bluuebunny/crossref_metadata_2025_split huggingface dataset:
Confidence-based laboratory test reduction recommendation algorithm
Authors: Huang Tongtong , Li Linda T. , Bernstam Elmer V. , Jiang Xiaoqian 
Published: May 2023

Abstract
Background
We propose a new deep learning model to identify unnecessary hemoglobin (Hgb) tests for patients admitted to the hospital, which can help reduce health risks and healthcare costs.

Methods
We collected internal patient data from a teaching hospital in Houston and external patient data from the MIMIC III database. The study used a conservative definition of unnecessary laboratory tests, which was defined as stable (i.e., stability) and below the lower normal bound (i.e., normality). Considering that machine learning models may yield less reliable results when trained on noisy inputs containing low-quality information, we estimated prediction confidence to assess the reliability of predicted outcomes. We adopted a “select and predict” design philosophy to maximize prediction performance by selectively considering samples with high prediction confidence for recommendations. Our model accommodated irregularly sampled observational data to make full use of variable correlations (i.e., with other laboratory test values) and temporal dependencies (i.e., previous laboratory tests performed within the same encounter) in selecting candidates for training and prediction.

Results
The proposed model demonstrated remarkable Hgb prediction performance, achieving a normality AUC of 95.89% and a Hgb stability AUC of 95.94%, while recommending a reduction of 9.91% of Hgb tests that were deemed unnecessary. Additionally, the model could generalize well to external patients admitted to another hospital.

Conclusions
This study introduces a novel deep learning model with the potential to significantly reduce healthcare costs and improve patient outcomes by identifying unnecessary laboratory tests for hospitalized patients.
Development and usability evaluation of an electronic health report form to assess health in young people: a mixed-methods approach
Authors: Lostelius Petra V , Mattebo Magdalena , Adolfsson Eva Thors , Söderlund Anne , Andersén Mikael , Vadlin Sofia , Revenäs Åsa 
Published: May 2023

Abstract
Background
Electronic Patient-Reported Outcomes (ePROs) have potential to improve health outcomes and healthcare. The development of health-technology applications, such as ePROs, should include the potential users and be theoretically grounded. Swedish Youth Health Clinics (YHCs) offer primarily sexual and psychological healthcare for young people aged 12 to 25 years old. Young people in healthcare settings are considered a vulnerable group. The development of a collection of Patient-Reported Outcomes (PROs) in an Electronic Health Report Form (eHRF) for identifying health and health-related problems in young people, was preceded by a qualitative interview study, exploring young people’s views on using an eHRF at YHCs and which questions about health an eHRF should contain. The aim of the current study was to develop and evaluate the usability of an eHRF prototype for identifying health and health-related problems in young people visiting YHCs.

Methods
This study used a participatory design. During the development, an expert panel consisting of eight researchers and one Information Technology worker, participated. A wide literature search was performed to find PROs to construct an eHRF prototype to cover health areas. A mixed methods usability evaluation included 14 participants (young people, healthcare professionals, and an expert panel).

Results
The development resulted in an eHRF prototype, containing ten reliable and valid health questionnaires addressing mental-, physical-, and sexual health and social support, a self-efficacy question, and background questions, in total 74 items. The interviews in the usability evaluation resulted in three categories describing the usability of the eHRF: ‘Captures the overall health of young people but needs clarification’, ‘Fun, easy, and optional and will keep young people’s interest’, and ‘Potential contribution to improve the health consultation’. The quantitative results support the usability of the eHRF for YHCs.

Conclusions
The participatory approach contributed to development of the eHRF prototype to cover health areas adapted for the target population. The usability evaluation showed that the eHRF was usable and had the potential for self-reflection and contributions to cooperation between young people and healthcare professionals during the health consultation.
Saving time and money in biomedical publishing: the case for free-format submissions with minimal requirements
Authors: Clotworthy Amy , Davies Megan , Cadman Timothy J. , Bengtsson Jessica , Andersen Thea O. , Kadawathagedara Manik , Vinther Johan L. , Nguyen Tri-Long , Varga Tibor V. 
Published: May 2023

Abstract
Background
Manuscript preparation and the (re)submission of articles can create a significant workload in academic jobs. In this exploratory analysis, we estimate the time and costs needed to meet the diverse formatting requirements for manuscript submissions in biomedical publishing.

Methods
We reviewed 302 leading biomedical journals’ submission guidelines and extracted information on the components that tend to vary the most among submission guidelines (the length of the title, the running title, the abstract, and the manuscript; the structure of the abstract and the manuscript, number of items and references allowed, whether the journal has a template). We estimated annual research funding lost due to manuscript formatting by calculating hourly academic salaries, the time lost to reformatting articles, and quantifying the total number of resubmissions per year. We interviewed several researchers and senior journal editors and editors-in-chief to contextualize our findings and develop guidelines that could help both biomedical journals and researchers work more efficiently.

