bluuebunny/crossref_metadata_2025_split huggingface dataset:
Elraglusib (9-ING-41), a selective small molecule inhibitor of Glycogen Synthase Kinase-3 beta, reduces expression of immune checkpoint molecules PD-1, TIGIT and LAG-3, and enhances CD8+ T cell cytolytic killing of melanoma cells.
Authors: Shaw Gary , Cavalcante Ludimila , Giles Francis , Taylor Alison 
Published: May 2022

Abstract
Background
Glycogen synthase kinase-3 (GSK-3) is a serine/threonine kinase with multiple roles in tumour growth, cell invasion and metastasis. We have previously established GSK-3 as an upstream regulator of PD-1 gene expression in CD8 + T cells and demonstrated that GSK-3 inhibition is as effective as anti-PD-1 mAb blockade in controlling tumour growth. Elraglusib (9-ING-41) is a specific small molecule inhibitor of GSK-3β with clinical activity in patients with advanced cancers, including a patient with refractory melanoma whose response provided the rationale for the current study.
Methods
The B16 melanoma mouse model was used to observe the effect of elraglusib on tumour growth either as a single agent or in combination (simultaneously and sequentially) with anti-PD1 mAb treatment. B16 tumour cells were implanted in either the flank, brain or both locations, Kaplan-Meier plots were used to depict survival and significance determined using log rank tests. Expression of the immune checkpoint molecules, TIGIT, LAG-3 and PD-1, were evaluated using flow cytometry alongside expression of the chemokine receptor, CXCR3. Further evaluation of PD-1 expression was determined through RT-qPCR and immunohistochemistry.
Results
We demonstrated that elraglusib has a suppressive effect against melanoma as a single agent and enhanced anti-PD1 therapy. There was a synergistic effect when elraglusib was used in combination with anti-PD1 mAb, and an even greater effect when used as sequential therapy. Suppression of tumour growth was associated with a reduced expression of immune checkpoint molecules, PD-1, TIGIT and LAG-3 with upregulation of CXCR3 expression.
Conclusions
These data highlight the potential of elraglusib as an immune-modulatory agent and demonstrate the benefit of a sequential approach with immune checkpoint inhibition followed by GSK-3β inhibition in melanoma and provide a rationale for clinical investigation of elraglusib combined with immune checkpoint inhibitory molecules, including those targeting PD-1, TIGIT and LAG-3. This has several potential implications for current immunotherapy regimes, including possibly reducing the intensity of anti-PD1 mAb treatment needed for response in patients receiving elraglusib, especially given the benign adverse event profile of elraglusib observed to date. Based on these data, a clinical study of elraglusib, an anti-PD1 mAb and chemotherapy is ongoing (NCT NCT05239182).
The diverging epigenomic landscapes of honeybee queens and workers revealed by multiomic sequencing
Authors: Zhang Yong , He Xu Jiang , Barron Andrew , Li Zhen , Jin Meng Jie , Wang Zilong , Huang Qiang , Zhang Li Zhen , Wu Xiaobo , Yan Wei Yu , Zeng Zhi Jiang 
Published: May 2022

Abstract
The role of the epigenome in phenotypic plasticity is unclear presently. Here we used a multiomics approach (RNA-seq, ChIP-seq, ATAC-seq and Hi-C) to explore the nature of the epigenome in developing honeybee (Apis mellifera) workers and queens. Our data showed that the distinct queen and worker epigenomic landscapes form during the developmental process. Differences in gene expression between workers and queens precede other epigenomic modifications, but the epigenomic differences between workers and queens become more extensive and more layered during development. Genes known to be important for caste differentiation were more likely to be multiply differentially regulated by more than one epigenomic system than other differentially expressed genes. This indicates a multidimensional regulation of expression of key genes, presumably to canalise differences in gene expression. Our data indicate that the epigenome interacts with diverging developmental trajectories rather than controlling them since different epigenomic landscapes form in concert with different developmental outcomes.
Effect of age on the structure and activity of the pharynx of the free- living nematode Metarhabditis andrassyana (Rhabditidae)
Authors: FATIMA HIBA , AHMAD IRFAN 
Published: May 2022

