bluuebunny/crossref_metadata_2025 huggingface dataset:
Decadal changes in the Sea of Marmara indicate degraded ecosystem conditions and unsustainable fisheries
Authors: Akoglu Ekin , Saygu İsmet , Demirel Nazli
Published: August 2024

Globally, all marine ecosystems are under pressure by anthropogenic stressors. However, semi-enclosed seas are at a greater risk of degradation due to their limited connectivity to open seas. This leads to a greater accumulation of pollutants and abrupt regime shifts triggered by unsustainable exploitation of living resources, as ecosystems exhibit low degrees of redundancy and more frequent large-scale episodic events such as harmful algal blooms. The Sea of Marmara is a semi-enclosed marine region that has been subjected to various anthropogenic stressors since the 1990s. Recently, local and governmental authorities have employed basin-wide ecosystem management plans to control and manage point and nonpoint (diffuse) sources of pollutants. However, the management of fisheries in relation to the dynamics of the Sea of Marmara food web has attracted less attention from policymakers, even though fisheries exploitation is one of the most significant anthropogenic pressures. In this study, we capitalized on a previous static ecosystem model of the Sea of Marmara by revising and extending it to simulate the changes between 1990 and 2020. We delineated the temporal dynamics and regime shifts in the food web in terms of ecosystem structure and function by using ecological indicators and developed quantitative management advice for its fisheries. The results showed that the ecosystem has experienced three regimes since 1990, with regime shifts occurring with the onset of the 2000s and the mid 2010s. The first regime exhibited high diversity and material cycling, the second regime was characterized by low diversity and increased impact of fisheries, and the third regime culminated in a fished-down food web state. The analysis of fishery dynamics showed that the majority of harvested species were overexploited. We suggest that the implementation of quotas for exploited species should be considered an immediate solution to the unsustainable exploitation of fish stocks and can help restore ecosystem conditions.
FAIR ADCP data with OSADCP: a workflow to process ocean current data from vessel-mounted ADCPs
Authors: Kopte Robert , Becker Marius , Fischer Tim , Brandt Peter , Krahmann Gerd , Betz Maximilian , Faber Claas , Winter Christian , Karstensen Johannes , Wiemer Gauvain
Published: August 2024

This paper presents the open-source Python software OSADCP developed for the processing of vessel-mounted Acoustic Doppler Current Profiler (VMADCP) data. At this stage, the toolbox is designed for processing VMADCP measurements from open-ocean applications of Teledyne RDI Ocean Surveyor ADCPs and the data acquisition software VMDAS. Based on the VMDAS ENX binary output format, the software contains implementations for cleaning and vector-averaging of single-ping velocity data, verification of the position data, and applying misalignment and amplitude corrections. The procedures of OSADCP are described in detail to encourage the scientific community to use it for their own purposes. The toolbox is an integral part of a workflow implemented on the German marine research vessels in the framework of the Underway Research Data project of the German Marine Research Alliance (DAM). It aims to ensure standardized data acquisition measures, reliable data transfer from the ADCP to shore both near-real-time and in delayed-mode, processing and quality control, and dissemination of the curated data product in the data repository PANGAEA. From PANGAEA, data sets are forwarded to the European marine data hubs Copernicus Marine Service and EMODnet. The workflow that forms the framework for OSADCP is described here as an example of scientific data management that follows the FAIR data guidelines.
Salinity threshold for phosphorus limitation in an estuary-coast continuum
Authors: Cai Shujie , Liu Weiran , Tong Zhuyin , Lin Lizhen , Ou Linjian , Xiao Wupeng , Huang Bangqin
Published: August 2024

River-derived nutrient imbalances can induce phosphorus (P) limitation in coastal plankton, but the salinity thresholds that govern this phenomenon have received little attention. Here, we provide a first insight into threshold responses in P-limitation along the salinity gradient in coastal ecosystems. Our seasonal sampling in the northern South China Sea showed a clear nonlinear decrease in alkaline phosphatase activity (APA) with increasing salinity. A pivotal finding was the identification of a salinity threshold at 32.83, presenting an early-warning indicator for P-limitation detection. Using a mixed-effects model, we further revealed that the robust positive correlation between phytoplankton biomass and APA gradually weakened as salinity increased toward this threshold. This implies a shift in phytoplankton’s P-limitation at this salinity threshold and the contribution of heterotrophic bacteria in APA within high-salinity seawater. These insights highlight the importance of refining monitoring strategies with salinity and APA dynamics as early-warning indicators for nutrient limitation in coastal ecosystems.
Marine sponge-derived natural products: trends and opportunities for the decade of 2011-2020
Authors: Mehbub Mohammad Ferdous , Yang Qi , Cheng Ying , Franco Christopher Milton Mathew , Zhang Wei
Published: August 2024

