bluuebunny/crossref_metadata_2025_split huggingface dataset:
The association between age and vital signs documentation of trauma patients in prehospital settings: analysis of a nationwide database in Japan
Authors: Shinohara Mafumi , Muguruma Takashi , Toida Chiaki , Gakumazawa Masayasu , Abe Takeru , Takeuchi Ichiro 
Published: October 2022

Abstract
Background
Emergency medical service (EMS) providers are the first medical professionals to make contact with patients in an emergency. However, the frequency of care by EMS providers for severely injured children is limited. Vital signs are important factors in assessing critically ill or injured patients in the prehospital setting. However, it has been reported that documentation of pediatric vital signs is sometimes omitted, and little is known regarding the performance rate of vital sign documentation by EMS providers in Japan. Using a nationwide data base in Japan, this study aimed to evaluate the relationship between patients’ age and the documentation of vital signs in prehospital settings.

Methods
This study was a secondary data analysis of the Japan Trauma Data Bank. The inclusion criterion was patients with severe trauma, as defined by an Injury Severity Score ≥ 16. Our primary outcome was the rate of recording all four basic vital signs, namely blood pressure, heart rate, respiratory rate, and level of consciousness in the prehospital setting among different age groups. We also compared the prehospital vital sign completion rate, that is, the rate at which all four vital signs were recorded in a prehospital setting based on age groups. Multivariate analysis was performed to evaluate factors associated with the prehospital vital sign completion rate.

Results
We analyzed 75,777 severely injured patients. Adults accounted for 94% (71400) of these severely injured patients, whereas only 6% of patients were children. The rate of prehospital recording of vital signs was lower in children ≤5 years than in adult patients for all four vital signs. When the adult group was used as a reference, the adjusted odds ratios of vital sign completion rate in infants (0 years), younger children (1–5 years), older children (6–11 years), and teenagers (12–17 years) were 0.09, 0.30, 0.78, and 0.87, respectively.

Conclusions
Analysis of the nationwide trauma registry showed that younger children tended to have a lower rate of vital sign documentation in prehospital settings.
Statistical methods and graphical displays of quality of life with survival outcomes in oncology clinical trials for supporting the estimand framework
Authors: Sakamaki Kentaro , Kawahara Takuya 
Published: October 2022

Abstract
Background
Although there are discussions regarding standards of the analysis of patient-reported outcomes and quality of life (QOL) in oncology clinical trials, that of QOL with death events is not within their scope. For example, ignoring death can lead to bias in the QOL analysis for patients with moderate or high mortality rates in the palliative care setting. This is discussed in the estimand framework but is controversial. Information loss by summary measures under the estimand framework may make it challenging for clinicians to interpret the QOL analysis results. This study illustrated the use of graphical displays in the framework. They can be helpful for discussions between clinicians and statisticians and decision-making by stakeholders.

Methods
We reviewed the time-to-deterioration analysis, prioritized composite outcome approach, semi-competing risk analysis, survivor analysis, linear mixed model for repeated measures, and principal stratification approach. We summarized attributes of estimands and graphs in the statistical analysis and evaluated them in various hypothetical randomized controlled trials.

Results
Graphs for each analysis method provide different information and impressions. In the time-to-deterioration analysis, it was not easy to interpret the difference in the curves as an effect on QOL. The prioritized composite outcome approach provided new insights for QOL considering death by defining better conditions based on the distinction of OS and QOL. The semi-competing risk analysis provided different insights compared with the time-to-deterioration analysis and prioritized composite outcome approach. Due to the missing assumption, graphs by the linear mixed model for repeated measures should be carefully interpreted, even for descriptive purposes. The principal stratification approach provided pure comparison, but the interpretation was difficult because the target population was unknown.

Conclusions
Graphical displays can capture different aspects of treatment effects that should be described in the estimand framework.
Neuromyelitis optica spectrum disease coexisting with subacute combined degeneration: a case report
Authors: Zeng Yixuan , Bai Runtao , Zhou Yanxia , Ren Lijie 
Published: October 2022

Abstract
Background
Subacute combined degeneration (SCD) is a demyelinating disease characterized by vitamin B12 deficiency related segmental degeneration of the dorsal or lateral columns of the spinal cord. However, few cases have been reported as a comorbidity of SCD and neuromyelitis optica spectrum disease (NMOSD).

