bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of insomnia and levels of depression and anxiety symptoms on quality of life in people with epilepsy
Authors: Zhong Rui , Li Zhuan , Chen Qingling , Zhang Hanyu , Zhang Xinyue , Lin Weihong 
Published: July 2022

Abstract
Objectives
The association between insomnia and quality of life (QOL) in epilepsy is poorly understood and may involve interactive variables. We aimed to investigate whether and how insomnia, levels of depression and anxiety symptoms interact to influence QOL in people with epilepsy (PWE).

Methods
A consecutive cohort of 179 PWE was enrolled. We collected data on insomnia, levels of depression and anxiety symptoms, and QOL. The Insomnia Severity Index (ISI), Depression Inventory for Epilepsy (NDDI-E), Generalized Anxiety Disorder-7 (GAD-7), and QOL in Epilepsy Inventory (QOLIE-31) were used. The direct, indirect, and total effects of insomnia on QOL were estimated based on a moderated mediation model.

Results
Depression symptom levels mediated the association between insomnia and QOL (B = 0.09 SE = 0.03, p = 0.01). Depression symptom levels accounted for 34.7% of the total effect of insomnia on QOL. The mediating effect of depression symptom levels was positively moderated by anxiety symptom levels (B = 0.09, SE = 0.03, p = 0.01).

Conclusion
The effect of insomnia on QOL can be partially explained by the mediation of depression symptom levels. Additionally, improving anxiety symptoms may attenuate the indirect effect of insomnia on QOL through depression symptom levels.
Evaluation of open reduction of distal humerus fractures in children after implementation of an enhanced recovery after surgery program
Authors: Lu Jialing , Xue Mingfeng , Fu Peng , Qian Damei , Chen Xingguang , Yao Danhua , Zhang Yanli 
Published: July 2022

Abstract
Objective
This study assessed whether an enhanced recovery after surgery (ERAS) protocol could be beneficial for children with distal humerus fractures.

Methods
Children with distal humerus fractures (n = 85) were randomly assigned to the ERAS and control groups and subjected to different perioperative managements. This was followed by the evaluation of their intraoperative characteristics (operation time and bleeding), postoperative characteristics (food intake conditions, pain scores, and discharge time), and postoperative functions.

Results
The operation time, intraoperative bleeding, and postoperative hematological indices did not differ significantly between the two groups. Preoperative thirst and hunger were considerably less and the initial food intake duration following surgery was markedly shorter in the ERAS group than in the control group, whereas no difference between the groups was observed in the incidences of postoperative nausea and vomiting. A markedly reduced highest postoperative pain score and reduced mean pain score and demand for additional analgesic interventions were observed in the ERAS group compared with those in the control group, although the differences were not statistically significant. No noticeable between-group differences were observed in the incidences of postoperative incision problems, aspirational pneumonia, and gastroesophageal reflux. The total length of hospital stay was not significantly different between the two groups. However, the length of postoperative hospital stay was remarkably shorter and the elbow joint function at 2 months after surgery was significantly improved in the ERAS group compared with those in the control group.

Conclusion
The ERAS protocol can ameliorate preoperative discomfort and postoperative pain, shorten the postoperative hospital stay, and accelerate postoperative functional recovery without increasing the risks of postoperative nausea, vomiting, and poor incision healing and is, therefore, worthy of clinical application.
Oral health status and practices of 6- to 7-year-old children in Amman, Jordan: a cross-sectional study
Authors: Aljafari Ahmad , ElKarmi Rawan , Nasser Osama , Atef Ala’a , Hosey Marie Therese 
Published: July 2022

Abstract
Background
Dental caries affects the majority of children in Jordan, with some evidence of its prevalence steadily increasing. Previous studies have shown that families struggle to establish good oral health practices. The aim of this study was to evaluate the current oral health status and practices of 6- to7-year-old children in Amman, Jordan.r

Methods
A cross-sectional cohort study. The sample consisted of 6- to 7-year-old children attending six randomly selected schools in Amman, Jordan. Measures collected were: I) Caries experience (d3mft/D3MFT), II) Oral hygiene, measured using the Simplified Oral Hygiene Index, III) Dietary, toothbrushing, and dental attendance practices, measured using diaries and parental questionnaires, IV) Participants’ basic characteristics: age, education and employment. Data were analysed using SPSS20.

