bluuebunny/crossref_metadata_2025_split huggingface dataset:
DRAMP 4.0: an open-access data repository dedicated to the clinical translation of antimicrobial peptides
Authors: Ma Tianyue , Liu Yanchao , Yu Bingxin , Sun Xin , Yao Huiyuan , Hao Chen , Li Jianhui , Nawaz Maryam , Jiang Xun , Lao Xingzhen , Zheng Heng 
Published: November 2024

Abstract
Antimicrobial peptides (AMPs) are potential candidates for treating multidrug-resistant bacterial infections, yet only a small number of them have progressed into clinical trials. The main challenges include the poor stability and hemolytic/cytotoxic properties of AMPs. Considering this, in the update of the Data Repository of Antimicrobial Peptides (DRAMP), a new annotation on serum and protease stability is added, and special efforts were made to update the hemolytic/cytotoxic information of AMPs. The DRAMP 4.0 currently holds 30 260 entries (8 001 newly added), consisting of 11 612 general entries, 17 886 patent entries, 96 clinical entries, 377 specific entries, 110 entries with stability data, and 179 expanded entries. A total of 2891 entries possess experimentally determined hemolytic activity information, while 2674 entries contain cytotoxicity data by experimental validation. The update also covers new annotations, statistics, categories, functions, and download links. DRAMP is available online at http://dramp.cpu-bioinfor.org/.
DDDR-18. TARGETTING GLIOBLASTOMA MULTIFORME USING A MULTIACTION ANTICANCER ANTI-INFLAMMATORY THERAPEUTIC STRATEGY
Authors: Fatima Shadma , Gamage Kasuni , Sajinovic Mila , Herman David , Scott Kieran F , de Souza Paul 
Published: November 2024

Abstract
Glioblastoma multiforme (GBM) represents a significant challenge in adult brain tumor management, characterized by its aggressive nature and poor prognosis despite multimodal therapies. Current standard chemotherapy, Temozolomide (TMZ), offers limited survival benefits. In a recent breakthrough, the cyclic peptide cyclo-((2-Nal)-Leu-Ser-(2-Nal)-Arg) acetate (c2), initially developed for prostate cancer, demonstrates remarkable promise against GBM. By selectively inhibiting the inflammatory phospholipase enzyme sPLA2IIA, c2 significantly impedes GBM cell proliferation, surpassing TMZ efficacy in multiple resistant cell lines. Moreover, c2 exhibits potential to inhibit tumor growth and metastasis, confirmed in 3D tumoroid and wound healing assays. Mechanistic insights reveal modulation of crucial cellular pathways, including viral entry, cytoskeletal structure, and signaling cascades. Preclinical investigations demonstrate c2’s ability to penetrate the blood-brain barrier and attenuate tumor progression markers. At multiple levels, c2 is shown to target inhibition of ERBB2 and EGFR signalling and also have impacts on HIF1-NF-kB axis. This study proposes c2 as a potent anti-GBM candidate, warranting evaluations for its pharmacological profile, safety, and efficacy. With its potential to address the urgent need for effective GBM therapies, c2 holds promise as a significant advancement in GBM treatment, offering hope for improved patient outcomes.
Multiomic analyses reveal new targets of polycomb repressor complex 2 in Schwann lineage cells and malignant peripheral nerve sheath tumors
Authors: Bhunia Minu M , Stehn Christopher M , Jubenville Tyler A , Novacek Ethan L , Larsson Alex T , Madala Mahathi , Suppiah Suganth , Velez-Reyes Germán L , Williams Kyle B , Sokolowski Mark , Williams Rory L , Finnerty Samuel J , Temiz Nuri A , Caride Ariel , Bhagwate Aditya V , Nagaraj Nagaswaroop K , Lee Jeong-Heon , Ordog Tamas , Zadeh Gelareh , Largaespada David A 
Published: November 2024

Abstract

Background
Malignant peripheral nerve sheath tumors (MPNSTs) can arise from atypical neurofibromas (ANF). Loss of the polycomb repressor complex 2 (PRC2) is a common event. Previous studies on PRC2-regulated genes in MPNST used genetic add-back experiments in highly aneuploid MPNST cell lines which may miss PRC2-regulated genes in NF1-mutant ANF-like precursor cells. A set of PRC2-regulated genes in human Schwann cells (SCs) has not been defined. We hypothesized that PRC2 loss has direct and indirect effects on gene expression resulting in MPNST, so we sought to identify PRC2-regulated genes in immortalized human Schwann cells (iHSCs).

