bluuebunny/crossref_metadata_2025 huggingface dataset:
The potential of convolutional neural networks for identifying neural states based on electrophysiological signals: experiments on synthetic and real patient data
Authors: Rodriguez Fernando , He Shenghong , Tan Huiling
Published: June 2023

Processing incoming neural oscillatory signals in real-time and decoding from them relevant behavioral or pathological states is often required for adaptive Deep Brain Stimulation (aDBS) and other brain-computer interface (BCI) applications. Most current approaches rely on first extracting a set of predefined features, such as the power in canonical frequency bands or various time-domain features, and then training machine learning systems that use those predefined features as inputs and infer what the underlying brain state is at each given time point. However, whether this algorithmic approach is best suited to extract all available information contained within the neural waveforms remains an open question. Here, we aim to explore different algorithmic approaches in terms of their potential to yield improvements in decoding performance based on neural activity such as measured through local field potentials (LFPs) recordings or electroencephalography (EEG). In particular, we aim to explore the potential of end-to-end convolutional neural networks, and compare this approach with other machine learning methods that are based on extracting predefined feature sets. To this end, we implement and train a number of machine learning models, based either on manually constructed features or, in the case of deep learning-based models, on features directly learnt from the data. We benchmark these models on the task of identifying neural states using simulated data, which incorporates waveform features previously linked to physiological and pathological functions. We then assess the performance of these models in decoding movements based on local field potentials recorded from the motor thalamus of patients with essential tremor. Our findings, derived from both simulated and real patient data, suggest that end-to-end deep learning-based methods may surpass feature-based approaches, particularly when the relevant patterns within the waveform data are either unknown, difficult to quantify, or when there may be, from the point of view of the predefined feature extraction pipeline, unidentified features that could contribute to decoding performance. The methodologies proposed in this study might hold potential for application in adaptive deep brain stimulation (aDBS) and other brain-computer interface systems.
Mood and anxiety disorders within the Research Domain Criteria framework of Positive and Negative Valence Systems: a scoping review
Authors: Böttger Sarah Jane , Förstner Bernd R. , Szalek Laura , Koller-Schlaud Kristin , Rapp Michael A. , Tschorn Mira
Published: June 2023

Introduction

While a growing body of research is adopting Research Domain Criteria (RDoC)-related methods and constructs, there is still a lack of comprehensive reviews on the state of published research on Positive Valence Systems (PVS) and Negative Valence Systems (NVS) in mood and anxiety disorders consistent with the RDoC framework.

Methods

Five electronic databases were searched to identify peer-reviewed publications covering research on “positive valence” and “negative valence” as well as “valence,” “affect,” and “emotion” for individuals with symptoms of mood and anxiety disorders. Data was extracted with a focus on disorder, domain, (sub-) constructs, units of analysis, key results, and study design. Findings are presented along four sections, distinguishing between primary articles and reviews each for PVS, NVS, and cross-domain PVS and NVS.

Results

A total of 231 abstracts were identified, and 43 met the inclusion criteria for this scoping review. Seventeen publications addressed research on PVS, seventeen on NVS, and nine covered cross-domain research on PVS and NVS. Psychological constructs were typically examined across different units of analysis, with the majority of publications incorporating two or more measures. Molecular, genetic, and physiological aspects were mainly investigated via review articles, primary articles focused on self-report, behavioral, and, to a lesser extent, physiological measures.

Conclusions

This present scoping review shows that mood and anxiety disorders were actively studied using a range of genetic, molecular, neuronal, physiological, behavioral, and self-report measures within the RDoC PVS and NVS. Results highlight the essential role of specific cortical frontal brain structures and of subcortical limbic structures in impaired emotional processing in mood and anxiety disorders. Findings also indicate overall limited research on NVS in bipolar disorders and PVS in anxiety disorders, a majority of self-report studies, and predominantly observational studies. Future research is needed to develop more RDoC-consistent advancements and intervention studies targeting neuroscience-driven PVS and NVS constructs.
Recording cilia activity in ctenophores: effects of nitric oxide and low molecular weight transmitters
Authors: Norekian Tigran P. , Moroz Leonid L.
Published: June 2023

Cilia are the major effectors in Ctenophores, but very little is known about their transmitter control and integration. Here, we present a simple protocol to monitor and quantify cilia activity and provide evidence for polysynaptic control of cilia coordination in ctenophores. We also screened the effects of several classical bilaterian neurotransmitters (acetylcholine, dopamine, L-DOPA, serotonin, octopamine, histamine, gamma-aminobutyric acid (GABA), L-aspartate, L-glutamate, glycine), neuropeptide (FMRFamide), and nitric oxide (NO) on cilia beating in Pleurobrachia bachei and Bolinopsis infundibulum. NO and FMRFamide produced noticeable inhibitory effects on cilia activity, whereas other tested transmitters were ineffective. These findings further suggest that ctenophore-specific neuropeptides could be major candidates for signal molecules controlling cilia activity in representatives of this early-branching metazoan lineage.
Untargeted metabolomics analysis in drug-naïve patients with severe obsessive–compulsive disorder
Authors: Li Zheqin , Gao Jian , Lin Liangjun , Zheng Zifeng , Yan Susu , Wang Weidi , Shi Dongdong , Wang Zhen
Published: June 2023

Introduction

Obsessive–compulsive disorder (OCD), characterized by the presence of obsessions and/or compulsions, is often difficult to diagnose and treat in routine clinical practice. The candidate circulating biomarkers and primary metabolic pathway alteration of plasma in OCD remain poorly understood.

