bluuebunny/crossref_metadata_2025_split huggingface dataset:
Robotic-assisted thoracoscopic resection of anterior mediastinal cystic teratoma: a case report and literature review
Authors: Ramcharran Harry , Wallen Jason 
Published: April 2022

Abstract
Background
Mediastinal teratomas are rare tumors that frequently occur in the anterior mediastinum. The majority of these tumors are benign and slow growing. Due to their low malignant potential, the treatment for these tumors is surgical resection. More recently, the surgical management has shifted from invasive approaches such as a sternotomy to minimally invasive ones such as robotic-assisted thoracoscopic resections utilizing lung isolation ventilation. We present a rare case of a locally advanced mediastinal teratoma requiring resection, which was initially attempted thoracoscopically using double lung ventilation.

Case presentation
A 43 year-old female was found to have an anterior mediastinal mass during work-up for an intermittent cough in 2009. Chest imaging and biopsy at the time showed evidence of a cystic teratoma without concerning features. She underwent imaging surveillance until 2018, when repeat chest imaging showed increasing growth and worrisome radiologic features concerning for malignant degeneration. She underwent an elective robotic-assisted thoracoscopic resection utilizing double lung ventilation, but due to extensive involvement of the right lung, pericardium, superior vena cava, and right phrenic nerve the patient had to be repositioned and started on single lung ventilation mid-procedure to facilitate a safe and complete resection.

Conclusions
Anterior mediastinal teratomas can be successfully removed by robotic-assisted thoracoscopic resections utilizing single lung ventilation. Though robotic-assisted thoracoscopic resection utilizing double lung ventilation can be effective in performing certain procedures such as lung wedge resections, thymectomy, pleural biopsies and minimally invasive cardiac procedures, it is limited in removing locally advanced mediastinal tumors.
Assessing the value of orphan drugs using conventional cost-effectiveness analysis: Is it fit for purpose?
Authors: Postma Maarten J. , Noone Declan , Rozenbaum Mark H. , Carter John A. , Botteman Marc F. , Fenwick Elisabeth , Garrison Louis P. 
Published: April 2022

AbstractConventional cost-effectiveness analysis—i.e., assessing pharmaceuticals through a cost per quality-adjusted life year (QALY) framework—originated from a societal commitment to maximize population health given limited resources. This "extra-welfarist" approach has produced pricing and reimbursement systems that are not well- aligned with the unique considerations of orphan drugs. This framework has been slow to evolve along with our increased understanding of the impact of rare diseases, which in turn has complicated the assessment of orphan drugs meant to treat rare diseases. Herein, we (i) discuss the limitations of conventional cost-effectiveness analysis as applied to assessing access to, as well as the pricing and reimbursement of, orphan drugs, (ii) critically appraise alternative and supplemental approaches, and (iii) offer insights on plausible steps forward.
Dose-finding studies in drug development for rare genetic diseases
Authors: Wang Lingshan , Wang Jie , Feng Ji , Doi Mary , Pepe Salvatore , Pacanowski Michael , Schuck Robert N. 
Published: April 2022

