bluuebunny/crossref_metadata_2025_split huggingface dataset:
Precision medicine and its implementation in patients with NTRK fusion genes: perspective from developing countries
Authors: Cardona Andrés F. , Arrieta Oscar , Ruiz-Patiño Alejandro , Sotelo Carolina , Zamudio-Molano Nataly , Zatarain-Barrón Zyanya Lucia , Ricaurte Luisa , Raez Luis , Álvarez Marco Polo Peralta , Barrón Feliciano , Rojas Leonardo , Rolfo Christian , Karachaliou Niki , Molina-Vila Miguel Angel , Rosell Rafael 
Published: July 2020

Precision oncology is the field that places emphasis on the diagnosis and treatment of tumors that harbor specific genomic alterations susceptible to inhibition or modulation. Although most alterations are only present in a minority of patients, a substantial effect on survival can be observed in this subgroup. Mass genome sequencing has led to the identification of a specific driver in the translocations of the tropomyosin receptor kinase family (NTRK) in a subset of rare tumors both in children and in adults, and to the development and investigation of Larotrectinib. This medication was granted approval by the US Food and Drug Administration for NTRK-positive tumors, regardless of histology or age group, as such, larotrectinib was the first in its kind to be approved under the premise that molecular pattern is more important than histology in terms of therapeutic approach. It yielded significant results in disease control with good tolerability across a wide range of diseases including rare pediatric tumors, salivary gland tumors, gliomas, soft-tissue sarcomas, and thyroid carcinomas. In addition, and by taking different approaches in clinical trial design and conducting allocation based on biomarkers, the effects of target therapies can be isolated and quantified. Moreover, and considering developing nations and resource-limited settings, precision oncology could offer a tool to reduce cancer-related disability and hospital costs. In addition, developing nations also present patients with rare tumors that lack a chance of treatment, outside of clinical trials. This, in turn, offers the possibility for international collaboration, and contributes to employment, education, and health service provisions. The reviews of this paper are available via the supplemental material section.
Activating transcription factor 3 (ATF3) as a perspective biomarker of Crohn’s disease
Authors: Kobayashi Nobuyuki , Arihiro Seiji , Shimada Kazuya , Hoshino Atsushi , Saijo Hiroki , Oka Naomi , Saruta Masayuki , Kondo Kazuhiro 
Published: July 2020

Introduction:Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the intestinal tract. Known types are Crohn’s disease (CD) and ulcerative colitis (UC), but their cause remains unclear and there is no convenient biomarker for IBD. The present study aimed to demonstrate an association between the onset of CD and activating transcription factor 3 (ATF3); as a new biomarker, measurement of blood ATF3 mRNA would be useful for distinguishing between CD and UC.Methods:First, in a mouse model of IBD in which damage to the intestinal mucosa was chemically induced with dextran sulfate sodium (DSS), intestinal ATF3 mRNA was evaluated. Next, in human subjects, CD and UC patients, blood ATF3 mRNA and intestinal ATF3 protein production were evaluated.Results:In the mouse model of IBD, intestinal ATF3 mRNA was elevated compared with the control ( P < 0.0001). In CD patients, blood ATF3 mRNA was elevated as compared with normal controls (NCs) and UC patients ( P < 0.05). In addition, we observed an increase in ATF3 production in the intestinal tract specific to CD.Conclusion:ATF3 is involved in the onset of CD, and blood ATF3 mRNA measurements would be useful for distinguishing it from UC.
Effects of short-term warm water immersion on cardiac baroreflex sensitivity in healthy men
Authors: Sugawara Jun , Tomoto Tsubasa 
Published: July 2020

AbstractWarm water immersion (WWI) causes dizziness presumably due to a substantial drop of blood pressure. The aim of this study was to elucidate the effects of short-term WWI on cardiac baroreflex sensitivity (BRS) and the contribution of arterial stiffness to the cardiac BRS. Twelve apparent healthy men (44 ± 12 years) performed the single stand-up test after 5-min sitting in the bathtub without (Control) and with 41 °C warm water at the heart level (WWI). Cardiac BRS gain was evaluated by R–R interval response to the standing-induced drop of systolic blood pressure. In addition, before and 10 min after the single stand-up test, carotid arterial β-stiffness index was evaluated in the supine rest. BRS gain was blunted (2.9 ± 1.6 vs. 1.8 ± 1.1 ms/mmHg, P = 0.005), whereas β-stiffness index was not changed significantly after WWI. BRS gain correlated with β-stiffness index before (r = − 0.626, P = 0.028) and after WWI (r = − 0.672, P = 0.015). ANCOVA revealed that these slopes of linear regression lines remained unchanged after WWI (P = 0.350). These results indicate that a short-term WWI acutely deteriorates cardiac BRS. Individuals with stiffer arteries are relatively more susceptible to WWI because of their poor baseline BRS, which might be one of the causes of bathing-related falling in elderly persons as well as frailty.
Efficient implied alignment
Authors: Washburn Alex J. , Wheeler Ward C. 
Published: July 2020

