bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of two-stage designs of Phase 2 single-arm trials in glioblastoma: a systematic review
Authors: Yoo Wonsuk , Kim Seongho , Garcia Michael , Mehta Shwetal , Sanai Nader 
Published: December 2022

Abstract
Background
Due to economical and ethical reasons, the two-stage designs have been widely used for Phase 2 single-arm trials in oncology because the designs allow us to stop the trial early if the proposed treatment is likely to be ineffective. Nonetheless, none has examined the usage for published articles that had applied the two-stage designs in Phase 2 single-arm trials in brain tumor. A complete systematic review and discussions for overcoming design issues might be important to better understand why oncology trials have shown low success rates in early phase trials.

Methods
We systematically reviewed published single-arm two-stage Phase 2 trials for patients with glioblastoma and high-grade gliomas (including newly diagnosed or recurrent). We also sought to understand how these two-stage trials have been implemented and discussed potential design issues which we hope will be helpful for investigators who work with Phase 2 clinical trials in rare and high-risk cancer studies including Neuro-Oncology. The systematic review was performed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA)-statement. Searches were conducted using the electronic database of PubMed, Google Scholar and ClinicalTrials.gov for potentially eligible publications from inception by two independent researchers up to May 26, 2022. The followings were key words for the literature search as index terms or free-text words: “phase II trials”, “glioblastoma”, and “two-stage design”. We extracted disease type and setting, population, therapeutic drug, primary endpoint, input parameters and sample size results from two-stage designs, and historical control reference, and study termination status.

Results
Among examined 29 trials, 12 trials (41%) appropriately provided key input parameters and sample size results from two-stage design implementation. Among appropriately implemented 12 trials, discouragingly only 3 trials (10%) explained the reference information of historical control rates. Most trials (90%) used Simon’s two-stage designs. Only three studies have been completed for both stages and two out of the three completed studies had shown the efficacy.

Conclusions
Right implementation for two-stage design and sample size calculation, transparency of historical control and experimental rates, appropriate selection on primary endpoint, potential incorporation of adaptive designs, and utilization of Phase 0 paradigm might help overcoming the challenges on glioblastoma therapeutic trials in Phase 2 trials.
Hyperammonemia in a septic patient with Ureaplasma parvum arthritis: a case report
Authors: Pan Xiaohong , Xu Jiekun , Pan Lei , Wang Caihong , Qiu Junke , Huang Xiaqing , Yan Chenxi , Mao Minjie 
Published: December 2022

Abstract
Background
Septic arthritis requires prompt diagnosis and treatments. Rare pathogens should be considered when patients respond poorly to the initial antibiotic treatments. Ureaplasma parvum is an opportunistic pathogen that commonly resides in the human urogenital tract. Its infection commonly causes hyperammonemia. Hyperammonemia from Ureaplasma parvum septic arthritis has never been reported previously.

Case presentation
A 65-year-old male presented with fever and left lower leg pain and swelling for more than ten days. Septic arthritis and sepsis were considered after laboratory tests and arthrocentesis. However, he responded poorly to the antibiotic treatments, including cefoperazone-sulbactam, imipenem-cilastatin, and linezolid. His mental status deteriorated rapidly with elevated blood ammonia levels with unremarkable liver function test and sonogram examination results. Despite the treatments with lactulose, L-ornithine L-aspartate, mannitol, and hemodialysis therapy to lower his ammonia level, his blood ammonia level remained persistently high. Finally, metagenomic sequencing of the left knee synovial fluid reported Ureaplasma parvum, which was considered to contribute to his hyperammonemia.

Conclusion
Ureaplasma parvum could cause septic arthritis with hyperammonemia. Genetic tests, such as polymerase chain reaction and next-generation sequencing techniques, could provide a sensitive and fast diagnosis of Ureaplasma parvum.
MRI comparative study of diffuse midline glioma, H3 K27-altered and glioma in the midline without H3 K27-altered
Authors: Zhao Ji-ping , Liu Xue-jun , Lin Hao-zhi , Cui Chun-xiao , Yue Ying-jie , Gao Song , Xu Hong-zhang 
Published: December 2022

Abstract
Purpose
The MRI features of Diffuse midline glioma, H3 K27-altered and glioma in the midline without H3 K27-altered were compared and analyzed, and the changes in the apparent diffusion coefficient (ADC) of the two groups were quantitatively analyzed.

