bluuebunny/crossref_metadata_2025_split huggingface dataset:
Emerging therapies for glioblastoma: current state and future directions
Authors: Rong Liang , Li Ni , Zhang Zhenzhen 
Published: April 2022

AbstractGlioblastoma (GBM) is the most common high-grade primary malignant brain tumor with an extremely poor prognosis. Given the poor survival with currently approved treatments for GBM, new therapeutic strategies are urgently needed. Advances in decades of investment in basic science of glioblastoma are rapidly translated into innovative clinical trials, utilizing improved genetic and epigenetic profiling of glioblastoma as well as the brain microenvironment and immune system interactions. Following these encouraging findings, immunotherapy including immune checkpoint blockade, chimeric antigen receptor T (CAR T) cell therapy, oncolytic virotherapy, and vaccine therapy have offered new hope for improving GBM outcomes; ongoing studies are using combinatorial therapies with the aim of minimizing adverse side-effects and augmenting antitumor immune responses. In addition, techniques to overcome the blood-brain barrier (BBB) for targeted delivery are being tested in clinical trials in patients with recurrent GBM. Here, we set forth the rationales for these promising therapies in treating GBM, review the potential novel agents, the current status of preclinical and clinical trials, and discuss the challenges and future perspectives in glioblastoma immuno-oncology.
A longitudinal, retrospective registry-based validation study of RETTS©, the Swedish adult ED context version
Authors: Wireklint Sara C. , Elmqvist Carina , Fridlund Bengt , Göransson Katarina E. 
Published: April 2022

Abstract
Background
Triage and triage related work has been performed in Swedish Emergency Departments (EDs) since the mid-1990s. The Rapid Emergency Triage and Treatment System (RETTS©), with annual updates, is the most applied triage system. However, the national implementation has been performed despite low scientific foundation for triage as a method, mainly related to the absence of adjustment to age and gender. Furthermore, there is a lack of studies of RETTS© in Swedish ED context, especially of RETTS© validity. Hence, the aim the study was to determine the validity of RETTS©.

Methods
A longitudinal retrospective register study based on cohort data from a healthcare region comprising two EDs in southern Sweden. Two editions of RETTS© was selected; year 2013 and 2016, enabling comparison of crude data, and adjusted for age-combined Charlson comorbidity index (ACCI) and gender. All patients ≥ 18 years visiting either of the two EDs seeing a physician, was included. Primary outcome was ten-day mortality, secondary outcome was admission to Intensive Care Unit (ICU). The data was analysed with descriptive, and inferential statistics.

Results
Totally 74,845 patients were included. There was an increase in patients allocated red or orange triage levels (unstable) between the years, but a decrease of admission, both to general ward and ICU. Of all patients, 1031 (1.4%) died within ten-days. Both cohorts demonstrated a statistically significant difference between the triage levels, i.e. a higher risk for ten-day mortality and ICU admission for patients in all triage levels compared to those in green triage level. Furthermore, significant statistically differences were demonstrated for ICU admission, crude as well as adjusted, and for adjusted data ten-day mortality, indicating that ACCI explained ten-day mortality, but not ICU admission. However, no statistically significant difference was found for the two annual editions of RETTS© considering ten-day mortality, crude data.

Conclusion
The annual upgrade of RETTS© had no statistically significant impact on the validity of the triage system, considering the risk for ten-day mortality. However, the inclusion of ACCI, or at least age, can improve the validity of the triage system.

Graphical Abstract
High-flow nasal cannula versus conventional oxygen therapy in acute COPD exacerbation with mild hypercapnia: a multicenter randomized controlled trial
Authors: Xia Jingen , Gu Sichao , Lei Wei , Zhang Jihua , Wei Hui , Liu Chao , Zhang Han , Lu Rongli , Zhang Liqiong , Jiang Mingyan , Hu Chao , Cheng Zhenshun , Wei Chaojie , Chen Yusheng , Lu Fengfeng , Chen Min , Bi Hong , Liu Hui , Yan Cunzi , Teng Hong , Yang Yang , Liang Chen , Ge Yanlei , Hou Pengguo , Liu Jialin , Gao Weiwei , Zhang Yi , Feng Yingying , Tao Cheng , Huang Xu , Pan Pinhua , Luo Hong , Yun Chunmei , Zhan Qingyuan 
Published: April 2022

Abstract
Background
High-flow nasal cannula (HFNC) can improve ventilatory function in patients with acute COPD exacerbation. However, its effect on clinical outcomes remains uncertain.