Results
Among the analyzed journals, we found a huge diversity in submission requirements. By calculating average researcher salaries in the European Union and the USA, and the time spent on reformatting articles, we estimated that ~ 230 million USD were lost in 2021 alone due to reformatting articles. Should the current practice remain unchanged within this decade, we estimate ~ 2.5 billion USD could be lost between 2022 and 2030—solely due to reformatting articles after a first editorial desk rejection. In our interviews, we found alignment between researchers and editors; researchers would like the submission process to be as straightforward and simple as possible, and editors want to easily identify strong, suitable articles and not waste researchers’ time.

Conclusions
Based on the findings from our quantitative analysis and contextualized by the qualitative interviews, we conclude that free-format submission guidelines would benefit both researchers and editors. However, a minimum set of requirements is necessary to avoid manuscript submissions that lack structure. We developed our guidelines to improve the status quo, and we urge the publishers and the editorial-advisory boards of biomedical journals to adopt them. This may also require support from publishers and major international organizations that govern the work of editors.
A novel mutation in RNF216 gene in a Turkish case with Gordon Holmes syndrome
Authors: Durmaz Çelik Nazlı , Erzurumluoğlu Ebru , Özben Serkan , Toprak Uğur , Yorulmaz Göknur , Artan Sevilhan , Özkan Serhat 
Published: May 2023

Abstract
Background
Gordon Holmes syndrome (GHS) is a rare autosomal recessive disorder characterized by hypogonadotropic hypogonadism, cognitive decline, and cerebellar ataxia. Mutations in the Ring Finger Protein 216 (RNF216) gene have been known to be associated with GHS therewithal RNF216 mutations have been detected in cases with Huntington-like disease, 4H syndrome (hypodontia, hypomyelination, ataxia and hypogonadotropic hypogonadism), and congenital hypogonadotropic hypogonadism.

Case presentation
Here we report a novel homozygous frameshift mutation in RNF216 gene c.1860_1861dupCT (p.Cys621SerfsTer56) in a patient with hypogonadotropic hypogonadism, ataxia, and cognitive decline diagnosed with GHS also co-occurrence of parkinsonism and dystonia which was not reported before.

Conclusions
We report an extremely rare case of GHS. The core features of GHS are well defined, but genotype–phenotype correlations are still limited. To understand the pathophysiology of different phenotypes, the type and localization of novel mutations need to be defined, and the effect of these different variants on clinical features needs to be determined. Further studies should explain the factors of phenotypic variability present in GHS patients with RNF216 mutations.
A fully automated micro‑CT deep learning approach for precision preclinical investigation of lung fibrosis progression and response to therapy
Authors: Buccardi Martina , Ferrini Erica , Pennati Francesca , Vincenzi Elena , Ledda Roberta Eufrasia , Grandi Andrea , Buseghin Davide , Villetti Gino , Sverzellati Nicola , Aliverti Andrea , Stellari Franco Fabio 
Published: May 2023

AbstractMicro-computed tomography (µCT)-based imaging plays a key role in monitoring disease progression and response to candidate drugs in various animal models of human disease, but manual image processing is still highly time-consuming and prone to operator bias. Focusing on an established mouse model of bleomycin (BLM)-induced lung fibrosis we document, here, the ability of a fully automated deep-learning (DL)-based model to improve and speed-up lung segmentation and the precise measurement of morphological and functional biomarkers in both the whole lung and in individual lobes. µCT-DL whose results were overall highly consistent with those of more conventional, especially histological, analyses, allowed to cut down by approximately 45-fold the time required to analyze the entire dataset and to longitudinally follow fibrosis evolution and response to the human-use-approved drug Nintedanib, using both inspiratory and expiratory μCT. Particularly significant advantages of this µCT-DL approach, are: (i) its reduced experimental variability, due to the fact that each animal acts as its own control and the measured, operator bias-free biomarkers can be quantitatively compared across experiments; (ii) its ability to monitor longitudinally the spatial distribution of fibrotic lesions, thus eliminating potential confounding effects associated with the more severe fibrosis observed in the apical region of the left lung and the compensatory effects taking place in the right lung; (iii) the animal sparing afforded by its non-invasive nature and high reliability; and (iv) the fact that it can be integrated into different drug discovery pipelines with a substantial increase in both the speed and robustness of the evaluation of new candidate drugs. The µCT-DL approach thus lends itself as a powerful new tool for the precision preclinical monitoring of BLM-induced lung fibrosis and other disease models as well. Its ease of operation and use of standard imaging instrumentation make it easily transferable to other laboratories and to other experimental settings, including clinical diagnostic applications.
Use of rapid diagnostic tests for the detection of ancient malaria infections in dental pulp from the sixth century in Versailles, France
Authors: Boualam Mahmoud A. , Heitzmann Annick , Mousset Florence , Aboudharam Gérard , Drancourt Michel , Pradines Bruno 
Published: May 2023

Abstract
Background
Paleomicrobiological data have clarified that Plasmodium spp. was circulating in the past in southern European populations, which are now devoid of malaria. The aim of this study was to evaluate the efficacy of immunodetection and, more particularly, rapid diagnostic tests (RDT), in order to further assess Plasmodium infections in ancient northern European populations.

