bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinician reports of self-awareness after traumatic brain injury: a retrospective chart review
Authors: Mamman Rinni , Cheng Anika , Tsow Rebecca , Schmidt Julia 
Published: September 2022

Abstract
Background
Impaired self-awareness (i.e., a lack of insight) is experienced by most individuals who have sustained a moderate to severe traumatic brain injury (TBI). During the early recovery period post-injury, these individuals may not be able to recognize their abilities and limitations, hence, negatively impacting their daily life and function. Although there are assessments and interventions to improve self-awareness after TBI, little is known about how clinicians assess and address this impairment in an inpatient rehabilitation setting.

Objective
To examine how clinicians assess, report, and provide interventions for impaired self-awareness after TBI.

Methods
A retrospective chart review was conducted on interdisciplinary rehabilitation clinician entries for individuals with TBI (n = 67) who received inpatient rehabilitation within a five-year period (2014–2019). A reflexive thematic analysis was used to identify themes pertaining to self-awareness.

Results
Three themes were generated to explore clinician responses to their clients’ impaired self-awareness: 1) ‘recalling and understanding’ described clinician observations of client behaviors and expressions of self-awareness, 2) ‘applying and analyzing’ identified clinicians providing relevant tasks and advice to clients, and 3) ‘evaluating and creating’ described clinicians actively interacting with clients by providing feedback, guided prompts, and a follow-up plan.

Conclusion
Clinicians produced varied responses to clients’ impaired self-awareness after TBI. Findings may help to develop research priorities and integrated knowledge translation initiatives to increase evidence-based practice for impaired self-awareness after TBI.
Degradation kinetics of artesunate for the development of an ex-tempore intravenous injection
Authors: Gashe Fanta , Wynendaele Evelien , De Spiegeleer Bart , Suleman Sultan 
Published: September 2022

Abstract
Background
Artesunate is recommended by the World Health Organization (WHO) for parenteral treatment of severe Plasmodium falciparum malaria. However, artesunate is inherently unstable in an aqueous solution and hydrolyses rapidly after its preparation for injection. Therefore, the aim of the study was to evaluate the stabilizing effects of phosphate buffer and mannitol against short-term (ex-tempore) artesunate hydrolysis.

Methods
A HPLC–UV isocratic method was developed using a reversed-phase fused core column (HALO RP-C18) and a mobile phase consisting of a mixture of 45% ammonium formate 10 mM in water (pH 4.5) and 55% methanol. Artesunate was formulated as aqueous solutions using a design of experiment (DOE) to investigate the artesunate stabilizing effects of pH (8–10), phosphate buffer strength (0.3–0.5 M), and mannitol (0–0.22 mmol/mL). The solutions were incubated at predefined temperatures (5, 25, and 40 °C) with subsequent analysis. Arrhenius equation was applied to model and evaluate the stability results.

Results
The developed HPLC-based method using fused-core stationary phase allowed to selectively quantify artesunate in the presence of its main hydrolysis degradants; namely β-dihydroartemisinin (β-DHA) and α-dihydroartemisinin (α-DHA) within 10 min. By applying the Arrhenius equation, the rate of hydrolysis of the drug increased approximately by 3.4 as the temperature raised by 10 °C. Buffer strength was found to be the main factor affecting the hydrolysis rate constants at 5 and 25 °C (p < 0.05), the activation energy (p = 0.009), and the frequency factor (p = 0.045). However, the effect of the buffer was predominant on the activation energy and hydrolysis rate constants, revealing its stabilizing effect on the drug at lower buffer strength (0.3 M). Within the investigated range (pH = 8–10), pH was found to influence the activation energy, with a positive stabilizing effect in the pH range of 8–9. The addition of mannitol as stabilizing agent into artesunate aqueous formulation did not show an improved response.

