bluuebunny/crossref_metadata_2025_split huggingface dataset:
Strategies to facilitate adolescent access to medicines: Improving regulatory guidance
Authors: Bucci-Rechtweg Christina , Siapkara Angeliki , An Haack Bonnet Kristina , Corriol Rohou Solange , Haf Davies Elin , Dehlinger Kremer Martine , Gamalo Margaret , Moreno Carmen , Nelson Robert M , Thomas Turner Rhian 
Published: November 2022

Background: Historically, pediatric medicines are developed after adult trials are completed, even when identical drug targets and disease similarities exist across the populations. This has resulted in significant delays in the authorization of medicines for adolescent use, limiting access to beneficial drugs. This study sought to understand how adolescent inclusion in adult trials is positioned in regulatory guidance documents as they set critical expectations for trial design and regulatory decision-making. Methods: This study utilized a qualitative analysis approach. Guidance documents were identified via Food and Drug Administration and European Medicines Agency websites. Utilizing a blinded adjudication process, the documents were classified as permissive, exclusionary, or silent regarding recommendations about adolescent inclusion in adult clinical trials. A post hoc analysis of similarities and differences between the Food and Drug Administration and European Medicines Agency guidance documents was conducted to assess the possible role of regional pediatric research laws on age-inclusive trial methodologies as well as emergent themes by therapeutic area. Results: In total, 96 Food and Drug Administration (1977 to 2019) and 106 European Medicines Agency (1987 to 2019) guidance documents were identified for analysis. The guidance contained explicit or implicit recommendations supporting adolescent inclusion in adult trials in 32% of Food and Drug Administration and 15% of European Medicines Agency documents, while 14% and 21%, respectively, were found to be exclusionary. A large number of guidance documents were silent regarding the applicability of adolescent-inclusive trial designs (53% and 64%, Food and Drug Administration and European Medicines Agency, respectively). Analysis by therapeutic area revealed the most permissive of adolescent inclusion in Food and Drug Administration guidance for infectious diseases and conditions requiring blood products in European Medicines Agency guidance. A more holistic approach to age-inclusive trial design was identified in disease guidance published by the Food and Drug Administration Oncology Center of Excellence. Discussion: There are many influences on the development and/or revision of regulatory guidance documents. Substantial scientific knowledge and regulatory precedence for the inclusion of adolescents within adult trials are available to inform research approaches. Our study has identified important opportunities for the enhancement of guidance. For example, contextualization of developmental factors influencing adolescent disease progression provides insights into the role of adolescent inclusion. If addressed, guidance documents can facilitate broader acceptance of age-inclusive trial methodologies and accelerate adolescent access to medicines.
Anatomically reduced fixation should always be considered when treating B and C proximal epiphyseal humeral fractures
Authors: Tarallo Luigi , Micheloni Gian Mario , Giorgini Andrea , Lombardi Martina , Limone Beatrice , Catani Fabio , Porcellini Giuseppe 
Published: November 2022

Abstract
Background
Proximal humeral fractures are commonly observed in elderly patients. Management of these injuries is controversial. Literature comparing locking plate fixation, arthroplasty, and conservative treatments show no clear advantages for any of these management strategies. Thus far, no study has considered anatomically reduced fractures obtained after locking plate treatment. To clarify the best surgical procedure in middle-aged patients, we considered outcomes and major complications leading to surgical revision following an anatomically reduced fracture fixed with locking plate and reverse shoulder arthroplasty (RSA) in the treatment of type B/C fractures in patients between 50 and 75 years of age.

Methods
This is a retrospective study including 59 patients between 50 and 75 years of age with type B/C proximal humeral fracture treated with RSA or with locking plate fixation (resulting in an anatomical reduction) between January 2010 and December 2018. Preoperative radiographs and computed tomography (CT) were evaluated in all patients. Clinical and radiologic follow-up was performed using range of motion (ROM), the Constant–Murley Score (CMS), the Oxford Shoulder Score (OSS), the Simple Shoulder Test (SST), the Subjective Shoulder Value (SSV), and visual analog scale (VAS). Major complications were considered.

