bluuebunny/crossref_metadata_2025_split huggingface dataset:
Educational Interventions to Improve Advance Care Planning Discussions, Documentation and Billing
Authors: Henage Cristine B. , McBride J. Marvin , Pino Joseph , Williams Jessica , Vedovi Jill , Cannady Nicole , Buno Liz Riley , Chatman Toni , Busby-Whitehead Jan , Roberts Ellen 
Published: August 2020

Background/Objectives: To determine the impact of educational interventions, clinic workflow redesign, and quality improvement coaching on the frequency of advance care planning (ACP) activities for patients over the age of 65. Design: Nonrandomized before-and-after study. Setting: 13 ambulatory care clinics with 81 primary care providers in eastern and central North Carolina. Participants: Patients across 13 primary care clinics staffed by 66 physicians, 8 physician assistants and 7 family nurse practitioners. Interventions: Interprofessional, interactive ACP training for the entire interprofessional team and quality improvement project management with an emphasis on workflow redesign. Measurements: From July 2017 through June 2018—number of ACP discussions, number of written ACP documents incorporated into the electronic medical record (EMR), number of ACP encounters billed. Results: Following the interventions, healthcare providers were more than twice as likely to conduct ACP discussions with their patients. Patients were 1.4 times more likely to have an ACP document included in their electronic medical record. Providers were significantly ( p < 0.05) more likely to bill for an ACP encounter in only one clinic. Conclusions: Implementing ACP education for all clinic staff, planning for workflow changes to involve the entire interprofessional team and supporting ACP activities with quality improvement coaching leads to statistically significant improvements in the frequency of ACP discussions, the number of ACP documents included in the electronic medical record and number of ACP encounters billed.
A prospective study on the association between post-voiding residual volume and quality of life during bacille Calmette-Guérin (BCG) instillation therapy for non–muscle-invasive bladder cancer
Authors: Kikuchi Daichi , Kato Yoichiro , Takayama Misato , Kanzaki Seiko , Ito Akito , Ikarashi Daiki , Maekawa Shigekatsu , Kato Renpei , Seo Takashi , Owari Yukihisa , Nozawa Tatsuru , Isurugi Kazumasa , Fujisawa Hiromitsu , Ujiie Takashi , Kanehira Mitsugu , Takata Ryo , Obara Wataru 
Published: August 2020

Objectives: The aim of this study was to investigate the relationship between quality of life (QOL) and residual urine volume in patients undergoing bacille Calmette-Guérin (BCG) therapy. Methods: Patients requiring BCG therapy, including those with carcinoma in situ, were enrolled prospectively. The urine volume collected through urethral catheterization was measured as post-voiding residual volume (PVR) during BCG therapy. Patients were divided into two groups: small PVR (SPVR), with PVR less than 30 ml, and large PVR (LPVR), with PVR greater than or equal to 30 ml. QOL status was assessed using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 system before and after BCG therapy. Moreover, some patients were assessed by International Prostate Symptom Score (IPSS) at the same time as assessment with the EORTC QLQ-C30 system. The primary end point was the evaluation of QOL during BCG therapy. Results: Among the 69 patients with non–muscle-invasive bladder cancer included in this study, 43 were in the SPVR group and 26 were in the LPVR group. The proportions of women and analgesic use in the SPVR group were higher than that in the LPVR group; however, medication use for dysuria in the SPVR group was less than that in the LPVR group. In the QOL analyses, cognitive function and emotional function in the functional scale and fatigue, nausea/vomiting, and dyspnoea in the symptomatic scale were worse in the SPVR group than in the LPVR group. In the multivariate analysis, fatigue was worse in the SPVR group than in the LPVR group. Conclusions: During BCG therapy, patients in the SPVR group had worse QOL, especially fatigue, than those in the LPVR group. Level of evidence: Not applicable for this multicentre audit.
Revealing the diversity of amber source plants from the Early Cretaceous Crato Formation, Brazil
Authors: Seyfullah Leyla J. , Roberts Emily A. , Schmidt Alexander R. , Ragazzi Eugenio , Anderson Ken B. , Rodrigues do Nascimento Daniel , Ferreira da Silva Filho Wellington , Kunzmann Lutz 
Published: August 2020

