bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptomic analysis reveals proinflammatory signatures associated with acute myeloid leukemia progression
Authors: Stratmann Svea , Yones Sara A. , Garbulowski Mateusz , Sun Jitong , Skaftason Aron , Mayrhofer Markus , Norgren Nina , Herlin Morten Krogh , Sundström Christer , Eriksson Anna , Höglund Martin , Palle Josefine , Abrahamsson Jonas , Jahnukainen Kirsi , Munthe-Kaas Monica Cheng , Zeller Bernward , Tamm Katja Pokrovskaja , Cavelier Lucia , Komorowski Jan , Holmfeldt Linda 
Published: October 2021

AbstractNumerous studies have been performed over the last decade to exploit the complexity of genomic and transcriptomic lesions driving the initiation of acute myeloid leukemia (AML). These studies have helped improve risk classification and treatment options. Detailed molecular characterization of longitudinal AML samples is sparse, however; meanwhile, relapse and therapy resistance represent the main challenges in AML care. To this end, we performed transcriptome-wide RNA sequencing of longitudinal diagnosis, relapse, and/or primary resistant samples from 47 adult and 23 pediatric AML patients with known mutational background. Gene expression analysis revealed the association of short event-free survival with overexpression of GLI2 and IL1R1, as well as downregulation of ST18. Moreover, CR1 downregulation and DPEP1 upregulation were associated with AML relapse both in adults and children. Finally, machine learning–based and network-based analysis identified overexpressed CD6 and downregulated INSR as highly copredictive genes depicting important relapse-associated characteristics among adult patients with AML. Our findings highlight the importance of a tumor-promoting inflammatory environment in leukemia progression, as indicated by several of the herein identified differentially expressed genes. Together, this knowledge provides the foundation for novel personalized drug targets and has the potential to maximize the benefit of current treatments to improve cure rates in AML.
Adding venetoclax to fludarabine/busulfan RIC transplant for high-risk MDS and AML is feasible, safe, and active
Authors: Garcia Jacqueline S. , Kim Haesook T. , Murdock H. Moses , Cutler Corey S. , Brock Jennifer , Gooptu Mahasweta , Ho Vincent T. , Koreth John , Nikiforow Sarah , Romee Rizwan , Shapiro Roman , Loschi Fiona , Ryan Jeremy , Fell Geoffrey , Karp Hannah Q. , Lucas Fabienne , Kim Annette S. , Potter Danielle , Mashaka Thelma , Stone Richard M. , DeAngelo Daniel J. , Letai Anthony , Lindsley R. Coleman , Soiffer Robert J. , Antin Joseph H. 
Published: October 2021

Abstract
Adding the selective BCL-2 inhibitor venetoclax to reduced-intensity conditioning chemotherapy (fludarabine and busulfan [FluBu2]) may enhance antileukemic cytotoxicity and thereby reduce the risk of posttransplant relapse. This phase 1 study investigated the recommended phase 2 dose (RP2D) of venetoclax, a BCL-2 selective inhibitor, when added to FluBu2 in adult patients with high-risk acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), and MDS/myeloproliferative neoplasms (MPN) undergoing transplant. Patients received dose-escalated venetoclax (200-400 mg daily starting day −8 for 6-7 doses) in combination with fludarabine 30 mg/m2 per day for 4 doses and busulfan 0.8 mg/kg twice daily for 8 doses on day −5 to day −2 (FluBu2). Transplant related–toxicity was evaluated from the first venetoclax dose on day −8 to day 28. Twenty-two patients were treated. At study entry, 5 patients with MDS and MDS/MPN had 5% to 10% marrow blasts, and 18 (82%) of 22 had a persistent detectable mutation. Grade 3 adverse events included mucositis, diarrhea, and liver transaminitis (n = 3 each). Neutrophil/platelet recovery and acute/chronic graft-versus-host-disease rates were similar to those of standard FluBu2. No dose-limiting toxicities were observed. The RP2D of venetoclax was 400 mg daily for 7 doses. With a median follow-up of 14.7 months (range, 8.6-24.8 months), median overall survival was not reached, and progression-free survival was 12.2 months (95% confidence interval, 6.0-not estimable). In patients with high-risk AML, MDS, and MDS/MPN, adding venetoclax to FluBu2 was feasible and safe. To further address relapse risk, assessment of maintenance therapy after venetoclax plus FluBu2 transplant is ongoing. This study was registered at clinicaltrials.gov as #NCT03613532.
Inflammatory complications of CGRP monoclonal antibodies: a case series
Authors: Ray Jason C. , Allen Penelope , Bacsi Ann , Bosco Julian J. , Chen Luke , Eller Michael , Kua Hock , Lim Lyndell L. , Matharu Manjit S. , Monif Mastura , Ruttledge Martin , Stark Richard J. , Hutton Elspeth J. 
Published: October 2021