Methods
A commercially available RDT, PALUTOP® + 4 OPTIMA, which is routinely used to detect malaria, was used to detect Plasmodium antigens from proteins recovered from ancient specimens extracted from 39 dental pulp samples. These samples were collected from 39 individuals who were buried in the sixth century, near the site of the current Palace of Versailles in France. Positive and negative controls were also used. Antigens detected were quantified using chemiluminescence imaging system analysis.

Results
Plasmodium antigens were detected in 14/39 (35.9%) individuals, including Plasmodium vivax antigens in 11 individuals and Plasmodium falciparum antigens co-detected in two individuals, while Pan-Plasmodium antigens were detected in three individuals. Controls all yielded expected results.

Conclusions
The data reported here showed that RDTs are a suitable tool for detecting Plasmodium spp. antigens in ancient dental pulp samples, and demonstrated the existence of malaria in Versailles, France, in the sixth century. Plasmodium vivax, which is regarded as being responsible for an attenuated form of malaria and less deadly forms, was the most prevalent species. This illustrates, for the first time in ancient populations, co-infection with P. falciparum, bringing into question the climate-driven ecosystems prevailing at that time in the Versailles area.
The deformities of acute diaphyseal clavicular fractures: a three-dimensional analysis
Authors: Chao Yi-Hsuan , Chou Ying-Chao , Lin Chun-Li 
Published: May 2023

Abstract
Background
Although minimally invasive surgeries have gained popularity in many orthopaedic fields, minimally invasive approaches for diaphyseal clavicular fracture have not been widely performed, which is attributed to difficulties in performing a closed reduction of fracture deformities of a curved bone in a three-dimensional space. The goal of this study was to investigate the radiographic parameters of fracture deformities in a three-dimensional space and to identify the risk factors for deformities.

Methods
The computed tomography images of 100 patients who sustained a clavicle fracture were included. Five parameters were used to analyze the deformities: change in clavicle length, fracture displacement, and fragment rotation around the X, Y, Z axes. The change in length was assessed using the length of the endpoint line. The displacement was assessed using the distance between the fracture midpoints. The rotation deformities were assessed using the Euler angles. The correlation between the parameters was evaluated with the Pearson correlation coefficient. The risk factors were evaluated using univariable analysis and multiple regression analysis.

Results
The average change in length was − 5.3 ± 8.3 mm. The displacement was 11.8 ± 7.1 mm. The Euler angles in the Z-Y-X sequences were -1 ± 8, 1 ± 8, and − 8 ± 13 degrees. The correlation coefficient between the change in length and the displacement was − 0.724 (p < 0.001). The variables found to increase the risk of shortening and displacement were right-sided fracture (p = 0.037), male sex (p = 0.015), and multifragmentary type (p = 0.020). The variables found to increase the risk of rotation deformity were the number of rib fractures (p = 0.001) and scapula fracture (p = 0.025).

Conclusions
There was a strong correlation between shortening and displacement. The magnitude of anterorotation around the X axis was greater than the magnitude of retraction around the Z axis and depression around the Y axis. The risk factors for shortening and displacement included right-sided fracture, male sex, and multifragmentary type. The risk factor for retraction around the Z axis was the number of rib fractures, and the risk factor for depression around the Y axis was scapula fracture. These results could be useful adjuncts in guiding minimally invasive surgical planning for diaphyseal clavicular fractures.
Determinants of maternal and neonatal PFAS concentrations: a review
Authors: McAdam Jordan , Bell Erin M. 
Published: May 2023