Methods

We recruited 32 drug-naïve patients with severe OCD and 32 compared healthy controls and applied the untargeted metabolomics approach by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) to assess their circulating metabolic profiles. Both univariate and multivariate analyses were then utilized to filtrate differential metabolites between patients and healthy controls, and weighted Correlation Network Analysis (WGCNA) was utilized to screen out hub metabolites.

Results

A total of 929 metabolites were identified, including 34 differential metabolites and 51 hub metabolites, with an overlap of 13 metabolites. Notably, the following enrichment analyses underlined the importance of unsaturated fatty acids and tryptophan metabolism alterations in OCD. Metabolites of these pathways in plasma appeared to be promising biomarkers, such as Docosapentaenoic acid and 5-Hydroxytryptophan, which may be biomarkers for OCD identification and prediction of sertraline treatment outcome, respectively.

Conclusion

Our findings revealed alterations in the circulating metabolome and the potential utility of plasma metabolites as promising biomarkers in OCD.
Post-ischemic reorganization of sensory responses in cerebral cortex
Authors: Hayley P. , Tuchek C. , Dalla S. , Borrell J. , Murphy M. D. , Nudo R. J. , Guggenmos D. J.
Published: June 2023

Introduction

Sensorimotor integration is critical for generating skilled, volitional movements. While stroke tends to impact motor function, there are also often associated sensory deficits that contribute to overall behavioral deficits. Because many of the cortico-cortical projections participating in the generation of volitional movement either target or pass-through primary motor cortex (in rats, caudal forelimb area; CFA), any damage to CFA can lead to a subsequent disruption in information flow. As a result, the loss of sensory feedback is thought to contribute to motor dysfunction even when sensory areas are spared from injury. Previous research has suggested that the restoration of sensorimotor integration through reorganization or de novo neuronal connections is important for restoring function. Our goal was to determine if there was crosstalk between sensorimotor cortical areas with recovery from a primary motor cortex injury. First, we investigated if peripheral sensory stimulation would evoke responses in the rostral forelimb area (RFA), a rodent homologue to premotor cortex. We then sought to identify whether intracortical microstimulation-evoked activity in RFA would reciprocally modify the sensory response.

Methods

We used seven rats with an ischemic lesion of CFA. Four weeks after injury, the rats’ forepaw was mechanically stimulated under anesthesia and neural activity was recorded in the cortex. In a subset of trials, a small intracortical stimulation pulse was delivered in RFA either individually or paired with peripheral sensory stimulation.

Results

Our results point to post-ischemic connectivity between premotor and sensory cortex that may be related to functional recovery. Premotor recruitment during the sensory response was seen with a peak in spiking within RFA after the peripheral solenoid stimulation despite the damage to CFA. Furthermore, stimulation in RFA modulated and disrupted the sensory response in sensory cortex.

Discussion

The presence of a sensory response in RFA and the sensitivity of S1 to modulation by intracortical stimulation provides additional evidence for functional connectivity between premotor and somatosensory cortex. The strength of the modulatory effect may be related to the extent of the injury and the subsequent reshaping of cortical connections in response to network disruption.
Protocol for mapping of the supplementary motor area using repetitive navigated transcranial magnetic stimulation
Authors: Engelhardt Melina , Kern Giulia , Karhu Jari , Picht Thomas
Published: June 2023

Background

Damage to the supplementary motor area (SMA) can lead to impairments of motor and language function. A detailed preoperative mapping of functional boarders of the SMA could therefore aid preoperative diagnostics in these patients.

Objective

The aim of this study was the development of a repetitive nTMS protocol for non-invasive functional mapping of the SMA while assuring effects are caused by SMA rather than M1 activation.

Methods

The SMA in the dominant hemisphere of 12 healthy subjects (28.2 ± 7.7 years, 6 females) was mapped using repetitive nTMS at 20 Hz (120% RMT), while subjects performed a finger tapping task. Reductions in finger taps were classified in three error categories (≤15% = no errors, 15–30% = mild, >30% significant). The location and category of induced errors was marked in each subject’s individual MRI. Effects of SMA stimulation were then directly compared to effects of M1 stimulation in four different tasks (finger tapping, writing, line tracing, targeting circles).

Results

Mapping of the SMA was possible for all subjects, yet effect sizes varied. Stimulation of the SMA led to a significant reduction of finger taps compared to baseline (BL: 45taps, SMA: 35.5taps; p < 0.01). Line tracing, writing and targeting of circles was less accurate during SMA compared to M1 stimulation.

Conclusion

Mapping of the SMA using repetitive nTMS is feasible. While errors induced in the SMA are not entirely independent of M1, disruption of the SMA induces functionally distinct errors. These error maps can aid preoperative diagnostics in patients with SMA related lesions.
Dysfunction of basal ganglia functional connectivity associated with subjective and cognitive fatigue in multiple sclerosis
Authors: Langley Christelle , Masuda Naoki , Godwin Simon , De Marco Giovanni , Smith Angela Davies , Jones Rosemary , Bruce Jared , Thai Ngoc Jade
Published: June 2023

Objectives

Central fatigue is one of the most common symptoms in multiple sclerosis (MS). It has a profound impact on quality of life and a negative effect on cognition. Despite its widespread impact, fatigue is poorly understood and very difficult to measure. Whilst the basal ganglia has been implicated in fatigue the nature of its role and involvement with fatigue is still unclear. The aim of the present study was to establish the role of the basal ganglia in MS fatigue using functional connectivity measures.

