditionally used in phylogenetic studies of poplars to investigate relationships in sections Aigeiros Duby and Tacamahaca Spach. Targeted deep sequencing of NTS 5S rDNA, ITS, DSH 2, DSH 5, DSH 8, DSH 12, DSH 29, 6, 15, 16, X18, trnG-psbK-psbI, rps2-rpoC2, rpoC2-rpoC1, as well as SDR and ARR17 gene was performed for 379 poplars. The SDR and ARR17 gene together with traditionally used multicopy and single-copy loci of nuclear and chloroplast DNA allowed us to obtain a clustering that is most consistent with poplar systematics based on morphological data and to shed light on several controversial hypotheses about the origin of the studied taxa (for example, the inexpediency of separating P. koreana, P. maximowiczii, and P. suaveolens into different species). We present a scheme of relationships between species and hybrids of sections Aigeiros and Tacamahaca based on molecular genetic, morphological, and geographical data. The geographical proximity of species and, therefore, the possibility of hybridization between them appear to be more important than the affiliation of species to the same section. We speculate that sections Aigeiros and Tacamahaca are distinguished primarily on an ecological principle (plain and mountain poplars) rather than on a genetic basis. Joint analysis of sequencing data for the SDR and chloroplast genome loci allowed us to determine the ancestors of P. × petrovskoe – P. laurifolia (female tree) × P. × canadensis (male tree), and P. × rasumovskoe – P. nigra (female tree) × P. suaveolens (male tree). Thus, the efficiency of using the SDR for the study of poplars of sections Aigeiros and Tacamahaca and the prospects of its use for the investigation of species of the genus Populus were shown.
Genetic basis of maize maternal haploid induction beyond MATRILINEAL and ZmDMP
Authors: Trentin Henrique Uliana , Krause Matheus Dalsente , Zunjare Rajkumar Uttamrao , Almeida Vinícius Costa , Peterlini Edicarlos , Rotarenco Valeriy , Frei Ursula Karoline , Beavis William Dale , Lübberstedt Thomas
Published: October 2023

In maize, doubled haploid (DH) lines are created in vivo through crosses with maternal haploid inducers. Their induction ability, usually expressed as haploid induction rate (HIR), is known to be under polygenic control. Although two major genes (MTL and ZmDMP) affecting this trait were recently described, many others remain unknown. To identify them, we designed and performed a SNP based (~9007) genome-wide association study using a large and diverse panel of 159 maternal haploid inducers. Our analyses identified a major gene near MTL, which is present in all inducers and necessary to disrupt haploid induction. We also found a significant quantitative trait loci (QTL) on chromosome 10 using a case-control mapping approach, in which 793 noninducers were used as controls. This QTL harbors a kokopelli ortholog, whose role in maternal haploid induction was recently described in Arabidopsis. QTL with smaller effects were identified on six of the ten maize chromosomes, confirming the polygenic nature of this trait. These QTL could be incorporated into inducer breeding programs through marker-assisted selection approaches. Further improving HIR is important to reduce the cost of DH line production.
Securing maize reproductive success under drought stress by harnessing CO2 fertilization for greater productivity
Authors: Li Yangyang , Zhang Pengpeng , Sheng Wenjing , Zhang Zixiang , Rose Ray J. , Song Youhong
Published: October 2023

Securing maize grain yield is crucial to meet food and energy needs for the future growing population, especially under frequent drought events and elevated CO2 (eCO2) due to climate change. To maximize the kernel setting rate under drought stress is a key strategy in battling against the negative impacts. Firstly, we summarize the major limitations to leaf source and kernel sink in maize under drought stress, and identified that loss in grain yield is mainly attributed to reduced kernel set. Reproductive drought tolerance can be realized by collective contribution with a greater assimilate import into ear, more available sugars for ovary and silk use, and higher capacity to remobilize assimilate reserve. As such, utilization of CO2 fertilization by improved photosynthesis and greater reserve remobilization is a key strategy for coping with drought stress under climate change condition. We propose that optimizing planting methods and mining natural genetic variation still need to be done continuously, meanwhile, by virtue of advanced genetic engineering and plant phenomics tools, the breeding program of higher photosynthetic efficiency maize varieties adapted to eCO2 can be accelerated. Consequently, stabilizing maize production under drought stress can be achieved by securing reproductive success by harnessing CO2 fertilization.
Method for selecting ornamental species for different shading intensity in urban green spaces
Authors: Francini Alessandra , Toscano Stefania , Ferrante Antonio , Romano Daniela
Published: October 2023

In urban areas, ornamental plants face different constraints, such as the shading of buildings and trees. Therefore, the selection of suitable species and their integration or combination with pre-existing plants is very important. Trees, shrubs, and herbaceous plant species must be distributed according to plant light requirements and shading intensity. Ornamental plants are classified into two groups based on their light intensity or shade tolerance: sun and shade species. To properly position the plants, especially in the immediate vicinity of buildings, it is necessary to study the projection of shadows during the year and the most critical periods, such as July and August. The position of ornamental species with different shading tolerances can be obtained by characterizing the leaf gas exchange for each species. Among the physiological parameters, the most important is the light compensation point, which is the light intensity corresponding to a net photosynthesis equal to zero. This means that the assimilation of carbon dioxide through photosynthesis is equal to the carbon dioxide emitted by respiration. This steady state represents the most critical condition for plants to endure the summer. The distribution of species inside a green area should be determined by considering the minimum light intensity that allows sufficient photosynthesis to compensate for the respiration rate. In this context, non-destructive leaf gas exchange, chlorophyll a fluorescence, and chlorophyll content can be useful tools for selecting suitable ornamental plants under diverse shading conditions.