bluuebunny/crossref_metadata_2025_split huggingface dataset:
Current understanding of ferroptosis in the progression and treatment of pancreatic cancer
Authors: Dong Shi , Li Xin , Jiang Wenkai , Chen Zhou , Zhou Wence 
Published: September 2021

AbstractPancreatic cancer is a highly malignant tumour of the digestive tract. Despite advances in treatment, its 5-year survival rate remains low, and its prognosis is the worst among all cancers; innovative therapeutic methods are needed. Ferroptosis is a form of regulatory cell death driven by iron accumulation and lipid peroxidation. Recent studies have found that ferroptosis plays an important role in the development and treatment response of tumours, particularly pancreatic cancer. This article reviews the current understanding of the mechanism of ferroptosis and ferroptosis-related treatment in pancreatic cancer.
Donut-like MOFs of copper/nicotinic acid and composite hydrogels with superior bioactivity for rh-bFGF delivering and skin wound healing
Authors: Wang Tian-Long , Zhou Zi-Fei , Liu Jun-Feng , Hou Xiao-Dong , Zhou Zhi , Dai Yun-Lu , Hou Zhi-Yong , Chen Feng , Zheng Long-Po 
Published: September 2021

Abstract
Background
Skin injury and the resultant defects are common clinical problems, and usually lead to chronic skin ulcers and even life-threatening diseases. Copper, an essential trace element of human body, has been reported to promote the regeneration of skin by stimulating proliferation of endothelial cell and enhance angiogenesis.

Results
Herein, we have prepared a new donut-like metal–organic frameworks (MOF) of copper-nicotinic acid (CuNA) by a simple solvothermal reaction. The rough surface of CuNA is beneficial for loading/release basic fibroblast growth factor (bFGF). The CuNAs with/without bFGF are easily processed into a light-responsive composite hydrogel with GelMA, which not only show excellent mechanical properties, but also display superior biocompatibility, antibacterial ability and bioactivity. Moreover, in the in vivo full-thickness defect model of skin wound, the resultant CuNA-bFGF@GelMA hydrogels significantly accelerate the wound healing, by simultaneously inhibiting the inflammatory response, promoting the new blood vessels formation and the deposition of collagen and elastic fibers.

Conclusions
Considering the superior biocompatibility, antibacterial ability and bioactivity, the CuNA and its composite light-responsive hydrogel system will be promising in the applications of skin and even other tissue regeneration.

Graphic abstract
HIV diagnosis period influences ART initiation: findings from a prospective cohort study in China
Authors: Yang Tinglong , Yang Xueying , Li Linghua , Xu Huifang , Fan Lirui , Li Quanmin , Fan Xiaoyan , Chen Weiyi , Du Xuan , Hao Chun , Li Jinghua , Hao Yuantao , Gu Jing 
Published: September 2021

Abstract
Background
We estimated the predictive effects of ART-related perceptions on the actual ART uptake behavior among ART naïve PLWH stratified by different time of HIV diagnosis under the new strategy.

Methods
A prospective cohort study was conducted among ART naïve PLWH in Guangzhou, China from June 2016 to June 2017. Cox regression model was used to evaluate the predictive effects of ART-related perceptions on ART initiation among PLWH stratified by different timepoint of HIV diagnosis (i.e., before or after the update of the new treatment policy).

Results
Among 411 participants, 150 and 261 were diagnosed before (pre-scaleup group) and after (post-scaleup group) the implementation of the new strategy, respectively. The ART initiation rate in the post-scaleup group (88.9%) was higher than that in the pre-scaleup group (73.3%) (p < 0.001). A significant difference of mean score was detected in each HBM construct between pre- and post-scaleup groups (p < 0.05). After adjusting for significant background variables, among all participants, only the self-efficacy [adjusted HR (HRa) = 1.23, 95% CI 1.06 to 1.43, p = 0.006], has a predictive effect on ART initiation; in pre-scaleup group, all constructs of HBM-related ART perceptions were predictors of ART initiation (HRa = 0.71 to 1.83, p < 0.05), while in post-scaleup group, no significant difference was found in each construct (p > 0.05).

