Early Stage Research Articles

Approaches and considerations in the endoscopic treatment of T1 colorectal cancer.

The detection of early colorectal cancer (CRC) is increasing through the implementation of screening programs. This increased detection enhances the likelihood of minimally invasive surgery and significantly lowers the risk of recurrence, thereby improving patient survival and reducing mortality rates. T1 CRC, the earliest stage, is treated endoscopically in cases with a low risk of lymph node metastasis (LNM). The advantages of endoscopic treatment compared with surgery include minimal invasiveness and limited tissue disruption, which reduce morbidity and mortality, preserve bowel function to avoid colectomy, accelerate recovery, and improve cost-effectiveness. However, T1 CRC has a risk of LNM. Thus, selection of the appropriate treatment between endoscopic treatment and surgery, while avoiding overtreatment, is challenging considering the potential for complete resection, LNM, and recurrence risk.

Preferences of physicians for treatment-related toxicity vs. recurrence in melanoma (GERMELATOX-A): the doctors’ perspective

IntroductionAdjuvant treatment with immune checkpoint inhibitors, such as PD1-antibodies (ICI) ± CTLA4-antibodies (cICI) or targeted therapy with BRAF/MEK inhibitors (TT), has shown a significant improvement in disease-free survival (DFS) for high-risk melanoma patients. However, due to specific side effects, the choice of treatment is often influenced by the risk of toxicity. Therefore, the role of physicians in treatment decisions of patients is crucial. This study investigated for the first time in a multicenter setting the attitudes and preferences of dermatooncologists in Germany and Switzerland regarding adjuvant treatment with (c)ICI and TT.MethodsIn the GERMELATOX-A study, 108 physicians (median age: 32 yrs, 67.6% female) from 11 skin cancer centers were surveyed to rate typical side effect scenarios of (c)ICI and TT treatments and then compared to patients’ ratings evaluated in a previous analysis from the same centers. The scenarios described mild-to-moderate or severe toxicity and included melanoma relapse leading to death. The physicians were asked about the level of side effects they would tolerate in exchange for a reduction in melanoma relapse and an increase in survival at 5 years.ResultsThe preferences of physicians and patients revealed significant differences regarding adjuvant melanoma treatment with (c)ICI and TT (p < 0.05). Compared to patients, physicians tend to value a melanoma relapse less severe, according to a visual analog scale. They were also less threatened by all scenarios of side effects during adjuvant treatment with (c)ICI or TT, compared to patients. Physicians required lower risk reductions for disease-free survival (DFS) and overall survival (OS) for both ICI and TT and their drug-related side effects to accept these treatments. In case of severe side effects, physicians required similar 5-year DFS rates for ICI and TT (60–65%), while patients needed a 15% improvement of 5-year DFS for ICI compared to TT (80%/65%). For survival, physicians expected an OS improvement of + 10% for all three treatment modalities, whereas patients required a higher increase: + 18–22% for ICI and + 15% for TT.ConclusionOur study highlights the importance of understanding the patient’s perspective and a potential difference to the doctor’s view when making decisions about adjuvant melanoma treatment with (c)ICI and TT, especially as these treatments are increasingly being implemented in earlier stages.

EfficientTrain++: Generalized Curriculum Learning for Efficient Visual Backbone Training.

The superior performance of modern computer vision backbones (e.g., vision Transformers learned on ImageNet-1K/22K) usually comes with a costly training procedure. This study contributes to this issue by generalizing the idea of curriculum learning beyond its original formulation, i.e., training models using easier-to-harder data. Specifically, we reformulate the training curriculum as a soft-selection function, which uncovers progressively more difficult patterns within each example during training, instead of performing easier-to-harder sample selection. Our work is inspired by an intriguing observation on the learning dynamics of visual backbones: during the earlier stages of training, the model predominantly learns to recognize some 'easier-to-learn' discriminative patterns in the data. These patterns, when observed through frequency and spatial domains, incorporate lower-frequency components, and the natural image contents without distortion or data augmentation. Motivated by these findings, we propose a curriculum where the model always leverages all the training data at every learning stage, yet the exposure to the 'easier-to-learn' patterns of each example is initiated first, with harder patterns gradually introduced as training progresses. To implement this idea in a computationally efficient way, we introduce a cropping operation in the Fourier spectrum of the inputs, enabling the model to learn from only the lower-frequency components. Then we show that exposing the contents of natural images can be readily achieved by modulating the intensity of data augmentation. Finally, we integrate these two aspects and design curriculum learning schedules by proposing tailored searching algorithms. Moreover, we present useful techniques for deploying our approach efficiently in challenging practical scenarios, such as large-scale parallel training, and limited input/output or data pre-processing speed. The resulting method, EfficientTrain++, is simple, general, yet surprisingly effective. As an off-the-shelf approach, it reduces the training time of various popular models (e.g., ResNet, ConvNeXt, DeiT, PVT, Swin, CSWin, and CAFormer) by [Formula: see text] on ImageNet-1K/22K without sacrificing accuracy. It also demonstrates efficacy in self-supervised learning (e.g., MAE). Code is available at: https://github.com/LeapLabTHU/EfficientTrain.