Abstract
Background
Given a binary tree $\mathcal {T}$
T
of n leaves, each leaf labeled by a string of length at most k, and a binary string alignment function ⊗, an implied alignment can be generated to describe the alignment of a dynamic homology for $\mathcal {T}$
T
. This is done by first decorating each node of $\mathcal {T}$
T
with an alignment context using ⊗, in a post-order traversal, then, during a subsequent pre-order traversal, inferring on which edges insertion and deletion events occurred using those internal node decorations.

Results
Previous descriptions of the implied alignment algorithm suggest a technique of “back-propagation” with time complexity $\mathcal {O}\left (k^{2} * n^{2}\right)$
O

k

2

∗

n

2

. Here we describe an implied alignment algorithm with complexity $\mathcal {O}\left (k * n^{2}\right)$
O

k
∗

n

2

. For well-behaved data, such as molecular sequences, the runtime approaches the best-case complexity of Ω(k∗n).

Conclusions
The reduction in the time complexity of the algorithm dramatically improves both its utility in generating multiple sequence alignments and its heuristic utility.
EGR2 is elevated and positively regulates inflammatory IFNγ production in lupus CD4+ T cells
Authors: Dai Rujuan , Heid Bettina , Xu Xiguang , Xie Hehuang , Reilly Christopher M. , Ahmed S. Ansar 
Published: July 2020

AbstractBackgroundRecent studies have shown that early growth response 2 (EGR2) is highly induced in activated T cells and regulates T cell functions. In normal C57BL/6 (B6) mice, deletion of EGR2 in lymphocytes results in the development of lupus-like systemic autoimmune disease, which implies indirectly an autoimmune protective role of EGR2. Conversely, increased EGR2 gene expression is suggested to link with high risk of human lupus. In the present studies we sought to clarify the expression and inflammation regulatory role of EGR2 in murine lupus T cells directly.ResultsWe performed RT-qPCR analysis and found a significant increase of EGR2 mRNA expression in human lupus PBMCs and in CD4+T cells from three different murine lupus models including MRL-lpr, B6-lpr, and B6.sle123mice at diseased stage when compared to age-matched control MRL or B6 mice. By performing intracellular flow cytometry analysis, we found that EGR2 protein expression was significantly increased in resting lupus (either MRL-lpror B6.sle123) CD4+T cells when compared to CD4+T cells from their respective non-autoimmune controls. However, there was no difference of EGR2 protein expression in anti-CD3 and anti-CD28 stimulated control and lupus CD4+T cells since there was a stronger induction of EGR2 in activated control CD4+T cells. EGR2 expression was significantly increased in MRL-lprmice at an age when lupus is manifested. To understand further the function of elevated EGR2 in lupus CD4+T cells, we inhibited EGR2 with a specific siRNA in vitro in splenocytes from MRL-lprand control MRL mice at 15 weeks-of-age. We found that EGR2 inhibition significantly reduced IFNγ production in PMA and ionomycin activated MRL-lprlupus CD4+T cells, but not control MRL CD4+T cells. We also found that inhibition of EGR2 in vitro suppressed the Th1 differentiation in both MRL and MRL-lprnaïve CD4+T cells.ConclusionsEGR2 is highly upregulated in human and murine lupus cells. Our in vitro data suggest a positive role of EGR2 in the regulation of Th1 differentiation and IFNγ production in lupus effector CD4+T cells.
Plant performance of enhancing licorice with dual inoculating dark septate endophytes and Trichoderma viride mediated via effects on root development
Authors: He Chao , Wang Wenquan , Hou Junling 
Published: July 2020

Abstract
Background
This study aimed to assess whether licorice (Glycyrrhiza uralensis) can benefit from dual inoculation by Trichoderma viride and dark septate endophytes (DSE) isolated from other medicinal plants.