Methods

The present study examined the functional connectivity (FC) of the basal ganglia in a functional MRI study with 40 female participants with MS (mean age = 49.98 (SD = 9.65) years) and 40 female age-matched (mean age = 49.95 (SD = 9.59) years) healthy controls (HC). To measure fatigue the study employed the subjective self-report Fatigue Severity Scale and a performance measure of cognitive fatigue using an alertness-motor paradigm. To distinguish physical and central fatigue force measurements were also recorded.

Results

The results suggest that decreased local FC within the basal ganglia plays a key role in cognitive fatigue in MS. Increased global FC between the basal ganglia and the cortex may sub serve a compensatory mechanism to reduce the impact of fatigue in MS.

Conclusion

The current study is the first to show that basal ganglia functional connectivity is associated with both subjective and objective fatigue in MS. In addition, the local FC of the basal ganglia during fatigue inducing tasks could provide a neurophysiological biomarker of fatigue.
The role of pyroptosis in cognitive impairment
Authors: Yang Xin , Tang Zhe
Published: June 2023

Cognitive impairment is a major global disease, manifests as a decline in cognitive functioning and endangers the health of the population worldwide. The incidence of cognitive impairment has increased rapidly with an increasingly aging population. Although the mechanisms of cognitive impairment have partly been elucidated with the development of molecular biological technology, treatment methods are very limited. As a unique form of programmed cell death, pyroptosis is highly pro-inflammatory and is closely associated with the incidence and progression of cognitive impairment. In this review, we discuss the molecular mechanisms of pyroptosis briefly and the research progress on the relationship between pyroptosis and cognitive impairment and its potential therapeutic values, to provide a reference for research in the field of cognitive impairment.
Cardiolipin externalization mediates prion protein (PrP) peptide 106–126-associated mitophagy and mitochondrial dysfunction
Authors: Yang Dongming , Li Jie , Li Zhiping , Zhao Mengyang , Wang Dongdong , Sun Zhixin , Wen Pei , Gou Fengting , Dai Yuexin , Ji Yilan , Li Wen , Zhao Deming , Yang Lifeng
Published: June 2023

Proper mitochondrial performance is imperative for the maintenance of normal neuronal function to prevent the development of neurodegenerative diseases. Persistent accumulation of damaged mitochondria plays a role in prion disease pathogenesis, which involves a chain of events that culminate in the generation of reactive oxygen species and neuronal death. Our previous studies have demonstrated that PINK1/Parkin-mediated mitophagy induced by PrP106−126 is defective and leads to an accumulation of damaged mitochondria after PrP106−126 treatment. Externalized cardiolipin (CL), a mitochondria-specific phospholipid, has been reported to play a role in mitophagy by directly interacting with LC3II at the outer mitochondrial membrane. The involvement of CL externalization in PrP106−126-induced mitophagy and its significance in other physiological processes of N2a cells treated with PrP106−126 remain unknown. We demonstrate that the PrP106−126 peptide caused a temporal course of mitophagy in N2a cells, which gradually increased and subsequently decreased. A similar trend in CL externalization to the mitochondrial surface was seen, resulting in a gradual decrease in CL content at the cellular level. Inhibition of CL externalization by knockdown of CL synthase, responsible for de novo synthesis of CL, or phospholipid scramblase-3 and NDPK-D, responsible for CL translocation to the mitochondrial surface, significantly decreased PrP106−126-induced mitophagy in N2a cells. Meanwhile, the inhibition of CL redistribution significantly decreased PINK1 and DRP1 recruitment in PrP106−126 treatment but had no significant decrease in Parkin recruitment. Furthermore, the inhibition of CL externalization resulted in impaired oxidative phosphorylation and severe oxidative stress, which led to mitochondrial dysfunction. Our results indicate that CL externalization induced by PrP106−126 on N2a cells plays a positive role in the initiation of mitophagy, leading to the stabilization of mitochondrial function.
The epidemiological patterns of non-Hodgkin lymphoma: global estimates of disease burden, risk factors, and temporal trends
Authors: Chu Yurou , Liu Yingyue , Fang Xiaosheng , Jiang Yujie , Ding Mei , Ge Xueling , Yuan Dai , Lu Kang , Li Peipei , Li Ying , Xu Hongzhi , Fan Juan , Zhou Xiangxiang , Wang Xin
Published: June 2023

Background

The incidence of non-Hodgkin’s lymphoma (NHL) has increased steadily over the past few decades. Elucidating its global burden will facilitate more effective disease management and improve patient outcomes. We explored the disease burden, risk factors, and trends in incidence and mortality in NHL globally.