The health-related quality of life of early-onset colorectal cancer patients: an Australian cross-sectional study.

Early-onset colorectal cancer (EOCRC) patients are more likely to have advanced disease and undergo more aggressive treatment modalities. However, current literature investigating the health-related quality of life (HRQoL) of EOCRC patients is scarce. This study aimed to determine the HRQoL of an Australian cohort of EOCRC patients including a subset who underwent pelvic exenteration (PE) or cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). A cross-sectional study of EOCRC patients treated at the Royal Prince Alfred Hospital, Sydney Australia was performed. Patients were divided into groups based on the time interval from their index operation: ≤2 years and >2 years. HRQoL was evaluated using the SF-36v2 questionnaire. A total of 50 patients were included. For patients ≤2 years from surgery, the median physical component summary (PCS) and mental health component summary (MCS) scores were 53.3 (36.4-58.9) and 47.3 (37.5-55.7). In the >2 years group, the median PCS and MCS scores were 50.6 (43.3-57.7) and 50.2 (39.04-56.2), respectively. Stage I (vs. stage II) disease and emergency (vs. elective) surgery conferred poorer PCS scores in patients ≤2 years from surgery. No other variables impacted PCS or MCS scores in EOCRC patients in either group. HRQoL of EOCRC patients was equivocal to the Australian population. Having an earlier stage of diagnosis and emergency index operation was associated with poorer levels of physical functioning in patients ≤2 years from surgery. However, because of the limitations of this study, these findings require validation in future large-scale prospective research.

Effects of non-ionizing radio frequency electromagnetic radiation on the development and behavior of early embryos of Danio rerio

ABSTRACT Biological effects of radio frequency electromagnetic radiation (RF-EMR) in the range of 900–1800 MHz emerging from the mobile phone were investigated and were found to influence the locomotor pattern when exposure was initiated from 1 hour post fertilization (hpf) in zebrafish embryos (ZE), Danio rerio. Mobile phones and other wireless devices offer tremendous advantages. However, on the flipside they are leading to an increased electromagnetic energy in the environment, an excess of which could be termed as electromagnetic pollution. Herein, we tried to understand the effects of RF-EMR emerging from the mobile phone, on the development and behavior of ZE, exposed to RF-EMR (specific absorption rate of 1.13 W/kg and 1800 MHz frequency) 1 hr daily, for 5 days. To understand if there could be any developmental stage-specific vulnerability to RF-EMR, the exposure was initiated at three different time points: 1hpf, 6hpf and 24hpf of ZE development. Observations revealed no significant changes in the survival rate, morphology, oxidative stress or cortisol levels. However, statistically significant variations were observed in the batch where exposure started at 1hpf, with respect to locomotion patterns (distance travelled: 659.1 ± 173.1 mm Vs 963.5 ± 200.4 mm), which could be correlated to anxiety-like behavior; along with a corresponding increase in yolk consumption (yolk sac area: 0.251 ± 0.019 mm2 Vs 0.225 ± 0.018 mm2). Therefore, we conclude that RF-EMR exposure influences the organism maximally during the earliest stage of development, and we also believe that an increase in the time of exposure (corresponding to the patterns of current usage of mobile phones) might reveal added afflictions.