Conclusions
The ART initiation rate was high particularly among participants who diagnosed after the new treatment strategy. The important role of the time of HIV diagnosis on ART initiation identified in this study suggested that future implementation interventions may consider to modify the ART-related perceptions for HIV patients who diagnosed before the implementation of the new ART strategy, while expand the accessibility of ART service for those who diagnosed after the implementation of the new strategy.
Dihydromyricetin attenuates palmitic acid-induced oxidative stress by promoting autophagy via SIRT3-ATG4B signaling in hepatocytes
Authors: Huang Li , Zeng Xianglong , Li Bo , Wang Cong , Zhou Min , Lang Hedong , Yi Long , Mi Mantian 
Published: September 2021

Abstract
Background
Oxidative stress in hepatocytes was important pathogenesis of nonalcoholic steatohepatitis (NASH). Autophagy was a cellular process that can remove damaged organelles under oxidative stress, and thus presented a potential therapeutic target against NASH. This work aimed to investigate whether autophagy was participated in the protective effects of dihydromyricetin (DHM) on palmitic acid (PA)-induced oxidative stress in hepatocytes and the underlying mechanism.

Methods
HepG2 and HHL-5 cell lines were pretreated with DHM (20 μM) for 2 h, followed by PA (0.2 mM) treatment for 16 h. The oxidative stress was assessed by the quantification of intracellular reactive oxygen species (ROS), mitochondrial ROS (mtROS), mitochondrial membrane potential (MMP) and mitochondrial ultrastructural analyses. The protein expressions of SIRT3, LC3I/II, P62 and ATG4B, as well as the acetylation of AGT4B were determined by western blotting using HepG2 and HepG2/ATG4B± cells with heterozygous knockout of ATG4B.

Results
Exposure to PA resulted in increased intracellular ROS and mtROS, decreased MMP and aggravated mitochondrial injury in HepG2 cells, which were notably attenuated by DHM treatment. DHM-induced inhibition of oxidative stress was associated with the induction of autophagy, characterized by upregulated ATG4B and LC3 II as well as downregulated P62 levels. Furthermore, the inhibitory effects of DHM on PA-induced autophagy arrest and oxidative stress were eliminated when pretreated with a SIRT3 inhibitor 3-TYP or conducted in HepG2/ATG4B± cells, suggesting that SIRT3 and ATG4B were involved in DHM-induced benefits. Moreover, DHM treatment increased the protein expression of SIRT3 and SIRT3-dependent deacetylation of ATG4B in HepG2 cells.

Conclusion
Our results demonstrated that DHM attenuated PA-induced oxidative stress in hepatocytes through induction of autophagy, which was mediated through the increased expression of SIRT3 and SIRT3-mediated ATG4B deacetylation following DHM treatment.
Infection risk varies within urbanized landscapes: the case of coyotes and heartworm
Authors: Worsley-Tonks Katherine E. L. , Gehrt Stanley D. , Anchor Chris , Escobar Luis E. , Craft Meggan E. 
Published: September 2021

AbstractBackgroundUrbanization can have profound effects on ecological interactions. For host–pathogen interactions, differences have been detected between urban and non-urban landscapes. However, host–pathogen interactions may also differ within highly heterogeneous, urbanized landscapes.MethodsWe investigated differences in infection risk (i.e., probability of infection) within urbanized landscapes using the coyote (Canis latrans) and mosquito-borne nematode,Dirofilaria immitis(the causative agent for canine heartworm), as a case study. We focused on a coyote population in Chicago for which extensive behavioral and heartworm infection data has been collected between 2001 and 2016. Our objectives were to: (i) determine how onset and duration of the heartworm transmission season varied over the 16-year period and across the urban–suburban gradient; and (ii) investigate how heartworm infection risk in coyotes varied over the years, across the urban–suburban gradient, by coyote characteristics (e.g., age, sex, resident status), and coyote use of the urbanized landscape (e.g., use of urban areas, mosquito habitats).ResultsWhile onset of the heartworm transmission season differed neither by year nor across the urban–suburban gradient, it was longer closer to the core of Chicago. Of the 315 coyotes sampled, 31.1% were infected withD. immitis. Older coyotes and coyotes sampled in later years (i.e., 2012–2016) were more likely to have heartworm. While coyote location in the urban–suburban gradient was not a significant predictor of infection, the proportion of urban land in coyote home ranges was. Importantly, the size and direction of this association varied by age class. For adults and pups, infection risk declined with urbanization, whereas for subadults it increased. Further, models had a higher predictive power when focusing on resident coyotes (and excluding transient coyotes). The proportion of mosquito habitat in coyote home ranges was not a significant predictor of infection.ConclusionsOur findings suggest that urbanization may affect host exposure to vectors ofD. immitis, that risk of infection can vary within urbanized landscapes, and that urbanization–wildlife infection associations may only be detected for animals with certain characteristics (e.g., age class and resident status).Graphical abstract
Current status of MSK radiology training: an international survey by the European Society of Musculoskeletal Radiology (ESSR) Young Club
Authors: Albano Domenico , Dalili Danoob , Huber Florian A. , Snoj Ziga , Vieira Ana , Messina Carmelo ,   the Young Club of the European Society of Musculoskeletal Radiology (ESSR)
Published: September 2021