Methods

The up-to-date data on age-standardized incidence and mortality rates of NHL were retrieved from the GLOBOCAN 2020, CI5 volumes I-XI, WHO mortality database, and Global Burden of Disease (GBD) 2019, focusing on geographic disparities worldwide. We reported incidence and mortality by sex and age, along with corresponding age-standardized rates (ASRs), the average annual percentage change (AAPC), and future burden estimates to 2040.

Results

In 2020, there were an estimated 545,000 new cases and 260,000 deaths of NHL globally. In addition, NHL resulted in 8,650,352 age-standardized DALYs in 2019 worldwide. The age-specific incidence rates varied drastically across world areas, at least 10-fold in both sexes, with the most pronounced increase trend found in Australia and New Zealand. By contrast, North African countries faced a more significant mortality burden (ASR, 3.7 per 100,000) than highly developed countries. In the past decades, the pace of increase in incidence and mortality accelerated, with the highest AAPC of 4.9 (95%CI: 3.6-6.2) and 6.8 (95%CI: 4.3-9.2) in the elderly population, respectively. Considering risk factors, obesity was positively correlated with age-standardized incidence rates (P< 0.001). And North America was the high-risk region for DALYs due to the high body mass index in 2019. Regarding demographic change, NHL incident cases are projected to rise to approximately 778,000 by 2040.

Conclusion

In this pooled analysis, we provided evidence for the growing incidence trends in NHL, particularly among women, older adults, obese populations, and HIV-infected people. And the marked increase in the older population is still a public health issue that requires more attention. Future efforts should be directed at cultivating health awareness and formulating effective and locally tailored cancer prevention strategies, especially in most developing countries.
Strategies to eliminate cervical cancer in China
Authors: Ji Lu , Chen Manli , Yao Lan
Published: June 2023

Cervical cancer is a widely distributed disease that is preventable and controllable through early intervention. The World Health Organization has identified three key measures, coverage populations and coverage targets to eliminate cervical cancer. The WHO and several countries have conducted model predictions to determine the optimal strategy and timing of cervical cancer elimination. However, specific implementation strategies need to be developed in the context of local conditions. China has a relatively high disease burden of cervical cancer but a low human papillomavirus vaccination rate and cervical cancer screening population coverage. The purpose of this paper is to review interventions and prediction studies for the elimination of cervical cancer and to analyze the problems, challenges and strategies for the elimination of cervical cancer in China.
Diagnostic value of mammography density of breast masses by using deep learning
Authors: Chen Qian-qian , Lin Shu-ting , Ye Jia-yi , Tong Yun-fei , Lin Shu , Cai Si-qing
Published: June 2023

Objective

In order to explore the relationship between mammographic density of breast mass and its surrounding area and benign or malignant breast, this paper proposes a deep learning model based on C2FTrans to diagnose the breast mass using mammographic density.

Methods

This retrospective study included patients who underwent mammographic and pathological examination. Two physicians manually depicted the lesion edges and used a computer to automatically extend and segment the peripheral areas of the lesion (0, 1, 3, and 5 mm, including the lesion). We then obtained the mammary glands’ density and the different regions of interest (ROI). A diagnostic model for breast mass lesions based on C2FTrans was constructed based on a 7: 3 ratio between the training and testing sets. Finally, receiver operating characteristic (ROC) curves were plotted. Model performance was assessed using the area under the ROC curve (AUC) with 95% confidence intervals (CI), sensitivity, and specificity.

Results

In total, 401 lesions (158 benign and 243 malignant) were included in this study. The probability of breast cancer in women was positively correlated with age and mass density and negatively correlated with breast gland classification. The largest correlation was observed for age (r = 0.47). Among all models, the single mass ROI model had the highest specificity (91.8%) with an AUC = 0.823 and the perifocal 5mm ROI model had the highest sensitivity (86.9%) with an AUC = 0.855. In addition, by combining the cephalocaudal and mediolateral oblique views of the perifocal 5 mm ROI model, we obtained the highest AUC (AUC = 0.877 P < 0.001).

Conclusions

Deep learning model of mammographic density can better distinguish benign and malignant mass-type lesions in digital mammography images and may become an auxiliary diagnostic tool for radiologists in the future.
The clinical outcomes of laparoscopic proximal gastrectomy with double-tract reconstruction versus tube-like stomach reconstruction in patients with adenocarcinoma of the esophagogastric junction based on propensity score-matching: a multicenter cohort study
Authors: Xu Zhiwen , Chen Jinping , Chen Shaoqin , Lin Hexin , Zhao Kang , Zheng Changyue , Liu Huibin , Chen Zhihua , Fu Yongan , Hong Qingqi , Lin Wei , Yan Su , You Jun
Published: June 2023

Purpose

Laparoscopic proximal gastrectomy with double-tract reconstruction (LPG-DTR) and laparoscopic proximal gastrectomy with tube-like stomach reconstruction (LPG-TLR) are both function-preserving procedures performed for treating AEG. However, there is no clinical consensus on the selection of digestive tract reconstruction after proximal gastrectomy, and the best way to reconstruct the digestive tract remains controversial. This study aimed at comparing the clinical outcomes of LPG-DTR and LPG-TLR to provide some reference to the choice of AEG surgical modalities.

Methods

This was a multicenter, retrospective cohort study. we collected clinicopathological and follow-up data of patients with consecutive cases diagnosed with AEG from January 2016 to June 2021 in five medical centers. According to the way of digestive tract reconstruction after tumor resection, patients who underwent LPG-DTR or LPG-TLR were included in the present study. Propensity score matching (PSM) was performed to balance baseline variables that might affect the study outcomes. The QOL of the patients was evaluated using the Visick grade.