The discovery of natural products derived from marine sources has demonstrated a consistent upward trajectory for the decade of 2011-2020, holding significant promise for the development of novel drugs and many other marine bioproducts. In recent years, the spotlight has shifted away from marine sponges (Porifera) towards marine microorganisms as the primary source of discovery. Despite reports of marine sponges spanning 20 different orders and being the subject of 769 papers between 2011 and 2020, they only contributed to 19.29% of all new compounds discovered, in contrast to 51.94% by marine microorganisms and phytoplankton. 563 new compounds were reported from marine sponge-associated microbes, more than doubling the number for the previous decade (2001-2010). It heralds a positive outlook for a sustainable resource strategy as the extraction of bioactive compounds produced by pure cultures of sponge-associated microbes could overcome supply challenges that arise with isolation from host sponges for the same compound. However, the application of novel marine natural products (MNPs) remains challenging due to the limited yield of compounds from large amounts of sponges. This review covers the literature published between 2011 and 2020, focusing on MNPs isolated from marine sponges. A total of 2603 new compounds are documented, detailing their chemical classification, biological activities, source country or geographic locations, and the taxonomic information of the source organisms, including order, family, genus, and species.
A review on algae-mediated adsorption and catalytic processes for organic water pollution remediation
Authors: Suresh R. , Rajendran Saravanan , Chen Wei-Hsin , Soto-Moscoso Matias , Sundaram Thanigaivel , Jalil Aishah Abdul , Rajamani Sekar Suresh Kumar
Published: August 2024

Wastewaters consist of organic pollutants that have environmental concerns. Wastewaters are treated by different methods, but efficient, low-cost, and sustainable techniques still need to be developed. Algae-based water pollution remediation techniques are considered to be sustainable approaches. This review exclusively discusses the facets of macro and microalgae in the treatment of organic toxicants. The current trends of algae-mediated water treatments have been discussed under adsorption and degradation methods. A focus on algae fuel cell, algae mediated activation of oxidizing agents, Fenton-like reactions, and photocatalysis was given. The need of algae-based adsorptive and catalytic materials was mentioned. The role of algae in the synthesis of catalysts which were employed in pollutant removal methods was also explained. The integrated algae-mediated water treatment techniques were also highlighted. The toxicant removal performances of different algae-based materials in the water medium were summarized. The conclusion and future prospects derived from the literature survey were described. This review will be helpful for researchers who are working in the field of sustainable water pollution remediation.
Subcutaneous foslevodopa in akinetic crisis. A case report from the neurological intensive care unit
Authors: Loeffler Moritz A. , Mengel Annerose , Single Constanze , Weiss Daniel , Feil Katharina
Published: August 2024

Introduction

Akinetic crisis is a severe deterioration of motor performance occurring in syndromes with pre- or postsynaptic dopaminergic deficit, necessitating effective dopamine replacement therapy. The subcutaneously applicable levodopa derivative foslevodopa represents a new therapeutic option for patients with advanced Parkinson’s disease as a continuous therapy. However, its potential role as a parenteral treatment option for akinetic crisis has not been investigated, yet.

The case

A 78 year-old patient who had developed akinetic-rigid symptomatology in the context of normal pressure hydrocephalus was admitted to our intensive care unit after experiencing an acute exacerbation of akinesia in the context of pulmonary infection. Off-label administration of subcutaneous foslevodopa was initiated after repeated failures to insert a gastric tube for enteral application of levodopa and contraindications against amantadine and apomorphine.

Results

Following the administration of a subcutaneous test dose, continuous application of foslevodopa via a B. Braun syringe pump was gradually increased to 0.3 mL/h during the daytime and 0.15 mL/h at night, corresponding to a levodopa equivalent dosage of 1,020 mg/d. This was accompanied by an improvement of the MDS-UPDRS III score from 85 points to 59 points after 72 h.

Discussion

Treatment of an akinetic crisis with subcutaneous foslevodopa in an intensive care unit setting has proven to be safe and effective in a patient with acute akinesia associated with dopamine-sensitive hydrocephalus. Due to the pathophysiological distinction from Parkinson’s disease, there may be differences in therapeutic response and side effects. Nevertheless, the method used here can serve as a protocol basis for the treatment of akinetic crises with foslevodopa in general and as a starting point for further research.
From immune dysregulation to organ dysfunction: understanding the enigma of Sepsis
Authors: Liu Zhi , Ting Yuan , Li Miao , Li Yukun , Tan Yingzheng , Long Yunzhu
Published: August 2024

Sepsis is a syndrome precipitated by immune dysregulation in response to infection, and represents a pivotal factor in global mortality attributed to diseases. The recent consensus delineates sepsis as a perilous state of organ dysfunction arising from the host’s maladaptive reaction to infection. It masks the complexity and breadth of the immune mechanisms involved in sepsis, which is characterized by simultaneous hyperinflammation and immunosuppression. Sepsis is highly correlated with the dysregulation of immune response, which is mainly mediated by various immune cells and their interactions. This syndrome can lead to a plethora of complications, encompassing systemic inflammatory response, metabolic disturbances, infectious shock, MODS, and DIC. Furthermore, more research studies have been conducted on sepsis in the past few years. The pathological characteristics of sepsis have been improved or treated by targeting signaling pathways like NF-B, JAK–STAT, PI3K-Akt, and p38-MAPK. Combined drug therapy is better than single drug therapy for sepsis. This article will review the latest progress in the pathogenesis and treatment of sepsis.
Characterization and genome sequence of N,N-dimethylformamide degradation in Paracoccus sulfuroxidans DM175A1-1 isolated from activated sludge of wastewater
Authors: Zheng Gang , Su Yue , Zhang Wenwu , Liu Xingping , Shao Li , Shen Zhibo , Zhang Dongdong , Wang Kaiyang , Miao Zhoudi
Published: August 2024