Methods
We engineered NF1-deficient iHSCs with loss of function SUZ12 or EED mutations. RNA sequencing revealed 1327 differentially expressed genes to define PRC2-regulated genes. To investigate MPNST pathogenesis, we compared genes in iHSCs to consistent gene expression differences between ANF and MPNSTs. Chromatin immunoprecipitation sequencing was used to further define targets. Methylome and proteomic analyses were performed to further identify enriched pathways.

Results
We identified potential PRC2-regulated drivers of MPNST progression. Pathway analysis indicates many upregulated cancer-related pathways. We found transcriptional evidence for activated Notch and Sonic Hedgehog (SHH) signaling in PRC2-deficient iHSCs. Functional studies confirm that Notch signaling is active in MPNST cell lines, patient-derived xenografts, and transient cell models of PRC2 deficiency. A combination of MEK and γ-secretase inhibition shows synergy in MPNST cell lines.

Conclusions
We identified PRC2-regulated genes and potential drivers of MPNSTs. Our findings support the Notch pathway as a druggable target in MPNSTs. Our identification of PRC2-regulated genes and pathways could result in more novel therapeutic approaches.
Associations between employees’ alcohol consumption, insomnia and HR management strength
Authors: Dao-Tran T-H , Townsend K , Loudoun R , Wilkinson A , Seib C 
Published: November 2024

Abstract

Background
Understanding of hazardous alcohol drinking and insomnia among Australian ambulance personnel is limited. Australian ambulance organizations have strengthened their organizational human resource management (HRM) to promote their employees’ healthy lifestyles, health and well-being.

Aims
To describe the prevalence of hazardous alcohol consumption and insomnia among Australian ambulance personnel and to explore their associations with the organizational HRM strength.

Methods
This cross-sectional study was conducted on 492 ambulance personnel randomly selected from three Australian states. The Alcohol Use Disorders tool, The Insomnia Severity Index and the Perceived HRM System Strength instrument measured alcohol consumption, insomnia and HRM strength. Descriptive analyses, bivariate association analyses and general linear models were used for data analysis.

Results
Twenty per cent of Australian ambulance personnel consumed alcohol at a hazardous level and 68% experienced clinically significant insomnia. There was no significant association between organizational HRM strength and ambulance personnel’s hazardous alcohol consumption. There was a significant association between organizational HRM strength (consensus) and ambulance personnel’s insomnia experience.

Conclusions
Hazardous alcohol consumption and insomnia were concerns among Australian ambulance personnel. Even though strengthening the HRM system might reduce their experience of insomnia, simply strengthening the HRM system could not reduce their hazardous alcohol consumption.
Wood hardness drives nest-site selection in woodpeckers of the humid Chaco
Authors: Di Sallo Facundo G , Cockle Kristina L 
Published: November 2024

ABSTRACT
Avian excavators (woodpeckers and other species) select nest sites based on the characteristics of the nest patch, nest tree, and substrate. These characteristics could increase foraging opportunities or reduce the risk of predation, but there is also a potentially important role for wood hardness in restricting nest-site selection, a role that has been little explored and is expected to vary among species according to their ability to excavate. We examined patterns of nest-site selection in 8 woodpecker species in the humid Chaco of South America, where the dominant trees have extremely hard wood. We hypothesized that (1) wood hardness is the main factor driving the selection of excavation sites, and (2) interspecific variation in body size and foraging behavior (traits frequently related to excavation ability) explain interspecific variation in the wood hardness of excavated nest substrates. From 2016 to 2019 in well-preserved forests of the Argentine Chaco, we compared nesting cavities excavated in wood (cases; n = 42) vs. potential wood substrates without cavities (matched controls) and made 187 focal observations of foraging woodpeckers. Woodpeckers selected nesting substrates with softer heartwood than potential substrates, regardless of any other characteristics of the tree or nest patch. Wood hardness around nest cavities increased with body size and the prevalence of chiseling during foraging, traits that were positively correlated. Woodpeckers often excavated in Prosopis spp. (Algarrobos) but rarely in Schinopsis balansae (Quebracho), a tree with exceptionally hard internal wood, in which cavity adopters frequently nest in non-excavated cavities. Wood hardness is critical to assessing the role of woodpeckers as cavity facilitators, understanding the costs and benefits of excavation, and interpreting excavation patterns across species and forests globally.
Defective flux and splicing abnormality restoration of stellar spectra in LAMOST based on deep learning
Authors: Wu Minglei , Bu Yude 
Published: November 2024