Results

A total of 124 eligible consecutive cases were finally included. Patients in both groups were matched using the PSM method, and 55 patients from each group were included in the analysis after PSM. There was no statistically significant difference between the two groups in terms of the operation time, amount of intraoperative blood loss, days of postoperative abdominal drainage tube placement, postoperative hospitalization days, total hospitalization cost, the total number of lymph nodes cleared, and the number of positive lymph nodes (P>0.05). There was a statistically significant difference between the two groups in terms of time to first flatus after surgery and postoperative soft food recovery time (P<0.05). For the nutritional status, the weight levels at 1 year after surgery was better in the LPG-DTR group than in the LPG-TLR group (P<0.05). There was no significant difference in Visick grade between the two groups (P>0.05).

Conclusion

The anti-reflux effect and quality of life of LPG-DTR for AEG were comparable to those of LPG-TLR. Compared with LPG-TLR, LPG-DTR provide better nutrition status for patients with AEG. LPG-DTR is a superior reconstruction method after proximal gastrectomy.
Deciphering the molecular mechanism of enhanced tumor activity of the EGFR variant T790M/L858R using melanoma cell lines
Authors: Shao Hanshuang , Wells Alan
Published: June 2023

Introduction

The abnormal expression and mutagenesis of EGFR drives both the development and progression of a multitude of human cancers. Further mutations within the tyrosine kinase region of the EGFR subsequently contribute to resistance to targeted drugs. What is not known is how these mutations affect progression-related behaviors of cancer cells.

Methods

The mutagenesis of EGFR T790M, L858R, and T790M/L858R was performed via oligo primer-guided polymerase chain reaction (PCR). GFP-tagged mammalian expression vectors were constructed and confirmed. Stable melanoma cell lines WM983A and WM983B expressing WT or mutant EGFRs were generated for determining the functions of WT and mutant EGFRs in migration, invasion, and resistance to doxorubicin. Immunoblotting and immunofluorescence were performed to detect the transphosphorylation and autophosphorylation of WT and mutant EGFRs and other molecules.

Results

The EGFR mutant T790M/L858R showed significantly higher basal autophosphorylation in melanoma cell lines WM983A and WM983B. Overexpression of WT EGFR significantly enhanced the protein level of E-cadherin (E-cad) via upregulating its mRNA. In contrast, L858R significantly downregulated E-cad. Biological activity assays show that T790M/L858R presented significant enhancement in vitro in invasion and migration, while WT and T790M moderately inhibited invasion and migration. In WM983A cells, enhanced invasion and migration by T790M/L858R required the downstream signaling pathways through Akt and p38. T790M/L858R dramatically triggers phosphorylation of actin cross-linking protein alpha-actinin-4 in the absence of EGF. This double mutant also conferred resistance to a general chemotherapy doxorubicin through Akt but not the p38 signaling pathway.

Conclusion

These findings suggest that T790M/L858R not only confers enhanced therapeutic resistance in cancer cell lines but also may promote tumor metastasis via its boosted downstream signaling pathways and/or direct phosphorylation of other key proteins.
Aberrant expression of bone morphogenetic proteins in the disease progression and metastasis of breast cancer
Authors: Liu Ming , Sui Laijian , Fang Ziqian , Jiang Wen G. , Ye Lin
Published: June 2023

Background

Bone morphogenetic proteins (BMPs) play crucial roles in the tumorigenesis and metastasis of cancers. Controversy remains about the exact implications of BMPs and their antagonists in breast cancer (BC), due to their diverse and complex biological functions and signalling. A comprehensive study of the whole family and their signalling in breast cancer is provoked.

Methods

Aberrant expression of BMP, BMP receptors and antagonists in primary tumours in breast cancer were analysed by using TCGA-BRCA and E-MTAB-6703 cohorts. Related biomarkers including ER, HER, proliferation, invasion, angiogenesis, lymphangiogenesis and bone metastasis were involved to identify the relationship with BMPs in breast cancer.

Results

The present study showed BMP8B was significantly increased in breast tumours, while BMP6 and ACVRL1 were decreased in breast cancer tissues. The expressions of BMP2, BMP6, TGFBR1 and GREM1 were significantly correlated with BC patients’ poor overall survival. Aberrant expression of BMPs, together with BMP receptors, were explored in different subtypes of breast cancer according to ER, PR and HER2 status. Furthermore, higher levels of BMP2, BMP6 and GDF5 were revealed in triple negative breast cancer (TNBC) whilst BMP4, GDF15, ACVR1B, ACVR2B and BMPR1B were relatively higher in Luminal type BC. ACVR1B and BMPR1B were positively correlated with ERα but were inversely correlated with ERβ. High expression of GDF15, BMP4 and ACVR1B were associated with poorer overall survival in HER2 positive BC. BMPs also play dual roles in tumour growth and metastasis of BC.

