bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating the performance of temporal pattern discovery: new application using statins and rhabdomyolysis in OMOP databases
Authors: Lavallee M. , Yu T. , Evans L. , Van Hemelrijck M. , Bosco C. , Golozar A. , Asiimwe A. 
Published: February 2022

Abstract
Background
Temporal pattern discovery (TPD) is a method of signal detection using electronic healthcare databases, serving as an alternative to spontaneous reporting of adverse drug events. Here, we aimed to replicate and optimise a TPD approach previously used to assess temporal signals of statins with rhabdomyolysis (in The Health Improvement Network (THIN) database) by using the OHDSI tools designed for OMOP data sources.

Methods
We used data from the Truven MarketScan US Commercial Claims and the Commercial Claims and Encounters (CCAE). Using an extension of the OHDSI ICTemporalPatternDiscovery package, we ran positive and negative controls through four analytical settings and calculated sensitivity, specificity, bias and AUC to assess performance.

Results
Similar to previous findings, we noted an increase in the Information Component (IC) for simvastatin and rhabdomyolysis following initial exposure and throughout the surveillance window. For example, the change in IC was 0.266 for the surveillance period of 1–30 days as compared to the control period of − 180 to − 1 days. Our modification of the existing OHDSI software allowed for faster queries and more efficient generation of chronographs.

Conclusion
Our OMOP replication matched the we can account forwe can account for of the original THIN study, only simvastatin had a signal. The TPD method is a useful signal detection tool that provides a single statistic on temporal association and a graphical depiction of the temporal pattern of the drug outcome combination. It remains unclear if the method works well for rare adverse events, but it has been shown to be a useful risk identification tool for longitudinal observational databases. Future work should compare the performance of TPD with other pharmacoepidemiology methods and mining techniques of signal detection. In addition, it would be worth investigating the relative TPD performance characteristics using a variety of observational data sources.
Pattern of utilization, disease presentation, and medication prescribing and dispensing at 51 primary healthcare centers during the Hajj mass gathering
Authors: Yezli Saber , Yassin Yara , Mushi Abdulaziz , Almuzaini Yasir , Khan Anas 
Published: February 2022

Abstract
Background
The majority of pilgrims seeking healthcare during Hajj are seen at primary healthcare centers (PHCCs). Data on the utilization of these facilities during Hajj can aid in directing optimal health services delivery and allocation of resources during the pilgrimage.

Method
We investigated the pattern of disease presentation, caseload, and medication prescribing and dispensing at 51 PHCCs during the 2019 Hajj. Data on patients’ demographics, diagnoses, and prescribed medications were retrieved from each PHCC’s electronic records and analyzed. Data were also used to calculate six of the World Health Organization (WHO) indicators for drug use at these facilities.

Results
Data were captured for 99,367 patients who were mostly Hajj pilgrims (95.4%), male (69.1%) from the Eastern Mediterranean (60.8%) and had a mean age of 46.6 years (SD = 14.9). Most patients (85.2%) were seen in Mina and towards the end of Hajj. The majority of patients (96.0%) had a single diagnosis; most commonly, respiratory (45.0%), musculoskeletal (17.2%), and skin (10.5%) diseases. Patients were prescribed 223,964 medications, mostly analgesics (25.1%), antibacterials for systemic use (16.5%), anti-inflammatory and antirheumatic products (16.4%), and cough and cold preparations (11.9%). On average, 2.25 (SD = 0.94) medications were prescribed per consultation, with low (1.3%) prevalence of polypharmacy. An antibiotic and an injectable were prescribed in 43.6 and 2.67% of patient encounters, respectively. Most (92.7%) of the prescribed drugs were actually dispensed, in an average time of 8.06 min (SD = 41.4). All PHCCs had a copy of the essential drugs list available, on which all the prescribed drugs appeared.