Transscleral ciliary surgery in glaucoma:from destructive surgery to minimally invasive surgery

Over the years, there has been significant advancement in the safety and effectiveness of external cyclosurgery for glaucoma. This progress ranges from the initial "cyclodestructive surgery" to modern cycloplasty techniques, expanding beyond end-stage glaucoma treatment. Notably, innovative approaches like micropulse transscleral cycloplasty and ultrasonic cycloplasty are now being employed in earlier stages of glaucoma with better visual acuity, qualifying as minimally invasive procedures. Through a comprehensive review of the historical evolution of external cyclosurgery, elucidation of the mechanisms, clinical outcomes, and potential complications associated with novel cycloplasty techniques, and integration of practical clinical insights, this article aims to furnish clinicians with a profound comprehension of external cyclosurgery for glaucoma.

Diagnostic performance of lactate dehydrogenase as a potential biomarker in predicting preeclampsia and associated factors

BackgroundPreeclampsia (PE), a pregnancy specific syndrome, is defined as new-onset hypertension (≥140/90 mmHg) and proteinuria diagnosed after gestational week 20 or new-onset pre-eclampsia associated signs in the absence of proteinuria, and it may tend to present as late as 4–6 weeks’ postpartum period. It is a leading cause of maternal mortality in both developed and developing countries. In order to prevent PE, the disease must be diagnosed at its earliest stage, however, the triads of high blood pressure, edema and albuminuria is neither specific nor sensitive enough for diagnosing the disease. Lactate dehydrogenase (LDH) is useful biochemical marker reflecting the occurrence of complications associated with preeclampsia. Besides, it has been suggested as potential biomarker to predict the severity of preeclampsia and as indicator of multi-organ involvement. The aim of this study was to investigate the diagnostic accuracy of LDH, which is affordable and easy to test, as a potential clinical biomarker to predict onset of preeclampsia.MethodsA hospital based cross-sectional study was conducted as of September 9 to December 24, 2022 at Debre Birhan Comprehensive Specialized Hospital (DBCSH). A total of 132 study subjects (66 preeclamptic and 66 normotensive controls) were enrolled in the study. A receiver operating characteristics (ROC) curve was used to calculate the area under the curve (AUC) and determine diagnostic accuracy of LDH. Youden’s index was used to identify an optimal cut-off point for LDH in detecting preeclampsia associated complications.ResultAUC for LDH was found to be 0.963 (95% CI, 0.91, 1.0; p = 0.000) from ROC curve analysis. An optimal cut-off point for LDH was 376.5 U/L having a sensitivity and specificity of 87.5 and 90.8%, respectively.ConclusionSerum LDH had an AUC of greater than 0.8 and showed good diagnostic accuracy in predicting development of preeclampsia. Disease duration, gestational age, systolic and diastolic blood pressure among enormous number of predictor variables had association with serum level of LDH.

Lung cancer detection based on computed tomography image using convolutional neural networks.

Lung cancer is the most common type of cancer, accounting for 12.8% of cancer cases worldwide. As initially non-specific symptoms occur, it is difficult to diagnose in the early stages. Image processing techniques developed using machine learning methods have played a crucial role in the development of decision support systems. This study aimed to classify benign and malignant lung lesions with a deep learning approach and convolutional neural networks (CNNs). The image dataset includes 4459 Computed tomography (CT) scans (benign, 2242; malignant, 2217). The research type was retrospective; the case-control analysis. A method based on GoogLeNet architecture, which is one of the deep learning approaches, was used to make maximum inference on images and minimize manual control. The dataset used to develop the CNNs model is included in the training (3567) and testing (892) datasets. The model's highest accuracy rate in the training phase was estimated as 0.98. According to accuracy, sensitivity, specificity, positive predictive value, and negative predictive values of testing data, the highest classification performance ratio was positive predictive value with 0.984. The deep learning methods are beneficial in the diagnosis and classification of lung cancer through computed tomography images.

Identification of potential hub genes and regulatory networks of smoking-related endothelial dysfunction in atherosclerosis using bioinformatics analysis.