N,N-dimethylformamide (DMF) is an organic solvent with stable chemical properties and high boiling point. Based on its good solubility, DMF is widely used in synthetic textile, leather, electronics, pharmaceutical and pesticide industries. However, the DMF pollutes the environment and does harm to human liver function, kidney function, and nerve function. Herein, an efficient DMF-degrading strain, DM175A1-1, was isolated and identified as Paracoccus sulfuroxidans. This strain can use DMF as the sole source of carbon and nitrogen. Whole-genome sequencing of strain DM175A1-1 revealed that it has a 3.99-Mbp chromosome a 120-kbp plasmid1 and a 40-kbp plasmid2. The chromosome specifically harbors the dmfA1 and dmfA2 essential for the initial steps of DMF degradation. And it also carries the some part of genes facilitating subsequent methylotrophic metabolism and glutathione-dependent pathway. Through further DMF tolerance degradation experiments, DM175A1-1 can tolerate DMF concentrations up to 10,000 mg/L, whereas the majority of Paracoccus strains could only show degradation activity below 1,000 mg/L. And the efficiency of organic nitrogen conversion to NH3-N in DMF can reach 99.0% when the hydraulic retention time (HRT) is controlled at 5 days. Meanwhile, it showed a significant degradation effect at a pharmaceutical enterprise in Zhejiang Province with high concentration of DMF wastewater. This study provides a new strain Paracoccus sulfuroxidans DM175A1-1 which shows a significant influence on DMF degradation, and reveals the characterization on its DMF degradation. It lays the foundation for the application of biological method in the efficient degradation of DMF in industrial wastewater.
The changes of rhizosphere microbial communities in pepper varieties with different capsaicinoids
Authors: Li Xin , Zhang Yan , Zhou Chi , Li Xuefeng , Zou Xuexiao , Ou Lijun , Tao Yu
Published: August 2024

Capsaicinoids are produced uniquely in pepper fruits, and its level determines the commercial quality and health-promoting properties of pepper. So, it is particularly important to increase capsaicinoids content in pepper. Rhizosphere microbiota is critical to plant growth and performance, and affected by plant varieties. However, the impact of pepper varieties with different capsaicinoids yields on the rhizosphere microbiota is poorly understood. Using high-throughput sequencing of the 16S rRNA and internal transcribed spacer (ITS) region, we investigated the rhizosphere microbial community among five pepper varieties containing different capsaicinoids. Our results demonstrated that pepper variety significantly influenced the diversity and structure of rhizosphere microbial community. Bacterial diversity in varieties with high capsaicinoids content was significantly higher than in varieties with low capsaicinoids content, while fungal diversity was opposite to bacterial diversity. The correlation analysis revealed that 19 dominant bacterial genera (e.g., Chujaibacter, Rhodanobacter, and Gemmatimonas) were significantly correlated with capsaicinoids content, and nine of them were also significantly associated with soil nutrients, whereas only one fungal genus (Podospora) was significantly correlated with capsaicinoids content. Additionally, almost all genera which significantly correlated to capsaicinoids content were biomarkers of the five pepper varieties and the correlation was well corresponding to the capsaicinoids content. Overall, our results confirmed that the variety of pepper significantly affected the rhizosphere microbial community in the fields, and bacteria and fungi responded differently to capsaicinoids, which may affect the biosynthesis of capsaicinoids and contribute to further improvement of capsaicinoids production in pepper fruits.
Identification of specific genes as molecular markers for rapid and accurate detection of oil-tea Camellia anthracnose pathogen Colletotrichum fructicola in China
Authors: Cao Lingxue , Shi Kailin , Liu Yongyi , Xie Xiaonan , Sun Xizhe , Dong Wentong , Wang Congya , Ma Lisong
Published: August 2024

Introduction

Camellia anthracnose is caused by multiple Colletotrichum species, resulting in severe yield losses of oil-tea Camellia. Colletotrichum fructicola is one of the major anthracnose pathogens of oil-tea Camellia worldwide. However, developing unique molecular markers for the rapid and accurate detection of Colletotrichum fructicola from diverse Colletotrichum species, as well as early monitoring and effective control of the disease, remains largely unexplored.

Methods

C. fructicola-specific genes were obtained using a BLAST search of the sequences of predicted genes in C. fructicola against the genome sequences of Colletotrichum fungal pathogens. In this study, Colletotrichum fructicola-specific molecular markers were developed for rapid and accurate detection of C. fructicola among Camellia anthracnose causing fungal pathogens.

Results

Using genomic DNA-based end-point PCR and qPCR, three C. fructicola-specific genes with the ability to distinguish C. fructicola from other oil-tea Camellia anthracnose-related Colletotrichum species, including Colletotrichum camelliae, Colletotrichum gloeosporioides, and Colletotrichum siamense, and oil-tea Camellia fungal pathogens belonging to the genus Neopestalotiopsis, Pestalotiopsis, and Alternaria, were validated as molecular markers. In addition, these three molecular markers were highly sensitive to detecting C. fructicola using DNA extracted from the inoculated leaves of oil-tea Camellia.