Conclusion
Respiratory illnesses are the main reason for PHCCs visits during Hajj, and analgesics and antibiotics are the most common medications prescribed to pilgrims. Our results, including the calculated WHO drug use indicators, contribute to evidence-based optimization of primary healthcare services during Hajj.
Case report and successful management of canine aortic endocarditis caused by Actinomyces neuii subsp. anitratus (Winkia neuii subsp. anitrata)
Authors: Giannoulopoulos G. , Errington K. 
Published: February 2022

Abstract
Background
Canine aortic valve endocarditis carries a poor prognosis. In the current literature there are only two reports of infectious endocarditis associated with Actinomyces; Actinomyces turicensis and an Actinomyces-like organism. Endocarditis due to Actinomyces neuii subsp. anitratus (now known as Winkia neuii subsp. anitrata) has rarely been reported in humans, and to the best of our knowledge, has never been reported in dogs.

Case presentation
A 4 year-3 months old female neutered Great Dane presented with lethargy, hyporexia, ‘praying position’ stance, acute onset of cherry eye and pyrexia. A subtle diastolic heart murmur was detected on thoracic auscultation and echocardiology revealed an irregular lesion adhered to the ventricular aspect of the aortic valve, suggestive of aortic valve endocarditis. Peripheral blood was collected for blood culture. Following 10 days of incubation, blood cultures yielded a growth of aerobic gram-positive filamentous rods which were further biochemically (BioMerieux API Coryne profiling strip) identified as Actinomyces neuii subsp. anitratus. The patient was treated with marbofloxacin and amoxicillin/clavulanic acid for five consecutive months. On repeat echogram, following treatment completion, there was no evidence of aortic valve endocarditis. To the best of our knowledge this is the first case report documenting successful treatment of aortic valve endocarditis caused by Actinomyces neuii subsp. anitratus in a dog.

Conclusions
Despite the poor prognosis of canine infectious aortic valve endocarditis, patients with Actinomyces neuii subsp. anitratus infection might have a favourable outcome. It is therefore important identifying the underling infectious cause, as it may have a significant impact on prognosis and treatment outcome when it is caused by Actinomyces neuii subsp. anitratus.
Limited medial osteochondral lesions of the talus associated with chronic ankle instability do not impact the results of endoscopic modified Broström ligament repair
Authors: Feng Shi-Ming , Chen Jie , Ma Chao , Migliorini Filippo , Oliva Francesco , Maffulli Nicola 
Published: February 2022

Abstract
Background
The arthroscopic modified Broström procedure, with repair of the anterior talofibular ligament and extensor retinaculum, produces good functional outcomes in patients with chronic lateral ankle instability (CLAI). CLAI can be associated with osteochondral lesions of the talus (OLTs). It remains unclear whether associated limited OLTs affect clinical outcomes in such patients.

Methods
This retrospective cohort study included 92 CLAI patients with and without OLTs undergoing an all-inside arthroscopic modified Broström procedure from June 2016 to May 2019. The patients were divided into non-lesion group (n = 32) and lesion group (n = 60) according to whether CLAI was associated or not with OLTs. All the osteochondral lesions less than 15 mm in diameter were managed with bone marrow stimulation techniques (arthroscopic microfracture) at the time of the arthroscopic modified Broström procedure. The Visual Analogue Scale (VAS) scores, American Orthopedic Foot and Ankle Society (AOFAS) scores, Karlsson Ankle Function Score (KAFS), Anterior Talar Translation (ATT), Active Joint Position Sense (AJPS), and the rate of return to sports were compared in both groups.

Results
Increase in all the functional scores (VAS, AOFAS, KAFS, ATT, and AJPS) in both groups was, respectively, recorded 1 year and 2 years after surgery. At the 1-year and 2-year follow-up, there was no significant difference in the VAS, AOFAS, KAFS, ATT, and AJPS scores between the non-lesion and lesion groups.

Conclusion
In patients with CLAI who underwent an arthroscopic modified Broström procedure, the presence of limited OLTs (less than 15 mm in diameter), which required arthroscopic microfracture, did not exert any influence on outcome.