AbstractBackgroundThe small patient populations inherent to rare genetic diseases present many challenges to the traditional drug development paradigm. One major challenge is generating sufficient data in early phase studies to inform dose selection for later phase studies and dose optimization for clinical use of the drug. However, optimizing the benefit-risk profile of drugs through appropriate dose selection during drug development is critical for all drugs, including those being developed to treat rare diseases. Recognizing the challenges of conducting dose finding studies in rare disease populations and the importance of dose selection and optimization for successful drug development, we assessed the dose-finding studies and analyses conducted for drugs recently approved for rare genetic diseases.ResultsOf the 40 marketing applications for new molecular entity (NME) drugs and biologics approved by the United States Food and Drug Administration for rare genetic diseases from 2015 to 2020, 21 (53%) of the development programs conducted at least one dedicated dose-finding study. In addition, the majority of drug development programs conducted clinical studies in healthy subjects and included population pharmacokinetic and exposure–response analyses; some programs also conducted clinical studies in patient populations other than the disease for which the drug was initially approved. The majority of primary endpoints utilized in dedicated dose-finding studies were biomarkers, and the primary endpoint of the safety and efficacy study matched the primary endpoint used in the dose finding study in 9 of 13 (69%) drug development programs where primary study endpoints were assessed.ConclusionsOur study showed that NME drug development programs for rare genetic diseases utilize multiple data sources for dosing information, including studies in healthy subjects, population pharmacokinetic analyses, and exposure–response analyses. In addition, our results indicate that biomarkers play a key role in dose-finding studies for rare genetic disease drug development programs. Our findings highlight the need to develop study designs and methods to allow adequate dose-finding efforts within rare disease drug development programs that help overcome the challenges presented by low patient prevalence and other factors. Furthermore, the frequent reliance on biomarkers as endpoints for dose-finding studies underscores the importance of biomarker development in rare diseases.
Tauopathies: new perspectives and challenges
Authors: Zhang Yi , Wu Kai-Min , Yang Liu , Dong Qiang , Yu Jin-Tai 
Published: April 2022

Abstract
Background
Tauopathies are a class of neurodegenerative disorders characterized by neuronal and/or glial tau-positive inclusions.

Main body
Clinically, tauopathies can present with a range of phenotypes that include cognitive/behavioral-disorders, movement disorders, language disorders and non-specific amnestic symptoms in advanced age. Pathologically, tauopathies can be classified based on the predominant tau isoforms that are present in the inclusion bodies (i.e., 3R, 4R or equal 3R:4R ratio). Imaging, cerebrospinal fluid (CSF) and blood-based tau biomarkers have the potential to be used as a routine diagnostic strategy and in the evaluation of patients with tauopathies. As tauopathies are strongly linked neuropathologically and genetically to tau protein abnormalities, there is a growing interest in pursuing of tau-directed therapeutics for the disorders. Here we synthesize emerging lessons on tauopathies from clinical, pathological, genetic, and experimental studies toward a unified concept of these disorders that may accelerate the therapeutics.

Conclusions
Since tauopathies are still untreatable diseases, efforts have been made to depict clinical and pathological characteristics, identify biomarkers, elucidate underlying pathogenesis to achieve early diagnosis and develop disease-modifying therapies.
DICE: Dual mTorc Inhibition in advanCed/recurrent Epithelial ovarian cancer resistant to standard treatment—a study protocol for a randomised trial investigating a novel therapy called TAK228
Authors: Fiorentino Francesca , Krell Jonathan , de la Rosa Consuelo Nohpal , Webber Lee 
Published: April 2022

Abstract
Background
The standard initial treatment for ovarian cancer is surgery and platinum-based chemotherapy and potentially maintenance therapy with avastin or inhibitors of poly-ADP ribose polymerase (PARP). While a proportion of women are cured by this approach, the vast majority will relapse and become resistant to platinum chemotherapy either initially or on subsequent treatment. There is an unmet need to improve response to treatment and quality of life in these women. TAK228 is a novel therapy that can be added to standard treatment in the participant population and the aim of the DICE trial is to assess its effectiveness. Laboratory and clinical research has shown that these ovarian cancers may respond to the molecular target of a drug such as TAK228, and there have been studies using it in other advanced solid tumours including endometrial cancer.

Methods
One hundred twenty-four eligible women will be recruited from participating research sites in the United Kingdom (UK) and Germany. Randomised participants will receive either weekly paclitaxel alone (standard treatment, n = 62) or TAK228 plus weekly paclitaxel (n = 62) until the cancer significantly worsens; there are significant adverse events or any other protocol-defined stopping criteria. Participants will be monitored for response to treatment (using radiological imaging), adverse events and quality of life during both randomised treatment and subsequent follow-up.