Methods
This randomized controlled trial was conducted from July 2017 to December 2020 in 16 tertiary hospitals in China. Patients with acute COPD exacerbation with mild hypercapnia (pH ≥ 7.35 and arterial partial pressure of carbon dioxide > 45 mmHg) were randomly assigned to either HFNC or conventional oxygen therapy. The primary outcome was the proportion of patients who met the criteria for intubation during hospitalization. Secondary outcomes included treatment failure (intolerance and need for non-invasive or invasive ventilation), length of hospital stay, hospital cost, mortality, and readmission at day 90.

Results
Among 337 randomized patients (median age, 70.0 years; 280 men [83.1%]; median pH 7.399; arterial partial pressure of carbon dioxide 51 mmHg), 330 completed the trial. 4/158 patients on HFNC and 1/172 patient on conventional oxygen therapy met the criteria for intubation (P = 0.198). Patients progressed to NPPV in both groups were comparable (15 [9.5%] in the HFNC group vs. 22 [12.8%] in the conventional oxygen therapy group; P = 0.343). Compared with conventional oxygen therapy, HFNC yielded a significantly longer median length of hospital stay (9.0 [interquartile range, 7.0–13.0] vs. 8.0 [interquartile range, 7.0–11.0] days) and a higher median hospital cost (approximately $2298 [interquartile range, $1613–$3782] vs. $2005 [interquartile range, $1439–$2968]). There were no significant differences in other secondary outcomes between groups.

Conclusions
In this multi-center randomized controlled study, HFNC compared to conventional oxygen therapy did not reduce need for intubation among acute COPD exacerbation patients with mild hypercapnia. The future studies should focus on patients with acute COPD exacerbation with respiratory acidosis (pH < 7.35). However, because the primary outcome rate was well below expected, the study was underpowered to show a meaningful difference between the two treatment groups.
Trial registration: NCT03003559. Registered on December 28, 2016.
PolyMyalgia Rheumatica treatment with Methotrexate in Optimal Dose in an Early disease phase (PMR MODE): study protocol for a multicenter double-blind placebo controlled trial
Authors: Marsman Diane E. , Bolhuis Thomas E. , den Broeder Nathan , den Broeder Alfons A. , van der Maas Aatke 
Published: April 2022

Abstract
Background
Polymyalgia rheumatica (PMR) is an inflammatory rheumatic disease affecting people older than 50, resulting in pain and stiffness of the neck, shoulder, and pelvic girdle. To date, glucocorticoids (GC) remain the cornerstone of treatment, but these have several drawbacks. Firstly, a large proportion of patients do not achieve GC-free remission within either the first (over 70%) or second year of treatment (over 50%). Secondly, GC-related adverse events (AE) occur in up to 65% of patients and can be severe.
The current EULAR/ACR guidelines for PMR recommend early introduction of methotrexate (MTX) as a GC sparing agent in patients at risk for worse prognosis. However, earlier trials of low to medium quality only studied MTX dosages of 7.5–10 mg/week with no to modest effect. These doses may be suboptimal as MTX is recommended in higher doses (25 mg/week) for other inflammatory rheumatic diseases. The exact role, timing, and dose of MTX in PMR remain unclear, and therefore, our objective is to study the efficacy of MTX 25 mg/week in recently diagnosed PMR patients.

Methods
We set up a double-blind, randomized, placebo-controlled superiority trial (PMR MODE) to assess the efficacy of MTX 25 mg/week versus placebo in a 1:1 ratio in 100 recently diagnosed PMR patients according to the 2012 EULAR/ACR criteria. All patients will receive prednisolone 15 mg/day, tapered to 0 mg over the course of 24 weeks. In case of primary non-response or disease relapse, prednisolone dose will be temporarily increased. Assessments will take place at baseline, 4, 12, 24, 32, and 52 weeks. The primary outcome is the difference in proportion of patients in GC-free remission at week 52.

Discussion
No relapsing PMR patients were chosen, since the possible benefits of MTX may not outweigh the risks at low doses and effect modification may occur. Accelerated tapering was chosen in order to more easily identify a GC-sparing effect if one exists. A composite endpoint of GC-free remission was chosen as a clinically relevant endpoint for both patients and rheumatologist and may reduce second order (treatment) effects.

