bluuebunny/crossref_metadata_2025_split huggingface dataset:
Density of Health Workforce Correlates to Disease Outcomes: Evidence From Global Data in Otolaryngology
Authors: Stanford‐Moore Gaelen Britton , Cahill Gabrielle , Raj Ankit , Irakoze Pacifique , Alkire Blake , Bhutta Mahmood F. 
Published: March 2022

ObjectiveTo better understand the impact of the otolaryngology‐specific workforce on the burden of related diseases.Study DesignRetrospective analysis of existing workforce density data as compared with the incidence, mortality, and morbidity data for 4 otolaryngologic diseases.SettingAn overall 138 countries with known otolaryngology–head and neck surgery workforce and epidemiologic data.MethodsWe obtained raw data on workforce estimates of ear, nose, and throat surgical specialists from the World Health Organization. Disease burdens for 4 conditions were estimated via 2 ratios, the mortality:incidence ratio (MIR) and YLD:incidence ratio (years lost to disability), as specified in the Global Burden of Disease database. These were correlated to country‐specific otolaryngologist density data in univariate and multivariate analyses.ResultsIncreased density of the ear, nose, and throat workforce correlated with better outcomes for otolaryngologic‐treated surgical diseases. A 10% increase in otolaryngology workforce density was associated with a 0.27% reduction in YLD:incidence ratio for chronic otitis media, a 0.94% reduction in MIR for lip and oral cavity cancer, a 1.46% reduction in MIR for laryngeal cancer, and a 1.34% reduction in MIR for pharyngeal cancer (all P <. 001)—an effect that remained after adjustment for health systems factors for all conditions but chronic otitis media.ConclusionThe density of the surgical workforce is assumed to affect disease outcomes, but ours is the first analysis to show that increased workforce density for a specific surgical specialty correlates with improved disease outcomes. While there is a consensus to increase access to health care providers, quantifying the effect on disease outcomes is an important metric for those performing health economics modeling, particularly where resources are limited.
Single cell lineage reconstruction using distance-based algorithms and the R package, DCLEAR
Authors: Gong Wuming , Kim Hyunwoo J. , Garry Daniel J. , Kwak Il-Youp 
Published: March 2022

AbstractBackgroundDCLEAR is an R package used for single cell lineage reconstruction. The advances of CRISPR-based gene editing technologies have enabled the prediction of cell lineage trees based on observed edited barcodes from each cell. However, the performance of existing reconstruction methods of cell lineage trees was not accessed until recently. In response to this problem, the Allen Institute hosted the Cell Lineage Reconstruction Dream Challenge in 2020 to crowdsource relevant knowledge from across the world. Our team won sub-challenges 2 and 3 in the challenge competition.ResultsThe DCLEAR package contained the R codes, which was submitted in response to sub-challenges 2 and 3. Our method consists of two steps: (1) distance matrix estimation and (2) the tree reconstruction from the distance matrix. We proposed two novel methods for distance matrix estimation as outlined in the DCLEAR package. Using our method, we find that two of the more sophisticated distance methods display a substantially improved level of performance compared to the traditional Hamming distance method. DCLEAR is open source and freely available from R CRAN and from under the GNU General Public License, version 3.ConclusionsDCLEAR is a powerful resource for single cell lineage reconstruction.
Determining the applicability of the RSNA radiology lexicon (RadLex) in high-grade glioma MRI reporting—a preliminary study on 20 consecutive cases with newly diagnosed glioblastoma
Authors: Huckhagel Torge , Stadelmann Christine , Abboud Tammam , Riedel Christian 
Published: March 2022

Abstract
Background
The implementation of a collective terminology in radiological reporting such as the RSNA radiological lexicon (RadLex) yields many benefits including unambiguous communication of findings, improved education, and fostering data mining for research purposes. While some fields in general radiology have already been evaluated so far, this is the first exploratory approach to assess the applicability of the RadLex terminology to glioblastoma (GBM) MRI reporting.

Methods
Preoperative brain MRI reports of 20 consecutive patients with newly diagnosed GBM (mean age 68.4 ± 10.8 years; 12 males) between January and October 2010 were retrospectively identified. All terms related to the tumor as well as their frequencies of mention were extracted from the MRI reports by two independent neuroradiologists. Every item was subsequently analyzed with respect to an equivalent RadLex representation and classified into one of four groups as follows: 1. verbatim RadLex entity, 2. synonymous/multiple equivalent(s), 3. combination of RadLex concepts, or 4. no RadLex equivalent. Additionally, verbatim entities were categorized using the hierarchical RadLex Tree Browser.

