bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring the relationship between age and prognosis in glioma: rethinking current age stratification
Authors: Jia Zetian , Li Xiaohui , Yan Yaqi , Shen Xuxuan , Wang Jiuxin , Yang He , Liu Shuo , Han Chengxi , Hu Yuhua 
Published: September 2022

Abstract
Background
The age of glioma plays a unique role in prognosis. We hypothesized that age is not positively correlated with survival prognosis and explored its exact relationship.

Methods
Glioma was identified from the SEER database (between 2000 and 2018). A multivariate Cox proportional regression model and restricted cubic spline (RCS) plot were used to assess the relationship between age and prognosis.

Results
A total of 66465 patients with glioma were included. Hazard ratios (HR) for ten-year by age: 0–9 years, HR 1.06 (0.93–1.20); 10–19 years: reference; 20–29 years, HR 0.90 (0.82–1.00); 30–39 years, HR 1.14 (1.04–1.25); 40–49 years, HR 2.09 (1.91–2.28); 50–59 years, HR 3.48 (3.19–3.79); 60–69 years, HR 4.91 (4.51–5.35);70–79 years, HR 7.95 (7.29–8.66); 80–84 years, HR 12.85 (11.74–14.06). After adjusting for covariates, the prognosis was not positively correlated with age. The smooth curve of RCS revealed this non-linear relationship: HR increased to 10 years first, decreased to 23 years, reached its lowest point, and became J-shaped.

Conclusion
The relationship between age and glioma prognosis is non-linear. These results challenge the applicability of current age groupings for gliomas and advocate the consideration of individualized treatment guided by precise age.
Effectiveness of combined extracorporeal shock-wave therapy and hyaluronic acid injections for patients with shoulder pain due to rotator cuff tendinopathy: a person-centered approach with a focus on gender differences to treatment response
Authors: Pellegrino Raffaello , Di Iorio Angelo , Brindisino Fabrizio , Paolucci Teresa , Moretti Antimo , Iolascon Giovanni 
Published: September 2022

Abstract
Background
Rotator cuff (RC) tendinopathy is a common shoulder pain condition. Extracorporeal shockwave therapy (ESWT) and hyaluronic acid peritendinous injection are viable treatment options for RC tendinopathy.
The aim of this study is to evaluate the response in two different therapeutic rehabilitative approaches, the combined treatment ESWT plus hyaluronic acid injections (E + Hy) compared to ESWT alone (ESWT-al), in a cohort of patients with RC tendinopathy according to gender differences.

Methods
This is a retrospective longitudinal cohort study of patients with painful RC tendinopathy. Patients that had received a clinical evaluation, a shoulder ultra sound examination, as well as the Shoulder Pain and Disability Index (SPADI) questionnaire, and the Numerical Rating Scale (NRS) for pain at baseline, 1-month (T1) and 2-month follow-ups (T2) were included.

Results
Medical records of 53 patients were analyzed. In the comparison between baseline to T1 and similarly from baseline to T2, a statistically significant reduction has been reported in the NRS (p < 0.001) and in the SPADI (p < 0.001) in the entire study group. At T1, patients in the E + Hy compared to ESWT-al group, showed a slight but statistically significant reductions in both NRS and SPADI score, while these changes were more evident at T2 (p < 0.001). Interestingly, a gender dimorphism in NRS and in SPADI was found, with female patients that apparently responded better to the combined E + Hy compared to ESWT-al approach.

Conclusion
This retrospective cohort study suggests that the combination of ESWT plus HyA injections seems to be more effective than ESWT alone in RC tendinopathy in both genders. Moreover, in ESWT alone treatment, male patients reported better outcomes compared to females. However, further randomized controlled trials should be structured to confirm and enforce these conclusions.
Clinical, metabolic, and immunological characterisation of adult Ugandan patients with new-onset diabetes and low vitamin D status
Authors: Kibirige Davis , Sekitoleko Isaac , Balungi Priscilla , Kyosiimire-Lugemwa Jacqueline , Lumu William 
Published: September 2022

Abstract
Background
Low vitamin D concentrations are associated with metabolic derangements, notably insulin resistance and pancreatic beta-cell dysfunction in Caucasian populations. Studies on its association with the clinical, metabolic, and immunologic characteristics in black African adult populations with new-onset diabetes are limited. This study aimed to describe the clinical, metabolic, and immunologic characteristics of a black Ugandan adult population with recently diagnosed diabetes and hypovitaminosis D.