Results
In the plate fixation group, ROM, CMS, SST, and VAS were higher than in the RSA group. Lower complication rates compared with the literature were observed in both groups. Anatomically reduced fracture fixed with plate and screw could outperform RSA in terms of outcome. In second-level centers where traumatology is performed by surgeons with great expertise in upper limb trauma, the choice between plate fixation and reverse arthroplasty should be made during surgery.

Conclusion
Anatomically reduced fractures showed better outcomes compared with RSA in type B/C fractures. Surgeons should always try to perform a reduction of the fracture in order to understand if a plate fixation could be feasible. If it is impossible to perform an anatomical reduction, we suggest to consider RSA. This is a retrospective observational study.
Transcriptional and biochemical analyses of Planomicrobium strain AX6 from Qinghai-Tibetan Plateau, China, reveal hydrogen peroxide scavenging potential
Authors: Bahadur Ali , Li Ting , Sajjad Wasim , Nasir Fahad , Zia Muhammad Amir , Wu Minghui , Zhang Gaosen , Liu Guangxiu , Chen Tuo , Zhang Wei 
Published: November 2022

Abstract
Background
The bacterial mechanisms responsible for hydrogen peroxide (H2O2) scavenging have been well-reported, yet little is known about how bacteria isolated from cold-environments respond to H2O2 stress. Therefore, we investigated the transcriptional profiling of the Planomicrobium strain AX6 strain isolated from the cold-desert ecosystem in the Qaidam Basin, Qinghai-Tibet Plateau, China, in response to H2O2 stress aiming to uncover the molecular mechanisms associated with H2O2 scavenging potential.

Methods
We investigated the H2O2-scavenging potential of the bacterial Planomicrobium strain AX6 isolated from the cold-desert ecosystem in the Qaidam Basin, Qinghai-Tibet Plateau, China. Furthermore, we used high-throughput RNA-sequencing to unravel the molecular aspects associated with the H2O2 scavenging potential of the Planomicrobium strain AX6 isolate.

Results
In total, 3,427 differentially expressed genes (DEGs) were identified in Planomicrobium strain AX6 isolate in response to 4 h of H2O2 (1.5 mM) exposure. Besides, Kyoto Encyclopedia of Genes and Genomes pathway and Gene Ontology analyses revealed the down- and/or up-regulated pathways following H2O2 treatment. Our study not only identified the H2O2 scavenging capability of the strain nevertheless also a range of mechanisms to cope with the toxic effect of H2O2 through genes involved in oxidative stress response. Compared to control, several genes coding for antioxidant proteins, including glutathione peroxidase (GSH-Px), Coproporphyrinogen III oxidase, and superoxide dismutase (SOD), were relatively up-regulated in Planomicrobium strain AX6, when exposed to H2O2.

Conclusions
Overall, the results suggest that the up-regulated genes responsible for antioxidant defense pathways serve as essential regulatory mechanisms for removing H2O2 in Planomicrobium strain AX6. The DEGs identified here could provide a competitive advantage for the existence of Planomicrobium strain AX6 in H2O2-polluted environments.
Metagenomic and proteomic analysis of bacterial retting community and proteome profile in the degumming process of kenaf bast
Authors: Xu Huan , Zhang Lixia , Feng Xiangyuan , Yang Qi , Zheng Ke , Duan Shengwen , Cheng Lifeng 
Published: November 2022

Abstract
Background
Data on the microbial community and functional proteins associated with degumming in kenaf remains scant. Here, we analyzed the microbial communities associated with kenaf (Hibiscus cannabinus) bast fibers during retting to identify potential candidate degumming bacteria. Retting liquids were collected and analyzed at 0 days, 10 days, and 34 days and then evaluated the yield and quality of kenaf fiber at the different retting times. Besides, the microbial communities were characterized using metagenomic and proteomic analysis by LC–MS/MS technology.