Results
A total of 160 radiological terms were gathered. 123/160 (76.9%) items showed literal RadLex equivalents, 9/160 (5.6%) items had synonymous (non-verbatim) or multiple counterparts, 21/160 (13.1%) items were represented by means of a combination of concepts, and 7/160 (4.4%) entities could not eventually be transferred adequately into the RadLex ontology.

Conclusions
Our results suggest a sufficient term coverage of the RadLex terminology for GBM MRI reporting. If applied extensively, it may improve communication of radiological findings and facilitate data mining for large-scale research purposes.
Determining factors of functioning in hemodialysis patients using the international classification of functioning, disability and health
Authors: Santos Luciana M. M. , Figueiredo Pedro Henrique S. , Silva Ana C. R. , Campos Patrícia C. , Gonçalves Gabriele T. , de Paula C Freitas Jaqueline , da Silva Junior Fidelis Antônio , Santos Jousielle Márcia , Alves Frederico L. , Rodrigues Vanessa G. B. , Maciel Emílio Henrique B. , Prates Maria Cecília S. M. , Sañudo Borja , Taiar Redha , Bernardo-Filho Mario , Lima Vanessa P. , Costa Henrique S. , Mendonça Vanessa A. , Lacerda Ana Cristina R. 
Published: March 2022

Abstract
Background
Hemodialysis (HD) treatment affects functioning, physical activity level, clinical biomarkers, and body composition. However, the association between these variables with functioning, considering International Classification of Functioning, Disability and Health (ICF) domains remains unclear. Thus, the aim of this study was to investigate the possible association between physical activity, biomarkers, and body composition with functioning in HD patients in reference to the ICF.

Methods
Eighty HD patients performed different tests grouped according to ICF domain: Body structure and function – handgrip strength (HS), 5-repetition sit-to-stand test, and 60-s sit-to-stand test (5-STS, 60-STS, respectively); Activity – short physical performance battery (SPPB); and Participation – participation scale questionnaire. Physical activity [Human Activity Profile questionnaire (HAP)], body composition (Dual-energy X-ray absorptiometry), Parathormone (PTH), and alkaline phosphatase were analyzed as possible variables associated with ICF domains. Data analyses were performed using simple and multiple regression models adjusted for age, duration of HD, and diuresis volume.

Results
In the body structure and function domain, appendicular lean mass, PTH level, and age were associated with HS (R2 = 0.558); HAP and PTH were associated with 5-STS (R2 = 0.263); and HAP, PTH, duration of HD, and age were associated with 60-STS (R2 = 0.337). In the activity domain, HAP, PTH, alkaline phosphatase, duration of HD, age, and body fat were associated with SPPB (R2 = 0.689). Finally, only HAP was associated with the participation scale (R2 = 0.067).

Conclusion
Physical activity and PTH levels are determinant protagonists of functioning in all ICF domains in hemodialysis patients.
An integrated modelling methodology for estimating global incidence and prevalence of hereditary spastic paraplegia subtypes SPG4, SPG7, SPG11, and SPG15
Authors: Vander Stichele Geert , Durr Alexandra , Yoon Grace , Schüle Rebecca , Blackstone Craig , Esposito Giovanni , Buffel Connor , Oliveira Inês , Freitag Christian , van Rooijen Stephane , Hoffmann Stéphanie , Thielemans Leen , Cowling Belinda S. 
Published: March 2022

Abstract
Background
Hereditary spastic paraplegias (HSPs) are progressively debilitating neurodegenerative disorders that follow heterogenous patterns of Mendelian inheritance. Available epidemiological evidence provides limited incidence and prevalence data, especially at the genetic subtype level, preventing a realistic estimation of the true social burden of the disease. The objectives of this study were to (1) review the literature on epidemiology of HSPs; and (2) develop an epidemiological model of the prevalence of HSP, focusing on four common HSP genetic subtypes at the country and region-level.