AbstractBackgroundAmber has been reported from the Early Cretaceous Crato Formation, as isolated clasts or within plant tissues. Undescribed cones of uncertain gymnosperm affinity have also been recovered with amber preserved in situ. Here, we provide multiple lines of evidence to determine the botanical affinity of this enigmatic, conspicuous cone type, and to better understand the diversity of amber-source plants present in the Crato Formation and beyond.ResultsA new taxon of amber-bearing pollen coneAraripestrobus resinosusgen. nov. et sp. nov. is described here from complete cones and characteristic disarticulated portions. The best-preserved cone portion has both in situ amber infilling the resin canals inside the preserved microsporophyll tissues and pollen of theEucommiidites-type. This places this genus within the Erdtmanithecales, an incompletely known gymnosperm group from the Mesozoic.FTIR analysis of the in situ amber indicates a potential araucariacean conifer affinity, although affinity with cupressacean conifers cannot be definitely ruled out. Pyr-GC-MS analysis of theAraripestrobus resinosusgen. nov. et sp. nov. in situ fossil resin shows that it is a mature class Ib amber, thought to indicate affinities with araucariacean and cupressacean, but not pinaceous, conifers. This is the first confirmed occurrence of this class of amber in the Crato Formation flora and in South America, except for an archaeological sample from Laguna Guatavita, Colombia.ConclusionsThe combined results of the cones’ novel gross morphology and the analyses of the in situ amber and pollen clearly indicate that the new taxon of resinous gymnosperm pollen cones from the Crato Formation is affiliated with Erdtmanithecales. The cone morphology is very distinct from all known pollen cone types of this extinct plant group. We therefore assume that the plant group that producedEucommiidites-type pollen is much more diverse in habits than previously thought. Moreover, the diversity of potential amber source plants from the Crato Formation is now expanded beyond the Araucariaceae and the Cheirolepidiaceae to include this member of the Erdtmanithecales. Despite dispersedEucommiiditespollen being noted from the Crato Formation, this is the first time macrofossils of Erdtmanithecales have been recognized from the Early Cretaceous of South America.
Hybrid transcriptome sequencing approach improved assembly and gene annotation in Cynara cardunculus (L.)
Authors: Puglia Giuseppe D. , Prjibelski Andrey D. , Vitale Domenico , Bushmanova Elena , Schmid Karl J. , Raccuia Salvatore A. 
Published: August 2020

Abstract
Background
The investigation of transcriptome profiles using short reads in non-model organisms, which lack of well-annotated genomes, is limited by partial gene reconstruction and isoform detection. In contrast, long-reads sequencing techniques revealed their potential to generate complete transcript assemblies even when a reference genome is lacking. Cynara cardunculus var. altilis (DC) (cultivated cardoon) is a perennial hardy crop adapted to dry environments with many industrial and nutraceutical applications due to the richness of secondary metabolites mostly produced in flower heads. The investigation of this species benefited from the recent release of a draft genome, but the transcriptome profile during the capitula formation still remains unexplored. In the present study we show a transcriptome analysis of vegetative and inflorescence organs of cultivated cardoon through a novel hybrid RNA-seq assembly approach utilizing both long and short RNA-seq reads.

Results
The inclusion of a single Nanopore flow-cell output in a hybrid sequencing approach determined an increase of 15% complete assembled genes and 18% transcript isoforms respect to short reads alone. Among 25,463 assembled unigenes, we identified 578 new genes and updated 13,039 gene models, 11,169 of which were alternatively spliced isoforms. During capitulum development, 3424 genes were differentially expressed and approximately two-thirds were identified as transcription factors including bHLH, MYB, NAC, C2H2 and MADS-box which were highly expressed especially after capitulum opening. We also show the expression dynamics of key genes involved in the production of valuable secondary metabolites of which capitulum is rich such as phenylpropanoids, flavonoids and sesquiterpene lactones. Most of their biosynthetic genes were strongly transcribed in the flower heads with alternative isoforms exhibiting differentially expression levels across the tissues.