Results
The data showed that increase in the retting time significantly improves the softness, dispersion, and fiber whiteness of the kenaf fiber. The relative abundance of Acinetobacter increased from 2.88% at the baseline to 6.64% at the 34th retting. On the other hand, some members of Clostridium were reduced from 3% at the baseline to 2% at the 34th retting. Analysis of carbohydrate active enzymes showed constant changes in the utilization of carbohydrates. Besides, benzoquinone reductase, cellobiose dehydrogenase, glucose 1-oxidase, aryl alcohol oxidase and alcohol oxidase were the top five most abundant enzymes in the retting liquids. This present results demonstrated that the expressions of B7GYR8, Q6RYW5 and Q6FFK2 proteins were suppressed in Acinetobacter with the retting time. On the contrary, P05149 was upregulated with the retting time. In Clostridium, P37698, P52040 and P54937 proteins were upregulated with the retting time.

Conclusion
In addition, bacteria Acinetobacter and Clostridium might be playing important roles in the kenaf degumming process. Similarly, up-regulation of P37698, P52040 and P54937 proteins is an important manifestation and mediates important roles in the degumming process.
Phenotypic differences among and within extant populations of Chrysanthemum arcticum L. and C. a. subsp. arcticum
Authors: Liu Yunjia , Anderson Neil O. 
Published: November 2022

AbstractBackgroundChrysanthemum arcticum, arctic daisy and its two subspecies (Chrysanthemum arcticumsubsp.arcticum,Chrysanthemum arcticumsubsp.polaré) are the only chrysanthemum species native to North America. A study on species’ variation in morphological and diagnostic traits is important to link morphological traits with previously described single nucleotide polymorphism (SNP) markers, particularly when the genomes are sequenced. The purpose of this study was to establish phenotypic differences and soil conditions among wildC. arcticumandC. a.subsp.arcticumpopulations, when grown in a uniform environment for two years, for potential linkages with our SNP library. Sixteen quantitative morphological traits and five qualitative morphological traits were investigated for 255 individuals from nineC. arcticumpopulations and 326 individuals from 21C. a.subsp.arcticumpopulations.ResultsIn long-day controlled environment,C. arcticumflowering rate was 0% in Year 1, increased to 2.7% in Year 2, whileC. a.subsp.arcticumflowering rate was 98.5% in Year 2. Two distinct clusters, distributed by taxonomic classification, were detected by Principal component analysis (PCoA) for 551 individuals fromC. arcticumandC. a.subsp.arcticum.Pearson’s correlation coefficient analysis indicated a positive and significant correlation between plant height, flower fresh and dry weights. Flower fresh weights were correlated with Δflower weight, while inflorescence length had showed a negative correlation with leaf number. Soil samples had high Na levels along with heavy metals. Thus, the species are salt-tolerant.ConclusionA high level of salt tolerance (Na) is tolerated by these maritime species which is a unique trait inChrysanthemum. A new diagnostic trait of inflorescence length was discovered to distinguish amongC. arcticumandC. a.subsp.arcticum.Significant flowering differences occurred among the speciesC. arcticumandC. a.subsp.arcticumunder same photoperiodic environment, including flowering rates and visible bud date. This study on the species’ variation in morphological and diagnostic traits is of importance to link morphological traits with single nucleotide polymorphism (SNP) markers.
High vaccine effectiveness against severe COVID-19 in the elderly in Finland before and after the emergence of Omicron
Authors: Baum Ulrike , Poukka Eero , Leino Tuija , Kilpi Terhi , Nohynek Hanna , Palmu Arto A. 
Published: November 2022

Abstract
Background
The elderly are highly vulnerable to severe COVID-19. Waning immunity and emergence of Omicron have caused concerns about reduced effectiveness of COVID-19 vaccines. The objective was to estimate vaccine effectiveness (VE) against severe COVID-19 among the elderly.

Methods
This nationwide, register-based cohort analysis included all residents aged 70 years and over in Finland. The follow-up started on December 27, 2020, and ended on March 31, 2022. The outcomes of interest were COVID-19-related hospitalization and intensive care unit (ICU) admission timely associated with SARS-CoV-2 infection. VE was estimated as one minus the hazard ratio comparing the vaccinated and unvaccinated and taking into account time since vaccination. Omicron-specific VE was evaluated as the effectiveness observed since January 1, 2022.