Discussion

These findings enable us to rapidly and uniquely detect the Camellia anthracnose disease caused by Colletotrichum fructicola, which will equip farmers with an effective tool for monitoring Camellia anthracnose disease in the field and taking timely control measurements in advance.
Screening canine sources for novel antimicrobials reveals the circular broad-spectrum bacteriocin, caledonicin, produced by Staphylococcus caledonicus
Authors: O’Connor Michelle , O’Connor Paula M. , Hourigan David , Murray Ellen , de Farias Felipe Miceli , Field Des , Hill Colin , Ross R. Paul
Published: August 2024

Introduction

Antimicrobial-resistant pathogens present an ongoing threat to human and animal health, with deaths linked to antimicrobial resistance (AMR) predicted to increase annually. While the misuse and overuse of antibiotics in humans undoubtedly contribute to this escalation, antibiotic use in the veterinary field, including companion animals, also plays a contributing role. Pet owners’ desire to improve the quality of life of their pets is likely to support antibiotic use in this field. Consequently, there is a need for antibiotic alternatives to treat bacterial infections. This study set out to screen for antimicrobial peptides known as bacteriocins from bacterial isolates of aerobic/microaerophilic environments of canine sources and determine their potential as antibiotic alternatives against clinically relevant pathogens.

Methods

Following a laboratory-based protocol, 22 bacterial isolates were subjected to whole-genome sequencing (WGS), and a total of 14 putative novel bacteriocins were identified from both class I and II bacteriocin classes. One particular bacteriocin, herein named caledonicin, was identified via in silico analysis from a Staphylococcus caledonicus strain and partially purified for further in vitro evaluation.

Results

Caledonicin is a 64-amino acid (IAANLGVSSGTAYS MANALNNISNVATA LTIIGTFTGVGTIGSGIA ATILAILKKKGVAAAAAF) novel circular bacteriocin most closely related to enterocin_NKR-5-3B based on core peptide alignment (39.1%), with a molecular weight of 6077.1 Da. Caledonicin exhibits a broad-spectrum of activity against a range of pathogenic bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus pseudintermedius (MRSP), and Listeria monocytogenes; and the gut-related bacterium associated with Crohn’s disease, Mediterraneibacter gnavus ATCC 29149 (previously Ruminococcus gnavus ATCC 29149).

Discussion

This represents the first bacteriocin screening study involving bacteria from canine sources and confirms this is a rich environment for bacteriocin-producing strains. This study also identifies and characterises the first novel bacteriocin from the staphylococcal species, Staphylococcus caledonicus.
Unified theory of alpha, mu, and tau rhythms via eigenmodes of brain activity
Authors: El Zghir Rawan Khalil , Gabay Natasha C. , Robinson P. A.
Published: August 2024

A compact description of the frequency structure and topography of human alpha-band rhythms is obtained by use of the first four brain activity eigenmodes previously derived from corticothalamic neural field theory. Just two eigenmodes that overlap in frequency are found to reproduce the observed topography of the classical alpha rhythm for subjects with a single, occipitally concentrated alpha peak in their electroencephalograms. Alpha frequency splitting and relative amplitudes of double alpha peaks are explored analytically and numerically within this four-mode framework using eigenfunction expansion and perturbation methods. These effects are found to result primarily from the different eigenvalues and corticothalamic gains corresponding to the eigenmodes. Three modes with two non-overlapping frequencies suffice to reproduce the observed topography for subjects with a double alpha peak, where the appearance of a distinct second alpha peak requires an increase of the corticothalamic gain of higher eigenmodes relative to the first. Conversely, alpha blocking is inferred to be linked to a relatively small attention-dependent reduction of the gain of the relevant eigenmodes, whose effect is enhanced by the near-critical state of the brain and whose sign is consistent with inferences from neural field theory. The topographies and blocking of the mu and tau rhythms within the alpha-band are explained analogously via eigenmodes. Moreover, the observation of three rhythms in the alpha band is due to there being exactly three members of the first family of spatially nonuniform modes. These results thus provide a simple, unified description of alpha band rhythms and enable experimental observations of spectral structure and topography to be linked directly to theory and underlying physiology.
Deep learning for detecting prenatal alcohol exposure in pediatric brain MRI: a transfer learning approach with explainability insights
Authors: Das Anik , Duarte Kaue , Lebel Catherine , Bento Mariana
Published: August 2024

Prenatal alcohol exposure (PAE) refers to the exposure of the developing fetus due to alcohol consumption during pregnancy and can have life-long consequences for learning, behavior, and health. Understanding the impact of PAE on the developing brain manifests challenges due to its complex structural and functional attributes, which can be addressed by leveraging machine learning (ML) and deep learning (DL) approaches. While most ML and DL models have been tailored for adult-centric problems, this work focuses on applying DL to detect PAE in the pediatric population. This study integrates the pre-trained simple fully convolutional network (SFCN) as a transfer learning approach for extracting features and a newly trained classifier to distinguish between unexposed and PAE participants based on T1-weighted structural brain magnetic resonance (MR) scans of individuals aged 2–8 years. Among several varying dataset sizes and augmentation strategy during training, the classifier secured the highest sensitivity of 88.47% with 85.04% average accuracy on testing data when considering a balanced dataset with augmentation for both classes. Moreover, we also preliminarily performed explainability analysis using the Grad-CAM method, highlighting various brain regions such as corpus callosum, cerebellum, pons, and white matter as the most important features in the model's decision-making process. Despite the challenges of constructing DL models for pediatric populations due to the brain's rapid development, motion artifacts, and insufficient data, this work highlights the potential of transfer learning in situations where data is limited. Furthermore, this study underscores the importance of preserving a balanced dataset for fair classification and clarifying the rationale behind the model's prediction using explainability analysis.
Association of cardiovascular risk factors and intraplaque neovascularization in symptomatic carotid plaque
Authors: Liu Zehao , Zhang Lianlian , Sun Bing , Ding Yasuo
Published: August 2024