Methods
The MRI images of 35 patients with Diffuse midline gliomas, H3 K27-altered and gliomas in the midline without H3 K27-altered were analyzed retrospectively. The location, edge, signal, peritumoral edema and enhancement characteristics of the lesions were observed, and the changes in ADC values were analyzed.

Results
In the H3 K27-altered group, 85.7% (12/14) of the tumors were located in the thalamus and brainstem compared with 28.6% (6/21) in the no H3 K27-altered group. In the H3 K27-altered group, for tumors only located in the midline area, only 14.3% (1/7) had irregular shapes and unclear boundaries, while for tumors also invaded the extramidline tissues 85.7% (6/7) had irregular shapes and unclear boundaries.The"basilar artery wrapped sign” was found in 6 patients with tumors located in the pons in the H3 K27-altered group, but none in the no H3 K27-altered group had this sign. In the H3 K27-altered group, only 14.3% (1/7) of the tumors confined to the midline area had small cystic degeneration and necrosis, while for tumors also invaded the extramidline tissues, 100% (7/7) of the tumors had cystic degeneration and necrosis, and the cystic degeneration and necrosis only located in the extramidline region of the tumor in 6 cases.A total of 78.6% (11/14) of tumors in the H3 K27-altered group showed mild to moderate enhancement, while 47.6% (10/21) of tumors in the no H3 K27-altered group showed mild to moderate enhancement. The average peritumoral edema index was 1.13 in the H3 K27-altered group and 1.75 in the no H3 K27-altered group. The average ADC value of tumor in the H3 K27-altered group was 7.83 × 10− 4 mm2/s, and the ratio to normal brain tissue was 0.844, while the values in the no H3 K27-altered group were 13.5 × 10− 4 mm2/s and 1.75, respectively.

Conclusion
Compared with gliomas in the midline without H3 K27-altered, The MRI findings and ADC value of Diffuse midline gliomas, H3K27-altered have some characteristics, which can help improve the diagnosis and differential diagnosis.
The acceptability of cervical electrical impedance spectroscopy within a multi-modal preterm birth screening package: a mixed methods study
Authors: Stern Victoria , Jones Georgina L. , Senbeto Sarah , Anumba Dilly 
Published: December 2022

Abstract
Background
Reducing the rate of preterm birth is a cornerstone of global efforts to address child mortality, however existing screening tests offer imperfect prediction. Cervical electrical impedance spectroscopy (EIS) is a novel technique to quantify the ripening changes which precede labour. Mid-trimester EIS measurements have been shown to accurately predict preterm birth in asymptomatic women. This study aimed to comprehensively evaluate the acceptability of cervical EIS to low and high-risk women as part of a package of screening tests performed during a larger prospective trial.

Methods
In this parallel convergent mixed methods study, 40 women completed questionnaires before and after screening tests (EIS, cervical length measurement and fetal fibronectin quantification). Quantitative outcomes were anxiety levels before and after screening (Spielberger State Trait Anxiety Inventory, STAI-6), pain (Short Form McGill Pain Questionnaire) and ratings of EIS device appearance and test acceptability (visual analogue scales). Twenty-one women (11 high-risk, 10 low-risk) also attended a semi-structured qualitative interview. Interviews were recorded and transcribed, then thematic analysis was performed. A convergence coding matrix was constructed to enable triangulation of quantitative and qualitative results.

Results
High risk women demonstrated a significant reduction in anxiety following screening (mean STAI-6 score 34.5 vs. 29.0, p = 0.002). A similar trend was observed among low-risk participants. Ratings of pain, EIS device appearance and procedural acceptability did not differ between groups. Mean pain ratings were low (visual analogue scale 0.97 and 1.01), comparing favourably to published evaluations of conventional screening tests. Qualitative analysis provided insight into both the physical consequences and emotional experiences of screening. Additional determinants of the screening experience included device design, pre-existing perspectives on intimate examination, attitudes to knowledge in pregnancy and interaction with clinical staff. Finally, a range of practical considerations regarding wider use of EIS were identified, with valuable complementary detail regarding acceptability for use in antenatal care.