Results
The cohort included 896,220 individuals. Comirnaty (BioNTech/Pfizer) VE against COVID-19-related hospitalization was 93% (95% CI 89–95%) and 85% (95% CI 82–87%) 14–90 and 91–180 days after the second dose; VE increased to 95% (95% CI 94–96%) 14–60 days after the third dose. VE of other homologous and heterologous three dose series was similar. Protection against severe COVID-19 requiring ICU treatment was even better. Since January 1, 2022, Comirnaty VE was 98% (95% CI 92–99%) and 92% (95% CI 87–95%) 14–90 and 91–180 days after the second and 98% (95% CI 95–99%) 14–60 days after the third dose.

Conclusions
VE against severe COVID-19 is high among the elderly. It waned slightly after two doses, but a third restored the protection. VE against severe COVID-19 remained high even after the emergence of Omicron.
A case report of severe systemic herpes simplex virus-1 (HSV-1) infection with multi-organ involvement after a course of oral corticosteroid treatment
Authors: Kim Myeongji , Jalal Ayesha , Rubio-Gomez Heysu , Bromberg Romina 
Published: November 2022

Abstract
Background
Herpes simplex virus (HSV) rarely causes organ-invasive infection. Diagnosis and treatment for such infections are often delayed, and mortality is high. We present the first reported case of disseminated HSV-1 infection in an adult causing liver failure, myocarditis, and encephalitis in a patient who recovered after receiving parenteral acyclovir treatment.

Case presentation
A 46-year-old female presented with fever, chills, and malaise after 2 weeks of oral corticosteroid treatment for uveitis. She was diagnosed with disseminated HSV-1 infection with multi-organ involvement causing hepatitis, encephalitis, and myocarditis. Diagnosis was made timely using serum polymerase chain reaction (PCR) for HSV DNA and the patient was given intravenous acyclovir treatment promptly, which led to her survival without significant morbidity.

Conclusions
Clinicians should have a low threshold for suspecting HSV infection and ordering HSV PCR to decrease morbidity and mortality when there is a high clinical suspicion of systemic HSV infection with multi-organ involvement. Serum PCR for HSV DNA is an excellent modality for an initial diagnostic approach. Further research is warranted to elucidate causality between a course of corticosteroid therapy and systemic HSV-1 infection without major immunosuppressive comorbidities or treatments.
The effect of vitamin D supplementation on oxidative stress and inflammatory biomarkers in pregnant women: a systematic review and meta-analysis of clinical trials
Authors: Motamed Soudabe , Nikooyeh Bahareh , Anari Razieh , Motamed Somayeh , Mokhtari Zeinab , Neyestani Tirang 
Published: November 2022

Abstract
Background
Vitamin D deficiency, a common problem among pregnant women, is linked with maternal inflammation, oxidative stress and consequent adverse pregnancy outcomes. The aim of this systematic review was to evaluate the effect of vitamin D supplementation on oxidative stress and inflammatory biomarkers in pregnant women according to the PRISMA guidance.

Methods
Four databases including PubMed/MEDLINE, Scopus, Web of Science and Cochrane were used for searching papers published until 25th July 2022. Clinical trials that assessed 25-Hydroxyvitamin D (25(OH)D), inflammatory markers (including high sensitivity C-reactive protein (hs-CRP) and certain cytokines) and oxidative stress markers (including malondialdehyde (MDA), total antioxidant capacity (TAC) and glutathione (GSH)) in pregnant women, were included in this review. The primary search of three databases displayed 21571 records. After removing duplicates and irrelevant articles, 17 eligible RCTs included for more evaluation. Random effect model and Der Simonian-Laird method were used to pool the data of studies. Risk of bias assessed according to version 2 of the Cochrane risk-of-bias tool for randomized trials.

Results
According to the meta-analysis result, vitamin D supplementation caused a significant increase in the maternal circulating concentrations of 25(OH)D (SMD 2.07; 95%, CI 1.51, 2.63; p < 0.001), TAC (SMD 2.13, 95% CI 1.04 to 3.23, p < 0.001) and GSH (SMD 4.37, 95% CI 2.9 to 5.74, p < 0.001) as well as a significant decrease in the levels of MDA (SMD -0.46, 95% CI -0.87 to -0.05, p = 0.02). However, it had no significant impact on hs-CRP concentrations (SMD 0.24; 95% CI, -0.55, 1.03; p = 0.50).