Conclusions
This novel hybrid sequencing approach allowed to improve the transcriptome assembly, to update more than half of annotated genes and to identify many novel genes and different alternatively spliced isoforms. This study provides new insights on the flowering cycle in an Asteraceae plant, a valuable resource for plant biology and breeding in Cynara and an effective method for improving gene annotation.
Association of TIM-3 expression with glucose metabolism in Jurkat T cells
Authors: Lee Mi Jin , Yun Su Jin , Lee Bokyoung , Jeong Eun , Yoon Gyesoon , Kim Kyongmin , Park Sun 
Published: August 2020

Abstract
Background
T cell activation is associated with increase in glycolysis and glutaminolysis. T cell immunoglobulin and mucin domain containing protein-3 (TIM-3), a T cell surface molecule, downregulates T cell activation and leads to insufficient immunity in cancer and chronic infection. TIM-3 regulates T cell activation possibly through alterations in metabolism; however, the relationship between TIM-3 expression and T cell metabolic changes has not been well studied.

Results
We investigated the association between TIM-3 expression and metabolic changes by analyzing glucose metabolism, glutamine metabolism, and mitochondrial function in TIM-3 overexpressing or knockout Jurkat T cell lines relative to their control cell lines. Glucose uptake and consumption, and lactate release were downregulated by TIM-3 expression but upregulated by TIM-3 knockout. Concomitantly, the expression of the glucose transporter, Glut1, but not Glut2, 3, or 4 was altered by TIM-3 expression. However, TIM-3 expression alone could not account for the change in glutamine consumption, glutamate release, and mitochondrial mass, ROS production or membrane potential in these cell lines.

Conclusion
Our results show the association of TIM-3 expression with T cell glucose metabolism. These results are significant in chronic infections and cancers where it is necessary to control TIM-3 expressing T cells.
Novel variant in NSDHL gene associated with CHILD syndrome and syndactyly- a case report
Authors: Hettiarachchi D. , Panchal Hetalkumar , Lai P. S. , Dissanayake V. H. W. 
Published: August 2020

Abstract
Background
Congenital hemidysplasia with ichthyosiform erythroderma and limb defects also known as CHILD syndrome is an X-linked dominant, male lethal genodermatosis with a prevalence of 1 in 100,000 live births. Mutations in NSDHL gene located at Xq28 potentially impair the function of NAD(P) H steroid dehydrogenase-like protein and is responsible for its pathogenesis.

Case presentation
The proband was a 9-month-old twin (T2) girl with a healthy twin sister (T1) of Sri Lankan origin born to non-consanguineous parents. She presented with right sided continuous icthyosiform erythroderma and ipsilateral limb defects and congenital hemidysplasia since birth. Notably the child had ipsilateral hand hypoplasia and syndactyly. There were other visceral abnormalities. We performed whole exome sequencing and found a novel heterozygous variant (NSDHL, c.713C > A, p.Thr238Asn).

Conclusion
We report a novel missense variant in the NSDHL gene that resides in a highly-conserved region. This variant affects the NAD(P) H steroid dehydrogenase-like protein function via reduction in the number of active sites resulting in the CHILD syndrome phenotype and syndactyly.
Use of terlipressin in critically ill children with liver disease
Authors: Saxena Romit , Anand Aravind , Deep Akash 
Published: August 2020

Abstract
Background
Terlipressin, a long-acting synthetic analogue of vasopressin has been used in the adult population for various indications including hepatorenal syndrome (HRS-AKI), esophageal variceal hemorrhage (EVH) and shock, but its use in pediatrics is still limited to individualized cases and data on safety and efficacy is scant.

Methods
We reviewed the patient records of children with liver disease and Acute Kidney Injury requiring terlipressin admitted to the Paediatric Intensive Care Unit (PICU) of King’s College Hospital, London from January 2010–December 2017, with special emphasis on its effect on renal parameters and adverse event profile.

Results
Twenty-one terlipressin administration records in a total of 16 patients (median) (IQR) 10 years (6.1–14.4) were included. The drug was initially given as a bolus dose in all cases, followed by either bolus or infusion with median dosage being 5.2 (3.8–6.7) mcg/kg/hour. After administration, a sustained increase of mean arterial pressure was observed. There was an improvement in serum creatinine (Cr) (at 24 h; p = 0.386) and increase in urine output (UO), especially in the hepatorenal syndrome subgroup (HRS-AKI). We found minimal evidence of gastrointestinal side effects including feeding intolerance and vasoconstrictive side effects including cyanosis / ischaemia of extremities.