Methods
Serum vitamin D concentrations were measured in 327 participants with recently diagnosed diabetes. Vitamin D deficiency, vitamin D insufficiency, and normal vitamin D status were defined as serum 25 hydroxyvitamin D levels of < 20 ng/ml, 21–29 ng/ml, and ≥ 30 ng/ml, respectively.

Results
The median (IQR) age, glycated haemoglobin, and serum vitamin D concentration of the participants were 48 years (39–58), 11% (8–13) or 96 mmol/mol (67–115), and 24 ng/ml (18–30), respectively. Vitamin D deficiency, vitamin D insufficiency, and normal vitamin D status were noted in 105 participants (32.1%), 140 participants (42.8%), and 82 participants (25.1%), respectively.
Compared with those having normal serum vitamin D levels, participants with vitamin D deficiency and insufficiency had higher circulating concentrations of interleukin (IL) 6 (29 [16–45] pg/ml, 23 [14–40] pg/ml vs 18 [14–32] pg/ml, p = 0.01), and IL-8 (24 [86–655] pg/ml, 207 [81–853] pg/ml vs 98 [67–224], p = 0.03). No statistically significant differences were noted in the markers of body adiposity, insulin resistance, and pancreatic beta-cell function between both groups.

Conclusion
Vitamin D deficiency and insufficiency were highly prevalent in our study population and were associated with increased circulating concentrations of pro-inflammatory cytokines. The absence of an association between pancreatic beta-cell function, insulin resistance, and low vitamin D status may indicate that the latter does not play a significant role in the pathogenesis of type 2 diabetes in our adult Ugandan population.
Practicing traditional Chinese medicine in the COVID-19 pandemic in Switzerland – an exploratory study
Authors: Bourqui Angélique , Rodondi Pierre-Yves , El May Emna , Dubois Julie 
Published: September 2022

Abstract
Background
To curb the spread of the first wave of the COVID-19 pandemic, the Swiss government declared a state of health emergency and ordered a legal restriction concerning the opening of healthcare institutions. In this study, we aimed to assess the proportion of traditional Chinese medicine (TCM) physicians and therapists who consulted patients regarding COVID-19 during the first wave of the pandemic in 2020 in Switzerland, as well as the extent to which COVID-19 affected their practices during the same period.

Methods
A retrospective study was performed by using a questionnaire from January to April 2021 among a random sample of TCM physicians and therapists based in Switzerland. The survey included questions on demographic characteristics, opening status of practices, channels of communication used for the medical encounter, and experience in managing the prevention, acute, and recovery stages of COVID-19 infection.

Results
Among the 320 participants, 76% consulted a patient regarding COVID-19 at least once. Overall, physicians and therapists consulted more patients during recovery (76.3%) and prevention (67.8%) than during the acute stage (19.8%) of the disease. Acupuncture was the most frequently used technique among TCM therapists and physicians consulting for prevention (80.4%) and recovery (92.5%), whereas Chinese pharmacopeia was the most used technique among those consulting for the acute stage (59.3%). Of those who closed their practices from March to April 2020 but kept consulting, telephone (30.4%) and home visits (29.9%) were the two principal methods of consultation.

Conclusions
The restriction concerning the opening of practices induced a loss of the health workforce, especially among TCM therapists. Nonetheless, TCM therapists and physicians consulted patients regarding COVID-19, especially during the recovery stage. As there is a demand for the use of TCM in the context of COVID-19, it raises the need for a better consideration of TCM in the Swiss health care system.
Design and validation of recombinant protein standards for quantitative Western blot analysis of cannabinoid CB1 receptor density in cell membranes: an alternative to radioligand binding methods
Authors: Saumell-Esnaola Miquel , Elejaga-Jimeno Ainhoa , Echeazarra Leyre , Borrega-Román Leire , Barrondo Sergio , López de Jesús Maider , González-Burguera Imanol , Gómez-Caballero Alberto , Goicolea María Aranzazu , Sallés Joan , García del Caño Gontzal 
Published: September 2022