Methods
First, we isolated and identified three DSE (Paraboeremia putaminum, Scytalidium lignicola, and Phoma herbarum) and Trichoderma viride from medicinal plants growing in farmland of China. Second, we investigated the influences of these three DSE on the performance of licorice at different T. viride densities (1 × 106, 1 × 107, and 1 × 108 CFU/mL) under sterilised condition in a growth chamber.

Results
Three DSE strains could colonize the roots of licorice, and they established a positive symbiosis with host plants depending on DSE species and T. viride densities. Inoculation of P. putaminum increased the root biomass, length, surface area, and root:shoot ratio. S. lignicola increased the root length, diameter and surface area and decreased the root:shoot ratio. P. herbarum increased the root biomass and surface area. T. viride increased the root biomass, length, and surface area. Structural equation model (SEM) analysis showed that DSE associated with T. viride augmented plant biomass and height, shoot branching, and root surface area. Variations in root morphology and biomass were attributed to differences in DSE species and T. viride density among treatments. P. putaminum or P. herbarum with low- or medium T. viride density and S. lignicola with low- or high T. viride density improved licorice root morphology and biomass.

Conclusions
DSE isolated from other medicinal plants enhanced the root growth of licorice plants under different densities T. viride conditions and may also be used to promote the cultivation of medicinal plants.
90 days impacts of remote ischemic preconditioning on patients undergoing open total aortic arch replacement: a post-hoc analysis of previous trial
Authors: Chen Yimeng , Wang Guyan , Zhou Hui , Yang Lijing , Zhang Congya , Yang Xiying , Lei Guiyu 
Published: July 2020

Abstract
Background
In the previous randomized controlled trial by our research group, we evaluated the effect of remote ischemic preconditioning (RIPC) in 130 patients (65 per arm) on acute kidney injury (AKI) within 7 days of open total aortic arch replacement. Significantly fewer RIPC-treated patients than sham-treated patients developed postoperative AKI, and, epically, RIPC significantly reduced serious AKI (stage II–III). However, the long-term effect of RIPC in patients undergoing open total aortic arch replacement is unclear.

Methods
This study was a post-hoc analysis. We aimed to assess the roles of RIPC in major adverse kidney events (MAKE), defined as consisting persistent renal dysfunction, renal replacement therapy and mortality, within 90 days after surgery in patients receiving open total aortic arch replacement.

Results
In this 90-day follow-up study, data were available for all study participants. We found that RIPC failed to improve the presence of MAKE within 90 days after surgery (RIPC: 7 of 65[10.8%]) vs sham: 15 of 65[23.1%]; P = 0.061). In those patients who developed AKI after surgery, we found that the rate of MAKE within 90 days after surgery differed between the RIPC group and the sham group (RIPC: 4 of 36[11.2%]; sham: 14 of 48[29.2%]; P = 0.046).

Conclusions
At 90 days after open total aortic arch replacement, we failed to find a difference between the renoprotective effects of RIPC and sham treatment. The effectiveness or ineffectiveness of RIPC should be further investigated in a large randomized sham-controlled trial.

Trial registration
This study was approved by the Ethics Committee of Fuwai Hospital (No. 2016–835) and our previous study was registered at clinicaltrials.gov before patient enrollment (NCT03141385; principal investigator: G.W.; date of registration: March 5, 2017).
Sentinel node theory helps tracking of primary lesions of cancers of unknown primary
Authors: Shao Yilin , Liu Xin , Hu Silong , Zhang Yingjian , Li Wentao , Zhou Xiaoyan , Wang Qifeng , Hou Yifeng , Chen Yong , Wang Yanli , Wang Yaohui , Luo Zhiguo , Hu Xichun 
Published: July 2020

Abstract
Background
Sentinel lymph node is the first stop of lymphatic spreading of cancer with known primary. The lymph node metastasis pattern of cancer of unknown primary (CUP) is unclear and has been presumed to follow the same pathway. To test this hypothesis, data of all 716 patients clinically diagnosed as CUP in our center were collected.

Methods
Diagnoses of lymph node metastasis were established by 18F-FDG PET-CT and/or biopsy pathology. Three hundred and forty-seven cases meeting the criteria were divided into three groups: pathology-confirmed primary with invasive biopsy or surgery of the suspicious lesion (group A, n = 64), primary still unknown even with invasive biopsy or surgery of the suspicious lesion (group B, n = 204), and others with no suspicious lesion or lesions who had not been sampled due to medical or other reasons (group C, n = 79). We assessed the clinicopathological features between these groups, and the relationship between lymph node metastasis pattern and confirmed primary site.