Background and purpose

Cardiovascular risk factors are known to contribute to the formation of atherosclerotic plaques, which can result in carotid stenosis. However, the extent to which these factors are associated with intraplaque neovascularization, a key indicator of plaque vulnerability, remains unclear. To investigate this relationship, a study was conducted utilizing contrast-enhanced ultrasound (CEUS) to assess intraplaque neovascularization in symptomatic patients.

Methods

A cohort of 157 symptomatic patients underwent evaluation using Contrast-Enhanced Ultrasound (CEUS) imaging to assess carotid intraplaque neovascularization, which was quantified based on the degree of plaque enhancement. The collected data encompassed baseline patient characteristics, results from biochemical examinations, cardiovascular risk factors, and medication usage history. Regression analyses were conducted to elucidate the relationship between carotid plaque neovascularization and various cardiovascular risk factors.

Results

Patients with intraplaque neovascularization were more prone to have diabetes mellitus (OR 3.81, 95% CI 1.94–7.46, p < 0.001), dyslipidemia (OR 2.36, 95% CI 1.22–4.55, p = 0.011) and hypertension (OR 2.92, 95% CI 1.50–5.71, p = 0.002). Smoking increased the risk of having intraplaque neovascularization (OR 2.25, 95% CI 1.12–4.54, p = 0.023). Treatment with statins was significantly lower in patients with intraplaque neovascularization (OR 0.37, 95% CI 0.19–0.72, p = 0.003). In the multivariate analysis, diabetes mellitus (OR 3.27, 95% CI 1.10–9.78, p = 0.034) was independently related to the presence of intraplaque neovascularization. Meanwhile, compared to the patients in the first tertile of serum glucose (< 6.20 mmol/L), the patients in the third tertile (> 13.35 mmol/L) had the most significance of intraplaque neovascularization (OR 5.55, 95% CI 1.85–16.66, p = 0.002).

Conclusion

The findings indicated that diabetes mellitus is a significant cardiovascular risk factor that is strongly associated with carotid intraplaque neovascularization.
Ovariectomy exacerbates the disturbance of excitation- inhibition balance in the brain of APP/PS-1/tau mice
Authors: Liu Fuwang , Liu Yanman , Shen Xuri , Du Jiarui , Zhang Hanting , Hou Xueqin
Published: August 2024

Introduction

The prevalence of Alzheimer’s disease (AD) is significantly gender-differentiated, with the number of female AD patients far exceeding that of males, accounting for two-thirds of the total prevalence. Although postmenopausal AD mice have been shown to have more prominent pathologic features and memory impairments than normal AD mice, the relevant molecular mechanisms leading to these outcomes have not been well elucidated. In the present study, we used the disturbance of excitation-inhibition balance in the postmenopausal brain as an entry point to explore the link between estrogen deficiency, disorders of the glutamatergic-GABAergic nervous system, and memory impairment.

Methods

Wild-type (WT) mice and APP/PS1/tau (3 × Tg-AD) mice (10 months old) were randomly divided into four groups: WT+Sham group, WT+OVX group, 3 × Tg-AD+Sham group and 3 × Tg-AD+OVX group. Ovariectomy (OVX) was performed in the WT+OVX group and the 3 × Tg-AD+OVX group, and sham surgery was performed in the WT+Sham group and the 3 × Tg-AD+Sham group. The learning and memory ability and the anxiety and depression-like behavior changes of mice were evaluated by behavioral experiments, and the association between estrogen-estrogen receptors pathway and glutamatergic/GABAergic nervous system and female AD was evaluated by neurochemical experiments.

Results

In WT and 3 × Tg-AD mice, OVX resulted in impaired learning and memory abilities and anxiety and depression-like behaviors; reduced estrogen levels and downregulated the expression of estrogen receptors; upregulated the expression of amyloid-β, amyloid precursor protein, presenilin 1, and p-tau; upregulated the expression of Bcl-2-associated X protein and downregulated the expression of B-cell lymphoma-2, promoting cell apoptosis; reduced the number of neuronal dendrites and downregulated the expression of postsynaptic density protein-95; more importantly, OVX increased brain glutamate levels but downregulated the expression of N-methyl-D-aspartate receptor-2B, excitatory amino acid transporter 1, excitatory amino acid transporter 2, γ-aminobutyric acid receptor-A and γ-aminobutyric acid receptor-B.