Conclusion

A shift pattern of BMPs was showed in different subtypes of breast cancer suggesting a subtype specific involvement. It provokes more research to shed light on the exact role of these BMPs and receptors in the disease progression and distant metastasis through a regulation of proliferation, invasion and EMT.
Intermediate and high-risk non-muscle-invasive bladder cancer: an overview of epidemiology, burden, and unmet needs
Authors: Grabe-Heyne Kristin , Henne Christof , Mariappan Paramananthan , Geiges Götz , Pöhlmann Johannes , Pollock Richard F.
Published: June 2023

Bladder cancer ranks among the most common cancers globally. At diagnosis, 75% of patients have non-muscle-invasive bladder cancer (NMIBC). Patients with low-risk NMIBC have a good prognosis, but recurrence and progression rates remain high in intermediate- and high-risk NMIBC, despite the decades-long availability of effective treatments for NMIBC such as intravesical Bacillus Calmette-Guérin (BCG). The present review provides an overview of NMIBC, including its burden and treatment options, and then reviews aspects that counteract the successful treatment of NMIBC, referred to as unmet treatment needs. The scale and reasons for each unmet need are described based on a comprehensive review of the literature, including insufficient adherence to treatment guidelines by physicians because of insufficient knowledge, training, or access to certain therapy options. Low rates of lifestyle changes and treatment completion by patients, due to BCG shortages or toxicities and adverse events as well as their impact on social activities, represent additional areas of potential improvement. Highly heterogeneous evidence for the effectiveness and safety of some treatments limits the comparability of results across studies. As a result, efforts are underway to standardize treatment schedules for BCG, but intravesical chemotherapy schedules remain unstandardized. In addition, risk-scoring models often perform unsatisfactorily due to significant differences between derivation and real-world cohorts. Reporting in clinical trials suffers from a lack of consistent outcomes reporting in bladder cancer clinical trials, paired with an under-representation of racial and ethnic minorities in many trials.
Fluorescein-guided surgery for high-grade glioma resection: a five-year-long retrospective study at our institute
Authors: Xi Chen , Jinli Sun , Jianyao Mao , Yan Chen , Huijuan Li , Zhongjie Shi , Zhangyu Li , Liwei Zhou , Yukui Li , Sifang Chen , Guowei Tan
Published: June 2023

Objective

This study investigates the extent of resection, duration of surgery, intraoperative blood loss, and postoperative complications in patients with high-grade glioma who received surgery with or without sodium fluorescein guidance.

Methods

A single-center retrospective cohort study was conducted on 112 patients who visited our department and underwent surgery between July 2017 and June 2022, with 61 in the fluorescein group and 51 in the non-fluorescein group. Baseline characteristics, intraoperative blood loss, surgery duration, resection extent, and postoperative complications were documented.

Results

The duration of surgery was significantly shorter in the fluorescein group than in the non-fluorescein group (P = 0.022), especially in patients with tumors in the occipital lobes (P = 0.013). More critically, the gross total resection (GTR) rate was significantly higher in the fluorescein group than in the non-fluorescein group (45.9% vs. 19.6%, P = 0.003). The postoperative residual tumor volume (PRTV) was also significantly lower in the fluorescein group than in the non-fluorescein group (0.40 [0.12-7.11] cm3 vs. 4.76 [0.44-11.00] cm3, P = 0.020). Particularly in patients with tumors located in the temporal and occipital lobes (temporal, GTR 47.1% vs. 8.3%, P = 0.026; PRTV 0.23 [0.12-8.97] cm3 vs. 8.35 [4.05-20.59] cm3, P = 0.027; occipital, GTR 75.0% vs. 0.0%, P = 0.005; PRTV 0.15 [0.13-1.50] cm3 vs. 6.58 [3.70-18.79] cm3, P = 0.005). However, the two groups had no significant difference in intraoperative blood loss (P = 0.407) or postoperative complications (P = 0.481).

Conclusions

Fluorescein-guided resection of high-grade gliomas using a special operating microscope is a feasible, safe, and convenient technique that significantly improves GTR rates and reduces postoperative residual tumor volume when compared to conventional white light surgery without fluorescein guidance. This technique is particularly advantageous for patients with tumors located in non-verbal, sensory, motor, and cognitive areas such as the temporal and occipital lobes, and does not increase the incidence of postoperative complications.
Diagnosis of primary lung cancer and benign pulmonary nodules: a comparison of the breath test and 18F-FDG PET-CT
Authors: Ding Xiangxiang , Lin Guihu , Wang Peiyu , Chen Haibin , Li Nan , Yang Zhi , Qiu Mantang
Published: June 2023