Conclusions
Cervical EIS is well tolerated and acceptable to both low and high-risk women when performed as part of a multi-modal screening package. These results provide useful insights to inform the design of future study and screening protocols.
Minoritised ethnic women’s experiences of inequities and discrimination in maternity services in North-West England: a mixed-methods study
Authors: Thomson Gill , Cook Julie , Crossland Nicola , Balaam Marie-Clare , Byrom Anna , Jassat Raeesa , Gerrard Sabina 
Published: December 2022

Abstract
Background
Minoritised ethnic perinatal women can experience judgemental and stigmatising care due to systemic racism. Discriminatory care contributes to increased risks of poor maternal and infant outcomes, including higher rates of mental ill-health. This study aimed to explore minoritised ethnic women’s experiences of maternity services, including maternity care and mental health support, within a North-West England locality. Here we use an equity lens to report the findings that describe if and how women’s personal, cultural, and spiritual needs were met, their experiences of discriminatory and prejudicial care, and to identify recommendations for service provision.

Methods
A mixed-methods study was undertaken comprising an online survey, interviews, and community consultations. Questions explored access to and experiences of antenatal care and education; information, communication, and choice; experiences of (dis)respect and judgement; mental health needs and support; cultural/religious needs and support; and overall experiences of maternity care. Eligibility criteria were: women, 18+ years, from self-reported minoritised ethnic backgrounds, who had given birth in the previous 2 years and received maternity care in the locality. Surveys were available in seven languages and distributed via social media, mother-baby groups, and community locations. English-speaking survey participants were invited to take part in a follow-up interview. Community staff were approached to collect data on behalf of the study team. Quantitative data were analysed descriptively (n, %) and merged with qualitative data into descriptive themes.

Results
Overall, 104 women provided data; most self-identified as Asian (65.0%) or Black (10.7%) and were aged between 30–34 (32.0%) or 25–29 years (23.3%). Four descriptive themes are reported: ‘accessing care’ details variations and barriers in accessing maternity care; ‘communication needs, and resources’ describes views on adaptions and resources for specific communication needs; ‘meeting religious and cultural needs’ outlines how various religious and cultural needs were met by maternity providers; ‘discriminatory or stigmatising care’ reports on experiences of pejorative and inequitable care.

Conclusions
An equity lens helped identify areas of discriminatory and inequitable care. Key recommendations include cultural safety training for staff; service-user engagement and co-production of research and resources, and appropriate facilities and recording systems to facilitate individualised, needs-based maternity care.
A pan-cancer analysis of the oncogenic role of ERCC6L
Authors: Lu Zhimin , Fei Lihong , Hou Guoxin 
Published: December 2022

Abstract
Background
Excision repair cross-complementation group 6 like (ERCC6L), a polo-like kinase 1 (PLK1)-interacting checkpoint helicase, confers a high risk of cancer and enhances the progression of a variety of cancers. The present investigation aimed to elucidate the pan-cancer expression patterns of ERCC6L and to examine the possibility of using this gene for patient diagnosis and prognosis.

Methods
The expression patterns of ERCC6L in normal and cancer patients at various clinical stages were explored based on TCGA datasets. Subsequently, Bioinformatics techniques were then used to analyze patient’s survival probabilities, Cox multivariate clinical parameters, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) terms related to ERCC6L, the correlation between mRNA expression levels and patient survival, genetic alterations or somatic mutations of ERCC6L, and immune infiltration.

Results
Most cancer types had higher ERCC6L mRNA levels than normal tissue. Higher ERCC6L expression levels were correlated with poor prognosis for cancer patients. Thus, ERCC6L may serve as an effective diagnostic and prognostic marker for multiple cancers. Moreover, ERCC6L expression levels were higher in patients with higher clinical tumor grades and were associated with poor prognoses at these stages. GO and KEGG analyses revealed a correlation between ERCC6L expression levels and chromatin and cell cycle events. We also found that the mRNA expression level of the ERCC6L promoter and a favorable prognosis was negatively correlated with the promoter’s methylation but not with copy number variation. A quantitative analysis of immune infiltration suggested a positive correlation between ERCC6L levels and the infiltration of Th2 immune cells in main cancer types. Finally, we examined the ERCC6L somatic mutations, especially single-nucleotide variants, and ERCC6L expression-related drug sensitivity.

