bluuebunny/crossref_metadata_2025_split huggingface dataset:
Independent risk factors for myasthenic crisis and disease exacerbation in a retrospective cohort of myasthenia gravis patients
Authors: Nelke Christopher , Stascheit Frauke , Eckert Carmen , Pawlitzki Marc , Schroeter Christina B. , Huntemann Niklas , Mergenthaler Philipp , Arat Ercan , Öztürk Menekse , Foell Dirk , Schreiber Stefanie , Vielhaber Stefan , Gassa Asmae , Stetefeld Henning , Schroeter Michael , Berger Benjamin , Totzeck Andreas , Hagenacker Tim , Meuth Sven G. , Meisel Andreas , Wiendl Heinz , Ruck Tobias 
Published: April 2022

Abstract
Background
Myasthenic crisis (MC) and disease exacerbation in myasthenia gravis (MG) are associated with significant lethality and continue to impose a high disease burden on affected patients. Therefore, we sought to determine potential predictors for MC and exacerbation as well as to identify factors affecting outcome.

Methods
We examined a retrospective, observational cohort study of patients diagnosed with MG between 2000 and 2021 with a mean follow-up of 62.6 months after diagnosis from eight tertiary hospitals in Germany. A multivariate Cox regression model with follow-up duration as the time variable was used to determine independent risk factors for MC and disease exacerbation.

Results
815 patients diagnosed with MG according to national guidelines were included. Disease severity at diagnosis (quantitative MG score or Myasthenia Gravis Foundation of America class), the presence of thymoma and anti-muscle specific tyrosine kinase-antibodies were independent predictors of MC or disease exacerbation. Patients with minimal manifestation status 12 months after diagnosis had a lower risk of MC and disease exacerbation than those without. The timespan between diagnosis and the start of immunosuppressive therapy did not affect risk. Patients with a worse outcome of MC were older, had higher MGFA class before MC and at admission, and had lower vital capacity before and at admission. The number of comorbidities, requirement for intubation, prolonged mechanical ventilation, and MC triggered by infection were associated with worse outcome. No differences between outcomes were observed comparing treatments with IVIG (intravenous immunoglobulin) vs. plasma exchange vs. IVIG together with plasma exchange.

Conclusions
MC and disease exacerbations inflict a substantial burden of disease on MG patients. Disease severity at diagnosis and antibody status predicted the occurrence of MC and disease exacerbation. Intensified monitoring with emphasis on the prevention of infectious complications could be of value to prevent uncontrolled disease in MG patients.

Graphical Abstract
Comprehensive Medical Support in Complex Emergencies (CMSCE): pilot course review
Authors: Quinn John M , Jigar Trisha , Reinwald Michael , Annan Percy S T , Aapore Thomas , Wilson James M , Bourdeaux Margaret Ellis , Ulrichs Timo , Bricknell Martin CM , Moore Alan , Goebbels Stefan , Haggenmiller Christian 
Published: April 2022

AbstractGlobal threats to health and health security are growing. Fragile and failed states, armed groups, ungoverned spaces, outbreaks and potential unknown “Disease X” threats, antimicrobial resistance (AMR), hybrid and gray zone conflict all exacerbate complex medical emergencies. These growing threats increase preventable morbidity and mortality of the most vulnerable populations. In an effort to promote best practices, standardize responses, and prevent excess death and disability in these contexts, The Kofi Annan International Peacekeeping Training Centre (KAIPTC), with support from multiple international partners and a volunteer facilitator faculty, administered the pilot course for military and civilian health officers involved in U.N. peacekeeping missions entitled, “Comprehensive Medical Support in Complex Emergencies (CMSCE 19).” This brief review paper provides a description of the process in designing and delivering an interdisciplinary course for providers and decision makers responding to complex emergencies. We conclude with best practices and next steps for course evolution.
Potential of RNA-binding protein human antigen R as a driver of osteogenic differentiation in osteoporosis
Authors: Liu Zelin , Li Baitao , Hu Hai , Li Xiaodong , Zhang Xiaofeng 
Published: April 2022

Abstract
Background
Emerging evidence has correlated the human antigen R (HuR) with the low-density lipoprotein receptor-related protein 6 (LRP6) gene, an important therapeutic target for osteoporosis. Herein, we sought to probe the regulatory role of HuR in the LRP6 gene and their interaction in the progression of osteoporosis.