AbstractBackgroundReplacement of radioligand binding assays with antibody-antigen interaction-based approaches for quantitative analysis of G protein-coupled receptor (GPCR) levels requires the use of purified protein standards containing the antigen. GPCRs in general and cannabinoid CB1receptor in particular show a progressive tendency to aggregate and precipitate in aqueous solution outside of their biological context due to the low solubility that the hydrophobic nature imprinted by their seven transmembrane domains. This renders full-length recombinant GPCRs useless for analytical purposes, a problem that can be overcome by engineering soluble recombinant fragments of the receptor containing the antigen.ResultsHere we generated highly soluble and stable recombinant protein constructs GST-CB1414–472and GST-CB1414-442containing much of the human CB1receptor C-terminal tail for use as standard and negative control, respectively, in quantitative Western blot analysis of CB1receptor expression on crude synaptosomes of the adult rat brain cortex. To this end we used three different antibodies, all raised against a peptide comprising the C-terminal residues 443–473 of the mouse CB1receptor that corresponds to residues 442–472 in the human homolog. Estimated values of CB1receptor density obtained by quantitative Western blot were of the same order of magnitude but slightly higher than values obtained by the radioligand saturation binding assay.ConclusionsCollectively, here we provide a suitable Western blot-based design as a simple, cost-effective and radioactivity-free alternative for the quantitative analysis of CB1receptor expression, and potentially of any GPCR, in a variety of biological samples. The discrepancies between the results obtained by quantitative Western blot and radioligand saturation binding techniques are discussed in the context of their particular theoretical bases and methodological constraints.
Strategies for efficient production of recombinant proteins in Escherichia coli: alleviating the host burden and enhancing protein activity
Authors: Zhang Zi-Xu , Nong Fang-Tong , Wang Yu-Zhou , Yan Chun-Xiao , Gu Yang , Song Ping , Sun Xiao-Man 
Published: September 2022

AbstractEscherichia coli, one of the most efficient expression hosts for recombinant proteins (RPs), is widely used in chemical, medical, food and other industries. However, conventional expression strains are unable to effectively express proteins with complex structures or toxicity. The key to solving this problem is to alleviate the host burden associated with protein overproduction and to enhance the ability to accurately fold and modify RPs at high expression levels. Here, we summarize the recently developed optimization strategies for the high-level production of RPs from the two aspects of host burden and protein activity. The aim is to maximize the ability of researchers to quickly select an appropriate optimization strategy for improving the production of RPs.
A self-assembled bilayer polypeptide-engineered hydrogel for spatiotemporal modulation of bactericidal and anti-inflammation process in osteomyelitis treatment
Authors: Xie Xiaoting , Wei Jiemao , Zhang Bin , Xiong Wei , He Zhiyi , Zhang Yayun , Gao Chenghao , Zhao Yuandi , Liu Bo 
Published: September 2022

Abstract
Background
Drug resistance of pathogens and immunosuppression are the main causes of clinical stagnation of osteomyelitis. The ideal treatment strategy for osteomyelitis is to achieve both efficient antibacterial and bone healing through spatiotemporal modulation of immune microenvironment.

Methods
In this study, a bilayer hydrogel based on genetically engineered polypeptide AC10A and AC10ARGD was prepared by self-assembly. Ag2S QDs@DSPE-mPEG2000-Ce6/Aptamer (AD-Ce6/Apt) was loaded in the top layer AC10A hydrogel (AA) for antibacterial, and bone marrow-derived mesenchymal stem cells (BMSCs) were loaded in the lower layer AC10ARGD hydrogel (MAR) for bone healing. The AD-Ce6/Apt can be released from the AA hydrogel to target S. aureus before bacterial biofilm formation and achieved significant bactericidal effect under irradiation with a 660 nm laser. Moreover, AD-Ce6/Apt can induce M1 type polarization of macrophages to activate the immune system and eliminate residual bacteria. Subsequently, BMSCs released from the MAR hydrogel can differentiate into osteoblasts and promote the formation of an anti-inflammatory microenvironment by regulating the M2 type polarization of macrophages. The bilayer AA-MAR hydrogel possessed good biocompatibility.

Results
The in vitro and in vivo results showed that the AA-MAR hydrogel not only realized efficient photodynamic therapy of S. aureus infection, but also promoted the transformation of immune microenvironment to fulfill the different needs of each stage, which ultimately improved bone regeneration and mechanical properties post-surgery.