Conclusions
Herein, we reported a comprehensive investigation of the tumor-promoting role of ERCC6L in various cancer types. ERCC6L is a candidate biomarker for diagnosing and unfavorable prognosis of specific cancers.
Mental health among patients with chronic musculoskeletal pain and its relation to number of pain sites and pain intensity, a cross-sectional study among primary health care patients
Authors: Garnæs Kirsti Krohn , Mørkved Siv , Tønne Torgrim , Furan Lars , Vasseljen Ottar , Johannessen Hege Hølmo 
Published: December 2022

Abstract
Background
Chronic musculoskeletal pain (CMP) is characterised by pain related to the muscles or the joints with a duration of three months or more and is associated with high symptomatic burden in patients in primary health care. CMP is commonly associated with impaired mental health, which may affect the rehabilitation process. The primary aim of this study was to compare symptoms of anxiety, depression, fatigue, and insomnia in patients in primary health care with and without CMP. The secondary aim was to assess difference in mental health symptoms related to number of pain sites and pain intensity.

Methods
This cross-sectional study was conducted in Trondheim, Norway. All patients aged 21–58 from randomly selected general practitioners (GPs) were invited to participate. Participants were classified into two groups according to presence of CMP. Symptoms of anxiety, depression, fatigue, and insomnia were assessed by the Hospital Anxiety and Depression Scale (HADS), Chalder Fatigue Questionnaire (CFQ), and Insomnia Severity Index (ISI), respectively, using an online survey system.

Results
From the patient lists of six GPs, we included 969 patients. Mean age 46 years (SD: 10.1), and 517 reported CMP. CMP patients reported higher mean symptom score for anxiety (5.4 vs 3.7), depression (3.4 vs 2.0), fatigue (14.2 vs 11.2), and insomnia (8.1 vs 4.4), all p < 0.01 compared to no-CMP patients. Symptoms of impaired mental health increased with increasing number of pain sites and pain intensity (p < 0.001).

Conclusions
Primary health care patients with CMP reported significantly more symptoms of anxiety, depression, fatigue, and insomnia than patients without CMP. The higher number of pain sites and pain intensity, the more mental health symptoms, especially of anxiety. Primary health care personnel have to address mental health issues when treating patients with CMP.

Trial registration
Clinicaltrials.gov (NCT02020772, 25/12/2013).
Evaluation of the clinical value of shear wave elastography for early detection and diagnosis of diabetic peripheral neuropathy: a controlled preliminary prospective clinical study
Authors: Wang Can , Wang Huiqin , Zhou Yi , Zhang Shiqi , Huang Meng 
Published: December 2022

Abstract
Purpose
This study aims to analyze the clinical application value of shear wave elastography (SWE) technique for early diagnosis of diabetic peripheral neuropathy (DPN).

Methods
Diabetic patients hospitalized in the Department of Endocrinology of the First Affiliated Hospital of Anhui Medical University from August 2021 to February 2022 were enrolled as DPN group (n=38) and non-DPN group (n=35) based on the neurophysiological examination results. 30 healthy subjects were recruited as the control group during the same period. Ultrasound examination of the tibial nerve and related laboratory tests were examined and collected for the total 103 study subjects. Statistical analysis of the collected data, and the receiver operating characteristic(ROC) curve for determination of the optimal cut-off values of mean stiffness of tibial nerve to detect DPN, with determination of area under curve (AUC), specificity, sensitivity, and Youden index.P value < 0.05 is considered statistically significant.

Results
Gender, age and BMI differences among three groups were insignificant (P>0.05). The difference of serological indicators between DPN and non-DPN groups was also not found (P>0.05), whereas longer duration of diabetes was observed in DPN group as compared to non-DPN group. As to the ultra-sound relevant parameters, the cross-sectional area and elastic modulus of the tibial nerve in both lower extremities among these three groups were not significantly different (Oneway ANOVA analysis) although the differences were indeed observed if we compared DPN group exclusively with non-DPN group, or compared non-DPN group with healthy group, or compared DPN group with healthy group (t test). Additionally, the mean elasticity (Emean) cut-off value for the diagnosis of DPN was preferably taken as 67.55 kPa.