Methods
A model was constructed estimating the incidence at birth, survival, and prevalence of four genetic subtypes of HSP based on the most appropriate published literature. The key model parameters were assessed by HSP clinical experts, who provided feedback on the validity of assumptions. A model was then finalized and validated through comparison of outputs against available evidence. The global, regional, and national prevalence and patient pool were calculated per geographic region and per genetic subtype.

Results
The HSP global prevalence was estimated to be 3.6 per 100,000 for all HSP forms, whilst the estimated global prevalence per genetic subtype was 0.90 (SPG4), 0.22 (SPG7), 0.34 (SPG11), and 0.13 (SPG15), respectively. This equates to an estimated 3365 (SPG4) and 872 (SPG11) symptomatic patients, respectively, in the USA.

Conclusions
This is the first epidemiological model of HSP prevalence at the genetic subtype-level reported at multiple geographic levels. This study offers additional data to better capture the burden of illness due to mutations in common genes causing HSP, that can inform public health policy and healthcare service planning, especially in regions with higher estimated prevalence of HSP.
Neuroimaging appearance of hypothalamic hamartomas in monozygotic twins with Pallister-Hall syndrome: case report and review of the literature
Authors: Consales Alessandra , Ardemani Giulia , Cinnante Claudia Maria , Catalano Mariana Rita , Giavoli Claudia , Villa Roberta , Iascone Maria , Fontana Camilla , Bedeschi Maria Francesca , Fumagalli Monica 
Published: March 2022

Abstract
Background
Pallister-Hall syndrome (OMIM #146510) is a rare autosomal dominant condition caused by a mutation in the GLI3 gene. The cardinal feature of Pallister-Hall syndrome is the presence of hypothalamic hamartomas, which may manifest with seizures, panhypopituitarism and visual impairment. In Pallister-Hall syndrome, dysplastic histogenetic processes responsible for hypothalamic hamartomas are thought to disrupt early craniofacial development. The clinical presentation of Pallister-Hall syndrome may include: characteristic facies (low-set and posteriorly angulated ears, short nose with flat nasal bridge), cleft palate and uvula, bifid epiglottis and laryngotracheal cleft, limb anomalies (e.g., polysyndactyly, short limbs and nail dysplasia), anal atresia, genitourinary abnormalities and congenital heart defects.

Case presentation
We report the case of two monochorionic diamniotic twins diagnosed with Pallister-Hall syndrome during the neonatal period, after the identification of a hypothalamic hamartoma on day 1 by cerebral ultrasound scan, later confirmed by brain magnetic resonance imaging. Cerebral ultrasound and magnetic resonance imaging presentations were identical in both twins.

Discussion and conclusions
We review previously published cases (four reports) of hypothalamic hamartomas identified via cerebral ultrasound and compare reported ultrasonographic features. Main differential diagnoses based on cerebral ultrasound findings are discussed. Full description of typical magnetic resonance imaging appearance is also provided. This is the first case reported in the literature of monochorionic diamniotic twins affected by genetically confirmed Pallister-Hall syndrome with identical hypothalamic hamartomas at cerebral ultrasound and magnetic resonance imaging. Moreover, this paper adds to the existing literature on the sonographic appearance of hypothalamic hamartomas. Considering the consistency in hypothalamic hamartomas’ sonographic appearance, we support the use of cerebral ultrasound as a first-line neuroimaging modality in case of clinical suspicion of Pallister-Hall syndrome.

Graphical Abstract
Clinic and genetic similarity assessments of atypical carcinoid, neuroendocrine neoplasm with atypical carcinoid morphology and elevated mitotic count and large cell neuroendocrine carcinoma
Authors: Zhang Ying , Wang Weiya , Hu Qianrong , Liang Zuoyu , Zhou Ping , Tang Yuan , Jiang Lili 
Published: March 2022

Abstract
Background
Pulmonary neuroendocrine neoplasms can be divided into typical carcinoid, atypical carcinoid, large cell neuroendocrine carcinoma, and small cell (lung) carcinoma. According to the World Health Organization, these four neoplasms have different characteristics and morphological traits, mitotic counts, and necrotic status. Importantly, “a grey-zone” neoplasm with an atypical carcinoid-like morphology, where the mitotic rate exceeds the criterion of 10 mitoses per 2 mm2, have still not been well classified. In clinical practice, the most controversial area is the limit of 11 mitoses to distinguish between atypical carcinoids and large cell neuroendocrine carcinomas.