Abstract
Study of pharynx in a Metarhabditis andrassyana (Tahseen et al., 2004) revealed that the activity of pharynx declined with age and was also reduced in the absence of E.coli. A comparison between presence and absence of bacteria in the same age group revealed a reduction in both 2 day old individuals and 8 day old individuals. However, when nematodes were placed together in groups of varying numbers, pharyngeal pulsations declined as the numbers of specimens increased from 5 to 15 in the presence or absence of bacteria as a food source with age. In old worms, abnormalities were observed in the structure of the pharynx.
Topology of gene regulatory compartments relative to the nuclear matrix
Authors: Cho Won-Ki , Park Gunhee , Ryu Kwangmin , Lee Junho , Kim Geunhee , Park Tae Lim , Shim Hwanyong , Lee YigJi , Kim Changyeop 
Published: May 2022

Abstract
Inside the nucleus, there are special compartments with characterized functions, some of which are involved in gene expression1. These compartments include transcriptional condensates and nuclear speckles, which contain factors required for transcription and splicing, respectively. While the characteristics of these intranuclear compartments were extensively investigated, spatial relationship between them is yet unclear. Meanwhile, RNA-protein structural network named the nuclear matrix has been observed inside the nucleus and suggested as a framework for the spatial segregation of the intranuclear space2-6. However, concept of the nuclear matrix was not widely accepted due to its lack of in vivo evidence7. Here, we report visualization of the nuclear matrix and intranuclear compartments using super-resolution fluorescence microscopy. We found the nuclear matrix is dynamic in live cells and easily disrupted upon transcription inhibition. Remarkably, we observed an orderly layered distribution of transcriptional condensates and nuclear speckles relative to the nuclear matrix. We also observed a separation of chromosome territories from transcriptional condensates and nuclear speckles by the nuclear matrix. Based on our findings, we propose a topological model for the regulation of transcription across the nuclear matrix.
Differences in mortality risk associated with statin use amongst Asian patients with prostate cancer undergoing androgen deprivation therapy: a retrospective cohort study
Authors: Tse Gary , Lee Yan Hiu Athena , Chan Jeffrey Shi Kai , Hui Jeremy Man Ho , Tang Pias , Liu Kang , Dee Edward , Ng Kenrick , Ng Chi Fai 
Published: May 2022

Abstract
Background: With known anticancer properties, statins have the potential to be an adjuvant cancer therapy, but their associations with mortality in prostate cancer (PCa) remain debatable. This study investigated the associations between statin use concurrent with androgen deprivation therapy (ADT) and mortality risks in Asian patients with PCa. Methods: Adults with PCa receiving any ADT attending public hospitals in Hong Kong between December 1999 and March 2021 were retrospectively identified, with follow-up until September 2021. Patients with <180 days of medical castration without subsequent bilateral orchidectomy, <180 days of concurrent statin use and ADT, or missing total cholesterol level at baseline were excluded. Statin users had ≥180 days of concurrent statin and ADT use, while non-users were those without any statin use. The primary outcome was PCa-related mortality. The secondary outcome was all-cause mortality. Inverse probability treatment weighting was used to balance covariates. Results: 4920 patients were studied (2578 statin users and 2342 non-users; mean age 76.1±8.2 years). Over a mean follow-up of 4.2±3.3 years, statin users had significantly lower risks of PCa-related mortality (weighted hazard ratio (wHR) 0.56 [95% confidence interval 0.48, 0.65], p<0.001) and all-cause mortality (0.57 [0.51, 0.63], p<0.001) regardless of the type of ADT. The associations appeared stronger in patients without chemotherapy or antiandrogens use. Conclusions: Statin use concurrent with ADT was associated with lower risks of mortality in Asian patients with PCa, warranting further studies of its role in the treatment of patients with PCa.
Characterizing mobility patterns of forest goersin southern Lao PDR using GPS loggers.
Authors: Rerolle Francois , Dantzer Emily , Phimmakong Toula , Lover Andrew , Hongvanthong Bouasy , Phetsouvanh Rattanaxay , Marshall John , Sturrock Hugh , Bennett Adam 
Published: May 2022