Conclusion

Our results suggested that OVX-induced estrogen-estrogen receptors pathway disruption caused learning and memory impairment and anxiety and depression-like behaviors, upregulated the expression of AD pathological markers, promoted apoptosis, destroyed neuronal structure, and most importantly, caused glutamatergic/GABAergic nervous system disorders.
Predicting radiotherapy efficacy and prognosis in tongue squamous cell carcinoma through an in-depth analysis of a radiosensitivity gene signature
Authors: Lai Jinzhi , Yang Hainan , Chen Junjun , Chen Shoubo , Chen Xiaofang
Published: August 2024

Background

Tongue squamous cell carcinoma (TSCC) is a prevalent tumor that affects many people worldwide. Radiotherapy is a common treatment option, but its efficacy varies greatly. This study seeks to validate the identified gene signature associated with radiosensitivity in TSCC, and its potential in predicting radiotherapy response and prognosis.

Methods

We analyzed 122 TSCC patients from TCGA database using the radiosensitivity signature and classified them into radiosensitive (RS) and radioresistant (RR) groups. Immune infiltration analysis methods were applied to investigate the immune status between different subgroups. Immunophenotype Score (IPS) and pRRophetic algorithm were employed to estimate the efficiency of treatment. A radioresistant TSCC cell line was established by gradually increasing radiation doses. Cell radiosensitivity was evaluated using the CCK-8 and colony formation assays. The expression of radiosensitivity-related genes was validated by qRT-PCR.

Results

Our study validated the predictive capacity of a previously identified “31-gene signature” in the TCGA-TSCC cohort, which effectively stratified patients into RS and RR groups. We observed that the RS group exhibited superior overall survival and progression-free survival rates relative to the RR group when treated with radiotherapy. The RS group was significantly enriched in most immune-related hallmark pathways, and may therefore benefit from immune checkpoint inhibitors. However, the RS group displayed lower sensitivity to first-line chemotherapy. A radioresistant TSCC cell line (CAL-27R) exhibited increased clonogenic potential and cell viability following irradiation, accompanied by downregulation of three radiosensitivity-related genes compared to its parental non-resistant cell (CAL-27). In addition, we constructed and validated a radiosensitivity-related prognostic index (PI) using 4 radiosensitivity-related genes associated with TSCC prognosis.

Conclusion

We assessed the ability of the radiosensitivity gene signature to predict outcomes in TSCC patients. our research provided valuable insights into the molecular pathways associated with radiosensitivity in TSCC and offered clinicians a practical tool to predict patient radiotherapy effectiveness and prognosis.
Proportion trends, cancer stage, and survival of patients with cancer diagnosed through emergency and nonemergency departments: a nationwide cohort study
Authors: Lin Ying-Chao , Kuo Wei-Yin , Kung Pei-Tseng , Tsai Wen-Chen
Published: August 2024

Introduction

To reduce mortality, the Taiwan government has vigorously promoted free cancer screening and preventive health screening services. Cancers are usually advanced by the time they are discovered in the emergency department. Through this study, we aimed to understand the characteristics of cancer patients diagnosed through the emergency department and thus identify high-risk populations by comparing cancer staging and survival rates in patients diagnosed in the emergency department and those diagnosed in the non-emergency department.

Methods

The retrospective study enrolled a total of 389,043 patients over the age of 20 who were newly diagnosed with one of the five major cancers (including lung cancer, colorectal cancer, breast cancer, prostate cancer, and oral cancer) between 2008 and 2017 and analyzed their diagnostic pathway, cancer stage at diagnosis, and survival time.

Results

Of the study participants, 59,423 patients (about 15.3%) were diagnosed with cancer through the emergency department. We found that a sizable proportion of older people and patients with low education and low incomes were diagnosed through emergency department visits, and those with a health condition comorbidity severity of 3 had the highest proportion diagnosed by the emergency department, advanced stages at diagnosis, and risk of death. These can be classified as high-risk groups. In addition, 76.4% of patients diagnosed in the emergency department had advanced cancer, and the risk of death was 1.46 times higher than that of patients diagnosed in the non-emergency department. Although cancer screening is available, it does not reduce the proportion of patients with advanced cancer who are diagnosed through or at the time of diagnosis in the emergency department.

Conclusions

The present study found that the government’s cancer screening did not affect the proportion or number of cancers diagnosed through emergency department visits. Therefore, the government should focus on more cancer screening, health education in high-risk groups, and strengthening the link between emergency and oncology departments to reduce the risk of death for patients diagnosed through emergency department visits.
Critical review of clinical data and expert-based recommendations for the use of bosutinib in the treatment of chronic myeloid leukemia
Authors: García-Gutiérrez Valentín , Gómez-Casares María Teresa , Xicoy Blanca , Casado-Montero Felipe , Orti Guillermo , Giraldo Pilar , Hernández-Boluda Juan Carlos
Published: August 2024