Conclusion
Phosphate buffer was the main stability determining factor of artesunate in the aqueous intravenous (i.v.) formulation and was found to be more effective in stabilizing artesunate at a buffer strength of 0.3 M in pH 8–9, while mannitol lacked stabilizing effect.
Long-term outcomes of cryoablation for biopsy-proven T1 stage renal cell carcinoma
Authors: Song Shangqing , Yang Qing , Gu Chengyuan , Yu Guopeng , Hua Bao , Gu Xin , Wang Linhui , Wang Zhong , Shi Guohai , Xu Bin 
Published: September 2022

Abstract
Background
To summarize our clinical experience of cryoablation in renal cell carcinoma (RCC) of Chinese population and to evaluate the long-term outcomes of laparoendoscopic single-site (LESS) cryoablation (LCA) as well as percutaneous CT-guided cryoablation (PCA) for biopsy-proven T1a and T1b RCC.

Methods
This was a multi-center, retrospective study investigating T1 stage RCC patients from 2011 to 2021. The patients were treated by LCA or PCA according to individual situation. Overall survival (OS), cancer-related survival (CSS), and progression-free survival (PFS) were evaluated for oncological outcomes, and kidney function, complications, and hospital stay were used to estimate technical outcomes.

Results
A total of 163 consecutive patients were included. Among them, 59 cases were treated by LCA and PCA was performed in 104 cases. All operations were processed successfully. Mean diameter of the mass was (2.9±1.4) cm; median blood volume was 45ml (10~200 ml). The mean operation time was 84.0 ± 24.5 min. The median postoperative hospital stay was 3 days (1~6 days). Compared with LCA, procedure time of PCA was shortened, the volume of bleeding was reduced, and the hospital stay was decreased. The overall adverse events rate was 9.8% (16/163). The mean preoperative and postoperative eGFR of LCA were 77.6±15.3 ml/min and 75.6±17.4 ml/min, respectively. Analogously, the values of PCA were 78.7±12.9 ml/min and 76.7±14.3 ml/min. Mean follow-up time was 64.2 ± 30.2 months (range, 7–127 months). Local recurrence was observed in 13 patients (8.0%), 4 (6.8%) cases of LCA and 9 (8.7%) cases of PCA. PFS at 5 and 10 years were 95.5% and 69.2% for LCA and 96.7% and 62.8% for PCA. In total, 26 patients (16.0%) (11 patients from LCA and 15 from PCA) died throughout the follow-up period. OS at 5 and 10 years were 93.8% and 31.4% for LCA, and 97.4% and 52.7% for PCA. Six patients (3.7%) (3 cases from LCA and 3 from PCA) died of metastatic RCC. CCS for LCA were 98.0% and 82.8% at 5 and 10 years, while the data were 100% and 86.4% for PCA.

Conclusion
LCA and PCA for T1 stage RCC provides satisfactory long-term oncological and renal function preservation outcomes, with acceptable complication rates.
Diagnostic biomolecules and combination therapy for pre-eclampsia
Authors: Qi Jingqi , Wu Bingbing , Chen Xiuying , Wei Wei , Yao Xudong 
Published: September 2022

AbstractPre-eclampsia (PE), associated with placental malperfusion, is the primary reason for maternal and perinatal mortality and morbidity that can cause vascular endothelial injury and multi-organ injury. Despite considerable research efforts, no pharmaceutical has been shown to stop disease progression. If women precisely diagnosed with PE can achieve treatment at early gestation, the maternal and fetal outcomes can be maximally optimized by expectant management. Current diagnostic approaches applying maternal characteristics or biophysical markers, including blood test, urine analysis and biophysical profile, possess limitations in the precise diagnosis of PE. Biochemical factor research associated with PE development has generated ambitious diagnostic targets based on PE pathogenesis and dissecting molecular phenotypes. This review focuses on current developments in biochemical prediction of PE and the corresponding interventions to ameliorate disease progression, aiming to provide references for clinical diagnoses and treatments.
Browning of the white adipose tissue regulation: new insights into nutritional and metabolic relevance in health and diseases
Authors: Machado Sabrina Azevedo , Pasquarelli-do-Nascimento Gabriel , da Silva Debora Santos , Farias Gabriel Ribeiro , de Oliveira Santos Igor , Baptista Luana Borges , Magalhães Kelly Grace 
Published: September 2022