Conclusion
This work presents an approach for spatiotemporal modulation of immune microenvironment in the treatment of osteomyelitis.

Graphical Abstract
Hemin-incorporating DNA nanozyme enabling catalytic oxygenation and GSH depletion for enhanced photodynamic therapy and synergistic tumor ferroptosis
Authors: Xiao Xiaoxiong , Chen Min , Zhang Yuchen , Li Liang , Peng Ying , Li Junyu , Zhou Wenhu 
Published: September 2022

AbstractPhotodynamic therapy (PDT) has emerged as a promising tumor treatment method via light-triggered generation of reactive oxygen species (ROS) to kill tumor cells. However, the efficacy of PDT is usually restricted by several biological limitations, including hypoxia, excess glutathione (GSH) neutralization, as well as tumor resistance. To tackle these issues, herein we developed a new kind of DNA nanozyme to realize enhanced PDT and synergistic tumor ferroptosis. The DNA nanozyme was constructed via rolling circle amplification, which contained repeat AS1411 G quadruplex (G4) units to form multiple G4/hemin DNAzymes with catalase-mimic activity. Both hemin, an iron-containing porphyrin cofactor, and chlorine e6 (Ce6), a photosensitizer, were facilely inserted into G4 structure with high efficiency, achieving in-situ catalytic oxygenation and photodynamic ROS production. Compared to other self-oxygen-supplying tools, such DNA nanozyme is advantageous for high biological stability and compatibility. Moreover, the nanostructure could achieve tumor cells targeting internalization and intranuclear transport of Ce6 by virtue of specific nucleolin binding of AS1411. The nanozyme could catalyze the decomposition of intracellular H2O2 into oxygen for hypoxia relief as evidenced by the suppression of hypoxia-inducible factor-1α (HIF-1α), and moreover, GSH depletion and cell ferroptosis were also achieved for synergistic tumor therapy. Upon intravenous injection, the nanostructure could effectively accumulate into tumor, and impose multi-modal tumor therapy with excellent biocompatibility. Therefore, by integrating the capabilities of O2 generation and GSH depletion, such DNA nanozyme is a promising nanoplatform for tumor PDT/ferroptosis combination therapy.
Circ_0136666 aggravates osteosarcoma development through mediating miR-1244/CEP55 axis
Authors: Gao Xiang , Xu Nanwei , Miao Kaisong , Huang Gao , Huang Yong 
Published: September 2022

Abstract
Background
Accumulating articles demonstrate that circular RNAs play pivotal functions in tumorigenesis. However, the working mechanism of circ_0136666 in osteosarcoma (OS) progression remains to be further clarified.

Methods
Real time-quantitative polymerase chain reaction and western blot assay were applied to determine RNA and protein expression, respectively. Cell proliferation was assessed by 5-Ethynyl-2′-deoxyuridine assay and colony formation assay. Transwell assays were carried out to assess cell migration and invasion abilities. Flow cytometry was performed to analyze cell apoptosis. Cell glycolysis was evaluated by analyzing the uptake of glucose and the production of lactate using the corresponding kits. Dual-luciferase reporter assay and biotinylated RNA-pull down assay were performed to confirm the target interaction between microRNA-1244 (miR-1244) and circ_0136666 or centrosomal protein 55 (CEP55). Xenograft tumor model was utilized to explore the role of circ_0136666 in tumor growth in vivo.

Results
Circ_0136666 expression was prominently elevated in OS tissues and cell lines. Circ_0136666 absence restrained the proliferation, migration, invasion and glycolytic metabolism and promoted the apoptosis of OS cells. Circ_0136666 negatively regulated miR-1244 expression by binding to it in OS cells. MiR-1244 overexpression suppressed the malignant behaviors of OS cells. CEP55 was a target of miR-1244 in OS cells. Circ_0136666 positively regulated CEP55 expression partly by sequestering miR-1244 in OS cells. CEP55 overexpression largely reversed circ_0136666 silencing-mediated influences in OS cells. Circ_0136666 silencing significantly suppressed tumor growth in vivo.