Abstract
Objectives
There is wide variation between Countries in the structures of residency programmes, need for subspecialisation, and health care system organisation. This survey was aimed at gathering information regarding current musculoskeletal (MSK) educational programmes offered both in European and non-European Countries.

Methods
We administered an online survey to European Society of Radiology (ESR) residents and radiologists aged up to 35 years. The questionnaire was further disseminated by delegates of the ESR Radiology Trainees Forum. Survey consisted of 20 questions about the structure and organisation of MSK training programmes.

Results
Overall, 972 participants from 86 Countries completed the survey, with a wide heterogeneity of answers. Of them, 636 were residents (65.9%), 329 were certified radiologists (34.1%), with a mean age of 30.8 ± 3 years. Almost half of the participants had a dedicated MSK rotation/block during residency, with a duration of 3–6 months in 62.5% of cases. A dedicated period in MSK Ultrasound was present in only one-third of residency programmes; 38% of participants were expected to learn interventional MSK procedures, but only 28.2% have been actively involved in interventions during their residency. Overall, 62.7% of participants rated the quality of their MSK training as poor to average. Almost all (93.1%) thought that MSK training could be improved in their residency, especially ultrasound practice (80.7%) and MRI reporting (71.1%).

Conclusions
There are significant inconsistencies in the structure of MSK training offered by different Countries. Radiology trainees are showing substantial interest in MSK training, which necessitates strategic investments to standardise and enhance its quality.
Accuracy of shear wave elastography in characterization of thyroid nodules in children and adolescents
Authors: Hazem Mohammed , Zakaria Ossama M. , Daoud Mohamed Yasser Ibrahim , Al Jabr Ibrahim Khalid , AlYahya Abdulwahab A. , Hassanein Ahmed Gaber , Alabdulsalam Abdulrahim A. , AlAlwan Mohammed Qasem , Hasan Nahla Mohamed Ali 
Published: September 2021

Abstract
Background
Thyroid nodules are an important health problem in children and adolescents. They possess a higher risk of malignancy in comparison to adults. This fact forms a great dilemma for clinicians. The aim of this study was to evaluate the reliability of shear wave elastography (SWE) as a non-invasive technique in the characterization of thyroid nodules in children and adolescents.

Methods
This prospective study included 56 patients with thyroid nodules. All the patients underwent clinical assessment, laboratory investigations, ultrasound, and Doppler examination, followed by an SWE assessment. Statistical analysis was performed and the best cut-off value to differentiate benign from malignant nodules was determined using the ROC curve and AUC.

Results
Seventy-two nodules were detected in the examined patients (ages ranged from 11 to 19 years, with mean age of 14.89 ± 2.3 years). Fifty-eight nodules (80.6%) were benign, and fourteen nodules (19.4%) were malignant (histopathologically proved). Highly suspicious criteria for prediction of malignancy by ultrasound and Doppler were hypoechoic echopattern, internal or internal and peripheral vascularity, microcalcifications, taller-than-wide dimensions, irregular outlines, and absence of halo (p < 0.05). The diagnostic performance for their summation was 70.69% sensitivity, 82.8% specificity, 80.45% accuracy, a 63.79% positive predictive value (PPV), and 87.9% negative predictive values (NPV). Regarding SWE, our results showed that 42.2 kPa was the best cut-off value, with AUC = 0.921 to differentiate malignant from benign nodules; the diagnostic performance was 85.71% sensitivity, 94.83% specificity, 93.06% accuracy, 76.9% PPV, and 93.2% NPV.