Abstract
Background: In the Greater Mekong Subregion (GMS), forest-going populations are considered high-risk populations for malaria and are increasingly targeted by national control programs’ elimination efforts. A better understanding of forest-going populations’ mobility patterns and risk associated with specific types of forest-going trips is necessary for countries in the GMS to achieve their objective of eliminating malaria by 2030.Methods: Between March and November 2018, as part of a focal test and treat intervention (FTAT), we recruited 2,904 forest-goers in southern Lao PDR. A subset of forest-goers carried an “i-Got-U” GPS logger for roughly two months, configured to collect GPS coordinates every 15 to 30 minutes. The utilization distribution (UD) surface around each GPS trajectory was used to extract trips to the forest and forest-fringes. Trips with shared mobility characteristics in terms of duration, timing and forest penetration were identified by a hierarchical clustering algorithm. Then, clusters of trips with increased exposure to dominant malaria vectors in the region were further classified as high-risk. Finally, we used gradient boosting trees to assess which of the forest-goers’ socio-demographic and behavioral characteristics best predicted their likelihood to engage in such high-risk trips. Results: A total of 122 forest-goers accepted carrying a GPS logger resulting in the collection of 803 trips to the forest or forest-fringes. Six clusters of trips emerged, helping to classify 385 (48%) trips with increased exposure to malaria vectors based on high forest penetration and whether the trip happened overnight. Age, outdoor sleeping structures and number of children were the best predictors of forest-goers’ probability of engaging in high-risk trips. The probability of engaging in high-risk trips was high (~33%) in all strata of the forest-going population.Conclusion: This study characterized the heterogeneity within the mobility patterns of forest-goers and attempted to further segment their role in malaria transmission in southern Lao People’s Democratic Republic (PDR). National control programs across the region can leverage these results to tailor their interventions and messaging to high-risk populations and accelerate malaria elimination.
Fe@Fe2O3-loaded biochar as an efficient heterogeneous Fenton catalyst for organic pollutants removal
Authors: Chen Diwei , Zheng Zhiyan , Zhang Feiji , Ke Rufu , Sun Nan , Wang Yonghao , Wang Yongjing 
Published: May 2022

Abstract
With increased demand for various chemical raw materials, sudden pollution incidents are more prone to occur during their transportation and usage, threatening the environment and human health. In this study, discarded tea stalks were recycled into composite materials (FSC-X00: X represents the calcination temperature) by impregnating tea stalks in Fe2+ solution combined with subsequent calcination. X-ray diffractometer (XRD) and X-ray photoelectron spectroscopy (XPS) patterns verified the existence of Fe0 and Fe2O3, and Fe2O3 was gradually reduced to Fe0 when the calcination temperature was raised from 700 °C to 900 °C. FSC-X00 was adopted as a heterogeneous catalyst for activating H2O2 to quickly degrade phenol in the water system. The degradation experiments indicated that FSC-600 exhibited superior degradation performance for phenol (20 mg/L) within 5 min and 80% total organic carbon (TOC) removal rate at pH = 3 within 30 min. The effects of the calcination temperature, the pH value and the amount of H2O2 on the degradation efficiency were investigated. Competing experiments showed that fulvic acid (FA) and inorganic salts Na+ had little effect on the degradation performance. The FSC-600 catalyst can be reused by thermal reduction. In addition, it was found that FSC-600 has a good degradation effect on ciprofloxacin (CIP), norfloxacin (NOR) and enrofloxacin (ENR), indicating that FSC-600 catalysts are a promising candidate for quick degradation of organic pollutants by Fenton reaction. Electron paramagnetic resonance (EPR) spectra analysis indicated that •OH is the dominant reactive oxygen species (ROS) and part 1O2 from O2 also participated in the degradation. This study provides an example of creating catalysts from organic solid waste for use in emergency treatment for phenol.
The Coupling of Carbon and Nitrogen Substituents with Nitroarenes: Vicarious
Nucleophilic Substitution of Hydrogen in Nitroarenes
Authors: Zou Dong , Han Gang 
Published: May 2022

Abstract:
In recent years, nitroarenes have been extensively exploited as green, efficient
electrophilic arylation reagents used in a variety of organic syntheses. Transition-metal-free
cross-coupling reactions and vicarious nucleophilic substitution (VNS) have become practical
and reliable synthetic methods to access momentous functionalized organic compounds. Thus,
the introduction of various substituents into nitroarenes has attracted considerable attention as
important synthetic approaches due to their simplicity and practicality. In this review, we
comprehensively summarize the coupling of several carbon and nitrogen substituents with
nitroarenes via nucleophilic substitution under mild conditions, followed by the application of
these transversions in the construction of carbon and heterocyclic rings.
Super Para-Magnetic Iron Oxide Nanoparticles (SPIONs) in the Treatment
of Cancer: Challenges, Approaches, and its Pivotal Role in Pancreatic,
Colon, and Prostate Cancer
Authors: Khan Sameea Ahmed , Sharma Rajesh 
Published: May 2022