Endothelial dysfunction, the earliest stage of atherosclerosis, can be caused by smoking, but its molecular mechanism requires further investigation. This study aimed to use bioinformatics analysis to identify potential mechanisms involved in smoking-related atherosclerotic endothelial dysfunction. The transcriptome data used for this bioinformatics analysis were obtained from the Gene Expression Omnibus (GEO) database. The GSE137578 and GSE141136 datasets were used to identify common differentially expressed genes (co-DEGs) in endothelial cells treated with oxidized low-density lipoprotein (ox-LDL) and tobacco. The co-DEGs were annotated using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomics (KEGG) databases. Additionally, a protein-protein interaction (PPI) network was constructed to visualize their interactions and screen for hub genes. GSE120521 dataset was used to verify the expression of hub genes in unstable plaques. The miRNA expression profile GSE137580 and online databases (starBase 2.0, TargetScan 8.0 and DGIdb v4.2.0) were used to predict the related non-coding RNAs and drugs. A total of 232 co-DEGs were identified, including 113 up-regulated genes and 119 down-regulated genes. These DEGs were primarily enriched in detrimental autophagy, cell death, transcription factors, and cytokines, and were implicated in ferroptosis, abnormal lipid metabolism, inflammation, and oxidative stress pathways. Ten hub genes were screened from the constructed PPI network, including up-regulated genes such as FOS, HMOX1, SQSTM1, PTGS2, ATF3, DDIT3, and down-regulated genes MCM4, KIF15, UHRF1, and CCL2. Importantly, HMOX1 was further up-regulated in unstable plaques (p= 0.034). Finally, a regulatory network involving lncRNA/circRNA-miRNA-hub genes and drug-hub genes was established. Atherosclerotic endothelial dysfunction is associated with smoking-induced injury. Through bioinformatics analysis, we identified potential mechanisms and provided potential therapeutic targets.

Callovian Marine Reptiles of European Russia

Our knowledge of marine reptiles of the Callovian age (Middle Jurassic) is majorly based on the collections from the Oxford Clay Formation of England, which yielded a diverse marine reptile fauna of plesiosaurians, ichthyosaurians, and thalattosuchians. However, outside of Western Europe, marine reptile remains of this age are poorly known. Here, we survey marine reptiles from the Callovian stage of European Russia. The fossils collected over more than a century from 28 localities are largely represented by isolated bones and teeth, although partial skeletons are also known. In addition to the previously described rhomaleosaurid and metriorhynchids, we identify pliosaurids of the genera Liopleurodon and Simolestes; cryptoclidid plesiosaurians, including Cryptoclidus eurymerus, Muraenosaurus sp., and cf. Tricleidus, and ophthalmosaurid ichthyosaurians, including the iconic Ophthalmosaurus icenicus. These findings expand the ranges of several Callovian marine reptile taxa far to the Eastern Europe, and support the exchange of marine reptile faunas between Western and Eastern European seas in the middle to late Callovian. However, some specimens from the lower Callovian of European Russia show differences from typical representatives of the middle Callovian Oxford Clay fauna, possibly representing the earlier stages of evolution of some of these marine reptiles not yet recorded in Western Europe or elsewhere.

Exploring cultural dynamics of Black Asian Minority Ethnic (BAME) women in addiction recovery: a comparison of three women from different ethnic backgrounds

Background The existing recovery capital (RC) literature primarily focuses on white males. This study aims to fill this gap by exploring addiction recovery among three culturally diverse UK women, utilizing CHIME-D (Connectedness, Hope/Optimism, Identity, Meaning, Empowerment, and Difficulties) and RC frameworks. It seeks to compare their recovery paths, combining quantitative data with lived experiences, and barriers specific to women in recovery. Methods The article will deploy a case study design involving a mixed methods approach to explore recovery pathways and resulting RC, based on in-depth interviews and recovery capital assessments with three women from white, black and Asian ethnic backgrounds. Results While one of the three participants, reports very strong and positive RC on the REC-CAP, the other two are at a much earlier stage in their journey. In contrast to the white female participant, who lacks personal RC and has significant barriers around ongoing substance use, the Black and Asian Minority Ethnic (BAME) participants report cultural challenges and difficulties engaging with mainstream services. Conclusion Recovery is a personal and individualized journey, but one that is predicated on social support, belonging and access to cultural and community resources. For BAME participants, accessing and engaging with appropriate peer support is essential in building RC and fulfilling the requirements of CHIME.

