bluuebunny/crossref_metadata_2025_split huggingface dataset:
The prognostic significance of pretreatment squamous cell carcinoma antigen levels in cervical cancer patients treated by concurrent chemoradiation therapy and a comparison of dosimetric outcomes and clinical toxicities between tomotherapy and volumetric modulated arc therapy
Authors: Cheng Yuan-Kai , Kuo Shih-Hsun , Yen Heng-Hsuan , Wu Jing-Hu , Chen Yu-Chieh , Huang Ming-Yii 
Published: May 2022

Abstract
Background
To analyze the prognostic factors associated with stage IB-IVA cervical cancer in patients who underwent concurrent chemoradiation therapy (CCRT) and to compare the clinical toxicities and dosimetric parameters of organs at risk between the different radiotherapy techniques.

Methods
This retrospective study enrolled 93 patients with stage IB-IVA cervical cancer who underwent definitive CCRT between April 2009 and December 2017. Nine patients (9.7%) received 3DCRT, 43 patients (46.2%) underwent VMAT, and 41 patients (44.1%) received tomotherapy, and all of them followed by brachytherapy using a 2D planning technique. The treatment outcomes and related prognostic factors were analyzed. We also compared the clinical toxicities and dosimetric parameters between the different techniques used for the last 30 patients.

Results
With a median follow-up of 52.0 months, the 5-year overall survival (OS), progression-free survival (PFS), locoregional recurrence–free survival (LRRFS), and distant metastases–free survival (DMFS) were analyzed. In a Cox proportional hazards regression model, pretreatment SCC Ag > 10 ng/mL was a significant prognostic factor for PFS (hazard ratio [HR] 2.20; 95% confidence interval [CI] 1.03–4.70; P = 0.041), LRRFS (HR, 3.48; 95% CI 1.07–11.26; P = 0.038), and DMFS (HR 2.80; 95% CI 1.02–7.67; P = 0.045). Increasing the rectal volume receiving a radiation dose exceeding 30 Gy (V30 of rectum; odds ratio [OR] 1.15; 95% CI 1.10–1.30; P = 0.03) was associated with a higher possibility of ≥ Grade 2 acute radiation therapy (RT)-related diarrhea. The median rectal V30 values were 56.4%, 97.5%, and 86.5% for tomotherapy, 3-dimensional conformal radiation therapy (3DCRT), and volumetric modulated arc therapy (VMAT), respectively (P < 0.001). In addition, the chance of experiencing ≥ Grade 2 acute diarrhea were 10.0%, 66.7%, and 54.5% for tomotherapy, 3DCRT, and VMAT, respectively (P = 0.029).

Conclusions
Patients with pretreatment SCC Ag ≤ 10 ng/mL have better PFS, LRRFS, and DMFS than those with pretreatment SCC Ag > 10 ng/mL. The rectal V30 is a significant predictor of severe acute diarrhea. Tomotherapy significantly decreased the rectal V30, reducing the severity of acute RT-related diarrhea during external beam RT.
Trial registration This study was approved by the institutional review board at Kaohsiung Medical University Hospital. The registration number is KMUHIRB-E(I)-20190054 and retrospectively registered on 2019/3.
Refractory post-thymectomy myasthenia gravis with onset at MGFA stage V: a case report
Authors: Zhou Rui-Qin , Li Lin-Jun , Wu Qing-Chen 
Published: May 2022

Abstract
Background
Post-thymectomy myasthenia gravis (PTMG) is defined as thymoma patients without signs of myasthenia gravis (MG) pre-operation, but develop MG after radical surgical resection. PTMG might be misdiagnosed not only because of its rare incidence, but also the uncertain interval between the removal of thymoma and the new onset MG. Additionally, some surgeons and anesthesiologists pay less attention to those asymptomatic thymoma patients in perioperative management, leading to the neglect of new onset PTMG, and miss the best time to treat it.

Case presentation
Majority of cases of PTMG with onset at stage I–II on the basis of Myasthenia Gravis Foundation of America (MGFA) classification have been reported, but rarely at stage V, which requiring intubation or non-invasive ventilation to avoid intubation. Herein, we presented a 70-year-old male with PTMG onset at MGFA stage V, meanwhile, he had severe pulmonary infection interfering with the diagnosis of PTMG, and eventually progressed to refractory PTMG, which requiring much more expensive treatments and longer hospital stays.