With the application of low-dose computed tomography in lung cancer screening, pulmonary nodules have become increasingly detected. Accurate discrimination between primary lung cancer and benign nodules poses a significant clinical challenge. This study aimed to investigate the viability of exhaled breath as a diagnostic tool for pulmonary nodules and compare the breath test with 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)–computed tomography (CT). Exhaled breath was collected by Tedlar bags and analyzed by high-pressure photon ionization time-of-flight mass spectrometry (HPPI-TOFMS). A retrospective cohort (n = 100) and a prospective cohort (n = 63) of patients with pulmonary nodules were established. In the validation cohort, the breath test achieved an area under the receiver operating characteristic curve (AUC) of 0.872 (95% CI 0.760–0.983) and a combination of 16 volatile organic compounds achieved an AUC of 0.744 (95% CI 0.7586–0.901). For PET-CT, the SUVmax alone had an AUC of 0.608 (95% CI 0.433–0.784) while after combining with CT image features, 18F-FDG PET-CT had an AUC of 0.821 (95% CI 0.662–0.979). Overall, the study demonstrated the efficacy of a breath test utilizing HPPI-TOFMS for discriminating lung cancer from benign pulmonary nodules. Furthermore, the accuracy achieved by the exhaled breath test was comparable with 18F-FDG PET-CT.
Promoter hypermethylation of SFRP1 as a prognostic and potentially predictive blood-based biomarker in patients with localized pancreatic ductal adenocarcinoma
Authors: Stubbe Benjamin Emil , Larsen Anders Christian , Madsen Poul Henning , Krarup Henrik Bygum , Pedersen Inge Søkilde , Lundbye-Christensen Søren , Hansen Carsten Palnæs , Hasselby Jane Preuss , Johansen Astrid Zedlitz , Thorlacius-Ussing Ole , Johansen Julia Sidenius , Henriksen Stine Dam
Published: June 2023

Introduction

Current prognostic blood-based biomarkers for pancreatic adenocarcinoma (PDAC) are limited. Recently, promoter hypermethylation of SFRP1 (phSFRP1) has been linked to poor prognosis in patients with gemcitabine-treated stage IV PDAC. This study explores the effects of phSFRP1 in patients with lower stage PDAC.

Methods

Based on a bisulfite treatment process, the promoter region of the SFRP1 gene was analyzed with methylation-specific PCR. Kaplan-Meier curves, log-rank tests, and generalized linear regression analysis were used to assess restricted mean survival time survival at 12 and 24 months.

Results

The study included 211 patients with stage I-II PDAC. The median overall survival of patients with phSFRP1 was 13.1 months, compared to 19.6 months in patients with unmethylated SFRP1 (umSFRP1). In adjusted analysis, phSFRP1 was associated with a loss of 1.15 months (95%CI -2.11, -0.20) and 2.71 months (95%CI -2.71, -0.45) of life at 12 and 24 months, respectively. There was no significant effect of phSFRP1 on disease-free or progression-free survival. In stage I-II PDAC, patients with phSFRP1 have worse prognoses than patients with umSFRP1.

Discussion

Results could indicate that the poor prognosis may be caused by reduced benefit from adjuvant chemotherapy. SFRP1 may help guide the clinician and be a possible target for epigenetically modifying drugs.
A novel mixed reality system to manage phantom pain in-home: results of a pilot clinical trial
Authors: Annapureddy Drupad , Annaswamy Thiru M. , Raval Gargi , Chung Yu-Yen , Prabhakaran Balakrishnan
Published: June 2023

Introduction

Mirror therapy for phantom limb pain (PLP) is a well-accepted treatment method that allows participants to use a mirror to visually perceive the missing limb. Mixed reality options are now becoming increasingly available, but an in-home virtual mirror therapy option has yet to be adequately investigated.

Methods

We had previously developed a mixed reality system for Managing Phantom Pain (Mr. MAPP) that registers the intact limb and mirrors it onto the amputated limb with the system's visual field, allowing the user to engage with interactive games targeting different large lower limb movements. Feasibility and pilot outcomes of treating patients with lower extremity PLP by using Mr. MAPP at home for 1 month were evaluated in this study. Pain intensity and interference were assessed using the McGill Pain Questionnaire, Brief Pain Inventory, and a daily exercise diary. Function was assessed using the Patient Specific Functional Scale (PSFS). The clinical trial registry number for this study is NCT04529083.

Results

This pilot study showed that it was feasible for patients with PLP to use Mr. MAPP at home. Among pilot clinical outcomes, statistically significant differences were noted in mean current pain intensity [1.75 (SD = 0.46) to 1.125 (SD = 0.35) out of 5, P = .011] and PSFS goal scores [4.28 (SD = 2.27) to 6.22 (SD = 2.58) out of 10, P = .006], with other outcome measures showing non-significant trends towards improvement.

Discussion

This pilot study revealed that in-home use of Mr. MAPP has potential to provide pain relief and improve function in patients with lower extremity PLP and is feasible. Each scale used provided unique perspective on the functional impact of PLP. Further expanded studies and investigation, including a fully powered clinical trial, with these scales are warranted.

Clinical Trial Registration

https://www.clinicaltrials.gov/ct2/show/NCT04529083, Identifier: NCT04529083.
BuShen HuoXue decoction improves fertility through intestinal hsp-16.2-mediated heat-shock signaling pathway in Caenorhabditis elegans
Authors: Wu Kanglu , Zhao Xudong , Xiao Xian , Chen Miao , Wu Liang , Jiang Chao , Jin Jing , Li Lei , Ruan Qinli , Guo Jun
Published: June 2023

Introduction: BuShen HuoXue (BSHX) decoction is commonly used in the clinical treatment of premature ovarian failure because it can increase estradiol level and decrease follicle-stimulating hormone level. In this study, we determined the potential therapeutic effects of BSHX decoction via anti-stress pathway and the underlying mechanism by using the nematode Caenorhabditis elegans as an assay system.