Results
In total, 942 children were recruited. Four hundred and fifty-seven were boys, 485 were girls. Their average age was 6.5 years. Eighty-nine percent had decay in their primary teeth. Mean d3mft was 5.1(1 (range = 0–12, SD = 2.9). Only 8% of carious teeth were restored. Mean DMFT score was 0.3 (range = 0–4, SD = 0.8). Mean debris score was 1.07 (range = 0–3, SD = 0.37). Children indicated that they brush their teeth 1.6 times a day (range = 0–3, SD = 0.6). The majority (81%) were unsupervised. Sixty-seven percent of parents did not know the appropriate fluoride toothpaste concentration. Children were having 1.5 sugary snacks in-between their meals (Range = 1–6, SD = 1.1). They scored a mean of 2.5 (Range = 0–5.87, SD = 1.7) in sweetened drinks intake (recommended ≤ 1) and 2.8 (Range = 0–18.57, SD = 1.5) in non-core food intake (recommended ≤ 2) on a dietary questionnaire. Most parents (84%) indicated that their child attends the dentist only when in pain, and 18% indicated that their child is extremely afraid of dentists. Only 32% and 18% were familiar with fluoride varnish and fissure sealants, respectively. Regression analysis revealed that debris score and dental attendance were reliable predictors of caries experience.

Conclusions
Six- to seven-year-old children in Amman, Jordan have a high caries experience. Most show signs of poor oral hygiene, excessive intake of cariogenic foods, and symptomatic dental attendance. Their parents lack knowledge on fluoride varnish and fissure sealants. There is a need for oral health promotion tailored to this cohort's need.
RGS1 and related genes as potential targets for immunotherapy in cervical cancer: computational biology and experimental validation
Authors: Zhang Siyang , Wang Han , Liu Jiao , Tao Tao , Zeng Zhi , Wang Min 
Published: July 2022

Abstract
Background
Effective treatment is needed for advanced, inoperable, or chemotherapy-resistant cervical cancer patients. Immunotherapy has become a new treatment modality for cervical cancer patients, and there is an urgent need to identify additional targets for cervical cancer immunotherapy.

Methods
In this study the core gene, RGS1, which affects immune status and the FIGO stage of cervical cancer patients was identified by WGCNA analysis and differential analysis using TCGA database. 10 related genes interacting with RGS1 were identified using PPI network, and the functional and immune correlations were analyzed. Based on the expression of RGS1 and related genes, the consensus clustering method was used to divide CESC patients into two groups (group 1, high expression of RGS1; group 2, low expression of RGS1). Then, the functional enrichment analysis was used to search for the functional differences in differentially expressed genes (DEGs) between group 1 and group 2. Immune infiltration analysis was performed using ESTIMATE, CIBERSORT, and ssGSEA, and the differences in expression of immune checkpoint inhibitors (ICIs) targets were assessed between the two groups. We investigated the effect of RGS1 on the clinical relevance of CESC patients, and experimentally verified the differences in RGS1 expression between cervical cancer patient tissues and normal cervical tissues, the role of RGS1 in cell function, and the effect on tumor growth in tumor-bearing mice.

Results
We found that RGS1 was associated with CD4, GNAI3, RGS2, GNAO1, GNAI2, RGS20, GNAZ, GNAI1, HLA-DRA and HLA-DRB1, especially CD4 and RGS2. Functional enrichment of DEGs was associated with T cell activation. Compared with group 2, group 1 had stronger immune infiltration and higher ICI target expression. RGS1 had higher expression in cervical cancer tissues than normal tissues, especially in HPV-E6 positive cancer tissues. In cervical cancer cell lines, knockdown of RGS1 can inhibited cell proliferation, migration, invasion, and tumor growth in nude mice and promoted apoptosis.

Conclusions
RGS1, as an oncogenic gene of cervical cancer, affects the immune microenvironment of patients with cervical cancer and may be a target of immunotherapy.
LncRNA RP3-525N10.2-NFKB1-PROS1 triplet-mediated low PROS1 expression is an onco-immunological biomarker in low-grade gliomas: a pan-cancer analysis with experimental verification
Authors: Zhou Yujie , Xiao Dongdong , Jiang Xiaobing 
Published: July 2022

Abstract
Background
Glioma is the most common cancer in the central nervous system, and low grade gliomas are notorious for many types of tumors and heterogeneity. PROS1 not only plays an important role in the blood coagulation system, and recent studies have found that it was correlated with the development of tumors, especially related to tumor immune infiltration. However, the study of underlying role and mechanism of PROS1 in gliomas, especially in low-grade gliomas, is almost absent.