Combining convolution neural networks with long‐short term memory layers to predict Parkinson's disease progression

AbstractParkinson's disease (PD) is a neurological condition that occurs in nearly 1% of the world's population. The disease is manifested by a sharp drop in dopamine production, resulting from the death of the related producing cells in an area of the midbrain called the substantia nigra. Early diagnosis and accurate staging of the disease are essential to apply the appropriate therapeutic approaches to slow cognitive and motor decline. At present, there is not a singular blood test or biomarker accessible for diagnosing PD or monitoring the progression of its symptoms. Clinical professionals identify the disease by assessing the symptoms, which, however, may vary from case to case, as well as their progression speed. Magnetic resonance imaging (MRIs) have been used for the past three decades to diagnose and distinguish between PD and other neurological conditions.However, to the best of our knowledge, no neural network models have been designed to identify the disease stage. This paper aims to fill this gap. Using the “Parkinson's Progression Markers Initiative” dataset, which reports the patient's MRI and an indication of the disease stage, we developed a model to identify the level of progression. The images and the associated scores were used for training and assessing different deep learning models. Our analysis distinguished four distinct disease progression levels based on a standard scale (Hoehn and Yah scale). The final architecture consists of the cascading of a 3D‐CNN network, adopted to reduce and extract the spatial characteristics of the MRI for efficient training of the successive LSTM layers, aiming at modeling the temporal dependencies among the data. Before training the model, the patient's MRI is preprocessed to correct acquisition errors by applying image registration techniques, to extract irrelevant content from the image, such as nonbrain tissue (e.g., skull, neck, fat). We also adopted template‐based data augmentation techniques to obtain a balanced dataset about progression classes. Our results show that the proposed 3D‐CNN + LSTM model achieves state‐of‐the‐art results by classifying the elements with 91.90 as macro averaged OVR AUC on four classes.

Plant virus transmission during seed development and implications to plant defense system

Most plants produce large amounts of seeds to disperse their progeny in the environment. Plant viruses have evolved to avoid plant resistance mechanisms and use seeds for their dispersal. The presence of plant pathogenic viruses in seeds and suppression of plant host defenses is a major worldwide concern for producers and seed companies because undetected viruses in the seed can represent a significant threat to yield in many economically important crops. The vertical transmission of plant viruses occurs directly through the embryo or indirectly by getting in pollen grains or ovules. Infection of plant viruses during the early development of the seed embryo can result in morphological or genetic changes that cause poor seed quality and, more importantly, low yields due to the partial or ubiquitous presence of the virus at the earliest stages of seedling development. Understanding transmission of plant viruses and the ability to avoid plant defense mechanisms during seed embryo development will help identify primary inoculum sources, reduce virus spread, decrease severity of negative effects on plant health and productivity, and facilitate the future of plant disease management during seed development in many crops. In this article, we provide an overview of the current knowledge and understanding of plant virus transmission during seed embryo development, including the context of host-virus interaction.

Examination of the role of mutualism in immune evasion

Though the earliest stages of oncogenesis, post initiation, are not well understood, it is generally appreciated that a successful transition from a collection of dysregulated cells to an aggressive tumour requires complex ecological interactions between cancer cells and their environment. One key component of tumorigenesis is immune evasion. To investigate the interplay amongst the ecological behaviour of mutualism and immune evasion, we used a computational simulation framework. Sensitivity analyses of the growth of a virtual tumour implemented as a 2D-hexagonal lattice model suggests tumour survival depends on the interplay between growth rates, mutualism and immune evasion. In 60% of simulations, cancer clones with low growth rates, but exhibiting mutualism were able to evade the immune system and continue progressing suggesting that tumours with equivalent growth rates and no mutualism are more likely to be eliminated than tumours with mutualism. Tumours with faster growth rates showed a lower dependence upon mutualism for progression. Geostatistical analysis showed decreased spatial heterogeneity over time for polyclonal tumours with a high division rate. Overall, these results suggest that in slow growing tumours, mutualism is critical for early tumorigenesis.

Shared decision making for patients with kidney failure to improve end-of-life care: Development of the DESIRE intervention.