Abstract
Sky surveys such as the Large Sky Area Multi-Object Fibre Spectroscopic Telescope can capture numerous spectra. However, many factors in astronomical observations, such as observation conditions and instrumental effects, can degrade spectrum quality, resulting in defective fluxes and splicing abnormality. These factors significantly reduce the precision of scientific information extracted from such spectra. In the past, these flux values were considered unreliable and their utilization was low. Thus, it is crucial to develop and utilize spectra restoration algorithms to improve spectra quality and enable further scientific exploration. Unfortunately, few research has been done on these low-quality spectra. In this paper, we propose a novel spectrum restoration algorithm, which is called the Anomaly Spectra Restoration Generative Adversarial Nets (Anomaly_GANs) based on Generative Adversarial Networks (GANs). The experiment shows that the performance of Anomaly_GANs is better than those of other methods concerning spectrum restoration. Therefore, our method can serve as an effective approach for spectrum restoration, providing a suitable replacement for previous methods.
Efficacy and safety assessment of probiotic Bacillus coagulans (Heyndrickxia coagulans) BCP92 for treatment of diarrhea
Authors: Shaikh Sohel S , Patel Snehal , Malik Anis , Kumar S Aakash 
Published: November 2024

Abstract
Objective: Probiotics offer a potentially new therapeutic approach for the treatment of diarrhea. This study aimed to determine the anti-diarrheal activity of Bacillus coagulans BCP92 (MTCC 25460) and its safety assessment (acute and sub-acute toxicity studies) in animal models and cell lines. Methods: The antidiarrheal activity was studied in mice using a castor oil-induced diarrhea model. In the acute toxicity study, the rats were orally fed 2000 mg/kg (4 × 1011 CFU/g) of B. coagulans BCP92 (MTCC 25460) as a single dose, and for sub-acute toxicity study rats received 250, 500, and 1,000 mg/kg/day for 28 days. At the end of the treatment, body weight, organ weight, food intake, biochemical parameters, hematological parameters, and histopathology were studied. B. coagulans BCP92 is effective against diarrhea by reducing the onset of diarrhea (latency), frequency of defecation, total fecal weight, and percentage of defecation. In-vitro MTT assay was performed on Vero cell lines. Results: In-vitro MTT assay showed a cytoprotective effect. In acute toxicity study, 2000 mg/kg dose did not cause any alteration in clinical signs, morbidity, or mortality. The findings of the subacute toxicity study showed no alterations in physical appearance and behavioral patterns. Moreover, no significant variations were found in organ weights and hematological and biochemical parameters of the treated groups in the control group. Furthermore, no visible histological changes were observed in the heart, lung, liver, and kidney of the high-dose treatment groups. Conclusion: Thus, the results of the present study conclude that B. coagulans BCP92 is safe for human use in the treatment of diarrhea.
Chronic inhalation exposure to the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) alters cardiac collagen in Wistar rats
Authors: Mariano Larissa Ferreira Rós , Mariano Thaoan Bruno , Floriano Rafael Stuani , Gomes Mariana Janini , Engel Letícia Estevam , Nai Gisele Albonguetti , Pacagnelli Francis Lopes 
Published: November 2024