Methods
HuR and downstream potential target genes were predicted by bioinformatics analysis to identify their potential functions in bone metabolism following osteoporosis. The effect of HuR on the osteoblastic differentiation and viability and apoptosis of mouse embryo osteoblast precursor cells (MC3T3-E1) was evaluated after artificial modulation of HuR expression.

Results
Bone phenotypes were observed in ovariectomized mice in response to adenovirus-mediated HuR overexpression. Poor expression of HuR was identified in the bone tissues of ovariectomized mice. Silencing of HuR inhibited the osteoblastic differentiation of MC3T3-E1 cells, as evidenced by decreased expression of Runx2 and Osterix along with reduced ALP activity. Mechanistically, HuR stabilized LRP6 mRNA and promoted its translation by binding to the 3'UTR of LRP6 mRNA, leading to activation of the downstream Wnt pathway. By this mechanism, osteoblastic differentiation of MC3T3-E1 cells was induced. In ovariectomized mice, overexpression of HuR alleviated osteoporosis-related phenotypes.

Conclusion
Overall, these data together support the promoting role of HuR in the osteoblastic differentiation, highlighting a potential novel strategy for osteoporosis treatment.
A systematic review and meta-analysis comparing complications following total hip arthroplasty for systemic lupus erythematosus versus for non-systemic lupus erythematosus
Authors: Huang Yiwei , Guan Danni , Li Yijin , Li Jiahao , Zeng Yirong 
Published: April 2022

Abstract
Background
Osteonecrosis of the femoral head is one of the most severe complications in systemic lupus erythematosus (SLE) patients. Total hip arthroplasty (THA) is an effective treatment for femoral head necrosis. However, there is no consensus on the specific effect of THA on SLE patients. The objective of the present study was to review the current evidence regarding rates of THA complications and postoperative function in systemic lupus erythematosus.

Methods
Two independent reviewers searched PubMed, Cochrane Library, and EMBASE from January 1, 2000, to December 29, 2021. The primary outcomes were postoperative complications, including deep vein thrombosis (DVT), hematoma, wound infection, dislocation, periprosthetic fracture, revision, mortality.

Results
A total of 179 articles yielded 28 studies eligible for inclusion with 10 studies used for meta-analysis. This study found a statistically significant difference in DVT, dislocation, wound infection, periprosthetic fracture, and revision.

Conclusions
This meta-analysis shows that SLE patients with THA are at an increased risk of DVT, wound infection, dislocation, periprosthetic fracture, revision, periprosthetic joint infection, following THA in comparison with non-SLE patients with THA. There was no adequate evidence to support the notion that the risk of seroma or hematoma following THA is increased in SLE. Also, there was no significant difference in HHS scores between SLE patients and non-SLE patients after THA.
Antepartum acute Stanford type A aortic dissection: a case report and literature review
Authors: Song Shibo , Lu Lin , Li Lihua , Peng Hua , Wu Xijie 
Published: April 2022

Abstract
Background
Aortic dissection in pregnancy is a life-threatening event that is associated with high maternal and foetal mortality. Most cases occur during the third trimester of pregnancy, Herein, we describe a case of a pregnant woman with acute type A aortic dissection at 28 weeks of gestation.

Case presentation
A previously healthy, 24-year-old gravida 2 para 1 woman was brought to the emergency department during at the 28 weeks of gestation and diagnosed with acute type A aortic dissection. Cesarean section was performed with the cardiac surgical team on standby for cardiopulmonary bypass and the patient delivered a baby weighing 1000 g. After the operation, we performed the Beatall procedure and total arch replacement with FET using the deep hypothermic circulatory arrest technique. Both the mother and child survived and recovered well. A review of the literature on antepartum acute aortic dissection during pregnancy is also presented.