To describe the development of a shared decision making intervention for planning end-of-life care for patients with kidney failure, their relatives and health professionals in kidney services. End-of-life care conversations within standard disease management consultations are challenging for patients with kidney failure, their relatives and health professionals. End-of-life care planning is about making difficult decisions in advance, which is why health professionals need shared decision making skills to be able to initiate end-of-life conversations. Health professionals report needing more skills to raise the issue of end-of-life care options within consultations and patients want to be able to discuss issues important to them about future care plans. The development design was guided by the UK Medical Research Council's framework and a user-centred approach was applied. Four workshops were conducted with end users. The Template for Intervention Description and Replication for Population Health and Policy interventions was used to shape which questions needed to be answered through the workshops and to present the intervention. The International Patient Decision Aid Standards (IPDAS) criteria set the standards to be achieved. Areas considered significant to a shared decision making intervention were training of health professionals, conversations about end-of-life care, planning and evaluation of the decisions, reporting decisions in health records and repetition of consultation. The development process went through 14 iterations. An intervention named DESIRE was developed that comprises: (1) a training programme for health professionals; (2) shared decision making conversations; and (3) a patient decision aid. The intervention met 30 out of 33 IPDAS criteria. DESIRE is intended to support shared decision making about planning end-of-life care among patients with kidney failure, their relatives and health professionals. The study provides important tools for the stakeholders engaged that can be used within different models of care. What problem did the study address? International guidelines recommend health professionals involve patients with kidney failure in making decisions about end-of-life care, but there is variation in how this is implemented within and across kidney services. Furthermore, patients, relatives and health professionals find it challenging to initiate conversations about end-of-life care. What were the main findings? The study resulted in the development of a complex intervention, called DESIRE, about shared decision making and planning end-of-life care for patients with kidney failure, their relatives and health professionals in kidney services, including a training programme for health professionals, shared decision making conversations and a patient decision aid. Where and on whom will the research have an impact? The research contributes a shared decision making intervention to patients in the later stage of kidney failure, their relatives and health professionals. We believe that the DESIRE intervention could be introduced during consultations with health professionals at an earlier stage of the patient's illness trajectory, as well as being applied to other chronic diseases. This intervention development research is reported according to the GUIDance for the rEporting of intervention Development (GUIDED) checklist and the DEVELOPTOOLS Reporting Checklist. Patients, relatives and health professionals have been involved throughout the research process as part of the research team and advisory board. For this study, the advisory board has particularly contributed to the development process of the DESIRE intervention by actively participating in the four workshops, in the iterations between the workshops and in the preparation of the manuscript.

Fumarate Hydratase-Deficient Renal Cell Carcinoma—A Clinicopathological Study of a Series of 11 Cases

Abstract Introduction Fumarate hydratase (FH)-deficient renal cell carcinoma (RCC) is a rare, molecularly defined renal tumor with aggressive behavior. The diagnosis of these tumors is challenging because of varied morphology and limited access to molecular testing and immunohistochemistry (IHC) for FH and 2-succinocysteine. We aim to elucidate the histomorphology, clinical presentation, and follow-up of this tumor in this first series of cases of FH-deficient RCCs from India. Objectives This article aims to understand and elucidate the clinical presentation, pathologic findings, treatment options, and outcomes of FH-deficient RCC. Materials and Methods Diagnosed cases of FH-deficient RCC between January 2021 and January 2023 including clinical details were retrieved from the electronic medical record database. Histopathological and immunohistochemical slides were reviewed. Results Out of 11 cases of FH-deficient RCC, 36% had been referred with a diagnosis of type 2 papillary RCC. One patient presented with metastatic disease. All had mixed histologic patterns with the predominant pattern being papillary and showed FH loss on IHC. The classically described inclusion like nucleoli was present only focally in most cases. A subset of tumors had low-grade solid-nested morphology and these patients presented at an earlier stage (T2a). Two patients on multikinase inhibitors are alive with disease at 14 months' follow-up. Conclusion FH-deficient RCCs can have varied histologic patterns within the same tumor and show loss of FH expression by IHC. A subset has low grade morphology and tends to have a more indolent course. It is important to have a high index of suspicion for this diagnosis due to its varied histological appearance and aggressive behavior.

Occurrence of Stem Rot on Acacia mangium Caused by Amauroderma subresinosum.