Conclusion
Terlipressin was found to be safe in critically sick children with liver disease with positive impact on renal parameters which might be taken as a surrogate marker of HRS reversal, though effects on outcomes are difficult to ascertain. It is important to be aware of all its side-effects and actively watch for them. Future prospective studies are warranted to validate these findings.
Pain trajectories of dorsomedial prefrontal intermittent theta burst stimulation versus sham treatment in depression
Authors: Malm Erika , Struckmann Wiebke , Persson Jonas , Bodén Robert 
Published: August 2020

Abstract
Background
Prefrontal repetitive transcranial magnetic stimulation is an established add-on treatment for major depressive disorder and is increasingly feasible with protocols of short duration, such as intermittent theta burst stimulation (iTBS). The most common and limiting side effect is pain at the site of application. Our objective was to investigate how pain develops over time in patients with depression receiving iTBS compared to sham stimulation.

Methods
This is a subsample from a randomized clinical trial. Patients received daily sessions of 2400 pulses of dorsomedial prefrontal iTBS or sham stimulation with transcutaneous electric stimulation during 2 to 3 weeks. After unmasking of treatment allocation, patients receiving sham treatment were offered active iTBS in an open phase. Patients rated pain on a scale from 0 to 10 after the last train of stimulation on the first, fifth and final treatment day. A Mann-Whitney U-test was conducted to test for group differences and related-samples Friedman’s tests to analyze changes in pain ratings over time.

Results
The scalp pain in the group receiving iTBS was rated higher than sham treatment on the first (U = 263.5, p = 0.035) and fifth day (U = 271.0, p = 0.020) but not on the final day (U = 210.5, p = 0.121). The pain decreased mainly during the first 5 days of treatment (χ2 = 0.875, p = 0.040). In the open phase the pain decreased from the first day to the final day (χ2 = 1.194, p = 0.001).

Conclusions
The subjective pain perception of active dorsomedial iTBS was higher than sham treatment but decreased over time, indicating an analgesic effect, or habituation. The result from this study can be used to inform patients about what to expect regarding pain during an iTBS treatment course.

Trial registration
Clinicaltrials.gov, NCT02905604. Registered 19 September 2016.
Twin pregnancy complicated with congenital Hemivertebra: report of two cases and literature review
Authors: Xu Tingting , Wang Xiaodong , Yu Haiyan , Zhao Fumin 
Published: August 2020

Abstract
Background
Hemivertebra deformity, involving one or multiple vertebral bodies, is one of the important causes of congenital scoliosis. Congenital fetal hemivertebrae could be diagnosed by ultrasonography and confirmed by fetal magnetic resonance imaging during pregnancy. However, reports of hemivertebrae in twins during the perinatal period are very rare.

Case presentation
We report two cases of congenital fetal hemivertebrae, each affecting one fetus in a dichorionic diamniotic (DCDA) twin pregnancy. We have also conducted a literature review of its prenatal screening, diagnosis, management, and outcomes. These two cases of congenital fetal hemivertebrae in one fetus of a DCDA twin were both initially found by ultrasonography and confirmed by fetal magnetic resonance imaging (MRI). One couple chose selective termination of the hemivertebrae fetus after they were extensively counseled by the multidisciplinary team regarding the treatment and prognosis of the hemivertebrae twin, and a healthy baby weighing 2320 g was delivered at the 37+ 1 gestational week. The other couple decided to continue the twin pregnancy and gave birth to two living newborns weighing 2580 g and 2060 g at 37+ 1 gestational weeks. These three babies were all in good health during follow-up.

Conclusions
Based on our center’s experience, comprehensive ultrasonography is necessary for early prenatal diagnosis of this condition. In addition, fetal MRI will confirm the diagnosis of hemivertebrae and provide parents with helpful information for their decision about the fate of the affected fetus.
Randomized double-blind clinical trial comparing safety and efficacy of the biosimilar BCD-022 with reference trastuzumab
Authors: Alexeev Sergey M. , Khorinko Andrey V. , Mukhametshina Guzel Z. , Shelepen Konstantin G. , Burdaeva Olga N. , Kulik Sergey A. , Satheesh Chiradoni Thugappa , Srivastava Kirti , Vikranth Mummaneni , Kryukov Fedor , Paltusova Anastasia N. , Shustova Mariya S. , Ivanov Roman A. 
Published: August 2020

Abstract
Background
BCD-022 is a trastuzumab biosimilar which was shown to be equivalent to reference trastuzumab in a wide panel of physicochemical studies as well as preclinical studies in vitro and in vivo. International multicenter phase III clinical trial was conducted to comparatively assess efficacy and safety of BCD-022 and reference trastuzumab in combination with paclitaxel used as the therapy of metastatic HER2(+) breast cancer. Pharmacokinetics and immunogenicity were also studied.