AbstractAdipose tissues are dynamic tissues that play crucial physiological roles in maintaining health and homeostasis. Although white adipose tissue and brown adipose tissue are currently considered key endocrine organs, they differ functionally and morphologically. The existence of the beige or brite adipocytes, cells displaying intermediary characteristics between white and brown adipocytes, illustrates the plastic nature of the adipose tissue. These cells are generated through white adipose tissue browning, a process associated with augmented non-shivering thermogenesis and metabolic capacity. This process involves the upregulation of the uncoupling protein 1, a molecule that uncouples the respiratory chain from Adenosine triphosphate synthesis, producing heat. β-3 adrenergic receptor system is one important mediator of white adipose tissue browning, during cold exposure. Surprisingly, hyperthermia may also induce beige activation and white adipose tissue beiging. Physical exercising copes with increased levels of specific molecules, including Beta-Aminoisobutyric acid, irisin, and Fibroblast growth factor 21 (FGF21), which induce adipose tissue browning. FGF21 is a stress-responsive hormone that interacts with beta-klotho. The central roles played by hormones in the browning process highlight the relevance of the individual lifestyle, including circadian rhythm and diet. Circadian rhythm involves the sleep–wake cycle and is regulated by melatonin, a hormone associated with UCP1 level upregulation. In contrast to the pro-inflammatory and adipose tissue disrupting effects of the western diet, specific food items, including capsaicin and n-3 polyunsaturated fatty acids, and dietary interventions such as calorie restriction and intermittent fasting, favor white adipose tissue browning and metabolic efficiency. The intestinal microbiome has also been pictured as a key factor in regulating white tissue browning, as it modulates bile acid levels, important molecules for the thermogenic program activation. During embryogenesis, in which adipose tissue formation is affected by Bone morphogenetic proteins that regulate gene expression, the stimuli herein discussed influence an orchestra of gene expression regulators, including a plethora of transcription factors, and chromatin remodeling enzymes, and non-coding RNAs. Considering the detrimental effects of adipose tissue browning and the disparities between adipose tissue characteristics in mice and humans, further efforts will benefit a better understanding of adipose tissue plasticity biology and its applicability to managing the overwhelming burden of several chronic diseases.
Hemothorax caused by costal exostosis injuring diaphragm: a case report and literature review
Authors: Pan Ruonan , Lu Xiaoqian , Wang Zhijun , Duan Lijun , Cao Dianbo 
Published: September 2022

Abstract
Background
Osteochondromas, also known as exostoses, are the most common benign tumors of bone and can be classified into isolated and multiple osteochondromas. A great majority of osteochondromas is asymptomatic, painless, slow-growing mass, and incidentally found. However, osteochondromas occurring in adolescence or in adult patients can grow in size and become symptomatic as a result of mechanical irritation of the surrounding soft tissues or peripheral nerves, spinal cord compression, or vascular injury.

Case presentation
We present a case of a 13-year-old girl with spontaneous hemothorax, the cause of which was identified by limited thoracotomy with the aid of video-assisted thoracic surgery to be bleeding from a diaphragmatic laceration incurred by a costal exostosis on the left sixth rib. Preoperative chest computed tomography (CT) depicted a bony projection arising from the rib and bloody effusion in the intrathoracic cavity, but was unable to discern the bleeding cause from the lung or the diaphragm. This case will highlight our awareness that costal exostosis possibly results in bloody pleural effusion. Meanwhile, English literatures about solitary costal exostosis associated with hemothorax were searched in PubMed and nineteen case reports were obtained. Combined our present case with available literature, a comprehensive understanding of this rare disease entity will further be strengthened.

Conclusions
Injury to the diaphragm is the primary cause of hemothorax caused by costal osteochondroma, including the present case. Thoracic CT scan can help establish a diagnosis of preoperative diagnosis of costal osteochondroma. Surgical intervention should be considered for those patients with symptomatic osteochondroma of the rib. Combined with our case and literature, prophylactic surgical removal of intrathoracic exostosis should be advocated even in asymptomatic patients with the presentation of an inward bony spiculation.
A large deletion encompassing exon 2 of the ectodysplasin A (EDA) gene in a British blue crossbred calf with hypohidrotic ectodermal dysplasia
Authors: Capuzzello Giovanni , Jacinto Joana Gonçalves Pontes , Häfliger Irene Monika , Chapman Gail E. , Martin Sara Soto , Viora Lorenzo , Jonsson Nicholas N. , Drögemüller Cord 
Published: September 2022

Abstract
Background
Hypohidrotic ectodermal dysplasia (HED) is a congenital syndrome of mammals affecting organs and tissues of ectodermal origin characterized by absence or hypoplasia of hair, teeth, and eccrine glands. The disorder has been reported in several species, including humans, mice, dogs and cattle, associated with variants in genes affecting the ectodysplasin pathway, including the X-linked ectodysplasin A (EDA) gene. Until now, nine pathogenic variants have been found in the bovine EDA gene. Here we report a novel variant in EDA in a crossbreed male Belgian Blue calf with HED, and provide an overview of the phenotypic and allelic heterogeneity of EDA-related forms of HED in cattle.