Abstract
Background
Calcitonin gene-related peptide (CGRP) is expressed throughout the body and is a known mediator of migraine, exerting this biological effect through activation of trigeminovascular, meningeal and associated neuronal pathways located in close proximity to the central nervous system. Monoclonal antibodies (mAb) targeting the CGRP pathway are an effective new preventive treatment for migraine, with a generally favourable adverse event profile. Pre-clinical evidence supports an anti-inflammatory/immunoregulatory role for CGRP in other organ systems, and therefore inhibition of the normal action of this peptide may promote a pro-inflammatory response.

Cases
We present a case series of eight patients with new or significantly worsened inflammatory pathology in close temporal association with the commencement of CGRP mAb therapy.

Conclusion
This case series provides novel insights on the potential molecular mechanisms and side-effects of CGRP antagonism in migraine and supports clinical vigilance in patient care going forward.
A novel formulation of theranostic nanomedicine for targeting drug delivery to gastrointestinal tract cancer
Authors: Lodhi Madeeha Shahzad , Khan Muhammad Tahir , Aftab Saira , Samra Zahoor Qadir , Wang Heng , Wei Dong Qing 
Published: October 2021

Abstract
Background
Theranostic nanomedicines contain a nanovehicle that has fluorescent properties and can be used for diagnostic, therapeutic and prognostic purposes. The transferrin receptor expression is 1000-fold higher in rapidly growing cancer cells as compared to the normal cells and, therefore, can be used in targeted drug delivery systems. The objective of the present study was to design a novel targeted gold nanoparticle (GNPs)-based theranostic formulation for gastrointestinal (GI) tract-related cancers. The synthesized GNPs were conjugated to transferrin and doxorubicin both separately and collectively to check their cytotoxic properties. The in vitro cytotoxicity of nanocomposites was observed against colon cancer cell line HCT-116. The doxorubicin conjugated nanocomposites showed almost the same cytotoxicity, but more effect at later hours (h). The IC50 and IC100 were 50 µg/ml and 250 µg/ml, respectively, equivalent to the doxorubicin weight for GNP theranostic nanomedicine.

Results
The maximum effect was observed after 12 h and nanomedicines were still active after 72 h of treatment. Our in vivo data proved that nanomedicine crossed all the barriers and was successfully delivered to the tumour cells. Theranostic nanomedicine’s (TNM) effect on body weight and survival rate on mice was many folds better than mice in pure doxorubicin group. It also showed almost 80% survival rate on day 40. The in vivo and in vitro results show the effects of prolonged drug release and the nanomedicine was not toxic to vital organs of the animal.

Conclusion
This is one of its kind studies in which a novel targeted nanomedicines approach was formulated for therapeutic as well as prognostic purposes against GI tract cancer.

Graphic Abstract
Protein–protein interaction prediction based on ordinal regression and recurrent convolutional neural networks
Authors: Xu Weixia , Gao Yangyun , Wang Yang , Guan Jihong 
Published: October 2021

Abstract
Background
Protein protein interactions (PPIs) are essential to most of the biological processes. The prediction of PPIs is beneficial to the understanding of protein functions and thus is helpful to pathological analysis, disease diagnosis and drug design etc. As the amount of protein data is growing fast in the post genomic era, high-throughput experimental methods are expensive and time-consuming for the prediction of PPIs. Thus, computational methods have attracted researcher’s attention in recent years. A large number of computational methods have been proposed based on different protein sequence encoders.