Results
In group A, the primary sites of 61 cases were compatible with sentinel node theory, resulting in a positive predictive value of 95%. No significant differences in age, sex, bone metastasis, or visceral metastasis observed between group A and group B, except that group A had a higher ratio of differentiated carcinoma (94% vs. 77%, P = 0.003).

Conclusion
To our knowledge, this is the first evidence indicating that the majority of clinical CUP cases follow the sentinel node theory to spread in lymph nodes, which helps tracking the primary, especially for differentiated carcinoma.
Pathogenic role of the vitreous in angle-closure glaucoma with autosomal recessive bestrophinopathy: a case report
Authors: Shi Yan , Tian Jiaxin , Han Ying , Oatts Julius , Wang Ningli 
Published: July 2020

Abstract
Background
Autosomal recessive bestrophinopathy (ARB) is caused by homozygous or compound heterozygous mutations in the BEST1 gene and always accompanied with refractory angle-closure glaucoma (ACG). The exact mechanism for the pan-ocular abnormalities in ARB is still unknown and the management of ACG in these cases is challenging.

Case presentation
A 26-year-old patient with a novel autosomal–recessively inherited c.1 A > G variant in BEST1 diagnosed as ARB and ACG, presented as widespread vitelliform deposits in the posterior pole, retinoschisis in the macula, vitreoretinal interface abnormalities, shallow anterior chamber depth (ACD) and angle closure with uncontrolled intraocular pressure (IOP). Combined phacoemulsification, intraocular lens implantation and goniosynechialysis did not improve any clinical presentation. However, low dose transscleral cyclophotocoagulation with subsequent vitreous liquefaction effectively lowered IOP, deepened ACD, and rehabilitated retinoschisis in both eyes.

Conclusions
This case implied vitreous condition may play a pathogenic role in formation of retinoschisis and ACG in the patients with ARB. Treatments that induce vitreous liquefaction could be used to treat young ACG patients with ARB or other kinds of ACG to avoid vision-threatening post-operative complications.
Histological demonstration of BSEP/ABCB11 inhibition in transient neonatal cholestasis: a case report
Authors: Baghdasaryan Anna , Ofner-Ziegenfuß Lisa , Lackner Carolin , Fickert Peter , Resch Bernhard , Morris Nicholas Mark , Deutschmann Andrea 
Published: July 2020

Abstract
Background
Idiopathic or transient neonatal cholestasis (TNC) represents a group of cholestatic disorders with unidentified origin and remains a diagnosis of exclusion. Dysfunction of hepatobiliary transporters mediating excretion of biliary constituents from hepatocytes may play a central role in the pathogenesis of cholestasis. Despite variants of bile salt (BS) export pump (BSEP/ABCB11) have already been described in TNC, the pathogenic role of BSEP dysfunction in TNC remained so far elusive.

Case presentation
We report on a newly-identified heterozygous ABCB11 missense variant (c.1345G > A, p.Glu449Lys) which was associated with prolonged cholestasis in a term infant after a complicated neonatal period. Moreover, we show for the first time almost completely abolished BSEP expression on the hepatocellular membrane in TNC.

Conclusion
This report demonstrates for the first time a close association between the prolonged cholestasis in infancy and impaired BSEP expression on the hepatocyte canalicular membrane in a heterozygous carrier of newly-identified ABCB11 variant.
Quitting the quitline: a qualitative study of patient experience of electronic referrals to quitlines
Authors: Albert Elizabeth L. , Rose Jeanmarie C. , Gill India J. , Flocke Susan A. 
Published: July 2020

Abstract
Background
The use of electronic referrals (eReferrals) to state quitlines (QLs) for tobacco-using patients is a promising approach for addressing smoking cessation on a large scale. However, QL contact, enrollment, and completion rates are low. The purpose of this study was to examine the eReferral to QL process from the patient’s perspective in order to inform strategies for improving QL engagement.

Methods
We conducted interviews with 55 patients who agreed to an eReferral at a primary care visit to 1 of 8 safety-net community health centers in Cuyahoga County, Ohio (September 2017–August 2018). Interviews were designed to explore the experiences of three subgroups of patients who subsequently: 1) declined participation in the QL; 2) were unreachable by the QL; or 3) were enrolled in or had completed the QL program. Analysis was guided by a phenomenological approach designed to identify emergent themes.