Methods
Basic and clinical information was obtained from patient medical records. A series of grey-zone patients (n = 8) were selected for exploring their clinicopathological features. In addition, patients with atypical carcinoids (n = 9) and classical large cell neuroendocrine carcinomas (n = 14) were also included to compare their similarity to these neoplasms with respect to tumour morphology and immunohistochemical staining.

Results
We found that these grey-zone tumour sizes varied and affected mainly middle-aged and older men who smoked. Furthermore, similar gene mutations were found in the grey-zone neoplasms and large cell neuroendocrine carcinomas, for the mutated genes of these two are mainly involved in PI3K-Akt signal pathways and Pathways in cancer, including a biallelic alteration of TP53/RB1 and KEAP1.

Conclusions
Our findings indicate that neuroendocrine neoplasm with atypical carcinoid morphology and elevated mitotic counts is more similar to large cell neuroendocrine carcinoma than atypical carcinoid. Furthermore, this study may help improve diagnosing these special cases in clinical practice to avoid misdiagnosis.
Serum untargeted lipidomics by UHPLC-ESI-HRMS aids the biomarker discovery of colorectal adenoma
Authors: Zhou Hailin , Nong Yanying , Zhu Yifan , Liang Yunxiao , Zhang Jiahao , Chen Hongwei , Zhu Pingchuan , Zhang Qisong 
Published: March 2022

Abstract
Background
Colorectal adenoma (CA) is an important precancerous lesion and early screening target of colorectal cancer (CRC). Lipids with numerous physiological functions are proved to be involved in the development of CRC. However, there is no lipidomic study with large-scale serum samples on diagnostic biomarkers for CA.

Methods
The serum lipidomics of CA patients (n = 50) and normal control (NR) (n = 50) was performed by ultra high performance liquid chromatography-high resolution mass spectrometry with electrospray ionization (UHPLC-ESI-HRMS). Univariate and multivariate statistical analyses were utilized to screen the differential lipids between groups, and combining the constituent ratio analysis and diagnostic efficiency evaluation by receiver operating characteristic (ROC) curve disclosed the potential mechanism and biomarkers for CA.

Results
There were obvious differences in serum lipid profiles between CA and NR groups. Totally, 79 differential lipids were selected by criterion of P < 0.05 and fold change > 1.5 or < 0.67. Triacylglycerols (TAGs) and phosphatidylcholines (PCs) were the major differential lipids with ratio > 60%, indicating these two lipid metabolic pathways showed evident disequilibrium, which could contribute to CA formation. Of them, 12 differential lipids had good diagnostic ability as candidate biomarkers for CA (AUC ≥ 0.900) by ROC analysis.

Conclusions
To our knowledge, this is the first attempt to profile serum lipidomics and explore lipid biomarkers of CA to help early screening of CRC. 12 differential lipids are obtained to act as potential diagnostic markers of CA. PCs and fatty acids were the main dysregulated biomarkers for CA in serum.
Pre-diagnostic faecal calprotectin levels in patients with colorectal cancer: a retrospective study
Authors: Blad Nathalie , Palmqvist Richard , Karling Pontus 
Published: March 2022

Abstract
Background
Faecal calprotectin (FC) is a potential biomarker for colorectal cancer (CRC) screening. There is uncertainty if tumor characteristics are associated with FC levels. We investigated how tumor stage and tumor localization influence the extent of FC levels in patients with CRC in clinical practice.

Methods
In two cohorts of patients with CRC, we retrospectively analyzed FC tests (CALPRO®) performed within three months prior to diagnosis. One hundred twenty-four patients with CRC were included (mean age 68 years, 44% women).

Results
Ninety-eight patients with CRC (79%) had a FC ≥ 50 µg/g. FC correlated positively with tumor stage (UICC based on WHO TNM classification) (rs 0.24; p = 0.007) and with CRP levels (rs 0.31, p = 001), and a negatively with B-haemoglobin (rs -0.21; p = 0.019). The patients with right-sided CRC had significantly more often a FC ≥ 50 µg/g than patients with left-sided CRC (92% vs 74% p = 0.027). In a binary logistic regression analysis, tumor stage III/IV (adjusted OR 3.47; CI 1.27–9.42) and right-sided tumor localization (adjusted OR 3.80; CI 1.01–14.3) were associated with FC ≥ 50 µg/g. Tumor stage III/IV (adjusted OR 2.30; CI 1.04–5.10) and acetylsalicylic use (adjusted OR 3.54; CI 1.03–12.2) were associated with FC ≥ 100 µg/g. In a cox regression analysis, a FC ≥ 100 µg/g was not associated with survival (Hazard OR 0.61; CI 0.24–1.52).