Conclusion
In the perioperative management of asymptomatic thymoma patients, careful preoperative evaluation including physical examination, electrophysiological test and acetylcholine receptor antibodies (AChR-Ab) level should be done to identify subclinical MG. Complete resection should be performed during thymectomy, if not, additional postoperative adjuvant therapy is neccessary to avoid recurrence. It’s important to identify PTMG at a early stage, especially when being interfered with by postoperative complications, such as lung infection, so that treatments could be initiated as soon as possible to avoid developing to refractory PTMG.
Rubus chingii Hu. unripe fruits extract ameliorates carbon tetrachloride-induced liver fibrosis and improves the associated gut microbiota imbalance
Authors: Wu Jianjun , Zhang Dingqi , Zhu Bo , Wang Siqi , Xu Yongbin , Zhang Congcong , Yang Hailing , Wang Shunchun , Liu Ping , Qin Luping , Liu Wei 
Published: May 2022

Abstract
Background
The unripe fruits of Rubus chingii Hu. (“Fu-peng-zi” in Chinese) is a well-known herbal tonic in traditional Chinese medicine (TCM) for tonifying liver and kidney. However, little is known regarding its therapeutic efficacy against liver fibrosis and the underlying mechanism.

Methods
The current research aims to explore the potential of Rubus chingii Hu. unripe fruits extract (RF) in the treatment of liver fibrosis and explore the underlying mechanism. RF was administered (450 and 900 mg·kg− 1 of body weight per day) orally to male C57BL/6 mice with CCl4-induced liver fibrosis for 3 weeks. The histopathological changes and fibrosis stage in liver tissue were assessed using hematoxylin and eosin (H&E) and Sirius red staining. The distribution of α-SMA and Col1A1 in the liver was analyzed to determine the hepatic stellate cells (HSCs) activation using immunohistochemistry and immunofluorescent analysis. Various biochemical markers in serum (ALT, AST) and liver (Hyp, IL1-β, IL6, TNF-α and MCP-1) were observed to assess the liver’s injury, fibrosis, and inflammation. In liver tissue, fibrosis-associated proteins including α-SMA, TGF-β1, Smad2/3, p-Smad2/3, and Smad4 were detected through a Western blot assay. Pyrosequencing-based analysis of bacterial 16 S ribosomal RNA from variable regions V3–V4 of fecal samples characterized the gut microbiota. Spearman’s rank correlation analysis was performed for the association between altered bacterial genera by RF and pharmacodynamics parameters.

Results
Three weeks of RF treatment can significantly lower liver inflammatory levels, pathological abnormalities, and collagen fibrous deposition in mice with CCl4-induced liver fibrosis. The expressions of α-SMA and Col1A1 were lowered by RF, while the expression levels of TGF-β/Smads signaling pathway-related proteins, including TGF-β1, p-Smad2/3, and Smad4, were dramatically decreased by RF. The RF treatment significantly increased or reduced 18 different bacterial species, restoring the CCl4-induced gut microbiota imbalance to the normal group’s levels. According to correlation analysis, the bacterial genera Bifidobacterium and Turicibacter were the most significant in restoring CCl4-induced liver fibrosis.

Conclusions
RF can reduce liver damage and delay the onset of liver fibrosis through modulating TGF-β/Smads signaling pathway. Furthermore, RF’s anti-liver fibrosis effect was related to balancing the gut microbial community, partly attained by increasing Bifidobacterium and Turicibacter in liver fibrosis.
Annual prevalence estimation of lymphatic malformation with a cutaneous component: observational study of a national representative sample of physicians
Authors: Gallagher Jack Ray , Martini J. , Carroll S. , Small A. , Teng J. 
Published: May 2022