Trial registration
Dutch Trial Registration, NL8366. Registered on 10 February 2020
DSCAM is differentially patterned along the optic axon pathway in the developing Xenopus visual system and guides axon termination at the target
Authors: Santos Rommel Andrew , Del Rio Rodrigo , Alvarez Alexander Delfin , Romero Gabriela , Vo Brandon Zarate , Cohen-Cory Susana 
Published: April 2022

Abstract
Background
The Xenopus retinotectal circuit is organized topographically, where the dorsal–ventral axis of the retina maps respectively on to the ventral-dorsal axis of the tectum; axons from the nasal-temporal axis of the retina project respectively to the caudal-rostral axis of the tectum. Studies throughout the last two decades have shown that mechanisms involving molecular recognition of proper termination domains are at work guiding topographic organization. Such studies have shown that graded distribution of molecular cues is important for topographic mapping. However, the complement of molecular cues organizing topography along the developing optic nerve, and as retinal axons cross the chiasm and navigate towards and innervate their target in the tectum, remains unknown. Down syndrome cell adhesion molecule (DSCAM) has been characterized as a key molecule in axon guidance, making it a strong candidate involved in the topographic organization of retinal fibers along the optic path and at their target.

Methods
Using a combination of whole-brain clearing and immunohistochemistry staining techniques we characterized DSCAM expression and the projection of ventral and dorsal retinal fibers starting from the eye, following to the optic nerve and chiasm, and into the terminal target in the optic tectum in Xenopus laevis tadpoles. We then assessed the effects of DSCAM on the establishment of retinotopic maps through spatially and temporally targeted DSCAM knockdown on retinal ganglion cells (RGCs) with axons innervating the optic tectum.

Results
Highest expression of DSCAM was localized to the ventral posterior region of the optic nerve and chiasm; this expression pattern coincides with ventral fibers derived from ventral RGCs. Targeted downregulation of DSCAM expression on ventral RGCs affected the segregation of medial axon fibers from their dorsal counterparts within the tectal neuropil, indicating that DSCAM plays a role in retinotopic organization.

Conclusion
These findings together with previous studies demonstrating cell-autonomous roles for DSCAM during the development of pre- and postsynaptic arbors in the Xenopus retinotectal circuit indicates that DSCAM exerts multiple roles in coordinating axon targeting and structural connectivity in the developing vertebrate visual system.
Machine learning to predict metabolic drug interactions related to cytochrome P450 isozymes
Authors: Wang Ning-Ning , Wang Xiang-Gui , Xiong Guo-Li , Yang Zi-Yi , Lu Ai-Ping , Chen Xiang , Liu Shao , Hou Ting-Jun , Cao Dong-Sheng 
Published: April 2022

AbstractDrug–drug interaction (DDI) often causes serious adverse reactions and thus results in inestimable economic and social loss. Currently, comprehensive DDI evaluation has become a major challenge in pharmaceutical research due to the time-consuming and costly process of the experimental assessment and it is of high necessity to develop effective in silico methods to predict and evaluate DDIs accurately and efficiently. In this study, based on a large number of substrates and inhibitors related to five important CYP450 isozymes (CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4), a series of high-performance predictive models for metabolic DDIs were constructed by two machine learning methods (random forest and XGBoost) and 4 different types of descriptors (MOE_2D, CATS, ECFP4 and MACCS). To reduce the uncertainty of individual models, the consensus method was applied to yield more reliable predictions. A series of evaluations illustrated that the consensus models were more reliable and robust for the DDI predictions of new drug combination. For the internal validation, the whole prediction accuracy and AUC value of the DDI models were around 0.8 and 0.9, respectively. When it was applied to the external datasets, the model accuracy was 0.793 and 0.795 for multi-level validation and external validation, respectively. Furthermore, we also compared our model with some recently published tools and then applied the final model to predict FDA-approved drugs and proposed 54,013 possible drug pairs with potential DDIs. In summary, we developed a powerful DDI predictive model from the perspective of the CYP450 enzyme family and it will help a lot in the future drug development and clinical pharmacy research.
Graphical Abstract
Effects of missing teeth and nasal septal deviation on maxillary sinus volume: a pilot study
Authors: Yamaguchi Kikue , Munakata Motohiro , Kataoka Yu , Uesugi Takashi , Shimoo Yoshiaki 
Published: April 2022

Abstract
Purpose
Tooth extraction and the projection of the tooth roots into the maxillary sinus are reported to greatly reduce the bone height from the alveolar ridge to the maxillary sinus floor, while missing teeth are reported to lead to the expansion of the maxillary sinus, all of which are important considerations during dental implant treatment for the maxillary molar region. Therefore, assessing the anatomical characteristics of the maxillary sinus acting as complicating factors is crucial before sinus augmentation. We conducted a three-dimensional examination of the effects of missing teeth and nasal septal deviation (NSD) on maxillary sinus volume (MSV).