Conclusion
Shear wave elastography is a non-invasive technique that can assist in the diagnosis of malignant thyroid nodules among children and adolescents.
The cross talk between gastric cancer stem cells and the immune microenvironment: a tumor-promoting factor
Authors: Becerril-Rico Jared , Alvarado-Ortiz Eduardo , Toledo-Guzmán Mariel E. , Pelayo Rosana , Ortiz-Sánchez Elizabeth 
Published: September 2021

AbstractCross talk between cancer cells and the immune system is determinant for cancer progression. Emerging evidence demonstrates that GC characteristics such as metastasis, treatment resistance, and disease recurrence are associated with a tumor subpopulation called gastric cancer stem cells (GCSCs). However, the specific interaction between GCSCs and the immune microenvironment is still under investigation. Although immune evasion has been well described for cancer stem cells (CSCs), recent studies show that GCSCs can also regulate the immune system and even benefit from it. This review will provide an overview of bidirectional interactions between CSCs and immune cells in GC, compiling relevant data about how CSCs can induce leukocyte reprogramming, resulting in pro-tumoral immune cells that orchestrate promotion of metastasis, chemoresistance, tumorigenicity, and even increase in number of cancer cells with stem properties. Some immune cells studied are tumor-associated macrophages (TAMs), neutrophils, Th17 and T regulatory (Treg) cells, mesenchymal stem cells (MSCs), and cancer-associated fibroblasts (CAFs), as well as the signaling pathways involved in these pro-tumoral activities. Conversely, although there are cytotoxic leukocytes that can potentially eliminate GCSCs, we describe mechanisms for immune evasion in GCSCs and their clinical implications. Furthermore, we describe current available immunotherapy targeting GCSC-related markers as possible treatment for GC, discussing how the CSC-modified immune microenvironment can mitigate or inactivate these immunotherapies, limiting their effectiveness. Finally, we summarize key concepts and relevant evidence to understand the cross talk between GCSCs and the immune microenvironment as an important process for effective design of therapies against GCSCs that improve the outcome of patients with GC.
Homology-directed gene-editing approaches for hematopoietic stem and progenitor cell gene therapy
Authors: Azhagiri Manoj Kumar K. , Babu Prathibha , Venkatesan Vigneshwaran , Thangavel Saravanabhavan 
Published: September 2021

AbstractThe advent of next-generation genome engineering tools like CRISPR-Cas9 has transformed the field of gene therapy, rendering targeted treatment for several incurable diseases. Hematopoietic stem and progenitor cells (HSPCs) continue to be the ideal target cells for gene manipulation due to their long-term repopulation potential. Among the gene manipulation strategies such as lentiviral gene augmentation, non-homologous end joining (NHEJ)-mediated gene editing, base editing and prime editing, only the homology-directed repair (HDR)-mediated gene editing provides the option of inserting a large transgene under its endogenous promoter or any desired locus. In addition, HDR-mediated gene editing can be applied for the gene knock-out, correction of point mutations and introduction of beneficial mutations. HSPC gene therapy studies involving lentiviral vectors and NHEJ-based gene-editing studies have exhibited substantial clinical progress. However, studies involving HDR-mediated HSPC gene editing have not yet progressed to the clinical testing. This suggests the existence of unique challenges in exploiting HDR pathway for HSPC gene therapy. Our review summarizes the mechanism, recent progresses, challenges, and the scope of HDR-based gene editing for the HSPC gene therapy.
Coping with extremes: lowered myocardial phosphofructokinase activities and glucose content but increased fatty acids content in highland Eurasian Tree Sparrows
Authors: Ding Boyang , Zhao Yuliang , Sun Yanfeng , Zhang Qian , Li Mo , Nabi Ghulam , Wu Yuefeng , Jiang Chuan , Li Dongming 
Published: September 2021

AbstractBackgroundEfficient and selective utilization of metabolic substrates is one of the key strategies in high-altitude animals to cope with hypoxia and hypothermia. Previous findings have shown that the energy substrate utilization of highland animals varies with evolutionary history and phylogeny. The heart is a proxy for the cardiopulmonary system, and the metabolic substrate utilization in the myocardium is also under the strong selective pressure of chronically hypoxic and hypothermic environments. However, little information is available on the physiological adjustments in relation to metabolic substrate utilization in the myocardium for coping with high-altitude environments.MethodsWe compared the metabolic enzyme activities, including hexokinase (HK), phosphofructokinase (PFK), pyruvate kinase (PK), citrate synthase (CS), carnitine palmitoyl transferase 1 (CPT-1), lactic dehydrogenase (LDH), and creatine kinase (CK), and metabolic substrate contents including glucose (Glu), triglyceride (TG), and free fatty acid (FFA) in the myocardium of a typical human commensal species, Eurasian Tree Sparrows (Passermontanus) between the Qinghai-Tibet Plateau (the QTP, 3230 m) and low altitude population (Shijiazhuang, 80 m), and between sexes.ResultsAmong the seven metabolic enzymes and three substrates investigated, we identified no significant differences in PK, CPT-1, HK, CS, LDH, and CK activities and TG content of the myocardium between high and low altitude populations. However, the QTP sparrows had significantly lower Glu content and PFK activities but higher FFA content relative to their lowland counterparts. In addition, male sparrows had higher myocardial HK and CS activities relative to females, independent of altitude.ConclusionsOur results showed that the QTP sparrows elevated fatty acid utilization rather than glucose preference in the myocardium relative to lowland counterpart, which contributes to uncovering both the physiological adjustments for adapting to the extreme conditions of the QTP, intraspecifically.
Palmitoylethanolamide for sleep disturbance. A double-blind, randomised, placebo-controlled interventional study
Authors: Rao Amanda , Ebelt Phillippa , Mallard Alistair , Briskey David 
Published: September 2021