Abstract
Background
Lymphatic malformations (LMs) represent a potentially life-threatening, rare disease of the lymphatic system characterized by development of abnormal vessels, outpouchings, or cysts filled with lymphatic fluid. There are three morphologic types of LMs based on the size of the individual cysts: macrocystic (typically > 2 cm), microcystic (generally < 2 cm), and mixed (includes aspects of both). Macrocystic LMs typically exist beneath the skin and often can involve vascular components and/or organs. Microcystic LMs often have a cutaneous component and clinically present with lymphorrhea, bleeding, pain, itching, malodor, and functional deficits. There are no treatments approved by the US Food and Drug Administration (FDA) for either macrocystic or microcystic lymphatic malformations. The totality of the epidemiologic literature for LM is limited to the incidence of the disease among various birth cohorts. This is the first nationally representative study to estimate the national managed prevalence for patients with microcystic LM or combined LM with a cutaneous component annually across physician specialties likely to manage this condition. We conducted a retrospective observational survey of a nationally representative sample of patient-care physicians in the United States most likely to manage lymphatic malformations with a cutaneous component (LMC). Once recruited, target physicians participated via an electronic questionnaire. We weighted study physician self-estimates of the number of LMC patients treated in the past 12 months to reflect the specialists’ corresponding proportion in the national universe. All patient information was anonymous; no personally identifiable information was collected.

Results
Of the 420 physicians who visited the study website, 316 agreed to be screened and to participate (75.2% participation rate). Our survey results indicated the estimated number of unique annually managed LMC patients by target specialists is 79,920 (CI 66,600–93,250). This number corresponds to managed prevalence of 24.1 LMC patients per 100,000 population (CI 19.6/100,000–28.4/100,000).

Conclusions
The study indicates that while rare, LMC affects a substantial number of people in the US (79,920) who are being managed by one or more specialists. By better understanding the prevalence of people living with LMC who require treatment, efforts to both increase disease awareness and to identify underserved populations in need of potential new treatments can be better focused.
Genetic determinants of syndactyly: perspectives on pathogenesis and diagnosis
Authors: Cassim Afraah , Hettiarachchi Dineshani , Dissanayake Vajira H. W. 
Published: May 2022

AbstractThe formation of the digits is a tightly regulated process. During embryogenesis, disturbance of genetic pathways in limb development could result in syndactyly; a common congenital malformation consisting of webbing in adjacent digits. Currently, there is a paucity of knowledge regarding the exact developmental mechanism leading to this condition. The best studied canonical interactions of Wingless‐type–Bone Morphogenic Protein–Fibroblast Growth Factor (WNT–BMP–FGF8), plays a role in the interdigital cell death (ICD) which is thought to be repressed in human syndactyly. Animal studies have displayed other pathways such as the Notch signaling, metalloprotease and non-canonical WNT-Planar cell polarity (PCP), to also contribute to failure of ICD, although less prominence has been given. The current diagnosis is based on a clinical evaluation followed by radiography when indicated, and surgical release of digits at 6 months of age is recommended. This review discusses the interactions repressing ICD in syndactyly, and characterizes genes associated with non-syndromic and selected syndromes involving syndactyly, according to the best studied canonical WNT-BMP-FGF interactions in humans. Additionally, the controversies regarding the current syndactyly classification and the effect of non-coding elements are evaluated, which to our knowledge has not been previously highlighted. The aim of the review is to better understand the developmental process leading to this condition.
Healthcare access, satisfaction, and health-related quality of life among children and adults with rare diseases
Authors: Bogart Kathleen , Hemmesch Amanda , Barnes Erica , Blissenbach Thomas , Beisang Arthur , Engel Patti ,   The Chloe Barnes Advisory Council on Rare Diseases, Tolar Jakub , Schacker Tim , Schimmenti Lisa , Brown Nicole , Morrison Kelly , Albright Tony , Klein Matt , Coleman Julia , Nelsen Karl , Blaylark Rae , LaFond Karri , Berkowitz Sheldon , Schultz Kris Ann , Hansen Kerry , Beiraghi Soraya , Joers Barbara , Tilstra David , Gaviglio Amy , Jones Lee A. , Miller Abigail , Foster Jackie 
Published: May 2022

Abstract
Background
Research in a variety of countries indicates that healthcare access and health-related quality of life are challenged among people with a variety of rare diseases (RDs). However, there has been little systematic research on the experiences of children and adults with RDs in the American healthcare system that identifies commonalities across RDs. This research aimed to: (1) Describe demographics, disease characteristics, diagnostic experiences, access to healthcare, knowledge about RDs, support from healthcare professionals, and patient satisfaction among people with RDs and their caregivers; (2) examine predictors of patient satisfaction among adults with RDs; (3) compare health-related quality of life and stigma to US population norms; 4) examine predictors of anxiety and depression among adults and children with RDs.