Abstract:
Super Para-magnetic Iron Oxide Nanoparticles (SPIONs) have been manifested for their
broad spectrum of applications ranging from biomedical imaging to the treatment of many diseases.
Many experiments are being conducted across the globe to especially investigate their potential in the
field of targeted treatment for malignant tissues. However, challenges pertaining to the desired delivery
of anticancer drugs in the body remain unresolved or unattended. The bare iron oxide nanoparticles are
liable to form agglomerates or get easily oxidized in the air which can lead to loss of their magnetism
and viability. Moreover, in several reactions, these magnetic nanoparticles leach into the solution/ suspension,
making it kinetically unstable. The nanoparticles, further readily metabolize in the stomach pH
or are phagocytosed by macrophages. In this article, we address these issues by shedding light on the
impact of controlling parameters like size, synthesis method, and surface engineering. After studying the
existing literature, it is noted that currently, these magnetically guided delivery systems are being rigorously
tested in areas like pancreatic cancer, colon cancer, and prostate cancer, which will be discussed
in this review. The fact that the major issue in the conventional treatment of these cancers is intrinsic
and acquired drug resistance is a key issue. In this context, the potential of SPIONs as efficient nanotherapeutics
is presented. The article provides a deeper insight into the research conducted on these
focused areas in cancer. This review also discusses, in brief, the consolidation of artificial intelligence in
cancer nanomedicine assuring a better treatment outcome in near future.
Recent Developments in the Synthesis and Anticancer Activity of Indole
and Its Derivatives
Authors: Wadhwa Pankaj , Kaur Balwinder , Venugopal Sneha , Verma Anil , Sahu Sanjeev Kumar , Kumar Deepak , Sharma Ajit 
Published: May 2022

Abstract:
Heterocyclic compounds are a class of compounds that is deeply intertwined with biological
processes and is found in about 90% of commercially available medicines. They serve a
critical function in medicinal chemistry and are focused in the field of medication development for
their intensive research due to their broad variety of biological effects because of their intriguing
molecular architecture, such as indoles are good candidates for drug development. It is a bicyclic
structure consisting of a six-membered benzene ring fused to a five-membered pyrrole ring with
several pharmacophores that yield a library of different lead compounds. Human cancer cells have
been demonstrated to be inhibited by indoles in the development of new anticancer medicines.
This is the first comprehensive review to focus on current methodologies for incorporating indole
moiety, with their mechanistic targets as anticancer drugs, in order to shed light on the logical development
of indole-based anticancer treatment options with high efficacy. This compiled data
may serve as a benchmark for modifying existing ligands in order to design novel potent molecules
through excellent yield synthesis techniques.
Transformation in Content of Bioactive Compounds of Glodok Fish (Boleopthalmus boddarti) Based on the Effect of Variations in Temperature and Frying Time
Authors: Ridho Moh. Rasyid , Patriono Enggar , Cahyani Ajeng , Avesena Muhammad , Fitria Syarifa 
Published: May 2022

Abstract:Objective: One species of glodok fish is Boleophthalmus boddarti. The fish was identified to contain bioactive compounds such as steroids, terpenoids, bufadienolid, carotatoksin, and corticosteroids. Bioactive compounds have benefits for human life. Methods: Lampung coastal communities consume glodok fish to cure asthma. They consume glodok fish by various processing methods, such as by frying. The frying process is expected to damage some nutrients such as vitamins and proteins, including the possibility of damaging bioactive compounds. However, there is no data regarding the effect of using different temperatures and times in the frying process on changes in bioactive content in the meat of the glodok fish. Sampling was carried out around the mouth of the Musi River, South Sumatra. The stages of the research consisted of the preparation process, treatment using 9 variations of temperature and frying time, sample extraction, analysis of the content of bioactive compounds by GC-MS. Results: The results showed that the bioactive compounds identified before fried fishes consisted of corticosteroids, steroids, carotenoids, monoterpenoids, sesquiterpenoids, and triterpenoids. Conclusion: Variations in the treatment resulted in cholesterol of the steroid group in the highest treatment at 14.36% and the loss of betamethasone acetate compounds in the corticosteroid group by 0.07% in the treatment sample.
Complete Healing of a Heel Bedsore using Argania Honey Dressing: Case
Report
Authors: Raghay Kawtar , Khattabi Leila , Dakkach Mohamed , Allouch Mohamed 
Published: May 2022