Conclusion
SWE has unique advantages in early detection and diagnosis of DPN, which deserve further research.
Evaluation of quality of life in endometriosis patients before and after surgical treatment using the EHP30 questionnaire
Authors: Tiringer D. , Pedrini A. S. , Gstoettner M. , Husslein H. , Kuessel L. , Perricos A. , Wenzl R. 
Published: December 2022

Abstract
Backround
Endometriosis is one of the most common gynecological illnesses causing extensive psychological, physical and social impact on patient’s life and exerts negative effects on health-related quality of Life (HRQoL). However, the effects of surgery on the postoperative HRQoL in the different endometriosis subgroups have not been fully evaluated.

Methods
We performed a comparative retrospective study between 2014 and 2018 at the Medical University of Vienna, including all patients with surgically confirmed endometriosis who had completed the standardized Endometriosis Health Profile-30 (EHP-30) questionnaire 1 day after surgery (the questions refer to the 4 weeks preoperatively) and 6–10 weeks postoperatively.

Results
Compared to preoperative values, we found significant benefits, regarding postoperative conditions, in our study group (n = 115) in all five categories, “pain” (HR 0.78, p < 0.001); “self-determination” (HR 0.92, p < 0.001); “emotional health” (HR 0.83, p < 0.001);” social environment” (HR 0.67, p < 0.001); and “self-image” (HR 0.47, p < 0.001). Patients with only peritoneal endometriosis had the lowest preoperative clinical symptoms and there were no significant changes in any of the categories. In the subgroups deep infiltrating endometriosis (DIE) and DIE + ovarian endometrioma, surgical intervention results in a significantly greater improvement in all categories of EHP 30 compared to ovarian endometrioma without DIE or peritoneal endometriosis.

Conclusion
Our study shows, that especially women with DIE—with or without ovarian endometrioma—demonstrate a more pronounced benefit from surgical therapy compared to patients with peritoneal endometriosis or endometrioma without DIE.
Cuscuta epithymum Murr. crude extract pre-conditioning protects C6 cells from L-glutamate-induced neurotoxicity
Authors: Pourhadi Masoumeh , Niknam Zahra , Ghasemi Rasoul , Zomorrod Mina Soufi , Niazi Vahid , Faizi Mehrdad , Zali Hakimeh , Mojab Faraz 
Published: December 2022

Abstract
Background
Cuscuta epithymum Murr. (C. epithymum), as an herbal medicine, has played an anti-cancerous role in various studies; however, its possible neuroprotective effects have been neglected. Here, we aimed to investigate the protective effects of C. epithymum seeds crude extract and different fractions on rat glioblastoma cells (C6) in L-glutamate oxidative condition.

Methods
Initially, the total phenolic content of C. epithymum crude extract and the fractions (all produced by maceration method) was determined. Subsequently, C6 cells were pre-treated with the various concentrations of crude extract and fractions 24 h before L-glutamate exposure. Likewise, C6 cells were treated with the same concentrations of crude extract and fractions 24 h after exposure to L-glutamate. The cell viability and morphology were compared in crude extract and fractions groups, then superoxide dismutase (SODs) activity, reactive oxygen species (ROS), and malondialdehyde (MDA) levels were measured. The flow cytometry test was used to study C. epithymum crude extract's effects on the cell cycle and also to quantify the apoptosis, necrosis, and live cells population in different groups.

Results
C. epithymum crude extract and fractions (hexanoic, dichloromethanolic, and methanolic) had concentration-dependent cytotoxicity (IC50:126.47, 2101.96, 140.97, and 218.96 µg/ml, respectively). The crude extract and methanolic fraction contained phenolic compounds (55.99 ± 2.795 and 50.80 ± 2.969 mg gallic acid/g extract), while in hexanoic and dichloromethanolic fractions, the phenolic content was undetectable. In the cell viability assay, in comparison to fractions, the crude extract showed a more protective effect against glutamate-induced oxidative condition (P < 0.0001). The crude extract increased the SODs activity (P < 0.001) and decreased MDA and ROS levels (P < 0.0001) in comparison to the glutamate group. The crude extract significantly increased the population of cells in G1 (from 63.04 to 76.29) and decreased the percentage of cells in G2 (from 11.56 to 6.7) and S phase (from 25.4 to 17.01). In addition, it decreased the apoptotic and necrotic cell populations (from 34 to 17.1) and also increased the percentage of live cells (from 66.8 to 83.4 percent) in the flow cytometry test.

Conclusion
C. epithymum crude extract plays a neuroprotective role by activating the defense mechanisms in cell against the oxidative condition.