Level of Evidence
Level III, a retrospective comparative study.
Protocol for a cluster randomized control trial of the impact of the Breaking the Man Code workshops on adolescent boys’ intentions to seek help
Authors: King Kylie , Schlichthorst Marisa , Chondros Patty , Rice Simon , Clark Anna , Le Long Khanh-Dao , Mihalopoulos Cathrine , Pirkis Jane 
Published: February 2022

AbstractBackgroundMales in Australia and many other countries account for three-quarters of all deaths by suicide. School-based programs to support young men’s wellbeing have become increasingly common in recent years and show much promise to tackle the issue of male suicide by fostering protective factors and mitigating harmful factors. However, only a few of these programs have been evaluated. This trial seeks to address the lack of knowledge about the potential for school-based gender-transformative programs to have a positive impact on boys.Breaking the Man Codeworkshops, delivered byTomorrow Manin Australia, challenge and transform harmful masculinities with young men with a view to ultimately reducing their suicide risk. The trial aims to examine whether adolescent boys who participate in theBreaking the Man Codeworkshop demonstrate an increase in their likelihood of seeking help for personal or emotional problems compared to boys waiting to take part in the workshop.MethodsA stratified cluster randomized controlled superiority trial with two parallel groups will be conducted. Schools will be randomly allocated 1:1, stratified by location of the schools (rural or urban), state (Victoria, NSW, or WA), and mode of workshop delivery (face-to-face or online), to the intervention group and waitlist control group.DiscussionTheBreaking the Man Codeworkshops show great promise as a school-based prevention intervention. The trial will fill a gap in knowledge that is critically needed to inform future interventions with boys and men. Some methodological challenges have been identified related to the COVID-19 pandemic in Australia, such as delays in ethics approvals and the need forTomorrow Manto introduce an online delivery option for the workshop. The trial protocol has been designed to mitigate these challenges. The findings from the trial will be used to improve the workshops and will assist others who are designing and implementing suicide prevention interventions for boys and men.Trial registrationAustralian New Zealand Clinical Trials Registry (ACTRN12620001134910). Registered on 30 October 2020
A novel DNA methylation signature associated with lymph node metastasis status in early gastric cancer
Authors: Chen Shang , Yu Yanqi , Li Tao , Ruan Weimei , Wang Jun , Peng Quanzhou , Yu Yingdian , Cao Tianfeng , Xue Wenyuan , Liu Xin , Chen Zhiwei , Yu Jiang , Fan Jian-Bing 
Published: February 2022

Abstract
Background
Lymph node metastasis (LNM) is an important factor for both treatment and prognosis of early gastric cancer (EGC). Current methods are insufficient to evaluate LNM in EGC due to suboptimal accuracy. Herein, we aim to identify methylation signatures for LNM of EGC, facilitate precision diagnosis, and guide treatment modalities.

Methods
For marker discovery, genome-wide methylation sequencing was performed in a cohort (marker discovery) using 47 fresh frozen (FF) tissue samples. The identified signatures were subsequently characterized for model development using formalin-fixed paraffin-embedded (FFPE) samples by qPCR assay in a second cohort (model development cohort, n = 302, training set: n = 151, test set: n = 151). The performance of the established model was further validated using FFPE samples in a third cohorts (validation cohort, n = 130) and compared with image-based diagnostics, conventional clinicopathology-based model (conventional model), and current standard workups.

Results
Fifty LNM-specific methylation signatures were identified de novo and technically validated. A derived 3-marker methylation model for LNM diagnosis was established that achieved an AUC of 0.87 and 0.88, corresponding to the specificity of 80.9% and 85.7%, sensitivity of 80.6% and 78.1%, and accuracy of 80.8% and 83.8% in the test set of model development cohort and validation cohort, respectively. Notably, this methylation model outperformed computed tomography (CT)-based imaging with a superior AUC (0.88 vs. 0.57, p < 0.0001) and individual clinicopathological features in the validation cohort. The model integrated with clinicopathological features demonstrated further enhanced AUCs of 0.89 in the same cohort. The 3-marker methylation model and integrated model reduced 39.4% and 41.5% overtreatment as compared to standard workups, respectively.