Methods
Patients with no previous treatment for metastatic HER2(+) breast cancer were randomly assigned 1:1 to BCD-022 or reference trastuzumab and were treated with trastuzumab + paclitaxel. Therapy continued for 6 cycles of therapy (every 3 weeks), until progression of the disease or unbearable toxicity. Primary study endpoint was overall response rate. Study goal was to prove equivalent efficacy of BCD-022 and reference trastuzumab. Equivalence margins for 95% CI for difference in overall response rates were set at [− 20%; 20%].

Results
In total 225 patients were enrolled into the study, 115 in BCD-022 arm and 110 in reference trastuzumab arm. Overall response rate was 49.6% in BCD-022 arm and 43.6% in reference trastuzumab arm. Limits of 95% CI for difference of overall response rates between arms were [(− 8.05)-19.89%], thus, they lied within predetermined equivalence margins [− 20%; 20%]. Profile of adverse events was similar between groups (any AEs were reported in 93.81% of patients in BCD-022 arm and 94.55% of patients in reference arm). No unexpected adverse reactions were reported throughout the study. No statistically significant differences regarding antibody occurrence rate (either BAb or NAb) was found between BCD-022 (n = 3; 2.65%) and comparator (n = 4; 3.64%). Both drug products are characterized with low occurrence rate and short life of anti-trastuzumab antibodies. Pharmacokinetics assessment after 1st and 6th study drug injection also demonstrated equivalent PK parameters by all outcome measures: AUC0–504, Сmах, Тmax, T1/2. Analysis of Ctrough did not reveal any significant inter-group differences as well.

Conclusions
Thus, results of this study have demonstrated therapeutic equivalence of trastuzumab biosimilar BCD-022 and referent trastuzumab drug.

Trial registration
The trial was registered with ClinicalTrials.gov (Study Number NCT01764022). The date of registration was January 9, 2013.
MEIS1 promotes expression of stem cell markers in esophageal squamous cell carcinoma
Authors: Zargari Selma , Negahban Khameneh Shabnam , Rad Abolfazl , Forghanifard Mohammad Mahdi 
Published: August 2020

Abstract
Background
MEIS1 (Myeloid ecotropic viral integration site 1) as a homeobox (HOX) transcription factor plays regulatory roles in a variety of cellular processes including development, differentiation, survival, apoptosis and hematopoiesis, as well as stem cell regulation. Few studies have established pluripotency and self-renewal regulatory roles for MEIS1 in human esophageal squamous cell carcinoma (ESCC), and our aim in this study was to evaluate the functional correlation between MEIS1 and the stemness markers in ESCC patients and cell line KYSE-30.

Methods
Expression pattern of MEIS1 and SALL4 gene expression was analyzed in different pathological features of ESCC patients. shRNA in retroviral vector was used for constantly silencing of MEIS1 mRNA in ESCC line (KYSE-30). Knockdown of MEIS1 gene and the expression pattern of selected stemness markers including SALL4, OCT4, BMI-1, HIWI, NANOG, PLK1, and KLF4 were evaluated using real-time PCR.

Results
Significant correlations were observed between MEIS1 and stemness marker SALL4 in different early pathological features of ESCC including non-invaded tumors, and the tumors with primary stages of progression. Retroviral knockdown of MEIS1 in KYSE-30 cells caused a noteworthy underexpression of both MEIS1 and major involved markers in stemness state of the cells including SALL4, OCT4, BMI-1, HIWI and KLF4.

Conclusions
The results highlight the important potential role of MEIS1 in modulating stemness properties of ESCCs and cells KYSE-30. These findings may confirm the linkage between MEIS1 and self-renewal capacity in ESCC and support probable oncogenic role for MEIS1 in the disease.