Acacia mangium has the characteristics of developed root system, nitrogen fixation and soil improvement, fast growth and high yield, and improvement of soil fertility. It is often used as a windbreak tree species in rubber plantations, a highway shade tree, for coastal and mountain restoration in Hainan . In October 2021, a stem rot disease with an incidence of 3% was found in Baisha city(19°22'18″N,109°16'58″E), Hainan Province, China. In the early stage of the disease, the crown showed chlorotic leaves, followed by defoliation. In later stages, whole tree dieback was observed. The basal tissue of the stem of the diseased tree had white rot, and black-brown basidiocarps were observed about 1 m away from the ground. The basidiocarps surface of fresh was disinfected with 75 % ethanol, the epidermal tissue was removed, and the inner tissue blocks were transferred to PDA medium. After culturing in dark at 28°C for 3 days, a colony with white aerial mycelium was isolated and designated: HNBSMZXS20211011001. The basidiocarp was dark brown, sessile, mostly one-year-old, and the cap is nearly semi-circular, wooden, slightly shiny, with a size of 14.7 to 18.1cm × 9.5 to 10.1 cm. The base is thick (5 to 6.5 cm) and the edge is thin (0.3 to 0.7 cm). The basidiospores are oval, 10.7 to 13.65μm × 6.7 to 9.06μm in size, with a double-layer wall. The outer wall is transparent and the inner wall is light yellow. The basidiospores contain 1~2 oil droplets. The morphological features are consistent with those of Amauroderma subresinosum (Murrill) Corner (Zhang et al., 2000). The basidiocarps and type strain cultures were stored as accessions in the Laboratory of Plant Pathogen Fungus Biology, Hainan University. For pathogenicity tests, sawdust culture medium was used (soft sawdust 82%, wheat bran 15%, glucose 2%, gypsum 1%, mixed with water in proportion, sterilized at 121°C for 40min). The mycelium plug from a fresh culture (d=5mm) was taken from the edge of the colony of type strain, and transferred to the sterilized sawdust medium. When mycelium has colonized the media, it was used to inoculate plants. Media without mycelium was used as a control. Naturally growing seedlings (three year old) of A.mangium were selected from the teaching nurseries of Hainan University (20°6'25''N,110°32'24''E). First, 75 % alcohol was sprayed on the stem of the base of A.mangium for surface disinfection. After the surface was dried, a slight wound (about 4×2cm) was made on the surface with a sterilized scalpel. A inoculated and control sawdust media rods were tightly attached to the wound, moistened with cotton balls soaked in sterile water, and then fixed with plastic wrap, and the outer layer was wrapped with newsprint. Inoculation and controls were replicated three times. Two months after inoculated, the stems of the plants inoculated with the isolated fungus grew white hyphae and showed white rot symptoms, and the leaves became chlorotic and defoliated with complete tree decline in six months, which was consistent with the original symptoms observed. By comparison, white callus had grown on the edge of the stem wounds of the control plants. The same fungus was re-isolated from the inoculated plants and confirmed as A.subresinosum based on the internal transcribed spacer (ITS), the ribosomal large subunit(LSU), and the translation elongation factor 1-α(EF1-α) gene sequence, the fungus was not isolated from control plants thus fulfilling Koch's postulates. The ITS region of r-DNA, the ribosomal large subunit(LSU), the translation elongation factor 1-α gene(EF1-α) were amplified using ITS1/ITS4(White et al. 1990), LR0R/LR5(Hu et al. 2021), EF1-983F/EF1-1567R(Buckley et al. 2005) primers, respectively. The sequences of ITS (OQ674500), LSU (OQ674502) and EF1-α gene (OQ883944) were submitted to GenBank. Through with BLAST, the identities of the ITS, LSU and EF1-α sequences to A.subresinosum (GenBank Accession no. ITS: LC176755; LSU: MK119903 and EF1-α: MK121572) was 99.82%; 99.15% and 99.82%, respectively, the identities were more than 99 %. It was reported that A.subresinosum could infect Casuarina equisetifolia and Areca catechu(Chen et al., 2016; Cheng. 2017; Wu et al., 2019). However, this is the first report of Amauroderma subresinosum causing stem rot of Acacia mangiumin Hainan, China. This report will facilitate field diagnosis and provide scientific reference for further research on the disease.

Recruitment and retention of adolescents for an ecological momentary assessment measurement burst mental health study: The MHIM engagement strategy.