Results
Notably, the confidence score of a protein sequence pair could be regarded as a kind of measurement to PPIs. The higher the confidence score for one protein pair is, the more likely the protein pair interacts. Thus in this paper, a deep learning framework, called ordinal regression and recurrent convolutional neural network (OR-RCNN) method, is introduced to predict PPIs from the perspective of confidence score. It mainly contains two parts: the encoder part of protein sequence pair and the prediction part of PPIs by confidence score. In the first part, two recurrent convolutional neural networks (RCNNs) with shared parameters are applied to construct two protein sequence embedding vectors, which can automatically extract robust local features and sequential information from the protein pairs. Based on it, the two embedding vectors are encoded into one novel embedding vector by element-wise multiplication. By taking the ordinal information behind confidence score into consideration, ordinal regression is used to construct multiple sub-classifiers in the second part. The results of multiple sub-classifiers are aggregated to obtain the final confidence score. Following that, the existence of PPIs is determined by the confidence score. We set a threshold $$\theta$$
θ
, and say the interaction exists between the protein pair if its confidence score is bigger than $$\theta$$
θ
.

Conclusions
We applied our method to predict PPIs on data sets S. cerevisiae and Homo sapiens. Through experimental verification, our method outperforms state-of-the-art PPI prediction models.
CoolBox: a flexible toolkit for visual analysis of genomics data
Authors: Xu Weize , Zhong Quan , Lin Da , Zuo Ya , Dai Jinxia , Li Guoliang , Cao Gang 
Published: October 2021

Abstract
Background
Data visualization, especially the genome track plots, is crucial for genomics researchers to discover patterns in large-scale sequencing dataset. Although existing tools works well for producing a normal view of the input data, they are not convenient when users want to create customized data representations. Such gap between the visualization and data processing, prevents the users to uncover more hidden structure of the dataset.

Results
We developed CoolBox—an open-source toolkit for visual analysis of genomics data. This user-friendly toolkit is highly compatible with the Python ecosystem and customizable with a well-designed user interface. It can be used in various visualization situations like a Swiss army knife. For example, to produce high-quality genome track plots or fetch commonly used genomic data files with a Python script or command line, to explore genomic data interactively within Jupyter environment or web browser. Moreover, owing to the highly extensible Application Programming Interface design, users can customize their own tracks without difficulty, which greatly facilitate analytical, comparative genomic data visualization tasks.

Conclusions
CoolBox allows users to produce high-quality visualization plots and explore their data in a flexible, programmable and user-friendly way.
Population genomics provides insights into the population structure and temperature-driven adaptation of Collichthys lucidus
Authors: Zhao Linlin , Qu Fangyuan , Song Na , Han Zhiqiang , Gao Tianxiang , Zhang Zhaohui 
Published: October 2021

AbstractBackgroundUnderstanding the genetic structure and local adaptive evolutionary mechanisms of marine organisms is crucial for the management of biological resources. As the ecologically and commercially important small-sized shallow-sea fish,Collichthys lucidusplays a vital role in the structure and functioning of marine ecosystem processes.C. lucidushas been shown to have an obvious population structure. Therefore, it is an ideal candidate for investigating population differentiation and local adaptation under heterogeneous environmental pressure.ResultsA total of 184,708 high-quality single nucleotide polymorphisms (SNPs) were identified and applied to elucidate the fine-scale genetic structure and local thermal adaptation of 8C. luciduspopulations. Population structure analysis based on all SNPs indicated that the northern group and southern group ofC. lucidushave a strong differentiation. Moreover, 314 SNPs were found to be significantly associated with temperature variation, and annotations of genes containing temperature-related SNPs suggested that genes were involved in material (protein, lipid, and carbohydrate) metabolism and immune responses.ConclusionThe high genetic differentiation of 8C. luciduspopulations may have been caused by long-term geographic isolation during the glacial period. Moreover, we suspected that variation in these genes associated with material (protein, lipid, and carbohydrate) metabolism and immune responses was critical for adaptation to spatially heterogeneous temperatures in naturalC. luciduspopulations. In conclusion, this study could help us determine howC. luciduspopulations will respond to future ocean temperature rising.
Stool preparation under anaerobic conditions contributes to retention of obligate anaerobes: potential improvement for fecal microbiota transplantation
Authors: Shimizu Hirotaka , Arai Katsuhiro , Asahara Takashi , Takahashi Takuya , Tsuji Hirokazu , Matsumoto Satoshi , Takeuchi Ichiro , Kyodo Reiko , Yamashiro Yuichiro 
Published: October 2021