Case presentation
Herein, we describe a female patient (61-year-old) who had sensory deficits, paresthesia, and weakness of the distal extremities for over 2 months. She then received an initial diagnosis of SCD with typical inverted “V-sigh” hyperintensities over the posterior aspect of the spinal cord in magnetic resonance imaging (MRI - T2-weighted imaging), as well as megaloblastic anaemia in blood examinations. From the past history, there was no evidence of a dietary deficiency or gastric abnormalities. However, traditional treatment with vitamin B12 supplementation was ineffective. Hence, a demyelinating antibody examination showed that she had antibodies targeting aquaporin 4 (AQP4) in both the cerebrospinal fluid and serum, leading to the diagnosis of NMOSD. Her clinical symptoms were obviously improved after treatment with intravenous glucocorticoids.

Conclusion
People who have nutritional deficiency or altered gastrointestinal function are more likely to develop SCD. This case raises the awareness that the poor therapeutic effects of simple vitamin B12 supplementation could be explained by immunoreactions against AQP4. A better recognition will be of great importance for the correct diagnosis of the comorbidity, as well as for essential treatment and even a better prognosis.
Early clinical course of biopsy-proven IgA vasculitis nephritis
Authors: Butzer Sarina , Hennies Imke , Gimpel Charlotte , Gellermann Jutta , Schalk Gesa , König Sabine , Büscher Anja K. , Lemke Anja , Pohl Martin 
Published: October 2022

Abstract
Background
IgA vasculitis (IgAV) is the most common form of systemic vasculitis in childhood and frequently involves the kidney. A minority of patients with IgA vasculitis nephritis (IgAVN), especially those presenting with heavy proteinuria and/or kidney failure at onset, are at risk of chronic end-stage kidney disease. For deciding upon treatment intensity, knowledge of the short-term clinical course of IgAVN is needed to improve treatment algorithms.

Methods
For this retrospective multicenter study, the medical records of 66 children with biopsy-proven IgAVN were reviewed. Age, gender, medical history and therapeutic interventions were recorded. Laboratory data included serum creatinine, albumin, urinary protein excretion (UPE) and glomerular filtration rate (eGFR). Threshold values were determined for each parameter, full remission was defined as no proteinuria and eGFR > 90 ml/min/1.73m2.

Results
Median age at onset of IgAVN was 8.9 years. 14.1% of the children presented with nephrotic syndrome, 50% had an eGFR below 90 ml/min/1.73 m2 and 51.5% showed cellular crescents in renal histology. The treatment regimens varied notably. Forty-four patients were treated with immunosuppression; 17 patients with crescents or nephrotic syndrome were treated with corticosteroid (CS) pulse therapy. After 6 months, UPE had decreased from 3.7 to 0.3 g/g creatinine and the proportion of patients with a decreased eGFR had fallen from 50.0% to 35.5%. Thirteen children (26.5%) achieved full remission within 6 months.

Conclusions
In most patients with IgAVN proteinuria decreases slowly and kidney function improves, but full remission is reached only in a minority after 6 months. Persistent heavy proteinuria in the first two months rarely developed into long-term proteinuria. Therefore, decisions for more intense treatment should take into account the course of UPE over time.
For a comparison of treatment effects, patient numbers were too small. Prospective, randomized controlled trials are necessary to clarify risk factors and the effect of immunosuppressive therapies.
Are changes in pain associated with changes in heart rate variability in patients treated for recurrent or persistent neck pain?
Authors: Bakken Anders Galaasen , Eklund Andreas , Warnqvist Anna , O’Neill Søren , Hallman David M. , Axén Iben 
Published: October 2022

Abstract
Background
Persistent or recurrent neck pain is associated with perturbations in the autonomic nervous system balance, and nociceptive stimulation has been seen to influence this balance. However, very few prospective studies have addressed the extent to which changes in pain associate with changes in autonomic cardiac regulation. Therefore, we investigated if changes in pain vary with changes in heart rate variability in a cohort of patients treated for persistent or recurrent neck pain.