Methods
We selected participants with two or more missing teeth from patients who underwent maxillary sinus augmentation for a unilateral free-end saddle between April 2019 and December 2020. We calculated the MSV and NSD using cone-beam computed tomography (CBCT). We compared the relationships of the presence/absence of teeth and NSD with MSV bilaterally in each patient using the Wilcoxon t-test. p-values < 0.05 denoted statistical significance.

Results
This study included 30 patients (30 sinuses; 12 men, 18 women). The average patient age was 58.2 ± 10.2 years (men, 60.4 ± 3.7 years; women, 59.2 ± 4.5 years; range, 40–77 years). The mean number of missing teeth was 2.98 ± 1.01: 13 patients had two missing teeth and 17 had three or more missing teeth. Nine patients (30%) had NSD. The mean MSV on the ipsilateral and contralateral sides of the NSD was 21.50 ± 3.84 cm3 and 22.10 ± 3.56 cm3, respectively; thus, NSD did not affect MSV (p = 0.150). The mean MSV on the edentulous and non-edentulous sides was 21.58 ± 3.89 cm3 and 21.77 ± 4.30 cm3, respectively; thus, the MSV was significantly smaller on the edentulous side (p = 0.00036).

Conclusion
Although this study was a limited preoperative study, three-dimensional measurement of the maxillary sinus with CBCT in partially edentulous patients revealed that missing teeth lead to substantial reductions in MSV, while NSD was not associated with MSV.
Feasibility and Results of the Stentectomy Procedure Performed as Rescue Treatment for Acute Thrombosis of Self-Expandable Intracranial Stents: A Case Series
Authors: Barburoglu Mehmet , Aydin Kubilay , Onal Yilmaz , Cengiz Duygu , Velioglu Murat 
Published: April 2022

BACKGROUND:
Self-expandable stents have been increasingly used for endovascular treatment of intracranial aneurysms. Because the usage of intracranial stents has increased overall, total numbers of complications associated with these devices have increased. Thrombosis, distortion, or incomplete opening of stents are potential complications that may result in occlusion of the parent artery. In such cases, removal of the stent (stentectomy) may be the only solution to avoid serious clinical consequences.

OBJECTIVE:
To investigate the feasibility and efficacy of a novel stentectomy technique for removal of thrombosed self-expandable stents.

METHODS:
A retrospective review was performed of patients who underwent the stentectomy procedure. Initial and follow-up imaging and clinical outcomes were assessed. Immediate postprocedural and follow-up clinical statuses were assessed using the modified Rankin scale.

RESULTS:
Seven patients were included in this study (mean age: 54.1 years). The stentectomy was successful in 6 of 7 patients (85.7%). Seven stents in 6 patients were successfully removed to treat the acute in-stent thrombosis that was resistant to alternative bail-out treatments. The removed stents were self-expandable braided in 2 patients, flow diverters in 2 patients, and laser cut open-cell stents in 2 patients. Stentectomy failed to retrieve a thrombosed braided stent in 1 patient. The modified Rankin scale score of all patients who underwent a success stentectomy was ≤1.

CONCLUSION:
The stentectomy procedure using the defined technique is feasible to retrieve thrombosed stents and effective to restore the blood flow. It can be considered a last resort option to treat acute in-stent thrombosis resistant to alternative bail-out treatments.
Non-contact fluorescent detection of pesticide residues based on
segment prediction using PLS and a curve fitting algorithm
Authors: Cai Yuanxue , Bian Haiyi 
Published: April 2022