Abstract
Background
Fecal microbiota transplantation (FMT) in patients with ulcerative colitis has shown variable efficacy depending on the protocol used. A previous randomized controlled trial reported that anaerobic preparation of donor stool contributes to improved efficacy. Despite the suggestion that viable obligate anaerobes would be decreased through aerobic handling, there have been only a limited number of reports on how these aerobic or anaerobic procedures affect the composition of viable microbiota in the fecal slurries used for FMT.

Methods
We adopted 16S and 23S rRNA-targeted reverse transcription-quantitative polymerase chain reaction to quantify viable bacteria in fecal slurries. This study utilized specific primers designed to detect obligate anaerobes (including Clostridium coccoides group, C. leptum subgroup, Bacteroides fragilis group, Bifidobacterium, Atopobium cluster, and Prevotella) and facultative anaerobes (including total lactobacilli, Enterobacteriaceae, Enterococcus, Streptococcus, and Staphylococcus). We then calculated the ratio change (RC) between before and after mixing, and compared the resulting values between anaerobic-prep and aerobic-prep in samples fixed immediately after blending (RCAn0 vs. RCAe0) and in samples maintained (under anaerobic or aerobic conditions) for 1 h after blending (RCAn1 vs. RCAe1).

Results
For most obligate anaerobes, the median RC tended to be less than 1, indicating that the number of obligate anaerobes was decreased by the blending procedure. However, in samples maintained for 1 h after blending, anaerobic-prep counteracted the decrease otherwise seen for the C. coccoides group and B. fragilis groups (P < 0.01 for both). The C. leptum subgroup also tended to show higher RC by anaerobic-prep than by aerobic-prep, although this effect was not statistically significant. Among facultative anaerobes, Enterobacteriaceae, Enterococcus, and Staphylococcus showed median RC values of more than 1, indicating that these organisms survived and even grew after mixing. Moreover, oxygen exposure had no significant influence on the survival of the facultative anaerobes.

Conclusions
The conditions under which the blending procedure was performed affected the proportion of live anaerobes in fecal slurries. The obligate anaerobes tended to be decreased by blending processes, but anaerobic-prep significantly mitigated this effect. Anaerobic-prep may improve the efficacy of FMT by permitting the efficient transfer of obligate anaerobes to patients with ulcerative colitis.
Safety in training for ultrasound guided internal jugular vein CVC placement: a propensity score analysis
Authors: De Cassai Alessandro , Geraldini Federico , Pasin Laura , Boscolo Annalisa , Zarantonello Francesco , Tocco Martina , Pretto Chiara , Perona Matteo , Carron Michele , Navalesi Paolo 
Published: October 2021

Abstract
Background
Central venous catheter (CVC) placement is a routine procedure but is potentially associated with severe complications. Relatively small studies investigated if the use of ultrasound is effective in bridging the skill gap between proficient and not proficient operators, while patient safety during training remains a controversial topic. The first aim of this study was to evaluate if resident proficiency affects the failure rate in CVC positioning under ultrasound guidance. In addition, it aimed to investigate the different rate of complications between proficient and non proficient residents.

Methods
We conducted a cohort study including CVC placed by residents at the University Hospital of Padova, from November 1, 2012 to July 9, 2020 comparing proficient and non proficient residents. To avoid bias the two cohorts were matched using propensity score.

Results
A total of 356 residents positioned 2310 CVC during the 8 year study period. Among them, two groups of 1060 CVCs each were matched with a propensity score analysis. There was no difference in the failure rate among the groups (2.8 vs 2.7%, p-value 0.895).
Moreover, cohorts had the same rate of hematomas, catheter tip malposition, arterial puncture and pneumothorax. No cases of hemothorax were reported.