Conclusions
A novel 3-marker methylation model was established and validated that shows diagnostic potential to identify LNM in EGC patients and thus reduce unnecessary gastrectomy in EGC.
The outcome of using intravenous immunoglobulin (IVIG) in critically ill COVID-19 patients’: a retrospective, multi-centric cohort study
Authors: Salehi Mohammadreza , Barkhori Mehni Mahdi , Akbarian Mohammadmehdi , Fattah Ghazi Samrand , Khajavi Rad Nasim , Moradi Moghaddam Omid , Jamali Moghaddam SaeedReza , Hosseinzadeh Emam Masoumeh , Abtahi Sayed Hamidreza , Moradi Maryam , Ghiasvand Fereshteh 
Published: February 2022

Abstract
Background
During the COVID-19 pandemic, different treatments have been used in critically ill patients. Using intravenous immunoglobulin (IVIG) has been suggested in various studies as an effective option. Our study aims to access the efficacy of IVIG in critically ill COVID-19 patients.

Methods
In this retrospective matched cohort study, records of three tertiary centers with a large number of COVID-19 admissions were evaluated and used. Based on treatment options, patients were divided into two groups, standard COVID-19 treatment (109 patients) and IVIG treatment (74 patients) patients. Also, the effect of IVIG in different dosages was evaluated. Patients with IVIG treatment were divided into three groups of low (0.25 gr/kg), medium (0.5 gr/kg), and high (1 gr/kg) dose. Data analysis was performed using an independent t test and one-way analysis of variance (ANOVA) to compare the outcomes between two groups, including duration of hospitalization, intensive care unit (ICU) length of stay, and mortality rate.

Results
The duration of hospitalization in the IVIG group was significantly longer than standard treatment (13.74 days vs. 11.10 days, p < 0.05). There was no significant difference between the two groups in ICU length of stay, the number of intubated patients, and duration of mechanical ventilation (p > 0.05). Also, initial outcomes in IVIG subgroups were compared separately with the standard treatment group. The results indicated that only the duration of hospitalization in the IVIG subgroup with medium dose is significantly longer than the standard treatment group (p < 0.01).

Conclusion
Our data indicate that the use of IVIG in critically ill COVID-19 patients could not be beneficial, based on no remarkable differences in duration of hospitalization, ICU length of stay, duration of mechanical ventilation, and even mortality rate.
Laser desorption/ionization mass spectrometry of L-thyroxine (T4) using combi-matrix of α-cyano-4-hydroxycinnamic acid (CHCA) and graphene
Authors: Noh Joo-Yoon , Kim Moon-Ju , Park Jong-Min , Yun Tae-Gyeong , Kang Min-Jung , Pyun Jae-Chul 
Published: February 2022

AbstractAn optimal combi-matrix for MALDI-TOF mass spectrometry was presented for the analysis of L-thyroxine (T4) in human serum. For the selection of the optimal combi-matrix, several kinds of combi-matrices were prepared by mixing the conventional organic matrix of CHCA with nanomaterials, such as graphene, carbon nanotubes, nanoparticles of Pt and TiO2. In order to select the optimal combi-matrix, the absorption at the wavelength of laser radiation (337 nm) for the ionization of sample was estimated using UV–Vis spectrometry. And, the heat absorption properties of these combi-matrices were also analyzed using differential scanning calorimetry (DSC), such as onset temperature and fusion enthalpy. In the case of the combi-matrix of CHCA and graphene, the onset temperature and fusion enthalpy were observed to be lower than those of CHCA, which represented the enhanced transfer of heat to the analyte in comparison with CHCA. From the analysis of optical and thermal properties, the combi-matrix of CHCA and graphene was selected to be an optimal combination for the transfer of laser energy during MALDI-TOF mass spectrometry. The feasibility of the combi-matrix composed of CHCA and graphene was demonstrated for the analysis of T4 molecules using MALDI-TOF mass spectrometry. The combi-matrix of CHCA and graphene was estimated to have an improved limit of detection and a wider detection range in comparison with other kinds of combi-matrices. Finally, the MALDI-TOF MS results of T4 analysis using combi-matrix were statistically compared with those of the conventional immunoassay.
(Re-)Designing a measure of student’s attitudes toward science: a longitudinal psychometric approach
Authors: Tai Robert H. , Ryoo Ji Hoon , Skeeles-Worley Angela , Dabney Katherine P. , Almarode John T. , Maltese Adam V. 
Published: February 2022