Methods
We integrated the information of patients with LGG in The Cancer Genome Atlas (TCGA) cohort and Chinese Glioma Genome Atlas (CGGA) cohort. Then, we systematically demonstrated the differences and prognostic prognosis value of PROS1 based on multi-omics analyses. In addition, Cell counting kit-8 (CCK-8) assay, colony formation assay, 5-Ethynyl-2’-deoxyuridine (EdU) incorporation assay, and Transwell assays were performed to evaluate cell proliferation and invasion. qRT-PCR and immunohistochemistry were used to evaluate the expression of PROS1 in LGG.

Results
Various bioinformatics approaches revealed that PROS1 was a valuable prognostic marker and may influence tumour development via distinct mechanisms, including expression of DNA methyltransferase, RNA modification, and DNA mismatch repair system genes, copy number variation, single nucleotide variation frequency, genomic heterogeneity, cancer stemness, DNA methylation, and alternative PROS1 splicing. Our analyses indicated that the long non-coding RNA RP3-525N10.2 may “decoy” or “guide” the transcription factor NFKB1 and prevent its association with PROS1, thereby reducing PROS1 expression and improving poor LGG prognosis. PROS1 expression was also closely associated with tumour infiltration by immune cells, especially tumour-associated macrophages, as well as the expression of various immune checkpoint inhibitors, immunomodulators, and immune cell markers.

Conclusion
long non-coding RNA RP3-525N10.2-NFKB1-PROS1 triplet-mediated PROS1 expression could serve as a biomarker for cancer diagnosis, prognosis, therapy selection, and follow-up in LGG patients.
Co-expression of TNF receptors 1 and 2 on melanomas facilitates soluble TNF-induced resistance to MAPK pathway inhibitors
Authors: Sander Cindy A. , Rush Elizabeth A. , Shi Jian , Arantes Lidia M. R. B. , Tesi Raymond J. , Ross Mark A. , Calderon Michael J. , Watkins Simon C. , Kirkwood John M. , Ferris Robert L. , Butterfield Lisa H. , Vujanovic Lazar 
Published: July 2022

AbstractBackgroundThe effectiveness of MAPK pathway inhibitors (MAPKi) used to treat patients with BRAF-mutant melanoma is limited by a range of resistance mechanisms, including soluble TNF (solTNF)-mediated NF-kB signaling. solTNF preferentially signals through type-1 TNF receptor (TNFR1), however, it can also bind to TNFR2, a receptor that is primarily expressed on leukocytes. Here, we investigate the TNFR2 expression pattern on human BRAFV600E+ melanomas and its role in solTNF-driven resistance reprogramming to MAPKi.MethodsFlow cytometry was used to test TNFR1, TNFR2 and CD271 expression on, as well as NF-kB phosphorylation in human BRAF-mutant melanoma. The ability of melanoma cell lines to acquire MAPKi resistance in response to recombinant or macrophage-derived TNF was evaluated using the MTT cytotoxicity assay. Gene editing was implemented to knock out or knock in TNF receptors in melanoma cell lines. Knockout and knock-in cell line variants were employed to assess the intrinsic roles of these receptors in TNF-induced resistance to MAPKi. Multicolor immunofluorescence microscopy was utilized to test TNFR2 expression by melanoma in patients receiving MAPKi therapy.ResultsTNFR1 and TNFR2 are co-expressed at various levels on 4/7 BRAFV600E+ melanoma cell lines evaluated in this study. In vitro treatments with solTNF induce MAPKi resistance solely in TNFR2-expressing BRAFV600E+ melanoma cell lines. TNFR1 and TNFR2 knockout and knock-in studies indicate that solTNF-mediated MAPKi resistance in BRAFV600E+ melanomas is predicated on TNFR1 and TNFR2 co-expression, where TNFR1 is the central mediator of NF-kB signaling, while TNFR2 plays an auxiliary role. solTNF-mediated effects are transient and can be abrogated with biologics. Evaluation of patient specimens indicates that TNFR2 is expressed on 50% of primary BRAFV600E+ melanoma cells and that MAPKi therapy may lead to the enrichment of TNFR2-expressing tumor cells.ConclusionsOur data suggest that TNFR2 is essential to solTNF-induced MAPKi resistance and a possible biomarker to identify melanoma patients that can benefit from solTNF-targeting therapies.
Dose-escalated radiotherapy to 82 Gy for prostate cancer following insertion of a peri-rectal hydrogel spacer: 3-year outcomes from a phase II trial
Authors: See Andrew W. , Bowden Patrick , Wells Geoffrey , Appu Sree , Lawrentschuk Nathan , Liodakis Peter , Pandeli Chloe , Aarons Yolanda , Smyth Lloyd M. L. , McKenzie Dean P. 
Published: July 2022