Results
This large-scale survey included (n = 1128) adults with RD or parents or caregivers of children with RDs representing 344 different RDs. About one third of participants waited four or more years for a diagnosis and misdiagnosis was common. A subset of participants reported experiencing insurance-related delays or denials for tests, treatments, specialists, or services. Approximately half of participants felt their medical and social support was sufficient, yet less than a third had sufficient dental and psychological support. Patients were generally neither satisfied or dissatisfied with their healthcare providers. Major predictors of satisfaction were lower stigma, lower anxiety, shorter diagnostic odyssey, greater physical function, and less pain interference. Adults and children with RDs had significantly poorer health-related quality of life and stigma in all domains compared to US norms. Predictors of both anxiety and depression were greater stigma/poor peer relationships, fatigue, sleep disturbance, limited ability to participate in social roles, and unstable disease course.

Conclusions
People in the U.S. with RDs have poor health-related quality of life and high stigma. These factors are related to patient satisfaction and healthcare access, including diagnostic delays and misdiagnosis. Advocacy work is needed in order to improve healthcare access and ultimately health-related quality of life for children and adults with RDs.
Understanding the role of SGLT2 inhibitors in glycogen storage disease type Ib: the experience of one UK centre
Authors: Halligan Rebecca K. , Dalton R. Neil , Turner Charles , Lewis Katherine A. , Mundy Helen R. 
Published: May 2022

Abstract
Background
Glycogen storage disease type Ib (GSD Ib) is a severe disorder of carbohydrate metabolism due to bi-allelic variants in SLC37A4. It is associated with neutropaenia and neutrophil dysfunction, which has recently been attributed to the accumulation of 1,5-anhydroglucitol-6-phosphate (1,5AG6P) within neutrophils. Treatment with sodium-glucose co-transporter-2 (SGLT2) inhibitors, such as empagliflozin, is a novel therapy that reduces 1,5-anhydroglucitol (1,5AG) in plasma.

Results
We report our experience in treating 8 paediatric GSD Ib patients with empagliflozin with a cumulative treatment time greater than 12 years. Treatment with a median dose of 5 mg (0.22 mg/kg height weight) of empagliflozin resulted in improvement in bowel health, growth, and laboratory parameters. Plasma 1,5AG levels reduced by a median of 78%. Baseline 1,5AG levels in our cohort were higher than in adult patients with GSD Ib. Hypoglycaemia on empagliflozin treatment occurred in 50% of our cohort.

Conclusion
We report the largest single centre cohort of GSD Ib patients treated with empagliflozin to date. Treatment with SGLT2 inhibitors is a novel and favourable treatment option for neutropaenia and neutrophil dysfunction in GSD Ib. We suggest a low starting dose of empagliflozin with careful titration due to the risk of hypoglycaemia. The interpretation of 1,5AG levels and their role in treatment monitoring is yet to be established, and requires ongoing research.
Single-cell sequencing: a promising approach for uncovering the mechanisms of tumor metastasis
Authors: Han Yingying , Wang Dan , Peng Lushan , Huang Tao , He Xiaoyun , Wang Junpu , Ou Chunlin 
Published: May 2022

AbstractSingle-cell sequencing (SCS) is an emerging high-throughput technology that can be used to study the genomics, transcriptomics, and epigenetics at a single cell level. SCS is widely used in the diagnosis and treatment of various diseases, including cancer. Over the years, SCS has gradually become an effective clinical tool for the exploration of tumor metastasis mechanisms and the development of treatment strategies. Currently, SCS can be used not only to analyze metastasis-related malignant biological characteristics, such as tumor heterogeneity, drug resistance, and microenvironment, but also to construct metastasis-related cell maps for predicting and monitoring the dynamics of metastasis. SCS is also used to identify therapeutic targets related to metastasis as it provides insights into the distribution of tumor cell subsets and gene expression differences between primary and metastatic tumors. Additionally, SCS techniques in combination with artificial intelligence (AI) are used in liquid biopsy to identify circulating tumor cells (CTCs), thereby providing a novel strategy for treating tumor metastasis. In this review, we summarize the potential applications of SCS in the field of tumor metastasis and discuss the prospects and limitations of SCS to provide a theoretical basis for finding therapeutic targets and mechanisms of metastasis.
Artificial intelligence in Emergency Medical Services dispatching: assessing the potential impact of an automatic speech recognition software on stroke detection taking the Capital Region of Denmark as case in point
Authors: Scholz Mirjam Lisa , Collatz-Christensen Helle , Blomberg Stig Nikolaj Fasmer , Boebel Simone , Verhoeven Jeske , Krafft Thomas 
Published: May 2022