AbstractPer- and polyfluoroalkyl substances (PFAS) are used for their properties such as stain and water resistance. The substances have been associated with adverse health outcomes in both pregnant mothers and infants, including pre-eclampsia and low birthweight. A growing body of research suggests that PFAS are transferred from mother to fetus through the placenta, leading to in utero exposure. A systematic review was performed using the PubMed database to search for studies evaluating determinants of PFAS concentrations in blood matrices of pregnant mothers and neonates shortly after birth. Studies were included in this review if an observational study design was utilized, exposure to at least one PFAS analyte was measured, PFAS were measured in maternal or neonatal matrices, at least one determinant of PFAS concentrations was assessed, and results such as beta estimates were provided. We identified 35 studies for inclusion in the review and evaluated the PFAS and determinant relationships among the factors collected in these studies. Parity, breastfeeding history, maternal race and country of origin, and household income had the strongest and most consistent evidence to support their roles as determinants of certain PFAS concentrations in pregnant mothers. Reported study findings on smoking status, alcohol consumption, and pre-pregnancy body mass index (BMI) suggest that these factors are not important determinants of PFAS concentrations in pregnant mothers or neonates. Further study into informative factors such as consumer product use, detailed dietary information, and consumed water sources as potential determinants of maternal or neonatal PFAS concentrations is needed. Research on determinants of maternal or neonatal PFAS concentrations is critical to estimate past PFAS exposure, build improved exposure models, and further our understanding on dose–response relationships, which can influence epidemiological studies and risk assessment evaluations. Given the potential for adverse outcomes in pregnant mothers and neonates exposed to PFAS, it is important to identify and understand determinants of maternal and neonatal PFAS concentrations to better implement public health interventions in these populations.
Carbon dots-mediated synthesis of gold nanodendrites with extended absorption into NIR-II window for in vivo photothermal therapy
Authors: Liu Guoyong , Wang Shuxian , Wang Shumin , Wu Rongrong , Li Hui , Zha Menglei , Song Jibin , Yin Yuxin , Li Kai , Mu Jing , Shi Yu 
Published: May 2023

Abstract
Background
Photothermal therapy (PTT) in the second near-infrared (NIR-II) window has attracted extensive attention due to the benefits in high maximum permissible exposure and penetration depth. Current photothermal agents generally show a broadband absorption accompanied by a gradual attenuation of absorption in the NIR-II window, leading to poor effect of PTT. It remains a great challenge to gain photothermal agents with strong and characteristic absorption in NIR-II regions. To overcome this problem, based on carbon dots (CDs)-mediated growth strategy, we proposed a simple and feasible approach to prepare plasmonic gold nanodendrites (AuNDs) with NIR-II absorption to enhance the therapeutic effect of PTT.

Results
By rationally regulating the size and branch length of AuNDs, the AuNDs exhibited a broadband absorption from 300 to 1350 nm, with two characteristic absorption peaks located at 1077 and 1265 nm. The AuNDs demonstrated desired optical photothermal conversion efficiency (38.0%), which was further applied in NIR-II photoacoustic imaging (PAI) and PTT in human colon cancer cells (HCT 116)-tumor-bearing mice model. The tumor cells could be effectively eliminated in vivo under 1064 nm laser irradiation by the guidance of PAI.

Conclusions
We reported a simple but powerful synthetic method to obtain the unique AuNDs with strong and characteristic absorption peaks in the NIR-II window. This study provides a promising solution to tuning the growth of nanoparticles for bioimaging and phototherapy in the NIR-II window.

Graphical Abstract
Advanced glycation end-products and its soluble receptor are not independent predictors of incident dysglycaemia or metabolic syndrome in women with polycystic ovary syndrome: a prospective observational study
Authors: Tong Yu Wing , Ko Jennifer Ka Yee , Lam Karen Siu Ling , Tam Sidney , Lee Vivian Chi Yan , Ho Pak Chung , Ng Ernest Hung Yu , Li Raymond Hang Wun 
Published: May 2023

Abstract
Background
To evaluate the association of serum advanced glycation end-products (AGEs) and its soluble receptor of AGE (sRAGE) levels with dysglycaemia and metabolic syndrome in women with polycystic ovary syndrome (PCOS).

Methods
This was an analysis of a cohort of women with PCOS who were prospectively recruited for a longitudinal observational study on their endocrine and metabolic profile between January 2010 and December 2013. The association of serum AGEs and sRAGE levels with dysglycaemia and metabolic syndrome at the second-year visit (the index visit) and the sixth-year visit (the outcome visit) were determined. Comparisons of continuous variables between groups were made using the Mann–Whitney U-test. Spearman test was used for correlation analysis. Multivariate binary logistic regression analysis was employed to identify the factors independently associated with the outcome events.

Results
A total of 329 women were analysed at the index visit. Significantly lower serum levels of sRAGE (both p < 0.001), but no significant difference in AGEs, were observed in those with dysglycaemia or metabolic syndrome. At the outcome visit, those with incident metabolic syndrome had a significantly lower initial serum sRAGE levels (p = 0.008). The association of serum sRAGE with dysglycaemia and metabolic syndrome at the index visit was no longer significant in multivariate logistic regression after controlling for body mass index, free androgen index and homeostatic model assessment for insulin resistance (HOMA-IR). sRAGE was also not significantly associated with incident metabolic syndrome at the outcome visit on multivariate logistic regression.

Conclusions
Serum sRAGE levels are significantly lower in women with PCOS who have dysglycaemia or metabolic syndrome, and in those developing incident metabolic syndrome in four years. However, it does not have a significant independent association with these outcome measures after adjusting for body mass index, free androgen index and HOMA-IR.