Case presentation
A 45-day-old male crossbreed British Blue calf was referred with congenital hypotrichosis, oligodontia and omphalitis. On histopathological examination of the nasal planum, nasolabial glands and ducts were not observed. The density of hair follicles was low, and they were small, with a predominance of telogen-phase hairs, and some serocellular crusts. The phenotype of the calf resembled that of HED. Whole-genome sequencing (WGS) was performed and revealed a 21,899 base-pair deletion encompassing the coding exon 2 of EDA, predicted to result in an altered transcript and aberrant protein.

Conclusions
The clinicopathological and genetic findings were consistent with a case of X-linked HED. A very similar EDA deletion has been previously reported in a family of Holstein cattle with HED. The newly identified hemizygous EDA loss-of-function variant is certainly pathogenic and therefore is the genetic cause for the observed phenotype. This case report provides an additional example of the potential of WGS-based precise diagnostics in livestock species such as cattle to increase the diagnostic yield in rare diseases.
Effect of a self-help group intervention using Teaching Recovery Techniques to improve mental health among Syrian refugees in Norway: a randomized controlled trial
Authors: Hasha Wegdan , Igland Jannicke , Fadnes Lars T. , Kumar Bernadette N. , Heltne Unni M. , Diaz Esperanza 
Published: September 2022

Abstract
Background
Mental health symptoms among refugees are common, often related to chronic pain disorders, and their management is usually challenging. Studies evaluating the effect of group therapies among adult refugees to improve mental health symptoms are scarce.

Aims
To assess the effect of Teaching Recovery Techniques (TRT) on mental health and to reduce pain disorder among adult Syrian refugees.

Method
A randomized controlled trial was designed to study the effect of a self-help group intervention using TRT. The outcomes, mental health symptoms measured by Impact of Event Scale-Revised (IES-R) and General Health Questionnaire (GHQ-12) and chronic pain measured by Brief Pain Inventory (BPI), were reported as regression coefficients (B) with 95% confidence intervals.

Results
Seventy-six adults participated: 38 in the intervention and 38 in the control groups. Intention-to-treat analyses showed a significant effect on general mental health as measured by GHQ-12 with B (95% CI) of -3.8 (-7.2, -0.4). There was no effect of TRT on mental health when assessed by IES-R (-1.3 (-8.7, 6.2)) or on pain levels assessed by BPI (-0.04 (-4.0, 3.9)).

Conclusions
This self-help group intervention significantly improved general mental health symptoms among adult refugees but had no effect on trauma symptoms or chronic pain. Higher participation rates might be necessary to achieve the full potential of TRT.
Trial registration: The trial was registered with Clinical Trials.gov at https://clinicaltrials.gov/ct2/show/NCT03951909. To include user participation in the design of the interventions, the study was retrospectively registered on 19 February 2019.
ASXL1/2 mutations and myeloid malignancies
Authors: Medina Edward A. , Delma Caroline R. , Yang Feng-Chun 
Published: September 2022