Conclusions
We found the same rate of success and incidence of adverse complications among cohorts, meaning that the process of skill acquisition is safe as long as appropriate training and direct supervision by a senior consultant are available.
Determining diagnosis date of diabetes using structured electronic health record (EHR) data: the SEARCH for diabetes in youth study
Authors: Lenoir Kristin M. , Wagenknecht Lynne E. , Divers Jasmin , Casanova Ramon , Dabelea Dana , Saydah Sharon , Pihoker Catherine , Liese Angela D. , Standiford Debra , Hamman Richard , Wells Brian J. ,   the SEARCH for Diabetes in Youth Study Group
Published: October 2021

Abstract
Background
Disease surveillance of diabetes among youth has relied mainly upon manual chart review. However, increasingly available structured electronic health record (EHR) data have been shown to yield accurate determinations of diabetes status and type. Validated algorithms to determine date of diabetes diagnosis are lacking. The objective of this work is to validate two EHR-based algorithms to determine date of diagnosis of diabetes.

Methods
A rule-based ICD-10 algorithm identified youth with diabetes from structured EHR data over the period of 2009 through 2017 within three children’s hospitals that participate in the SEARCH for Diabetes in Youth Study: Cincinnati Children’s Hospital, Cincinnati, OH, Seattle Children’s Hospital, Seattle, WA, and Children’s Hospital Colorado, Denver, CO. Previous research and a multidisciplinary team informed the creation of two algorithms based upon structured EHR data to determine date of diagnosis among diabetes cases. An ICD-code algorithm was defined by the year of occurrence of a second ICD-9 or ICD-10 diabetes code. A multiple-criteria algorithm consisted of the year of first occurrence of any of the following: diabetes-related ICD code, elevated glucose, elevated HbA1c, or diabetes medication. We assessed algorithm performance by percent agreement with a gold standard date of diagnosis determined by chart review.

Results
Among 3777 cases, both algorithms demonstrated high agreement with true diagnosis year and differed in classification (p = 0.006): 86.5% agreement for the ICD code algorithm and 85.9% agreement for the multiple-criteria algorithm. Agreement was high for both type 1 and type 2 cases for the ICD code algorithm. Performance improved over time.

Conclusions
Year of occurrence of the second ICD diabetes-related code in the EHR yields an accurate diagnosis date within these pediatric hospital systems. This may lead to increased efficiency and sustainability of surveillance methods for incidence of diabetes among youth.
Prognostic factors of depression and depressive symptoms after hip fracture surgery: systematic review
Authors: Milton-Cole R. , Ayis S. , Lambe K. , O’Connell M. D. L. , Sackley C. , Sheehan K. J. 
Published: October 2021

Abstract
Background
Patients with hip fracture and depression are less likely to recover functional ability. This review sought to identify prognostic factors of depression or depressive symptoms up to 1 year after hip fracture surgery in adults. This review also sought to describe proposed underlying mechanisms for their association with depression or depressive symptoms.

Methods
We searched for published (MEDLINE, Embase, PsychInfo, CINAHL and Web of Science Core Collection) and unpublished (OpenGrey, Greynet, BASE, conference proceedings) studies. We did not impose any date, geographical, or language limitations. Screening (Covidence), extraction (Checklist for critical Appraisal and data extraction for systematic Reviews of prediction Modelling Studies, adapted for use with prognostic factors studies Checklist), and quality appraisal (Quality in Prognosis Studies tool) were completed in duplicate. Results were summarised narratively.

Results
In total, 37 prognostic factors were identified from 12 studies included in this review. The quality of the underlying evidence was poor, with all studies at high risk of bias in at least one domain. Most factors did not have a proposed mechanism for the association. Where factors were investigated by more than one study, the evidence was often conflicting.

Conclusion
Due to conflicting and low quality of available evidence it is not possible to make clinical recommendations based on factors prognostic of depression or depressive symptoms after hip fracture. Further high-quality research investigating prognostic factors is warranted to inform future intervention and/or stratified approaches to care after hip fracture.

Trial registration
Prospero registration: CRD42019138690.