Abstract
Background
Dose-escalation to above 80 Gy during external beam radiotherapy for localised prostate cancer leads to improved oncological outcomes but also substantially increased rectal toxicity. The aim of this study was to demonstrate the safety and efficacy of escalating the dose to 82 Gy following insertion of a peri-rectal hydrogel spacer (HS) prior to radiotherapy.

Methods
This was a single arm, open-label, prospective study of men with localised prostate cancer who were prescribed a course of intensity modulated radiotherapy escalated to 82 Gy in 2 Gy fractions following insertion of the SpaceOAR™ HS (Boston Scientific, Marlborough, MA). Patients were prescribed a standard course of 78 Gy in 2 Gy fractions where rectal dose constraints could not be met for the 82 Gy plan. The co-primary endpoints were the rate of grade 3 gastrointestinal (GI) and genitourinary (GU) adverse events (CTCAE, v4), and patient-reported quality of life (QoL) (EORTC QLQ-C30 and PR25 modules), up to 37.5 months post-treatment.

Results
Seventy patients received treatment on the study, with 64 (91.4%) receiving an 82 Gy treatment course. The median follow-up time post-treatment was 37.4 months. The rate of radiotherapy-related grade 3 GI and GU adverse events was 0% and 2.9%, respectively. There were 2 (2.9%) grade 3 adverse events related to insertion of the HS. Only small and transient declines in QoL were observed; there was no clinically or statistically significant decline in QoL beyond 13.5 months and up to 37.5 months post-treatment, compared to baseline. No late RTOG-defined grade ≥ 2 GI toxicity was observed, with no GI toxicity observed in any patient at 37.5 months post-treatment. Nine (12.9%) patients met criteria for biochemical failure within the follow-up period.

Conclusions
Dose-escalation to 82 Gy, facilitated by use of a hydrogel spacer, is safe and feasible, with minimal toxicity up to 37.5 months post-treatment when compared to rates of rectal toxicity in previous dose-escalation trials up to 80 Gy. Trials with longer follow-up of oncological and functional outcomes are required to robustly demonstrate a sustained widening of the therapeutic window.
Trial registration Australian New Zealand Clinical Trials Registry, ACTRN12621000056897, 22/01/2021. Retrospectively registered.
YKL-40 changes are not detected in post-mortem brain of patients with Alzheimer’s disease and frontotemporal lobar degeneration
Authors: Hok-A-Hin Yanaika S. , Hoozemans Jeroen J. M. , Hu William T. , Wouters Dorine , Howell Jennifer C. , Rábano Alberto , van der Flier Wiesje M. , Pijnenburg Yolande A. L. , Teunissen Charlotte E. , del Campo Marta 
Published: July 2022

Abstract
Background
YKL-40 (Chitinase 3-like I) is increased in CSF of Alzheimer’s disease (AD) and frontotemporal lobar degeneration (FTLD) patients and is therefore considered a potential neuroinflammatory biomarker. Whether changed YKL-40 levels in the CSF reflect dysregulation of YKL-40 in the brain is not completely understood yet. We aimed to extensively analyze YKL-40 levels in the brain of AD and different FTLD pathological subtypes. The direct relationship between YKL-40 levels in post-mortem brain and ante-mortem CSF was examined in a small set of paired brain-CSF samples.

Method
YKL-40 was analyzed in post-mortem temporal and frontal cortex of non-demented controls and patients with AD and FTLD (including FTLD-Tau and FTLD-TDP) pathology by immunohistochemistry (temporal cortex: 51 controls and 56 AD and frontal cortex: 7 controls and 24 FTLD patients), western blot (frontal cortex: 14 controls, 5 AD and 67 FTLD patients), or ELISA (temporal cortex: 11 controls and 7 AD and frontal cortex: 14 controls, 5 AD and 67 FTLD patients). YKL-40 levels were also measured in paired post-mortem brain and ante-mortem CSF samples from dementia patients (n = 9, time-interval collection: 1.4 years) by ELISA.