Abstract
Introduction: 2,4-dichlorophenoxyacetic acid (2,4-D) is one of the most used in the world and exposure to herbicides can affect animals and humans, causing toxic effects that include cardiotoxicity. This is the first study to evaluate cardiac remodeling after experimental simulation of environmental exposure by chronic inhalation (6 months) to the herbicide 2,4-D. Methods: Thirty male Wistar rats were exposed to two different concentrations of the 2,4-D formulation (low – 187.17 mg/m3; and high – 467.93 mg/m3) and the control group exposed to nebulization of chloride solution 0.9% sodium. Inhalation exposure lasted 6 months. Mice hearts were collected for histology. Results: There was a difference between exposure concentrations in relation to the increase in cardiac collagen (P &lt; 0.0001). In mice exposed to a low dose of 2,4-D and a decrease in the fractal dimension of cardiac collagen in the high dose of 2, 4-D (P = 0.010). Discussion: This study shows that chronic inhalation exposure to 2,4-D induces cardiotoxicity in rats, characterized by extracellular matrix reorganization and changes in collagen levels, highlighting the impact of the exposure route on cardiac outcomes. Conclusion: There was no difference in relation to anatomical parameters, cardiomyocyte area, collagen types I and III and analysis of arteriole thickness. Chronic exposure at different doses to the 2,4D herbicide had the potential to cause damage to cardiac remodeling by altering cardiac collagen in rats.
The novel immune landscape of immune‐checkpoint blockade in EBV‐associated malignancies
Authors: Zhang Feng , Li Wenjing , Zheng Xinglong , Ren Yinlong , Li Lijun , Yin Haiyan 
Published: November 2024

AbstractThe Epstein–Barr virus (EBV) is a ubiquitous gamma‐herpesvirus and a class 1 carcinogen that is closely associated with a series of malignant lymphomas and epithelial cell carcinomas. Although these EBV‐related cancers may exhibit different features in clinical symptoms and anatomical sites, they all have a characteristic immune‐suppressed tumor immune microenvironment (TIME) that is tightly correlated with an abundance of tumor‐infiltrating lymphocytes (TILs) that primarily result from the EBV infection. Overwhelming evidence indicates that an upregulation of immune‐checkpoint molecules is a powerful strategy employed by the EBV to escape immune surveillance. While previous studies have mainly focused on the therapeutic effects of PD‐1 and CTLA‐4 blockades in treating EBV‐associated tumors, several novel inhibitory receptors (e.g., CD47, LAG‐3, TIM‐3, VISTA, and DDR1) have recently been identified as potential targets for treating EBV‐associated malignancies (EBVaMs). This review retrospectively summarizes the biological mechanisms used for immune checkpoint evasion in EBV‐associated tumors. Its purpose is to update our current knowledge concerning the underlying mechanisms by which an immune checkpoint blockade triggers host antitumor immunity against EBVaMs. Additionally, this review may help investigators to more fully understand the correlation between EBV infection and tumor development and subsequently develop novel therapeutic strategies.
Biochemical, biophysical, and structural investigations of two mutants (C154Y and R312H) of the human Kir2.1 channel involved in the Andersen‐Tawil syndrome
Authors: Zuniga Dania , Zoumpoulakis Andreas , Veloso Rafael F. , Peverini Laurie , Shi Sophie , Pozza Alexandre , Kugler Valérie , Bonneté Françoise , Bouceba Tahar , Wagner Renaud , Corringer Pierre‐Jean , Fernandes Carlos A. H. , Vénien‐Bryan Catherine 
Published: November 2024

AbstractInwardly rectifying potassium (Kir) channels play a pivotal role in physiology by establishing, maintaining, and regulating the resting membrane potential of the cells, particularly contributing to the cellular repolarization of many excitable cells. Dysfunction in Kir2.1 channels is implicated in several chronic and debilitating human diseases for which there are currently no effective treatments. Specifically, Kir2.1‐R312H and Kir2.1‐C154Y mutations are associated with Andersen‐Tawil syndrome (ATS) in humans. We have investigated the impact of these two mutants in the trafficking of the channel to the cell membrane and function in Xenopus laevis oocytes. Despite both mutations being trafficked to the cell membrane at different extents and capable of binding PIP2 (phosphatidylinositol‐4,5‐bisphosphate), the main modulator for channel activity, they resulted in defective channels that do not display K+ current, albeit through different molecular mechanisms. Coexpression studies showed that R312H and C154Y are expressed and associated with the WT subunits. While WT subunits could rescue R312H dysfunction, the presence of a unique C154Y subunit disrupts the function of the entire complex, which is a typical feature of mutations with a dominant‐negative effect. Molecular dynamics simulations showed that Kir2.1‐C154Y mutation induces a loss in the structural plasticity of the selectivity filter, impairing the K+ flow. In addition, the cryo‐EM structure of the Kir2.1‐R312H mutant has been reconstructed. This study identified the molecular mechanisms by which two ATS‐causing mutations impact Kir2.1 channel function and provide valuable insights that can guide potential strategies for the development of future therapeutic interventions for ATS.
Percutaneous Screw Fixation for the Management of Delayed Unions in Pediatric Lateral Humeral Condylar Fractures
Authors: Chang Eric , Gajewski Christopher , Thompson Rachel M. , Silva Mauricio 
Published: November 2024