Method
This analysis is based on data from a randomized controlled trial in which participants were given home stretching exercises with or without spinal manipulative therapy for two weeks. As the effectiveness of the intervention (home stretching exercises and spinal manipulative therapy) was found to be equal to the control (home stretching exercises alone), all 127 participants were studied as one cohort in this analysis. During the intervention, pain levels were recorded using daily text messages, and heart rate variability was measured in the clinics three times over two weeks. Two approaches were used to classify patients based on changes in pain intensity: 1) Clinically important changes in pain were categorized as either "improved" or "not improved" and, 2) Pain development was measured using pain trajectories, constructed in a data driven approach. The association of pain categories and trajectories with changes in heart rate variability indices over time were then analysed using linear mixed models.

Results
Heart rate variability did not differ significantly between improved and not-improved patients, nor were there any associations with the different pain trajectories.

Conclusions
In conclusion, changes in pain after home stretching exercises with or without spinal manipulative therapy over two weeks were not significantly associated with changes in heart rate variability for patients with persistent or recurrent neck pain. Future studies should rely on more frequent measurements of HRV during longer treatment periods.

Trial registration
The trial was registered at ClinicalTrials.gov, registration number: NCT03576846.
Fracture of the lateral process of the talus with associated deltoid ligament injury: a report of 2 cases
Authors: Jin Xiang-Yun , Xiao Wei-Yuan , He Tao , Dong Yu-Qi , Zhang Chao 
Published: October 2022

Abstract
Background
Fractures of the lateral process of the talus (LTPF) are rare and only rarely are associated ligamentous injuries. The injury mechanism is commonly considered to be similar with ankle sprains, where excessive varus of the hindfoot leads to avulsion fractures of the lateral process of the talus. However, previous cadaveric studies have suggested that LTPF was more likely to be caused by eversion or external rotation force with dorsiflexion of the ankle. But no clinical evidence has been provided.

Case presentation
Two patients presented to the emergency department with ankle pain after ankle eversion or external rotation. Physical examination revealed tenderness and swelling on both medial and lateral sides of the ankles. Plain radiographs and computed tomography revealed LTPF and medial soft tissue swelling, and magnetic resonance imaging confirmed a discontinuity of the deltoid ligament in Case 1. Surgical exploration revealed rupture of the superficial layer of the deltoid ligaments with intact deep layer in both patients. Treatment included fixation of the lateral process of the talus with headless compression screws and repair of deltoid ligaments. Both patients achieved excellent clinical outcomes 1 year post injury.

Conclusion
There are many possibilities of the injury mechanism of LTPF. These two cases provided clinical evidence that eversion or external rotation force, in addition to inversion, was also an important mechanism of LTPF.
Trainee doctors’ perceptions of the surgeon stereotype and its impact on professional identification: a qualitative study
Authors: Wainwright David , Harris Michael , Wainwright Elaine 
Published: October 2022

Abstract
Background
The demography of the medical profession is changing as more women join the workforce. Traditional assumptions about the personal qualities required to be a successful surgeon may change as more women join the specialty. While exploring the attitudes and beliefs of doctors in their second ‘Foundation’ year of post-graduate training (FY2) about their choice of specialty, evidence emerged about how the stereotype of the surgeon influences professional identification and beliefs about person-specialty fit.

Methods
Qualitative telephone interviews with 24 FY2 doctors, 17 women and 7 men, in South-West England.

Results
Many participants reported exposure to stereotypes about the personal qualities desirable in a surgeon. Senior doctors and other trainees were the primary source of these stereotypical views. Experience on surgical placements could either reinforce stereotypes or challenge them, the latter particularly where senior surgeons provided positive role models. As more women enter the surgical specialties, they are increasingly challenging the traditional stereotype and sub-culture.