Abstract
Background
Sleep is essential for wellbeing, yet sleep disturbance is a common problem linked to a wide range of health conditions. Palmitoylethanolamide (PEA) is an endogenous fatty acid amide proposed to promote better sleep via potential interaction with the endocannabinoid system.

Methods
This double-blind, randomised study on 103 adults compared the efficacy and tolerability of 8 weeks of daily supplemented PEA formulation (350 mg Levagen + ®) to a placebo. Sleep quality and quantity were measured using wrist actigraphy, a sleep diary and questionnaires.

Results
At week 8, PEA supplementation reduced sleep onset latency, time to feel completely awake and improved cognition on waking. After 8 weeks, both groups improved their sleep quality and quantity scores similarly. There was no difference between groups at baseline or week 8 for sleep quantity or quality as measured from actigraphy or sleep diaries.

Conclusion
These findings support PEA as a potential sleeping aid capable of reducing sleep onset time and improving cognition on waking.

Trial registration
Australian
New Zealand Clinical Trials Registry ACTRN12618001339246. Registered 9th
August 2018.
RHOBTB2 gene associated epilepsy and paroxysmal movement disorder: two cases report and literature review
Authors: Niu Xueyang , Sun Yan , Yang Ying , Cheng Miaomiao , Tan Quanzhen , Zhang Jie , Zhang Yuehua 
Published: September 2021

Abstract
Background
RHOBTB2 gene is associated with developmental and epileptic encephalopathy-64(DEE-64), which is characterized by epilepsy, developmental delay, microcephaly, unspecific facial dysmorphism, and paroxysmal movement disorders. Most previous studies showed that the phenotypes of RHOBTB2 gene include developmental and epileptic encephalopathy(DEE) and DEE with paroxysmal movement disorders. Only one study showed that patient with RHOBTB2 variant had paroxysmal movement disorders with no epilepsy.

Case presentations
Two cases with RHOBTB2 variants are presented here: Case one was diagnosed as DEE, he had recurrent afebrile focal status epilepticus and paroxysmal extrapyramidal symptoms in infancy. Interictal electroencephalogram (EEG) showed focal discharges. Brain magnetic resonance imaging (MRI) showed cortical dysplasia. Epilepsy of case one was refractory. Nevertheless, case two only showed paroxysmal movement disorders alone in adolescence. Video EEG showed focal discharges during an interictal dystonic episode and he brain MRI was normal.

Conclusion
The phenotypes of RHOBTB2 gene include DEE, paroxysmal movement disorders, and DEE with paroxysmal movement disorders. RHOBTB2 can be one of the pathogenic genes of paroxysmal movement disorders.
Drug resistance: from bacteria to cancer
Authors: Patel Harsh , Wu Zhuo-Xun , Chen Yanglu , Bo Letao , Chen Zhe-Sheng 
Published: September 2021

AbstractThe phenomenon of drug resistance has been a hindrance to therapeutic medicine since the late 1940s. There is a plethora of factors and mechanisms contributing to progression of drug resistance. From prokaryotes to complex cancers, drug resistance is a prevailing issue in clinical medicine. Although there are numerous factors causing and influencing the phenomenon of drug resistance, cellular transporters contribute to a noticeable majority. Efflux transporters form a huge family of proteins and are found in a vast number of species spanning from prokaryotes to complex organisms such as humans. During the last couple of decades, various approaches in analyses of biochemistry and pharmacology of transporters have led us to understand much more about drug resistance. In this review, we have discussed the structure, function, potential causes, and mechanisms of multidrug resistance in bacteria as well as cancers.