Background:
Chronic wounds and injuries represent a significant burden for health care
professionals due to the difficulties related to their management. The selection and use of appropriate
dressings have become essential for successful treatment. Honey has been used for thousands of
years as a biological treatment because its bioactive components contribute to the healing process.

Objective:
This case report aims to demonstrate the efficiency of Argania honey dressing on pressure
ulcers.

Case Presentation:
The wound care was achieved using pure raw Argania honey with no additives,
pasteurization, or manipulation. A previous mechanical debridement process was necessary before
the application of honey dressings to a right heel bedsore in a 69-year-old man who suffered an ischemic
stroke.

Results:
This case report describes for the first time the complete healing of a right heel bedsore using
Argania honey dressing. Bedsore demonstrated rapid recovery and complete healing over approximately
18 weeks (124 days, between June and October 2021).

Conclusion:
With the rise of natural medicines and some pathologies that are resistant to conventional
treatments, Argania honey can be an asset for its therapeutic effects on the skin, but more
studies are needed to explain and identify the complexity of mechanisms involved to ensure this
complete healing process.
Parotid Gland Swelling as an Initial Presentation of Multiple Myeloma: A
Case Report
Authors: Singh Jitendra , Dewangan Ankita , Singh Swati , Kumar Nilesh , Kumar Kailash 
Published: May 2022

Introduction:
Parotid swellings are commonly encountered in ENT Clinics, the cause of which could range from neural conditions, endocrine problems, vitamin deficiencies, and sialadenitis, which may even be a manifestation of an underlying systemic disease. Multiple myeloma represents a clonal proliferation of plasma cells and is a condition in which a parotid swelling might be present, although very uncommon.

Case presentation:
We report a case of 60-year-old female presented with unilateral parotid swelling, which led to a diagnosis of multiple myeloma based on the investigations.

Conclusion:
Various imaging modalities are currently available to assess the extent of the swelling and evaluate the soft tissue and osseous involvement. The clinician must have a rigorous insight into the several clinical manifestations and the sites of involvement of the different conditions to make a proper diagnosis.
Effects of Semaglutide on Glycemic Control and Weight Loss in a Patient with Prader-Willi Syndrome: A Case Report
Authors: Sani Elena , Prato Giuliana Da , Zenti Maria Grazia , Bordugo Andrea , Trombetta Maddalena , Bonora Enzo 
Published: May 2022

Background:
Prader-Willi syndrome is the most frequent genetic cause of obesity and is
often complicated by glucose metabolism alterations. Conventional therapies prescribed for type 2
diabetes frequently failed to achieve adequate glycemic control in patients with Prader-Willi
syndrome. Beneficial effects of glucagon like peptide-1 receptor agonists exenatide and liraglutide
have been reported for the management of type 2 diabetes in Prader-Willi syndrome, but no data
are currently available in this population on the use of semaglutide.

Case Presentation:
We report for the first time the use of semaglutide 1 mg per week in a 33-yearold
man with Prader-Will syndrome complicated by poorly controlled diabetes and severe obesity.
After 12 months of semaglutide treatment, we observed an important reduction in glycated
hemoglobin levels (11.1% to 7.2%) and body weight (99.5 kg to 94.3 kg), with a notable decrease
in fat mass and insulin requirements. Interestingly, our patient had already tried liraglutide therapy
in adjunction to metformin and insulin therapy, reporting no substantial efficacy.

Conclusions:
The beneficial effects of semaglutide on glycemic control and weight reduction
provide a promising treatment for diabetes and obesity in Prader-Willi syndrome, even where other
glucagons like peptide-1 receptor agonists have failed. Further studies are required to confirm the
efficacy and safety of semaglutide in patients with Prader-Willi syndrome.