Conclusion
Gendered stereotypes about surgical roles persist, and for some this can hinder professional identification with the role. Positive role models and mentoring can encourage and support women who are interested a surgical career to identify with the role, but there is a need for a broader debate encompassing job redesign and surgical identities.
Both indirect maternal and direct fetal genetic effects reflect the observational relationship between higher birth weight and lower adult bone mass
Authors: Xia Jiang-Wei , Zhang Lin , Li Jin , Yuan Cheng-Da , Zhu Xiao-Wei , Qian Yu , Khederzadeh Saber , Gu Jia-Xuan , Xu Lin , Gao Jian-Hua , Liu Ke-Qi , Karasik David , Xie Shu-Yang , Chen Guo-Bo , Zheng Hou-Feng 
Published: October 2022

Abstract
Background
Birth weight is considered not only to undermine future growth, but also to induce lifelong diseases; the aim of this study is to explore the relationship between birth weight and adult bone mass.

Methods
We performed multivariable regression analyses to assess the association of birth weight with bone parameters measured by dual-energy X-ray absorptiometry (DXA) and by quantitative ultrasound (QUS), independently. We also implemented a systemic Mendelian randomization (MR) analysis to explore the causal association between them with both fetal-specific and maternal-specific instrumental variables.

Results
In the observational analyses, we found that higher birth weight could increase the adult bone area (lumbar spine, β-coefficient= 0.17, P < 2.00 × 10−16; lateral spine, β-coefficient = 0.02, P = 0.04), decrease bone mineral content-adjusted bone area (BMCadjArea) (lumbar spine, β-coefficient= − 0.01, P = 2.27 × 10−14; lateral spine, β-coefficient = − 0.05, P = 0.001), and decrease adult bone mineral density (BMD) (lumbar spine, β-coefficient = − 0.04, P = 0.007; lateral spine; β-coefficient = − 0.03, P = 0.02; heel, β-coefficient = − 0.06, P < 2.00 × 10−16), and we observed that the effect of birth weight on bone size was larger than that on BMC. In MR analyses, the higher fetal-specific genetically determined birth weight was identified to be associated with higher bone area (lumbar spine; β-coefficient = 0.15, P = 1.26 × 10−6, total hip, β-coefficient = 0.15, P = 0.005; intertrochanteric area, β-coefficient = 0.13, P = 0.0009; trochanter area, β-coefficient = 0.11, P = 0.03) but lower BMD (lumbar spine, β-coefficient = − 0.10, P = 0.01; lateral spine, β-coefficient = − 0.12, P = 0.0003, and heel β-coefficient = − 0.11, P = 3.33 × 10−13). In addition, we found that the higher maternal-specific genetically determined offspring birth weight was associated with lower offspring adult heel BMD (β-coefficient = − 0.001, P = 0.04).

Conclusions
The observational analyses suggested that higher birth weight was associated with the increased adult bone area but decreased BMD. By leveraging the genetic instrumental variables with maternal- and fetal-specific effects on birth weight, the observed relationship could be reflected by both the direct fetal and indirect maternal genetic effects.
Metabolic control analysis enables rational improvement of E. coli l-tryptophan producers but methylglyoxal formation limits glycerol-based production
Authors: Schoppel Kristin , Trachtmann Natalia , Korzin Emil J. , Tzanavari Angelina , Sprenger Georg A. , Weuster-Botz Dirk 
Published: October 2022