Results
We observed that YKL-40 post-mortem brain levels were similar between AD, FTLD, and controls as shown by immunohistochemistry, western blot, and ELISA. Interestingly, strong YKL-40 immunoreactivity was observed in AD cases with cerebral amyloid angiopathy (CAA; n = 6). In paired CSF-brain samples, YKL-40 concentration was 8-times higher in CSF compared to brain.

Conclusion
Our data suggest that CSF YKL-40 changes may not reflect YKL-40 changes within AD and FTLD pathological brain areas. The YKL-40 reactivity associated with classical CAA hallmarks indicates a possible relationship between YKL-40, neuroinflammation, and vascular pathology.
Microsurgical repair of severed thoracic spinal cord and clinical outcome: technical case report
Authors: Kaliaperumal Chandrasekaran 
Published: July 2022

AbstractBackgroundThis report describes a case of successful repair of severed thoracic spine in a young man who presented with a penetrating stab injury to spine resulting in Brown-Séquard syndrome. Surgical technique and post-operative management is discussed.Case presentationA 34-year-old fit and well healthy man was admitted with a history of stab injury to the thoracic spine at thoracic T2/3 level with ASIA impairment score (AIS) score D with an incomplete spinal cord affecting his left lower limb with complete paralysis and right lower limb paresis with impaired sensation below T6 level to L5. Neuroimaging confirmed a penetrating knife injury traversing the T2/3 level causing hemi-section of the spinal cord confirmed intraoperatively. He underwent an urgent exploratory surgery of his spine and a T2/3 laminectomy was performed to aid removal of the knife. The dura was noted to be contused and severed spinal cord was noted to be severed with associated cord oedema. A microsurgical repair of the severed cord was performed with duroplasty followed by intense neuro-rehabilitation. On a 3 month follow up his AIS score is E with lower limb power is 5/5 bilaterally and he is able to mobilise independently up to 8–10 steps without any supportive aid and with crutches he is independently functional and mobile.ConclusionThis is the first documented case of microsurgical repair of severed thoracic spinal cord secondary to traumatic knife injury. In the management of such scenario, apart from the removal of foreign body, repair of the cord with duroplasty should be carefully considered. The role of spinal neuroplasticity in healing following timely repair of the spinal cord along with intense rehabilitation remains the key. This had resulted in a good clinical and functional outcome with in a 18-month follow up.
Molecular characterization and genetic divergence of seven Culex mosquito (Diptera: Culicidae) species using Mt COI gene from Odisha State, India
Authors: Panda Deepika , Barik Tapan Kumar 
Published: July 2022

AbstractBackgroundCulexmosquitoes are involved in the transmission of arboviral diseases worldwide. Bio-ecology and identification of mosquitoes are of paramount importance to develop species-specific vector control strategies. Genetic-based species-specific approaches that reduce the burden of vector-borne diseases are made possible by molecular techniques.ResultsIn the present study, the mitochondrial COI gene ofCulexmosquitoes was used for molecular identification in addition to morpho-taxonomy. Our findings suggested the presence of importantCulexmosquito vectors viz,Culex vishnui,Culex tritaeniorhynchus, Culex bitaeniorhynchus, Culex quinquefasciatus, Culex gelidus, Culex fuscocephala, andCulex fuscanusin the southern part of Odisha state, India.We examined the phylogeny and genetic diversity of the above seven differentCulexpopulations from different geographical locations. An average intra-specific K2P distance of the COI gene was found to be 0.9%. Further, to measure the diversity of theCulexpopulation among different geographical strains, haplotype diversity and nucleotide diversity were compared.Culex fuscanusshowed high polymorphisms and mutations with high nucleotide diversity (0.013) and theCulex quinquefasciatusshowed the lowest variation inP(i), 0.0013 in the intra-population polymorphism analysis of COI sequences. Similarly, the Haplotype diversity (Hd) found inCulex gelidusandCulex fuscocephalawith the value of 0.972 andCulex quinquefasciatus(0.583) showed the lowest value of haplotype diversity. A haplotype network was constructed to establish the genealogical relationship between haplotypes. The phylogenetic tree was constructed that produces distinctive conspecific clusters in differentCulexspecies. Population genetic study has illustrated the occurrence of genetic differentiation within the population.ConclusionsThe findings of this study contribute to greater evidence that DNA barcode sequences can be used to monitor mosquito species diversity. This study also adds valuable information about the systematics and molecular biology of seven public health important mosquito species acting as a significant vector for Japanese encephalitis in various Asian continents. This information is further used for the effective implementation of region-specific vector control strategies.