AbstractMyeloid malignancies develop through the accumulation of genetic and epigenetic alterations that dysregulate hematopoietic stem cell (HSC) self-renewal, stimulate HSC proliferation and result in differentiation defects. The polycomb group (PcG) and trithorax group (TrxG) of epigenetic regulators act antagonistically to regulate the expression of genes key to stem cell functions. The genes encoding these proteins, and the proteins that interact with them or affect their occupancy at chromatin, are frequently mutated in myeloid malignancies. PcG and TrxG proteins are regulated by Enhancers of Trithorax and Polycomb (ETP) proteins. ASXL1 and ASXL2 are ETP proteins that assemble chromatin modification complexes and transcription factors. ASXL1 mutations frequently occur in myeloid malignancies and are associated with a poor prognosis, whereas ASXL2 mutations frequently occur in AML with t(8;21)/RUNX1-RUNX1T1 and less frequently in other subtypes of myeloid malignancies. Herein, we review the role of ASXL1 and ASXL2 in normal and malignant hematopoiesis by summarizing the findings of mouse model systems and discussing their underlying molecular mechanisms.
Optimizing a Bayesian hierarchical adaptive platform trial design for stroke patients
Authors: Gao Guangyi , Gajewski Byron J. , Wick Jo , Beall Jonathan , Saver Jeffrey L. , Meinzer Caitlyn ,   the STEP-STONE Executive Committee, Derdeyn Colin , Fiorella David , Jovin Tudor , Khatri Pooja , Mistry Eva , Mocco J. , Nogueira Raul , Siddiqui Adnan 
Published: September 2022

Abstract
Background
Platform trials are well-known for their ability to investigate multiple arms on heterogeneous patient populations and their flexibility to add/drop treatment arms due to efficacy/lack of efficacy. Because of their complexity, it is important to develop highly optimized, transparent, and rigorous designs that are cost-efficient, offer high statistical power, maximize patient benefit, and are robust to changes over time.

Methods
To address these needs, we present a Bayesian platform trial design based on a beta-binomial model for binary outcomes that uses three key strategies: (1) hierarchical modeling of subgroups within treatment arms that allows for borrowing of information across subgroups, (2) utilization of response-adaptive randomization (RAR) schemes that seek a tradeoff between statistical power and patient benefit, and (3) adjustment for potential drift over time. Motivated by a proposed clinical trial that aims to find the appropriate treatment for different subgroup populations of ischemic stroke patients, extensive simulation studies were performed to validate the approach, compare different allocation rules, and study the model operating characteristics.

Results and conclusions
Our proposed approach achieved high statistical power and good patient benefit and was also robust against population drift over time. Our design provided a good balance between the strengths of both the traditional RAR scheme and fixed 1:1 allocation and may be a promising choice for dichotomous outcomes trials investigating multiple subgroups.
Practical guidance for running late-phase platform protocols for clinical trials: lessons from experienced UK clinical trials units
Authors: Love Sharon B. , Cafferty Fay , Snowdon Claire , Carty Karen , Savage Joshua , Pallmann Philip , McParland Lucy , Brown Louise , Masters Lindsey , Schiavone Francesca , Hague Dominic , Townsend Stephen , Amos Claire , South Annabelle , Sturgeon Kate , Langley Ruth , Maughan Timothy , James Nicholas , Hall Emma , Kernaghan Sarah , Bliss Judith , Turner Nick , Tutt Andrew , Yap Christina , Firth Charlotte , Kong Anthony , Mehanna Hisham , Watts Colin , Hills Robert , Thomas Ian , Copland Mhairi , Bell Sue , Sebag-Montefiore David , Jones Robert , Parmar Mahesh K. B. , Sydes Matthew R. 
Published: September 2022

Abstract
Background
Late-phase platform protocols (including basket, umbrella, multi-arm multi-stage (MAMS), and master protocols) are generally agreed to be more efficient than traditional two-arm clinical trial designs but are not extensively used. We have gathered the experience of running a number of successful platform protocols together to present some operational recommendations.

Methods
Representatives of six UK clinical trials units with experience in running late-phase platform protocols attended a 1-day meeting structured to discuss various practical aspects of running these trials. We report and give guidance on operational aspects which are either harder to implement compared to a traditional late-phase trial or are specific to platform protocols.

Results
We present a list of practical recommendations for trialists intending to design and conduct late-phase platform protocols. Our recommendations cover the entire life cycle of a platform trial: from protocol development, obtaining funding, and trial set-up, to a wide range of operational and regulatory aspects such as staffing, oversight, data handling, and data management, to the reporting of results, with a particular focus on communication with trial participants and stakeholders as well as public and patient involvement.

Discussion
Platform protocols enable many questions to be answered efficiently to the benefit of patients. Our practical lessons from running platform trials will support trial teams in learning how to run these trials more effectively and efficiently.