Recruitment and long-term retention of adolescent participants in longitudinal research are challenging and may be especially so in studies involving remote measurement and biosampling components. The ability to effectively recruit and retain participants can be supported by the use of specific evidence-based engagement strategies that are built in from the earliest stages. Informed by a review of the evidence on effective engagement strategies and consultations with adolescents (via two Young Person Advisory Groups [YPAGs]; ages 11-13 and 14-17), the current protocol describes the planned participant engagement strategy for the Mental Health in the Moment Study: a multimodal measurement burst study of adolescent mental health across ages 11-19. The protocol incorporates engagement strategies in four key domains: consultations/co-design with the target population, incentives, relationship-building and burden/barrier reduction. In addition to describing general engagement strategies in longitudinal studies, we also discuss specific concerns regarding engagement in data collection methods such as biosampling and ecological momentary assessment where a paucity of evidence exists. Engagement strategies for adolescent mental health studies should be based on existing evidence and consultations with adolescents. We present our approach in developing the planned engagement strategies and also discuss limitations and future directions in engaging adolescents in longitudinal research. The study design for this project places a strong emphasis on the active engagement of adolescents throughout its development. Specifically, the feedback and suggestions provided by the YPAGs have been instrumental in refining our strategies for maximising the recruitment and retention of participants.

Catalyst or Obstacle? Green innovation and total factor energy efficiency

Green innovation possesses dual externalities of “innovation” and “environmental protection”, and enhancing energy efficiency serves as a crucial means to promote high-quality economic development. Building upon the energy rebound effect, we use the balanced panel data of cities at prefecture level and above in China from 2008 to 2018 to explore the impact of urban green innovation on total factor energy efficiency (TFEE). The findings of this study indicate that, firstly, the impact of green innovation on TFEE exhibits a positive U-shaped pattern, characterized by initial suppression followed by subsequent promotion. This conclusion remains robust after undergoing a series of rigorous robustness tests. Second, high-quality green innovation is found to reach the turning point more quickly, implying that substantial green innovation can cross the turning point in smaller quantities. Thirdly, on the whole, in comparison to non-resource-based cities, resource-based cities are capable of reaching the turning point at an earlier stage. Finally, the new energy demonstration cities have not yet reached the turning point, while the non-new energy demonstration cities have crossed the turning point. This study contributes novel insights into the relationship between green innovation and TFEE, which holds significant implications for the formulation and implementation of sustainable development policies.

Gonadotropin elevation is ootoxic to ovulatory oocytes and inhibits oocyte maturation, and activin decoy receptor ActRIIB:Fc therapeutically restores maturation

BackgroundElevated FSH often occurs in women of advanced maternal age (AMA, age ≥ 35) and in infertility patients undergoing controlled ovarian stimulation (COS). There is controversy on whether high endogenous FSH contributes to infertility and whether high exogenous FSH adversely impacts patient pregnancy rates.MethodsThe senescence-accelerated mouse-prone-8 (SAMP8) model of female reproductive aging was employed to assess the separate impacts of age and high FSH activity on the percentages (%) of viable and mature ovulated oocytes recovered after gonadotropin treatment. Young and midlife mice were treated with the FSH analog equine chorionic gonadotropin (eCG) to model both endogenous FSH elevation and exogenous FSH elevation. Previously we showed the activin inhibitor ActRIIB:Fc increases oocyte quality by preventing chromosome and spindle misalignments. Therefore, ActRIIB:Fc treatment was performed in an effort to increase % oocyte viability and % oocyte maturation.ResultsThe high FSH activity of eCG is ootoxic to ovulatory oocytes, with greater decreases in % viable oocytes in midlife than young mice. High FSH activity of eCG potently inhibits oocyte maturation, decreasing the % of mature oocytes to similar degrees in young and midlife mice. ActRIIB:Fc treatment does not prevent eCG ootoxicity, but it restores most oocyte maturation impeded by eCG.ConclusionsFSH ootoxicity to ovulatory oocytes and FSH maturation inhibition pose a paradox given the well-known pro-growth and pro-maturation activities of FSH in the earlier stages of oocyte growth. We propose the FOOT Hypothesis (“FSH OoToxicity Hypothesis), that FSH ootoxicity to ovulatory oocytes comprises a new driver of infertility and low pregnancy success rates in DOR women attempting spontaneous pregnancy and in COS/IUI patients, especially AMA women. We speculate that endogenous FSH elevation also contributes to reduced fecundity in these DOR and COS/IUI patients.Restoration of oocyte maturation by ActRIB:Fc suggests that activin suppresses oocyte maturation in vivo. This contrasts with prior studies showing activin A promotes oocyte maturation in vitro. Improved oocyte maturation with agents that decrease endogenous activin activity with high specificity may have therapeutic benefit for COS/IVF patients, COS/IUI patients, and DOR patients attempting spontaneous pregnancies.