Discussion
The primary objective/endpoint of the study is to compare the two treatments in terms of progression-free survival, or the length of time that each participant is alive without the cancer significantly worsening according to defined assessment criteria. If the addition of TAK228 to weekly paclitaxel chemotherapy is shown to significantly improve this statistically, and adverse events and quality of life are not significantly worse than standard treatment, then TAK228 plus weekly paclitaxel could potentially be taken forward within the context of a larger phase III trial.

Trial registration
ClinicalTrials.govNCT03648489. Registered on 27 August 2018.
Turning walking pneumonia into recurrent abscesses: a curious case of CVID and review of the literature
Authors: Gao David X. , Hussain Habiba , Bobber Brianna , Phan Peter 
Published: April 2022

Abstract
Background
Common variable immunodeficiency (CVID) is a primary immunodeficiency disorder associated with a broad symptom presentation that is still being characterized. We report a rare case of recurrent mycoplasma skin abscesses in a patient with a history of autoimmune disorders and prolonged mycoplasma pneumonia who was diagnosed with CVID.

Case presentation
A 34-year-old woman presented with a history of recurrent abscesses previously confirmed positive for Mycoplasma pneumoniae. Her past medical history of recurrent mycoplasma abscesses, prolonged mycoplasma pneumonia, and autoimmune disorders (mixed connective tissue disease and immune thrombocytopenia) raised suspicion of CVID. Workup included negative anti-mycoplasma antibody titers, hypogammaglobulinemia, and negative anti-pneumococcal antibody titers despite prior vaccination, solidifying the diagnosis of CVID. The patient was discharged on antibiotic and intravenous immunoglobulin therapy and now follows allergy and immunology long-term for treatment.

Conclusions
Her diagnostic history underscores the importance of considering the various criteria of CVID for diagnosis, and her unique presentation of M. pneumoniae skin abscesses highlights the broad sequelae patients with CVID can manifest.
More than three times as many Indigenous Australian clients at risk from drinking could be supported if clinicians used AUDIT-C instead of unstructured assessments
Authors: Conigrave James H. , Lee K. S. Kylie , Haber Paul S. , Vnuk Julia , Doyle Michael F. , Conigrave Katherine M. 
Published: April 2022

Abstract
Background
Aboriginal and Torres Strait Islander (‘Indigenous’) Australians experience a greater burden of disease from alcohol consumption than non-Indigenous peoples. Brief interventions can help people reduce their consumption, but people drinking at risky levels must first be detected. Valid screening tools (e.g., AUDIT-C) can help clinicians identify at-risk individuals, but clinicians also make unstructured assessments. We aimed to determine how frequently clinicians make unstructured risk assessments and use AUDIT-C with Indigenous Australian clients. We also aimed to determine the accuracy of unstructured drinking risk assessments relative to AUDIT-C screening. Finally, we aimed to explore whether client demographics influence unstructured drinking risk assessments.

Methods
We performed cross-sectional analysis of a large clinical dataset provided by 22 Aboriginal Community Controlled Health Services in Australia. We examined instances where clients were screened with unstructured assessments and with AUDIT-C within the same two-monthly period. This aggregated data included 9884 observations. We compared the accuracy of unstructured risk assessments against AUDIT-C using multi-level sensitivity and specificity analysis. We used multi-level logistic regression to identify demographic factors that predict risk status in unstructured assessments while controlling for AUDIT-C score.

Results
The primary variables were AUDIT-C score and unstructured drinking risk assessment; demographic covariates were client age and gender, and service remoteness. Clinicians made unstructured drinking risk assessments more frequently than they used AUDIT-C (17.11% and 10.85% of clinical sessions respectively). Where both measures were recorded within the same two-month period, AUDIT-C classified more clients as at risk from alcohol consumption than unstructured assessments. When using unstructured assessments, clinicians only identified approximately one third of clients drinking at risky levels based on their AUDIT-C score (sensitivity = 33.59% [95% CI 22.03, 47.52], specificity = 99.35% [95% CI 98.74, 99.67]). Controlling for AUDIT-C results and demographics (gender and service remoteness), clinicians using unstructured drinking risk assessments were more likely to classify older clients as being at risk from alcohol consumption than younger clients.