Conclusions
Elevated pre-diagnostic FC levels were common in patients with CRC in close proximity to diagnosis. Right-sided localization and tumor stage were significantly associated with a rise in FC levels.
Spontaneous closure of a chronic full-thickness idiopathic macular hole after Irvine-Gass syndrome resolution
Authors: da Costa Douglas Rodrigues , Braga Pedro Gomes Oliveira , Ariello Leonardo Eleuterio , Zacharias Leandro Cabral 
Published: March 2022

Abstract
Background
Full-thickness idiopathic macular hole (IMH) usually causes serious visual deformities and visual acuity loss. Pseudophakic cystic macular edema, also known as Irvine-Gass syndrome, is another entity that causes visual disturbances, and occurs mainly after cataract extraction. We present a case report of a patient that was diagnosed with a full-thickness macular hole that spontaneously closed after the resolution of an Irvine-Gass syndrome, which occurred after an uneventful cataract extraction.

Case presentation
A 75 years-old female presented with the complaints of decreased visual acuity and color contrast sensitivity on both eyes (OU) and central visual field deformations on her left eye (LE). She was diagnosed with a full-thickness IMH on her LE, and cataract on OU. After an uneventful cataract extraction via phacoemulsification, she developed an Irvine-Gass syndrome at her LE, which was treated topically. The IMH closed spontaneously after the resolution of the Irvine-Gass syndrome, and the patient is being followed with no further complaints.

Conclusion
The exact mechanism for spontaneous closure of full-thickness idiopathic macular holes is still not completely understood. In this case, we hypothesize that the coalesced intraretinal cysts caused by the Irvine-Gass syndrome formed a bridge-like structure connecting the inner walls of the macular hole, thus connecting the remnants of the Muller cells which enabled the full recovery of the normal foveal structure.
Comparing a mindfulness- and CBT-based guided self-help Internet- and mobile-based intervention against a waiting list control condition as treatment for adults with frequent cannabis use: a randomized controlled trial of CANreduce 3.0
Authors: Dey Michelle , Wenger Andreas , Baumgartner Christian , Herrmann Ute , Augsburger Mareike , Haug Severin , Malischnig Doris , Schaub Michael P. 
Published: March 2022

AbstractBackgroundThough Internet- and mobile-based interventions (IMIs) and mindfulness-based interventions (generally deliveredin-situ) appear effective for people with substance use disorders, IMIs incorporating mindfulness are largely missing, including those targeting frequent cannabis use.MethodsThis paper details the protocol for a three-arm randomized controlled trial comparing a mindfulness-based self-help IMI (arm 1) and cognitive-behavioral therapy (CBT)-based self-help IMI (arm 2) versus being on a waiting list (arm 3) in their effectiveness reducing cannabis use in frequent cannabis users. Predictors of retention, adherence and treatment outcomes will be identified and similarities between the two active intervention arms explored. Both active interventions last six weeks and consist of eight modules designed to reduce cannabis use and common mental health symptoms. With a targeted sample size ofn = 210 per treatment arm, data will be collected at baseline immediately before program use is initiated; at six weeks, immediately after program completion; and at three and six months post baseline assessment to assess the retention of any gains achieved during treatment.The primary outcome will be number of days of cannabis use over the preceding 30 days. Secondary outcomes will include further measures of cannabis use and use of other substances, changes in mental health symptoms and mindfulness, client satisfaction, intervention retention and adherence, and adverse effects. Data analysis will follow ITT principles and primarily employ (generalized) linear mixed models.DiscussionThis RCT will provide important insights into the effectiveness of an IMI integrating mindfulness to reduce cannabis use in frequent cannabis users.Trial registrationInternational Standard Randomized Controlled Trial Number Registry:ISRCTN14971662; date of registration: 09/09/2021.