Results
Reasons for QL program non-completion included changing life circumstances and events making cessation unviable; misunderstandings about the QL; discomfort with telephonic counseling; perceived lack of time for counseling; cell phone barriers; and having already quit smoking. We found that some individuals who were no longer engaged with the QL still desired continued support from the QL.

Conclusions
Participants intentionally and unintentionally disengage from the QL for a wide variety of reasons, several of which are mediated by low socioeconomic status. Integrating QL care with community-based resources that address these mediators could be a promising strategy.
Impact of comorbidity on the short- and medium-term risk of revision in total hip and knee arthroplasty
Authors: Arias-de la Torre Jorge , Smith Kayla , Dregan Alexandru , Valderas Jose M. , Evans Jonathan P. , Prieto-Alhambra Daniel , Lozano Luis , Molina Antonio J. , Martín Vicente , Domingo Laia , Muñoz Laura , Espallargues Mireia 
Published: July 2020

Abstract
Background
The impact of comorbidity on the risk of revision in patients undergoing Total Knee arthroplasty (TKA) and Total Hip Arthroplasty (THA) is not currently well known. The aim of this study was to analyze the impact of comorbidity on the risk of revision in TKA and THA.

Methods
Patients recorded in the Catalan Arthroplasty Register (RACat) between 01/01/2005 and 31/12/2016 undergoing TKA (n = 49,701) and THA (n = 17,923) caused by osteoarthritis were included. As main explanatory factors, comorbidity burden was assessed by the Elixhauser index, categorized, and specific comorbidities from the index were taken into account. Descriptive analyses for comorbidity burden and specific conditions were done. Additionally, incidence at 1 and 5 years’ follow-up was calculated, and adjusted Competing Risks models were fitted.

Results
A higher incidence of revision was observed when the number of comorbidities was high, both at 1 and 5 years for THA, but only at 1 year for TKA. Of the specific conditions, only obesity was related to the incidence of revision at 1 year in both joints, and at 5 years in TKA. The risk of revision was related to deficiency anemia and liver diseases in TKA, while in THA, it was related to peripheral vascular disorders, metastatic cancer and psychoses.

Conclusions
Different conditions, depending on the joint, might be related to higher revision rates. This information could be relevant for clinical decision-making, patient-specific information and improving the results of both TKA and THA.
Delayed gastric emptying after Pancreaticoduodenectomy: a propensity score-matched analysis and clinical Nomogram study
Authors: Cai Xianlei , Zhang Miaozun , Liang Chao , Xu Yuan , Yu Weiming 
Published: July 2020

Abstract
Background
Delayed gastric emptying (DGE) is a common and frustrating complication of pancreaticoduodenectomy (PD). Studies suggest that surgical methods and other clinical characteristics may affect the occurrence of DGE. Nevertheless, the results of such studies are conflicting. The objective of this work was to perform a propensity score matching analysis to compare the differences between pylorus-preserving pancreaticoduodenectomy (PPPD) and pylorus-removing pancreaticoduodenectomy (PrPD) and to develop and validate a nomogram to predict the probability of severe DGE (SDGE).

Methods
This retrospective study enrolled patients who underwent PD at our institution from December 2009 to December 2018. Propensity score matching was applied at a ratio of 1:1 to compare PPPD and PrPD groups. We compared incidence of complications, DGE, lengths of hospital stay, hospitalization costs, and mortality. Univariate and multivariate logistic regression analysis were performed to identify potential risk factors of severe DGE. Finally, a nomogram was developed and validated to predict severe DGE.

Results
The PPPD group had a significantly higher rate of postoperative pancreatic fistula (29.9% versus 17.4%, P < 0.05) and less blood loss (463.7 ml versus 694.9 ml, P < 0.05). After propensity score matching, the PPPD group had a significantly higher rate of postoperative DGE (19.2% versus 3.8%, P < 0.05), especially severe DGE (17.3% versus 0%) than the PrPD group. There were no significant differences in terms of lengths of hospital stay, hospitalization costs or mortality between the groups. Surgical method, biliary leakage, abdominal infection, and diabetes were independent risk factors for SDGE. The nomogram predicted SDGE with a training C - index of 0.798 and a validation C - index of 0.721.

Conclusion
PPPD increases the risk of DGE than PrPD, especially SDGE. Our prediction nomogram gives good prediction of SDGE after pancreaticoduodenectomy.