Chronic myeloid leukemia (CML), characterized by the presence of the BCR::ABL1 fusion gene, has undergone a transformative shift with the introduction of tyrosine kinase inhibitors (TKIs). The current availability of six different TKIs (imatinib, dasatinib, nilotinib, bosutinib, ponatinib, and asciminib) in clinical practice makes it important to know their efficacy and toxicity profile for treatment optimization. This review examines the latest insights regarding the use of bosutinib in CML treatment. Clinical trials have demonstrated the effectiveness of bosutinib, positioning it as a first-line treatment that can induce sustained molecular responses. Importantly, it can also be effective in patients who have experienced treatment failure or intolerance with prior TKIs, revealing the potential of bosutinib also in second- and later-line settings. Even in the advanced phase of CML, bosutinib has demonstrated its capacity to achieve molecular responses, expanding its usefulness. Real-world evidence studies echo these findings, emphasizing bosutinib’s effectiveness in achieving deep molecular responses, maintaining remissions, and serving as an alternative for patients intolerant or resistant to other TKIs as a second-line therapy. Notably, one of the greatest strengths of bosutinib is its favorable safety profile, in particular the low incidence of vascular complications with its use, which is undoubtedly a comparative advantage over other TKIs. In summary, the latest research highlights the versatility of bosutinib in CML treatment and underscores its pivotal role in optimizing patient management in challenging cases. Continuing research and investigation will further establish bosutinib’s place in the evolving landscape of CML therapy, offering an alternative for CML patients across different treatment stages.
Acute-phase plasma proteomics of rabbit lung VX2 tumors treated by image-guided microwave ablation
Authors: Cheng Lin , Peng Jin-zhao , Li Sheng-wei , Bie Zhi-xin , Li Xiao-Guang
Published: August 2024

Purpose

To explore the plasma proteomic changes of rabbit lung VX2 tumors treated by microwave ablation, and to explore the molecular pathway mechanisms that may be involved.

Methods

New Zealand white rabbits were inoculated with VX2 tumor cell suspension in the right lower lung and treated with microwave ablation after 2-3 weeks of tumor formation. Blood was collected at 5 time points (TP1~TP5) before and after ablation by cardiac blood sampling and pre-treated before proteomic analysis. The plasma proteome was analyzed by Data-Independent Acquisition (DIA).

Results

Different molecular pathways were activated at different time points:(i) TP1vsTP2: more proteins were down-regulated and enrichment analysis showed that the proteasome pathway was activated. The abnormal protein folding process involved in this pathway is closely related to the process of tumor development. (ii) TP2vsTP3: more proteins were up-regulated although the number of differentially differentiated proteins was lower and enrichment analysis showed that the phagosome pathway was activated. After microwave ablation inactivates tumor cells, it activates the phagosomal pathway for immune clearance of necrotic tumor tissue. (iii) TP3vsTP4: more down-regulated proteins, enrichment analysis showed that cysteine and methionine metabolism pathway was activated. Decreased metabolism of these amino acids suggests that cancer progression may be blocked after microwave ablation therapy. (iv) TP4vsTP5: the number of differential proteins was less and more down-regulated proteins, enrichment analysis showed that glutathione metabolism and metabolism of xenobiotics by cytochrome P450 pathway were activated. The down-regulated proteins in this pathway may suggest that microwave ablation may have reduced resistance to certain chemotherapeutic agents following.

Conclusions

In the process of lung cancer treatment by microwave ablation, the changes of proteins on the possible molecular pathways at each time point are related to lung cancer, and not only involve some simple inflammatory reactions, and some of the proteins released by destroying the tumor cells can be used as possible drug binding sites and reduce drug resistance.
Case report: Surgical treatment and literature review of a recurrent case of glucagonoma
Authors: Liu Zhipeng , Yang Faji , Hao Yijie , Jiang Qirong , Zhang Yisu , Zheng Qixuan , Jiang Yupeng , Lu Jun , Gao Hengjun
Published: August 2024

A 40-year-old male patient was admitted due to abdominal distension and discomfort in the upper abdomen persisting for three days. Enhanced CT of the upper abdomen revealed an irregularly dense soft tissue area in the body and tail of the pancreas, approximately 7.6 × 3.1 cm in size, with blurred boundaries, and indistinct separation from the splenic artery and vein. Multiple liver lesions of varying sizes and slightly lower densities were also observed. Liver tumor biopsy considering a neuroendocrine tumor G2, combined with the medical history, led to a diagnosis of pancreatic neuroendocrine tumor G2 with liver metastasis. Physical examination showed mild tenderness in the upper abdomen but no other significant positive signs. During treatment, the patient developed multiple red papular rashes around the mouth, on both lower limbs, and the perineum, accompanied by itching. The glucagon level was 1138.3 pg/L. The patient underwent resection of the pancreatic body and tail, splenectomy, partial liver tumor resection, and cholecystectomy. Within five days post-surgery, the skin lesions began to crust and flake off. On the 14th day post-surgery, the serum glucagon level was rechecked at 136.4 pg/L. As of April 2024, progression of liver lesions was noted, with no significant skin symptoms during the period.
Comparative complications of prepectoral versus subpectoral breast reconstruction in patients with breast cancer: a meta-analysis
Authors: Wu Yongxiao , Yu Lizhi , Huang Miaoyan , Huang Yanping , Li Chunyan , Liang Yiwen , Liang Weiming , Qin Tian
Published: August 2024

Introduction

This meta-analysis aims to evaluate the complications associated with prepectoral breast reconstruction (PBR) compared to subpectoral breast reconstruction (SBR) in patients diagnosed with breast cancer.

Materials and methods

A comprehensive search was performed in four databases, including Medline, Embase, Web of Science and CENTRAL, to collect literature published up until December 31, 2024. In addition, we conducted a thorough manual examination of the bibliographies of the identified papers, as well as pertinent reviews and meta-analyses. We conducted a search on three clinical trial registries, namely ClinicalTrials.gov, Controlled-trials.com, and Umin.ac.jp/ctr/index.htm. Meta-analyses were conducted on total complications, hematoma, infection, wound healing issues, necrosis, capsular contracture, rippling, animation deformity, and reoperation.