Fluorescence spectral analysis is an important method to detect the pesticide residues,
which is vital for food safety issues. It has been demonstrated that
the traditional curve fitting (CF) method can predict the
concentration of pesticide with a high accuracy. However, low
absorption of the samples at low concentration of pesticide is
required; moreover, the pre-process of fruit juice is time-consuming
and destructive to the samples. To overcome these disadvantages while
maintaining the high accuracy in the high concentration range, the
segment detection method is proposed in this paper. Two models were
employed to predict the concentration according to the fluorescence
intensity. The partial least squares (PLS) model was used to predict
the concentration of the samples when the fluorescence intensity at
356 nm was smaller than 1, while the CF method was used to predict the
concentration of samples when the fluorescence intensity at 356 nm was
larger than 1 in our system. In total, 101 samples with concentration
ranging from 0 to 0.0714 mg/mL were used to validate this method. The
results indicated that the PLS method exhibited a high sensitivity in
the low concentration range, while the CF method exhibited high
accuracy in the high concentration range.
Primary care providers’ and nurses’ knowledge, attitudes, and skills regarding latent TB infection testing and treatment: A qualitative study from Rhode Island
Authors: Szkwarko Daria , Kim Steven , Carter E. Jane , Goldman Roberta E. 
Published: April 2022

Background
Untreated latent tuberculosis infection (LTBI) is a major source of active tuberculosis disease in the United States. In 2016, the United States Preventive Services Task Force (USPSTF) recommended that screening for latent tuberculosis infection among individuals at increased risk be performed as routine preventive care. Traditionally, LTBI management–including both testing and treatment–has been conducted by specialists in the United States. It is believed that knowledge gaps among primary care team members and discomfort with LTBI treatment are significant barriers to LTBI management being conducted in primary care.

Methods and objectives
This qualitative study sought to evaluate the knowledge, attitudes, and skills of primary care team members regarding the LTBI care cascade, and to identify each stepwise barrier limiting primary care teams in following the USPSTF recommendations.

Results
We conducted 24 key informant interviews with primary care providers and nurses in Rhode Island. Our results demonstrate that overall, few primary care providers and nurses felt comfortable with LTBI management, and their confidence and comfort decreased throughout the cascade. Participants felt least confident with LTBI treatment and held misconceptions about LTBI testing, such as high cost. Although participants were not confident about LTBI treatment, most were enthusiastic about treating patients if provided additional training. Participants suggested that their lack of knowledge regarding LTBI treatment led to high rates of referral to specialist providers.

Conclusion
The gaps revealed in this study can inform training curricula for primary care team members in Rhode Island and nationally to shift the USPSTF policy into practice, and, ultimately, contribute to TB elimination in the United States.
An epidemiological study of pediatric COVID-19 in the era of the variant of concern
Authors: Chaiyakulsil Chanapai , Sritipsukho Paskorn , Satdhabudha Araya , Bunjoungmanee Pornumpa , Tangsathapornpong Auchara , Sinlapamongkolkul Phakatip , Sritipsukho Naiyana 
Published: April 2022

Background
There were limited epidemiological data of pediatric COVID-19 in Asia outside China, especially during the era of the variants of concern such as the Delta and Alpha variants. The objective was to describe the clinical epidemiology of pediatric COVID-19 in a tertiary care center in Thailand from April to August 2021. The identification of risk factors for the development of pneumonia in these children was also performed.

Methods
This retrospective cohort study was conducted by retrospective chart review of all children aged 0–15 years admitted to Thammasat University Hospital care system during the study period. The risk factors for the development of pneumonia were analyzed using logistic regression.

Results
A total of 698 children were included for analysis, of which 52% were male. The mean age of the cohort was 7.2 + 4.5 years old. Radiographic pneumonia was identified in 100 children (14.3%) and a total of 16 children (2.3%) were diagnosed with severe and critical diseases. The mortality rate was 0.1%. Children younger than 1 year and children with comorbidity were at higher risk of developing pneumonia (Adjusted odds ratios 2.99 (95% confidence interval (CI): 1.56–5.74) and 2.32 (95% CI: 1.15–4.67), respectively).

Conclusion
In the era of the variants of concern, the proportion of children with severe and critical diseases remained low. However, prudence must be taken in caring for younger children and children with comorbidity.
Handmade: A Scientist’s Search for Meaning through Making, Anna Ploszajski (2021)
Authors: Chandler Kimberley 
Published: April 2022

Review of: Handmade: A Scientist’s Search for Meaning through Making, Anna Ploszajski (2021)
London: Bloomsbury Publishing (Sigma), 320 pp., 288 pp., 288 pp.,
ISBN 978-1-47297-107-4, h/bk, £16.19
ISBN 978-1-47297-106-7, e-book (Epub and Mobi), £12.59
ISBN 978-1-47297-106-7, e-book (PDF), £12.59