Conclusions
Evidence-based screening tools like AUDIT-C can help clinicians ensure that Indigenous Australian clients (and their families and communities) who are at risk from alcohol consumption are better detected and supported.
An assessment on toxic and essential elements in rice consumed in Colombo, Sri Lanka
Authors: Chandrasiri Gayani Udeshika , Mahanama Kariyawasam Ranaweerage Ranjith , Mahatantila Kushani , Pitumpe Arachchige Pavithra Sajeewani , Midigama Liyanage Roshan Chathuranga 
Published: April 2022

AbstractBeing the dietary staple in most Asian countries, the concentrations of toxic and essential element content in rice is an important aspect in terms of both toxicological and nutritional standpoints. This study aimed to analyse trace elements (As, Cd, Pb, Hg, Cr, Ni, Zn, Cu, Mn, Fe, and Mo) in improved, traditional, and imported rice varieties consumed in Colombo district, Sri Lanka during 2018 and 2019. Further, the potential health risks were assessed in terms of maximum levels and provisional tolerable daily intake. Among the toxic elements analysed, As, Cd, Cr, and Pb were detected in certain rice varieties. Arsenic was detected in all three rice categories and the number of As detected samples were higher compared to other toxic elements in 2018 and 2019. In 2018, 4.2% of traditional rice exceeded As maximum level (0.2 mg/kg) whereas 2.1% of improved and 4.2% of traditional rice exceeded Pb maximum level (0.2 mg/kg). However, none of the toxic elements in rice exceeded the respective maximum levels in 2019. Only mean estimated daily intake of Pb through Kaluheenati exceeded the provisional tolerable daily intake value (0.0015 mg/kg bw/d) in 2018. Rice varieties that reported the highest toxic elements were Basmathi (imported), Samba (improved), and Kaluheenati, Madathawalu, Pachchaperuman, and Suwadel (traditional). With regard to essential elements, concentrations of Fe, Zn, Cu, Mn, and Mo in rice were positively correlated (p < 0.05) to each other, and the highest essential element concentration were found in traditional rice with red pericarp (i.e., Kaluheenati, Madathawalu, and Pachchaperuman).
Soil environment reshapes microbiota of laboratory-maintained Collembola during host development
Authors: Pathiraja Duleepa , Wee June , Cho Kijong , Choi In-Geol 
Published: April 2022

AbstractCollembola are soil-dwelling arthropods that play a key role in the soil ecosystem. Allonychiurus kimi (Lee) (Collembola: Onychiuridae) was isolated from the natural environment and has been maintained for 20 years under laboratory conditions. Though the morphological and physiological features of A. kimi are being widely used to evaluate the impact of pesticides and heavy metals on the soil ecosystem, variations observed in these features might be on account of its microbiota. However, the microbiota composition of the laboratory-maintained A. kimi is undetermined and how the community structure is changing in response to soil environments or interacting with the soil microbiota are still unknown. In this study, we determined the microbiota of laboratory-maintained A. kimi at both adult and juvenile stages and examined how the microbiota of A. kimi is affected by the microbial community in the soil environments. Chryseobacterium, Pandoraea, Sphingomonas, Escherichia–Shigella, and Acinetobacter were the core microbiota of A. kimi. Exposure of the laboratory-maintained A. kimi to different soil microbial communities drove dynamic shifts in the composition of A. kimi microbiota. Microbial association network analysis suggested that gut microbiota of lab-grown A. kimi was affected by exposing to soil microbial community. This study implies that shifts in the bacterial community of adult A. kimi can be utilized as an indicator to evaluate the soil ecosystem.
An empirical study of claims and qualifiers in ESL students’ argumentative writing based on Toulmin model
Authors: Yang Rui 
Published: April 2022