AbstractBackgroundAlthough efficientl-tryptophan production using engineeredEscherichia coliis established from glucose, the use of alternative carbon sources is still very limited. Through the application of glycerol as an alternate, a more sustainable substrate (by-product of biodiesel preparation), the well-studied intracellular glycolytic pathways are rerouted, resulting in the activity of different intracellular control sites and regulations, which are not fully understood in detail. Metabolic analysis was applied to well-known engineeredE. colicells with 10 genetic modifications. Cells were withdrawn from a fed-batch production process with glycerol as a carbon source, followed by metabolic control analysis (MCA). This resulted in the identification of several additional enzymes controlling the carbon flux tol-tryptophan.ResultsThese controlling enzyme activities were addressed stepwise by the targeted overexpression of 4 additional enzymes (trpC,trpB,serB,aroB). Their efficacy regardingl-tryptophan productivity was evaluated under consistent fed-batch cultivation conditions. Although process comparability was impeded by process variances related to a temporal, unpredictable break-off inl-tryptophan production, process improvements of up to 28% with respect to thel-tryptophan produced were observed using the new producer strains. The intracellular effects of these targeted genetic modifications were revealed by metabolic analysis in combination with MCA and expression analysis. Furthermore, it was discovered that theE. colicells produced the highly toxic metabolite methylglyoxal (MGO) during the fed-batch process. A closer look at the MGO production and detoxification on the metabolome, fluxome, and transcriptome level of the engineeredE. coliindicated that the highly toxic metabolite plays a critical role in the production of aromatic amino acids with glycerol as a carbon source.ConclusionsA detailed process analysis of a newl-tryptophan producer strain revealed that several of the 4 targeted genetic modifications of theE. colil-tryptophan producer strain proved to be effective, and, for others, new engineering approaches could be derived from the results. As a starting point for further strain and process optimization, the up-regulation of MGO detoxifying enzymes and a lowering of the feeding rate during the last third of the cultivation seems reasonable.
The recent advancements in the early detection of cancer biomarkers by DNAzyme-assisted aptasensors
Authors: Kamali Hossein , Golmohammadzadeh Shiva , Zare Hamed , Nosrati Rahim , Fereidouni Mohammad , Safarpour Hossein 
Published: October 2022

Abstract
Clinical diagnostics rely heavily on the detection and quantification of cancer biomarkers. The rapid detection of cancer-specific biomarkers is of great importance in the early diagnosis of cancers and plays a crucial role in the subsequent treatments. There are several different detection techniques available today for detecting cancer biomarkers. Because of target-related conformational alterations, high stability, and target variety, aptamers have received considerable interest as a biosensing system component. To date, several sensitivity-enhancement strategies have been used with a broad spectrum of nanomaterials and nanoparticles (NPs) to improve the limit and sensitivity of analyte detection in the construction of innovative aptasensors. The present article aims to outline the research developments on the potential of DNAzymes-based aptasensors for cancer biomarker detection.

Graphical Abstract
Preclinical development of carrier-free prodrug nanoparticles for enhanced antitumor therapeutic potential with less toxicity
Authors: Shim Man Kyu , Yang Suah , Park Jooho , Yoon Jun Sik , Kim Jinseong , Moon Yujeong , Shim Nayeon , Jo Mihee , Choi Yongwhan , Kim Kwangmeyung 
Published: October 2022

Abstract
Background
Nanomedicine has emerged as a promising strategy for cancer treatment. The most representative nanomedicine used in clinic is PEGylated liposomal doxorubicin DOXIL®, which is first FDA-approved nanomedicine. However, several shortcomings, such as low drug loading capacity, low tumor targeting, difficulty in mass production and potential toxicity of carrier materials, have hindered the successful clinical translation of nanomedicines. In this study, we report a preclinical development process of the carrier-free prodrug nanoparticles designed as an alternative formulation to overcome limitations of conventional nanomedicines in the terms of technical- and industrial-aspects.

Results
The carrier-free prodrug nanoparticles (F68-FDOX) are prepared by self-assembly of cathepsin B-specific cleavable peptide (FRRG) and doxorubicin (DOX) conjugates without any additional carrier materials, and further stabilized with Pluronic F68, resulting in high drug loading (> 50%). The precise and concise structure allow mass production with easily controllable quality control (QC), and its lyophilized powder form has a great long-term storage stability at different temperatures (− 4, 37 and 60 °C). With high cathepsin B-specificity, F68-FDOX induce a potent cytotoxicity preferentially in cancer cells, whereas their cytotoxicity is greatly minimized in normal cells with innately low cathepsin B expression. In tumor models, F68-FDOX efficiently accumulates within tumor tissues owing to enhanced permeability and retention (EPR) effect and subsequently release toxic DOX molecules by cathepsin B-specific cleavage mechanism, showing a broad therapeutic spectrum with significant antitumor activity in three types of colon, breast and pancreatic cancers. Finally, the safety of F68-FDOX treatment is investigated after single-/multi-dosage into mice, showing greatly minimized DOX-related toxicity, compared to free DOX in normal mice.

Conclusions
Collectively, these results provide potential preclinical development process of an alternative approach, new formulation of carrier-free prodrug nanoparticles, for clinical translation of nanomedicines.