Conclusion
In the present study, vitamin D supplementation led to increased levels of 25(OH)D, TAC and GSH and also decreased concentration of MDA. Nevertheless, because of low certainty of evidence, these findings have to be declared conservatively.

Trial registration
Registration code in PROSPERO website: CRD42020202600
Maternal vitamin D status in early pregnancy and its association with gestational diabetes mellitus in Shanghai: a retrospective cohort study
Authors: Cheng Yan , Chen Jiayuan , Li Tingting , Pei Jiangnan , Fan Yongfang , He Mulan , Liu Shuangping , Liu Junxiu , Zhang Qingying , Cheng Haidong 
Published: November 2022

AbstractBackgroundThere is growing interest regarding vitamin D and its potential role in gestational diabetes mellitus (GDM). We aimed to assess maternal vitamin D status in early pregnancy and its relationships with the risk of GDM in a Chinese population in Shanghai.MethodsThe retrospective cohort study included a total of 7816 pregnant women who underwent a 75-g oral glucose tolerance test (OGTT) during 24–28 weeks of gestation. Participants’ demographic information including maternal age, prepregnancy body mass index (BMI), gestational age, parity, season of blood collection, serum 25-hydroxy vitamin D [25(OH)D] data and other blood biomarker data at 6 to 14 weeks of gestation were retrospectivly extracted from the medical records in the hospital information system.ResultsIn the cohort, the prevalence of GDM was 8.6% and the prevalence of vitamin D deficiency and insufficiency in early pregnancy was 53.1 and 38.5%, respectively. The mean value of the serum 25(OH)D concentration was 19.6±7.5 ng/mL. The restricted cubic splines model showed an inverted J-shaped relationship in which the risk of GDM decreased when the 25(OH)D concentrations were ≥ 20 ng/mL. Logistic model analysis showed that 25(OH)D concentrations ≥ 30 ng/mL significantly decreased the risk of GDM (odds ratio = 0.63, 95% confidence interval: 0.45-0.89;P= 0.010) compared with 25(OH)D concentrations < 20 ng/ml.ConclusionsIn early pregnancy, vitamin D deficiency and insufficiency were very common, and a high level of vitamin D showed protective effects against the incidence risk of GDM.
Multimodal ultrasound for preoperative evaluation of dermatofibrosarcoma protuberans: a series of 40 cases
Authors: Gong Xia , Li Jia , Ding Angang , Chen Jun , Tao Xiaofeng , Xiong Ping , Rao Yamin , Liu Yang , Sun Qilin 
Published: November 2022

Abstract
Background
Dermatofibrosarcoma protuberans (DFSP) is a rare, low to intermediate-grade sarcoma, which needs imaging examination. Small series of ultrasound findings in DFSP have been published; however, the usefulness of elastography and contrast-enhanced ultrasound (CEUS) in DFSP has not been studied. We aim to study multimodal ultrasound findings and report the correlation between imagings and tiny extension in DFSP for preoperative evaluation.

Methods
Two-D ultrasound, 3-D color ultrasound, elastography, and CEUS findings were retrospectively evaluated. Forty histopathologically confirmed DFSPs were studied.

Results
On 2-D ultrasound, 26(65%) appeared as mostly hypoechoic lesions with occasional hyperechoic dots within the tumor matrix and lobulated lateral borders. Eight (20%) lesions were multilayered. Ninety-five percent of lesions showed increased vascularity. On 3-D ultrasound, DFSPs showed branch-shaped, striped, and wrapped color patterns. Power Doppler showed mainly artery of a moderate arterial peak systolic blood flow and low resistance index. DFSP is hard on elastography. On CEUS, DFSPs showed a long peak time, low peak and a small amount of perfusion around the tumor, 73.7% (14/19) of lesions showed a heterogeneous contrast enhancement and 89.5% (17/19) of lesions showed hyper-enhancement. CEUS showed better concordance than US with histology on the maximum diameter and depth (P < 0.05).

Conclusions
Multimodal ultrasound showed significant characteristics in DFSP, which would improve diagnostic accuracy. CEUS could be an effective tool to determine tiny tumor extension.