Background:
The use of in situ screw fixation for the treatment of pediatric lateral humeral condyle (LCH) delayed unions has recently been reported. While attractive, the currently available literature consists of small retrospective studies with mixed results. As such, the present study aims to describe the outcome of a group of children with delayed unions of LCH fractures treated with in situ fixation using a single, percutaneously placed cannulated screw in compression.

Methods:
A retrospective review of all pediatric patients (below 18 y) with lateral condyle fractures of the humerus treated surgically for delayed union between 2013 and 2023 at a single, tertiary referral center was completed. Clinical and radiologic variables related to the initial injury and delayed union were abstracted from the medical record, as were surgical variables. Radiographs were evaluated for union postoperatively; time to union was determined by the senior authors. Descriptive statistics were used to summarize demographic and outcome variables.

Results:
A total of 12 consecutive patients met the inclusion criteria. The mean age at the time of initial injury was 5.6 years; subjects were followed for a mean of 3.0 years following initial presentation. All were treated with a single, percutaneously placed screw in compression at a mean of 10.5 months after the original injury. Radiographic union was achieved in 11 (91.7%) patients. At the latest follow-up, all patients were pain free and demonstrated a functional arc of motion without evidence of avascular necrosis. A total of 2 patients required revision for loss of fixation. In one patient, a persistent lucent line was observed, and 1 patient was found to have a cubitus valgus deformity, both of which were not clinically relevant.

Conclusions:
Our results suggest that with the use of proper technique (a 4.5 cannulated screw inserted through the metaphyseal portion of the lateral condyle fragment, engaging the most medial/distal aspect of the humeral shaft), radiographic union and clinical healing can be achieved in the majority of patients. Percutaneous screw fixation should be considered as an option for cases of noninfected pediatric lateral condyle delayed unions.

Level of Evidence:
Level IV—evidence therapeutic studies
Safety of the contrast enhancement agent sulfur hexafluoride in ultrasound: Analysis of the Federal Drug Administration Adverse Event Reporting System database
Authors: Walker Courtney N. , Andrews Michael B. , Adler Douglas G. 
Published: November 2024

ABSTRACT

Background and Objectives
Sulfur hexafluoride is an inert gas that creates microbubbles to enhance diagnostic accuracy in a variety of ultrasound (US) studies and is widely used in EUS. We analyzed the reported adverse events (AEs) of the US contrast agent, sulfur hexafluoride, extensively used during EUS procedures using a US national database.

Methods
From December 2008 to January 2024, AEs reported in the Federal Drug Administration Adverse Event Reporting System database for sulfur hexafluoride were examined.

Results
There were 1069 individual reports analyzed. Reports were excluded if they contained drugs other than sulfur hexafluoride. Echocardiogram (70.9%) was the common diagnostic study in which sulfur hexafluoride was administered. The most common AE reported was anaphylactic reaction (n = 179, 16.7%), followed by hypotension (n = 162, 15.2%), cardiac arrest (n = 161, 15.1%), and dyspnea (n = 159, 14.9%). The most common gastrointestinal AE was nausea (n = 135, 12.6%). Severity of AEs ranged from nonserious to death. Death associated with sulfur hexafluoride use was reported in 58 patients (5.4% of AE reports).

Conclusions
Anaphylactic reaction was the most common AE reported with sulfur hexafluoride use, and severe AEs including death may be more common than prior large, retrospective, observational studies to date have suggested.