Conclusion
Women should have a comprehensive, systematic physical examination before getting pregnant. Women at high risks of aortic dissection must undergo multidisciplinary evaluation and be counseled before pregnancy, once they become pregnant, their consistent aortic root diameter should be consistently monitored, and their blood pressure strictly controlled.
Consequences of rare diagnoses for education and daily life: development of an observation instrument
Authors: Jaeger Gunilla , Röjvik AnnCatrin , Hjelmquist Erland , Hansla André , Falkman Kerstin W. 
Published: April 2022

Abstract
Background
Ågrenska, a Swedish national centre for rare diagnoses and health conditions, has arranged courses for families of children with rare diagnoses for over thirty years, and has experienced that the conditions often have complex and varying consequences in the children´s everyday lives, not least in educational contexts. Knowledge of these consequences and of how to adapt the environment and educational methods is often lacking and the children´s educational needs are not met. Many professionals also report a lack of sources of knowledge. Knowledge formation and dissemination about educational consequences of rare diagnoses are thus of utmost importance. For this purpose, a broad observation instrument was constructed in order to gather knowledge on a group level concerning how functional impairments affect school and everyday situations, how consequences vary within each diagnosis and if there are diagnosis-specific features that lead to specific every day and pedagogical consequences.

Results
The instrument consists of 119 quantitative and 65 qualitative items and covers ten domains: social and communicative ability, emotions and behaviours, communication and language, ability to manage his/her disability and everyday life, activities of daily life, gross and fine motor skills, perception and worldview, prerequisites for learning and basic school abilities. The instrument is intended for use by educational professionals with knowledge of typical development and was content validated against existing instruments. The items were considered relevant as they, with few exceptions, appear in well-known assessment tools. Interrater reliability was based on the observations of six children. Each child was observed by two educators. Interrater reliability was calculated for the quantitative items and items with fixed response options, including yes/no answers, a total of 100 items, which are usually observed during the course. Interrater reliability reached 91%. Factor analysis and Cronbach´s alpha indicated good statistical properties and a multinomial regression gave reasonable results.

Conclusions
The instrument can be used to gather knowledge on a group level of educational and everyday consequences of rare diagnoses. This knowledge can be used to adapt methods and environment to meet the educational needs and create conditions for optimal learning and participation for children with rare health conditions.
Targeting regulated cell death (RCD) with small-molecule compounds in triple-negative breast cancer: a revisited perspective from molecular mechanisms to targeted therapies
Authors: Liao Minru , Qin Rui , Huang Wei , Zhu Hong-Ping , Peng Fu , Han Bo , Liu Bo 
Published: April 2022

AbstractTriple-negative breast cancer (TNBC) is a subtype of human breast cancer with one of the worst prognoses, with no targeted therapeutic strategies currently available. Regulated cell death (RCD), also known as programmed cell death (PCD), has been widely reported to have numerous links to the progression and therapy of many types of human cancer. Of note, RCD can be divided into numerous different subroutines, including autophagy-dependent cell death, apoptosis, mitotic catastrophe, necroptosis, ferroptosis, pyroptosis and anoikis. More recently, targeting the subroutines of RCD with small-molecule compounds has been emerging as a promising therapeutic strategy, which has rapidly progressed in the treatment of TNBC. Therefore, in this review, we focus on summarizing the molecular mechanisms of the above-mentioned seven major RCD subroutines related to TNBC and the latest progress of small-molecule compounds targeting different RCD subroutines. Moreover, we further discuss the combined strategies of one drug (e.g., narciclasine) or more drugs (e.g., torin-1 combined with chloroquine) to achieve the therapeutic potential on TNBC by regulating RCD subroutines. More importantly, we demonstrate several small-molecule compounds (e.g., ONC201 and NCT03733119) by targeting the subroutines of RCD in TNBC clinical trials. Taken together, these findings will provide a clue on illuminating more actionable low-hanging-fruit druggable targets and candidate small-molecule drugs for potential RCD-related TNBC therapies.
Graphical abstract
Effects of double vs triple injection on block dynamics for ultrasound-guided intertruncal approach to the supraclavicular brachial plexus block in patients undergoing upper limb arteriovenous access surgery: study protocol for a double-blinded, randomized controlled trial
Authors: Luo Quehua , Liu Huiying , Deng Longjiao , Nong Lidan , Li Haifeng , Cai Yujing , Zheng Junyi , Shu Haihua , Yao Weifeng , Zhang Jianxing 
Published: April 2022