AbstractEnglish argumentative writing is difficult in second language writing for ESL students. Although there has been a lot of research on English argumentative writings, empirical research focusing on claims in argumentative writing is very scarce. Based on the Toulmin model, this paper studied the relationship between the claims and English argumentative writing performance. 117 time-limited writings were collected at a top university in Northeast China. The qualifiers were in the form of words, participle and sentence (QW, QP, QS), based on which claims were classified. Through the text analysis of each argumentative writing, 23 types of claims were extracted. Types of claims and 117 argumentative writings were scored respectively. Correlation analysis showed that claims based on qualifier divisions did not predict holistic writing performance. Claims in the higher-mark writings were also discussed. The findings led us to conclude corresponding pedagogy implications in promoting argumentative writings.
Accuracy of intravitreal injection volume for aflibercept pre-filled syringe and BD Luer-Lok one-milliliter syringe
Authors: Guest John-Michael , Malbin Brett , Abrams Gary , Parendo Anthony , Das Shibandri , Okeagu Chinwenwa , Ross Bing X. , Kumar Ashok , Lin Xihui 
Published: April 2022

Abstract
Background
To evaluate the accuracy of intravitreal injection volume of the pre-filled syringe (PFS) in which aflibercept is packaged compared to the BD Luer-Lok 1-mL syringe.

Methods
Ophthalmologists injected their typical intravitreal volume for aflibercept using either the PFS or BD Luer-Lok 1-mL syringe for 5 times each. The injected fluid was weighed using a micro-scale and converted to volume. The volume of fluid injected was also evaluated when the 0.05 mL line on the PFS was lined up to the tip or base of the dome-shaped plunger.

Results
Injection volume was measured for 12 physicians. The average injected fluid volume was 74.22 ± 15.87 µL for PFS and 53.42 ± 4.61 µL for the BD Luer-Lok 1-mL syringe (p < 0.0001). The average deviation in volume injected for the PFS was higher compared to the BD Luer-Lok 1-mL syringe (11.36 µL vs. 3.35 µL, p < 0.0001). When the PFS was lined up with the tip of the dome-shaped plunger at the 0.05-mL line, the average injected volume was 71.03% higher.

Conclusions
The intravitreal injection volume and variability using the new PFS were significantly higher than the volume injected using the BD Luer-Lok 1-mL syringe previously used, potentially leading to higher rates of visually significant elevation of intraocular pressures.
Spectral domain OCT features in type 2 macular telangiectasia (type 2 MacTel): its relevance with clinical staging and visual acuity
Authors: Venkatesh Ramesh , Reddy Nikitha Gurram , Mishra Pranjal , Agrawal Sameeksha , Mutalik Deepashri , Yadav Naresh Kumar , Chhablani Jay 
Published: April 2022

Abstract
Background
To report spectral domain optical coherence tomography (SDOCT) imaging findings in type 2 macular telangiectasia (MacTel) and correlate them with clinical stages and visual acuity.

Methods
This retrospective, cross-sectional study included type 2 MacTel cases who underwent SDOCT imaging with Spectralis machine. Macular SDOCT images were analysed. Imaging features were tested for correlation with different clinicals stages and visual acuity.

Results
212 eyes of 108 type 2 MacTel patients were included. Hyperreflective middle retinal layer (87%) was the most frequently detected abnormality. This was followed by inner retinal cavities (49%), outward bending of inner retinal layers (35%), retinal pigment clumps (35%) and foveal contour irregularity (31%). Hyperreflective middle retinal layers (p < 0.001), inner (p = 0.032) and outer retinal (p = 0.002) cavities and internal limiting membrane drape (p = 0.031) were associated with poor vision in non-proliferative group and presence of retinal pigment clumps (p = 0.002), subretinal fluid (p = 0.037) and foveal contour irregularity (p < 0.001) were associated with poor vision in proliferative group.

Conclusion
The described SDOCT features are practical for the diagnosis and staging in type 2 MacTel. Presence of hyperreflective middle retinal layers, hyporeflective inner and outer retinal cavities and internal limiting membrane drape were associated with poor vision in the non-proliferative group while retinal pigment clumps and subretinal neovascular membrane were associated with proliferative group and poor vision. Further long-term studies are required to describe the progressive and sequential changes on SDOCT.