AbstractBackground and purposeStroke recognition at the Emergency Medical Services (EMS) impacts the stroke treatment and thus the related health outcome. At the EMS Copenhagen 66.2% of strokes are detected by the Emergency Medical Dispatcher (EMD) and in Denmark approximately 50% of stroke patients arrive at the hospital within the time-to-treatment. An automatic speech recognition software (ASR) can increase the recognition of Out-of-Hospital cardiac arrest (OHCA) at the EMS by 16%. This research aims to analyse the potential impact an ASR could have on stroke recognition at the EMS Copenhagen and the related treatment.MethodsStroke patient data (n = 9049) from the years 2016–2018 were analysed retrospectively, regarding correlations between stroke detection at the EMS and stroke specific, as well as personal characteristics such as stroke type, sex, age, weekday, time of day, year, EMS number contacted, and treatment. The possible increase in stroke detection through an ASR and the effect on stroke treatment was calculated based on the impact of an existing ASR to detect OHCA from CORTI AI.ResultsThe Chi-Square test with the respective post-hoc test identified a negative correlation between stroke detection and females, the 1813-Medical Helpline, as well as weekends, and a positive correlation between stroke detection and treatment and thrombolysis. While the association analysis showed a moderate correlation between stroke detection and treatment the correlation to the other treatment options was weak or very weak. A potential increase in stroke detection to 61.19% with an ASR and hence an increase of thrombolysis by 5% in stroke patients calling within time-to-treatment was predicted.ConclusionsAn ASR can potentially improve stroke recognition by EMDs and subsequent stroke treatment at the EMS Copenhagen. Based on the analysis results improvement of stroke recognition is particularly relevant for females, younger stroke patients, calls received through the 1813-Medical Helpline, and on weekends.Trial registrationThis study was registered at the Danish Data Protection Agency (PVH-2014-002) and the Danish Patient Safety Authority (R-21013122).
Impact of critical illness and withholding of early parenteral nutrition in the pediatric intensive care unit on long-term physical performance of children: a 4-year follow-up of the PEPaNIC randomized controlled trial
Authors: Vanhorebeek Ilse , Jacobs An , Mebis Liese , Dulfer Karolijn , Eveleens Renate , Van Cleemput Hanna , Wouters Pieter J. , Verlinden Ines , Joosten Koen , Verbruggen Sascha , Van den Berghe Greet 
Published: May 2022

Abstract
Background
Many critically ill children face long-term developmental impairments. The PEPaNIC trial attributed part of the problems at the level of neurocognitive and emotional/behavioral development to early use of parenteral nutrition (early-PN) in the PICU, as compared with withholding it for 1 week (late-PN). Insight in long-term daily life physical functional capacity after critical illness is limited. Also, whether timing of initiating PN affects long-term physical function of these children remained unknown.

Methods
This preplanned follow-up study of the multicenter PEPaNIC randomized controlled trial subjected 521 former critically ill children (253 early-PN, 268 late-PN) to quantitative physical function tests 4 years after PICU admission in Leuven or Rotterdam, in comparison with 346 age- and sex-matched healthy children. Tests included handgrip strength measurement, timed up-and-go test, 6-min walk test, and evaluation of everyday overall physical activity with an accelerometer. We compared these functional measures for the former critically ill and healthy children and for former critically ill children randomized to late-PN versus early-PN, with multivariable linear or logistic regression analyses adjusting for risk factors.

Results
As compared with healthy children, former critically ill children showed less handgrip strength (p < 0.0001), completed the timed up-and-go test more slowly (p < 0.0001), walked a shorter distance in 6 min (p < 0.0001) during which they experienced a larger drop in peripheral oxygen saturation (p ≤ 0.026), showed a lower energy expenditure (p ≤ 0.024), performed more light and less moderate physical activity (p ≤ 0.047), and walked fewer steps per day (p = 0.0074). Late-PN as compared with early-PN did not significantly affect these outcomes.

Conclusions
Four years after PICU admission, former critically ill children showed worse physical performance as compared with healthy children, without impact of timing of supplemental PN in the PICU. This study provides further support for de-implementing the early use of PN in the PICU.
Trial registration ClinicalTrials.gov, NCT01536275; registered on February 22, 2012.