Abstract
Background
Ultrasound-guided intertruncal approach (IA) has been proposed to be an alternative and promising approach to the supraclavicular block (SCB), in which double injection (DI) of local anesthetics (LA) is sequentially administered between intertruncal planes. We would like to apply a refined injection technique, named triple injection (TI) technique, based on the 3 separate compartments visualized by ultrasound. The aim of this study is to compare the percentage of patients with complete sensory blockade at 20 min of DI vs TI technique, when they are applied in patients undergoing upper limb arteriovenous access surgery.

Methods
This study is a prospective parallel-group randomized controlled trial. A total of 86 end-stage renal disease patients will be randomly allocated to receive IA-SCB using either DI or TI technique with identical LA (0.5% ropivacaine 24 mL). The primary outcome is the percentage of patients with complete sensory blockade of all 4 terminal nerves (median, ulnar, radial, and musculocutaneous nerves) of the brachial plexus measured at 20 min after injection. The secondary outcomes will consist of the sensory or motor blockade of all individual nerves, onset times, performance time, diaphragmatic paralysis, surgical anesthesia, and adverse events.

Discussion
It is expected that ultrasound-guided IA-SCB with the TI technique results in better block dynamic in patients undergoing upper limb arteriovenous access surgery.

Trial registration
Chinese Clinical Trial Registry ChiCTR2100045075.
Patient and clinician characteristics and preferences for increasing participation in placebo surgery trials: a scoping review of attributes to inform a discrete choice experiment
Authors: Hinwood Madeleine , Wall Laura , Lang Danielle , Balogh Zsolt J. , Smith Angela , Dowsey Michelle , Clarke Phillip , Choong Peter , Bunzli Samantha , Paolucci Francesco 
Published: April 2022

Abstract
Background
Orthopaedic surgeries include some of the highest volume surgical interventions globally; however, studies have shown that a significant proportion of patients report no clinically meaningful improvement in pain or function after certain procedures. As a result, there is increasing interest in conducting randomised placebo-controlled trials in orthopaedic surgery. However, these frequently fail to reach recruitment targets suggesting a need to improve trial design to encourage participation. The objective of this study was to systematically scope the available evidence on patient and clinician values and preferences which may influence the decision to participate in placebo surgery trial.

Methods
A systematic review was conducted via a literature search in the MEDLINE, Embase, PsycInfo, CINAHL, and EconLit databases as of 19 July 2021, for studies of any design (except commentaries or opinion pieces) based on two key concepts: patient and clinician characteristics, values and preferences, and placebo surgery trials.

Results
Of 3424 initial articles, we retained 18 eligible studies. Characteristics, preferences, values, and attitudes of patients (including levels of pain/function, risk/benefit perception, and altruism) and of clinicians (including concerns regarding patient deception associated with placebo, and experience/training in research) influenced their decisions to participate in placebo-controlled trials. Furthermore, some aspects of trial design, including randomisation procedures, availability of the procedure outside of the trial, and the information and consent procedures used, also influenced decisions to participate.

Conclusion
Participant recruitment is a significant challenge in placebo surgery trials, and individual decisions to participate appear to be sensitive to preferences around treatment. Understanding and quantifying the role patient and clinician preferences may play in surgical trials may contribute to the optimisation of the design and implementation of clinical trials in surgery.
Cross-tissue and generation predictability of relative Wolbachia densities in the mosquito Aedes aegypti
Authors: Mejia Austin J. , Dutra H. L. C. , Jones M. J. , Perera R. , McGraw E. A. 
Published: April 2022

Abstract
Background
The insect endosymbiotic bacterium Wolbachia is being deployed in field populations of the mosquito Aedes aegypti for biological control. This microbe prevents the replication of human disease-causing viruses inside the vector, including dengue, Zika and chikungunya. Relative Wolbachia densities may in part predict the strength of this ‘viral blocking’ effect. Additionally, Wolbachia densities may affect the strength of the reproductive manipulations it induces, including cytoplasmic incompatibility (CI), maternal inheritance rates or induced fitness effects in the insect host. High rates of CI and maternal inheritance and low rates of fitness effects are also key to the successful spreading of Wolbachia through vector populations and its successful use in biocontrol. The factors that control Wolbachia densities are not completely understood.