Results

A total of 40 studies were included in the meta-analysis. Compared with SBR, PBR significantly reduced the incidence of animated malformations (OR=0.37, 95% CI: 0.19 to 0.70, P=0.003, I ²=12%), but increased the incidence of ripples (OR=2.39, 95% CI: 1.53 to 3.72, P=0.0001, I ²=10%) and seroma (OR=1.55, 95% CI: 1.02 to 2.35, P=0.04, increasing I ²=70%).

Conclusions

Our findings indicate that PBR and SBR have comparable safety profiles, with similar total complication rates. Specifically, PBR is more likely to cause rippling and seroma, whereas SBR is more prone to causing animation deformity.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024565837, identifier CRD42024565837.
Application of tissue pneumoperitoneum technique around lymph nodes in thoracoscopic lung cancer resection
Authors: Wang Fangqing , Chen Gang , Ruan Weimin , Wang Binkui , Zhu Zhaowang , Hu Weijian , Chen Sheng , Zang Lin
Published: August 2024

Background

Thoracoscopic surgery is a primary treatment for lung cancer, with lobectomy and mediastinal lymph node dissection being the predominant surgical approaches for invasive lung cancer. While many thoracic surgeons can proficiently perform lobectomy, thorough and standardized lymph node dissection remains challenging. This study aimed to explore a safer and more efficient surgical method for mediastinal lymph node dissection in lung cancer.

Methods

A prospective randomized controlled study was conducted, involving 100 patients with right lung cancer who were admitted to our hospital from January 2021 to April 2024 and met the inclusion criteria. These patients were randomly divided into an observation group (tissue pneumoperitoneum technique around lymph nodes group) and a control group (conventional surgery group). Thoracoscopic lobectomy and mediastinal lymph node dissection were performed. Intraoperative and postoperative related indicators were observed to validate the effectiveness and safety of the tissue pneumoperitoneum technique around lymph nodes.

Results

The observation group showed a significantly shorter lymph node dissection surgery time compared to the control group, with a statistically significant difference (p < 0.05). The number of lymph nodes dissected in the observation group was significantly higher than that in the control group, with a statistically significant difference (p < 0.05). Although the observation group had slightly more mediastinal lymph node stations dissected than the control group, the difference was not statistically significant (p > 0.05). The total drainage volume within three days postoperatively was comparable between the two groups, with no statistically significant difference (p > 0.05). The observation group had shorter chest tube indwelling time and postoperative hospital stay than the control group, with statistically significant differences (p < 0.05). The incidence of surgical complications was similar between the two groups, and there were no perioperative deaths.

Conclusion

The tissue pneumoperitoneum technique around lymph nodes is a more efficient method for mediastinal lymph node dissection in lung cancer, demonstrating safety and feasibility, and is worthy of promotion.
Large animal model species in pluripotent stem cell therapy research and development for retinal diseases: a systematic review
Authors: Bellingrath Julia-Sophia , Li Kang V. , Aziz Kanza , Izzi Jessica M. , Liu Ying V. , Singh Mandeep S.
Published: August 2024

Aim

Retinal cell therapy modalities, in the category of advanced therapy medicinal products (ATMPs), are being developed to target several retinal diseases. Testing in large animal models (LAMs) is a crucial step in translating retinal ATMPs into clinical practice. However, challenges including budgetary and infrastructure constraints can hinder LAM research design and execution. Here, to facilitate the comparison of the various LAMs in pluripotent retinal cell therapy research, we aimed to systematically evaluate the species distribution, reported scientific utility, and methodology of a range of LAMs.

Methods

A systematic search using the words retina, stem cell, transplantation, large animal, pig, rabbit, dog, and nonhuman primate was conducted in the PubMed, Embase, Science Direct and GoogleScholar databases in February 2023.

Results

We included 22 studies involving pluripotent stem cells (induced pluripotent stem cells or human embryonic stem cells) in LAMs, including non-human primates (NHP), pigs, dogs, and rabbits. Nearly half of the studies utilized wild-type animal models. In other studies, retinal degeneration features were simulated via laser, chemical, or genetic insult. Transplants were delivered subretinally, either as cell suspensions or pre-formed monolayers (with or without biodegradable scaffolding). The transplanted cells dose per eye varied widely (40,000 – 4,000,000 per dose). Cells were delivered via vitrectomy surgery in 15 studies and by an “ab externo” approach in one study. Structural outcomes were assessed using confocal scanning laser ophthalmoscopy imaging. Functional outcomes included multifocal electroretinogram and, in one case, a measure of visual acuity. Generally, cell suspension transplants exhibited low intraretinal incorporation, while monolayer transplants incorporated more efficiently. Immune responses posed challenges for allogeneic transplants, suggesting that autologous iPSC-derived transplants may be required to decrease the likelihood of rejection.

Conclusion

The use of appropriate LAMs helps to advance the development of retinal ATMPs. The anatomical similarity of LAM and human eyes allows the implementation of clinically-relevant surgical techniques. While the FDA Modernization Act 2.0 has provided a framework to consider alternative methods including tissue-on-a-chip and human cell culture models for pharmacologic studies, LAM testing remains useful for cell and tissue replacement studies to inform the development of clinical trial protocols.