Conclusion
Circ_0136666 silencing inhibited OS progression partly by targeting miR-1244/CEP55 signaling. Silencing circ_0136666 and CEP55 or restoring miR-1244 level might be a potential therapeutic strategy for OS.
A pregnant women with history of hashimoto's thyroiditis diagnosed with Kikuchi-Fujimoto disease: the first case report
Authors: Bazkke Bashar , Osman Joli , Shahrour Mohammad , Ziadeh Mohammad , Haji Mohamad Aya , Mouhandes Mohamed Imad Eddin , Niazi Ammar 
Published: September 2022

Abstract
Background
Kikuchi-Fujimoto disease (KFD) is a benign, self-limiting disorder characterized by regional lymphadenopathy. Clinical symptoms range from mild fever and tenderness to upper respiratory syndrome. A few cases have been observed during pregnancy or Hashimoto's disease. What we describe here is the first observed case of KFD in a pregnant woman with a history of Hashimoto's thyroiditis.

Case presentation
A 36-year-old woman presented to Aleppo University Hospital during the 13th week of gestation with a painful cervical node on the right side of her neck. The patient's previous medical history confirmed Hashimoto's thyroiditis for several years. After histopathological examinations and radiological investigations, she was diagnosed with Kikuchi-Fujimoto disease and treated with corticosteroids. Although the patient did not adhere to the treatment very well due to her concerns for the fetus, the clinical picture improved after delivery. The patient now is on follow-up and continuing the current treatment with corticosteroids.

Conclusions
Further investigations need to be conducted to understand the possible autoimmune etiology of KFD when it is associated with Hashimoto's thyroiditis disease. It is also necessary to understand the relationship between this disease and pregnancy.
RETSAT associates with DDX39B to promote fork restarting and resistance to gemcitabine based chemotherapy in pancreatic ductal adenocarcinoma
Authors: Tu Qiu , Liu Xiuyun , Yao Xiaoqing , Li Ruixue , Liu Gaojing , Jiang Honglv , Li Kaiqin , Chen Qiongfang , Huang Xiaoyan , Chang Qing , Xu Guoqiang , Zhu Hong , Shi Peng , Zhao Bo 
Published: September 2022

Abstract
Background
Severe hypoxia is a prominent character of pancreatic ductal adenocarcinoma (PDAC) microenvironment. In the process of gemcitabine based chemotherapy, PDAC cells are insulted from replication stresses co-induced by hypoxia and gemcitabine. However, PDAC cells get outstanding abilities to resist to such harsh conditions and keep proliferating, causing a major obstacle for current therapy. RETSAT (Retinol Saturase) is defined as a hypoxia convergent gene recently, with high expression in PDAC hypoxic sectors. This study aimed to explore the roles of RETSAT in replication stress resistance and hypoxia adaptation in PDAC cells, and decipher the underlying mechanism.

Methods
The expression of RETSAT was examined in TCGA (The Cancer Genome Atlas), human pancreatic cancer microarray, clinical specimens and cell lines. Functions of RETSAT were studied by means of DNA fiber assay and comet assay in monolayer cultured PDAC cell lines, three dimensional spheroids, patient derived organoids and cell derived xenograft mouse models. Mechanism was investigated by using iPOND (isolate proteins on nascent DNA) combined with mass spectrometry, immunoprecipitation and immunoblotting.

Results
First, we found the converse relationship of RETSAT expression and PDAC chemotherapy. That is, PDAC patients with high RETSAT expression correlated with poor survival, while ones holding low RETSAT expression were benefitted more in Gemcitabine based chemotherapy. Second, we identified RETSAT as a novel replication fork associated protein. HIF-1α signaling promotes RETSAT expression under hypoxia. Functionally, RETSAT promoted fork restarting under replication stress and maintained genomic stability. Third, we uncovered the interaction of RETSAT and R-loop unwinding helicase DDX39B. RETSAT detained DDX39B on forks to resolve R-loops, through which avoided fork damage and CHK1 initiated apoptosis. Targeting DDX39B using chemical CCT018159 sensitized PDAC cells and organoids to gemcitabine induced apoptosis, highlighting the synergetic application of CCT018159 and gemcitabine in PDAC chemotherapy.

Conclusions
This study identified RETSAT as a novel replication fork protein, which functions through interacting with DDX39B mediated R-loop clearance to promote fork restarting, leading to cellular resistance to replication stresses co-induced by tumor environmental hypoxia and gemcitabine in pancreatic ductal adenocarcinoma.