Methods
We used quantitative PCR-based methods to estimate relative density of the Wolbachia wAlbB strain in both the somatic and reproductive tissues of adult male and female mosquitoes, as well as in eggs. Using correlation analyses, we assessed whether densities in one tissue predict those in others within the same individual, but also across generations.

Results
We found little relationship among the relative Wolbachia densities of different tissues in the same host. The results also show that there was very little relationship between Wolbachia densities in parents and those in offspring, both in the same and different tissues. The one exception was with ovary–egg relationships, where there was a strong positive association. Relative Wolbachia densities in reproductive tissues were always greater than those in the somatic tissues. Additionally, the densities were consistent in females over their lifetime regardless of tissue, whereas they were generally higher and more variable in males, particularly in the testes.

Conclusions
Our results indicate that either stochastic processes or local tissue-based physiologies are more likely factors dictating Wolbachia densities in Ae. aegypti individuals, rather than shared embryonic environments or heritable genetic effects of the mosquito genome. These findings have implications for understanding how relative Wolbachia densities may evolve and/or be maintained over the long term in Ae. aegypti.

Graphical Abstract
Giant parathyroid adenoma: a case report
Authors: Mahmodlou Rahim , Sedokani Amin , Pezeshk Apameh , Najafinejad Bita 
Published: April 2022

Abstract
Background
Giant parathyroid adenoma is a type of parathyroid adenoma weighing > 3.5 g and having a size of more than 2 cm.

Case presentation
This report describes giant primary parathyroid adenoma with reference to the literature. We report the case of a 48-year-old Persian man referred to the clinic with knee and lower back pain. He had a history of mitral valve replacement and several episodes of bilateral nephrolithiasis. After a thorough assessment, a neck mass with a possible thyroid origin was detected, but further assessment showed it was of parathyroid origin. The resected mass was 9 × 6× 4 cm and weighed 122 g, and histopathology showed a giant parathyroid adenoma.

Conclusion
Giant parathyroid adenomas that weigh more than 110 g and are larger than 8 cm can lead to significant hypercalcemia. Despite giant parathyroid adenomas and high parathyroid hormone levels, a calcium crisis may not always occur in these patients, and the masses may be initially misdiagnosed as a thyroid mass.
Treatment of male and female spontaneously hypertensive rats with TNF-α inhibitor etanercept increases markers of renal injury independent of an effect on blood pressure
Authors: Snyder Elizabeth C. , Abdelbary Mahmoud , El-Marakby Ahmed , Sullivan Jennifer C. 
Published: April 2022

AbstractHypertension remains the leading risk factor for cardiovascular disease. Young females tend to be protected from hypertension compared with age-matched males. Although it has become increasingly clear that the immune system plays a key role in the development of hypertension in both sexes, few studies have examined how cytokines mediate hypertension in males versus females. We previously published that there are sex differences in the levels of the cytokine tumor necrosis factor (TNF)-α in spontaneously hypertensive rats (SHR). The goal of this study was to test the hypothesis that TNF-α inhibition with etanercept will lower BP in male and female SHR. However, as male SHR have a more pro-inflammatory status than female SHR, we further hypothesize that males will have a greater decrease in BP with TNF-α inhibition than females. Young adult male and female SHR were administered increasing doses of the TNF-α inhibitor etanercept or vehicle twice weekly for 31 days and BP was continuously measured via telemetry. Following treatment, kidneys and urine were collected and analyzed for markers of inflammation and injury. Despite significantly decreasing renal TNF-α levels, renal phospho-NFκB and urinary MCP-1 excretion, etanercept did not alter BP in either male or female SHR. Interestingly, treatment with etanercept increased urinary excretion of protein, creatinine and KIM-1 in both sexes. These results indicate that TNF-α does not contribute to sex differences in BP in SHR but may be vital in the maintenance of renal health.