Methods: Bisphenol A (BPA, 175 μg/mL) was used to establish a fertility-defective C. elegans model. Nematodes were cultivated according to standard methods. Brood size, DTC, the number of apoptotic cells and oocytes were used to evaluate the fertility of nematodes. Nematodes were cultivated at 35°C as heat stress. RNA isolation and RT-qPCR were used to detect the mRNA expression level of genes. Intestinal ROS and intestinal permeability were used to evaluate the function of intestinal barrier. BSHX decoction was extracted with water and analyzed by LC/Q-TOF.

Results and Discussion: In BPA-treated N2 nematodes, 62.5 mg/mL BSHX decoction significantly improved the brood size and the oocytes quality at different developmental stages. BSHX decoction improved resistance to heat stress through the hsf-1-mediated heat-shock signaling pathway. Further analysis showed that the decoction significantly improved the transcriptional levels of hsf-1 downstream target genes, such as hsp-16.1, hsp-16.2, hsp-16.41, and hsp-16.48. Other than hsp-16.2 expression in the gonad, the decoction also affected intestinal hsp-16.2 expression and significantly reversed the adverse effects induced by BPA. Moreover, the decoction ameliorated intestinal ROS and permeability. Thus, BSHX decoction can improve fertility by increasing intestinal barrier function via hsp-16.2-mediated heat-shock signaling pathway in C. elegans. These findings reveal the underlying regulatory mechanisms of hsp-16.2-mediated heat resistance against fertility defect.
Unstructured road extraction and roadside fruit recognition in grape orchards based on a synchronous detection algorithm
Authors: Zhou Xinzhao , Zou Xiangjun , Tang Wei , Yan Zhiwei , Meng Hewei , Luo Xiwen
Published: June 2023

Accurate road extraction and recognition of roadside fruit in complex orchard environments are essential prerequisites for robotic fruit picking and walking behavioral decisions. In this study, a novel algorithm was proposed for unstructured road extraction and roadside fruit synchronous recognition, with wine grapes and nonstructural orchards as research objects. Initially, a preprocessing method tailored to field orchards was proposed to reduce the interference of adverse factors in the operating environment. The preprocessing method contained 4 parts: interception of regions of interest, bilateral filter, logarithmic space transformation and image enhancement based on the MSRCR algorithm. Subsequently, the analysis of the enhanced image enabled the optimization of the gray factor, and a road region extraction method based on dual-space fusion was proposed by color channel enhancement and gray factor optimization. Furthermore, the YOLO model suitable for grape cluster recognition in the wild environment was selected, and its parameters were optimized to enhance the recognition performance of the model for randomly distributed grapes. Finally, a fusion recognition framework was innovatively established, wherein the road extraction result was taken as input, and the optimized parameter YOLO model was utilized to identify roadside fruits, thus realizing synchronous road extraction and roadside fruit detection. Experimental results demonstrated that the proposed method based on the pretreatment could reduce the impact of interfering factors in complex orchard environments and enhance the quality of road extraction. Using the optimized YOLOv7 model, the precision, recall, mAP, and F1-score for roadside fruit cluster detection were 88.9%, 89.7%, 93.4%, and 89.3%, respectively, all of which were higher than those of the YOLOv5 model and were more suitable for roadside grape recognition. Compared to the identification results obtained by the grape detection algorithm alone, the proposed synchronous algorithm increased the number of fruit identifications by 23.84% and the detection speed by 14.33%. This research enhanced the perception ability of robots and provided a solid support for behavioral decision systems.
Production status and research advancement on root rot disease of faba bean (Vicia faba L.) in China
Authors: Yu Haitian , Yang Feng , Hu Chaoqin , Yang Xin , Zheng Aiqing , Wang Yubao , Tang Yongsheng , He Yuhua , Lv Meiyuan
Published: June 2023

China is the largest producer of faba bean with a total harvested area of 8.11×105 ha and a total production of 1.69 ×106 tons (dry beans) in 2020, accounting for 30% of the world production. Faba bean is grown in China for both fresh pods and dry seed. East China cultivates large seed cultivars for food processing and fresh vegetables, while northwestern and southwestern China grow cultivars for dry seeds, with an increased production of fresh green pods. Most of the faba bean is consumed domestically, with limited exports. The absence of unified quality control measures and simple traditional cultivation practices contributes to the lower competitiveness of the faba bean industry in international markets. Recently, new cultivation methods have emerged with improved weed control, as well as better water and drainage management, resulting in higher quality and income for producers. Root rot disease in faba bean is caused by multiple pathogens, including Fusarium spp., Rhizoctonia spp., and Pythium spp. Fusarium spp. is the most prevalent species causing root rot in faba bean crops and is responsible for severe yield loss, with different species causing the disease in different regions in China. The yield loss ranges from 5% to 30%, up to 100% in severely infected fields. The management of faba bean root rot disease in China involves a combination of physical, chemical, and bio-control methods, including intercropping with non-host crops, applying rational nitrogen, and treating seeds with chemical or bio-seed treatments. However, the effectiveness of these methods is limited due to the high cost, the broad host range of the pathogens, and potential negative impacts on the environment and non-targeted soil organisms. Intercropping is the most widely utilized and economically friendly control method to date. This review provides an overview of the current status of faba bean production in China, the challenges faced by the industry due to root rot disease, and the progress in identifying and managing this disease. This information is critical for developing integrated management strategies to effectively control root rot in faba bean cultivation and facilitating the high-quality development of the faba bean industry.