Abstract
Background
Capturing measures of students’ attitudes toward science has long been a focus within the field of science education. The resulting interest has led to the development of many instruments over the years. There is considerable disagreement about how attitudes should be measured, and especially whether students’ attitudes toward science can or should be measured unidimensionally, or whether separate attitude dimensions or subscales should be considered. When it is agreed upon that the attitudes toward science construct should be measured along separate subscales, there is no consensus about which subscales should be used.

Methods
A streamlined version of the modified Attitudes Towards Science Inventory (mATSI), a widely used science measurement instrument, was validated for a more diverse sample as compared to the original study (Weinburgh and Steele in Journal of Women and Minorities in Science and Engineering 6:87–94, 2000). The analytical approach used factor analyses and longitudinal measurement invariance. The study used a sample of 2016 self-reported responses from 6 and 7th grade students. The factor analysis elucidated the factor structure of students’ attitudes toward science, and some modifications were made in accordance with the results. Measurement invariance analysis was used to confirm the stability of the measure.

Results
Our results support that the subscales, anxiety toward science and value and enjoyment of science, are two factors and stable over time.

Conclusions
Our results suggest that our proposed modified factor structure for students’ attitudes toward science is reliable, valid, and appropriate for use in longitudinal studies. This study and its resulting streamlined mATSI survey could be of value to those interested in studying student engagement and measuring middle-school students' attitudes toward science.
Neuronal GRK2 regulates microglial activation and contributes to electroacupuncture analgesia on inflammatory pain in mice
Authors: Chen Yu , Zhou Yang , Li Xiao-Chen , Ma Xue , Mi Wen-Li , Chu Yu-Xia , Wang Yan-Qing , Mao-Ying Qi-Liang 
Published: February 2022

Abstract
Background
G protein coupled receptor kinase 2 (GRK2) has been demonstrated to play a crucial role in the development of chronic pain. Acupuncture is an alternative therapy widely used for pain management. In this study, we investigated the role of spinal neuronal GRK2 in electroacupuncture (EA) analgesia.

Methods
The mice model of inflammatory pain was built by subcutaneous injection of Complete Freund’s Adjuvant (CFA) into the plantar surface of the hind paws. The mechanical allodynia of mice was examined by von Frey test. The mice were subjected to EA treatment (BL60 and ST36 acupuncture points) for 1 week. Overexpression and downregulation of spinal neuronal GRK2 were achieved by intraspinal injection of adeno associated virus (AAV) containing neuron-specific promoters, and microglial activation and neuroinflammation were evaluated by real-time PCR.

Results
Intraplantar injection with CFA in mice induced the decrease of GRK2 and microglial activation along with neuroinflammation in spinal cord. EA treatment increased the spinal GRK2, reduced neuroinflammation, and significantly decreased CFA-induced mechanical allodynia. The effects of EA were markedly weakened by non-cell-specific downregulation of spinal GRK2. Further, intraspinal injection of AAV containing neuron-specific promoters specifically downregulated neuronal GRK2, and weakened the regulatory effect of EA on CFA-induced mechanical allodynia and microglial activation. Meanwhile, overexpression of spinal neuronal GRK2 decreased mechanical allodynia. All these indicated that the neuronal GRK2 mediated microglial activation and neuroinflammation, and subsequently contributed to CFA-induced inflammatory pain.

Conclusion
The restoration of the spinal GRK2 and subsequent suppression of microglial activation and neuroinflammation might be an important mechanism for EA analgesia. Our findings further suggested that the spinal GRK2, especially neuronal GRK2, might be the potential target for EA analgesia and pain management, and we provided a new experimental basis for the EA treatment of pain.