bluuebunny/crossref_metadata_2025_split huggingface dataset:
OTTM: an automated classification tool for translational drug discovery from omics data
Authors: Yang Xiaobo , Zhang Bei , Wang Siqi , Lu Ye , Chen Kaixian , Luo Cheng , Sun Aihua , Zhang Hao 
Published: August 2023

Abstract
Omics data from clinical samples are the predominant source of target discovery and drug development. Typically, hundreds or thousands of differentially expressed genes or proteins can be identified from omics data. This scale of possibilities is overwhelming for target discovery and validation using biochemical or cellular experiments. Most of these proteins and genes have no corresponding drugs or even active compounds. Moreover, a proportion of them may have been previously reported as being relevant to the disease of interest. To facilitate translational drug discovery from omics data, we have developed a new classification tool named Omics and Text driven Translational Medicine (OTTM). This tool can markedly narrow the range of proteins or genes that merit further validation via drug availability assessment and literature mining. For the 4489 candidate proteins identified in our previous proteomics study, OTTM recommended 40 FDA-approved or clinical trial drugs. Of these, 15 are available commercially and were tested on hepatocellular carcinoma Hep-G2 cells. Two drugs—tafenoquine succinate (an FDA-approved antimalarial drug targeting CYC1) and branaplam (a Phase 3 clinical drug targeting SMN1 for the treatment of spinal muscular atrophy)—showed potent inhibitory activity against Hep-G2 cell viability, suggesting that CYC1 and SMN1 may be potential therapeutic target proteins for hepatocellular carcinoma. In summary, OTTM is an efficient classification tool that can accelerate the discovery of effective drugs and targets using thousands of candidate proteins identified from omics data. The online and local versions of OTTM are available at http://otter-simm.com/ottm.html.
A denoised multi-omics integration framework for cancer subtype classification and survival prediction
Authors: Pang Jiali , Liang Bilin , Ding Ruifeng , Yan Qiujuan , Chen Ruiyao , Xu Jie 
Published: August 2023

Abstract
The availability of high-throughput sequencing data creates opportunities to comprehensively understand human diseases as well as challenges to train machine learning models using such high dimensions of data. Here, we propose a denoised multi-omics integration framework, which contains a distribution-based feature denoising algorithm, Feature Selection with Distribution (FSD), for dimension reduction and a multi-omics integration framework, Attention Multi-Omics Integration (AttentionMOI) to predict cancer prognosis and identify cancer subtypes. We demonstrated that FSD improved model performance either using single omic data or multi-omics data in 15 The Cancer Genome Atlas Program (TCGA) cancers for survival prediction and kidney cancer subtype identification. And our integration framework AttentionMOI outperformed machine learning models and current multi-omics integration algorithms with high dimensions of features. Furthermore, FSD identified features that were associated to cancer prognosis and could be considered as biomarkers.
Longitudinal imaging highlights preferential basal ganglia circuit atrophy in Huntington’s disease
Authors: Liu Chin-Fu , Younes Laurent , Tong Xiao J , Hinkle Jared T , Wang Maggie , Phatak Sanika , Xu Xin , Bu Xuan , Looi Vivian , Bang Jee , Tabrizi Sarah J , Scahill Rachael I , Paulsen Jane S , Georgiou-Karistianis Nellie , Faria Andreia V , Miller Michael I , Ratnanather J Tilak , Ross Christopher A 
Published: August 2023

Abstract
Huntington’s disease is caused by a CAG repeat expansion in the Huntingtin gene (HTT), coding for polyglutamine in the Huntingtin protein, with longer CAG repeats causing earlier age of onset. The variable ‘Age’ × (‘CAG’—L), where ‘Age’ is the current age of the individual, ‘CAG’ is the repeat length and L is a constant (reflecting an approximation of the threshold), termed the ‘CAG Age Product’ (CAP) enables the consideration of many individuals with different CAG repeat expansions at the same time for analysis of any variable and graphing using the CAG Age Product score as the X axis. Structural MRI studies have showed that progressive striatal atrophy begins many years prior to the onset of diagnosable motor Huntington’s disease, confirmed by longitudinal multicentre studies on three continents, including PREDICT-HD, TRACK-HD and IMAGE-HD. However, previous studies have not clarified the relationship between striatal atrophy, atrophy of other basal ganglia structures, and atrophy of other brain regions. The present study has analysed all three longitudinal datasets together using a single image segmentation algorithm and combining data from a large number of subjects across a range of CAG Age Product score. In addition, we have used a strategy of normalizing regional atrophy to atrophy of the whole brain, in order to determine which regions may undergo preferential degeneration. This made possible the detailed characterization of regional brain atrophy in relation to CAG Age Product score. There is dramatic selective atrophy of regions involved in the basal ganglia circuit—caudate, putamen, nucleus accumbens, globus pallidus and substantia nigra. Most other regions of the brain appear to have slower but steady degeneration. These results support (but certainly do not prove) the hypothesis of circuit-based spread of pathology in Huntington’s disease, possibly due to spread of mutant Htt protein, though other connection-based mechanisms are possible. Therapeutic targets related to prion-like spread of pathology or other mechanisms may be suggested. In addition, they have implications for current neurosurgical therapeutic approaches, since delivery of therapeutic agents solely to the caudate and putamen may miss other structures affected early, such as nucleus accumbens and output nuclei of the striatum, the substantia nigra and the globus pallidus.
Evaluating medical undergraduates’ and dermatology faculty members’ perception of using three-dimensional images as part of dermatology education in a time of COVID-19: a mixed-methods study
Authors: Lim Delwyn Zhi Jie , Lim Yen Loo , Chua Sze-Hon , Lim Ziying Vanessa 
Published: August 2023

Abstract

Background
The coronavirus-19 pandemic has impacted the delivery of medical education in dermatology, leading to decreased patient contact. There arose a need to pioneer innovative teaching tools to augment current methods for now and beyond the pandemic.

Objectives
We aimed to assess the utility of three-dimensional (3D) images in the learning and teaching of dermatology by analysing the perceptions of medical undergraduates and faculty members in a qualitative and quantitative study.

Methods
Medical undergraduates (n = 119) and dermatology faculty members (n = 20) were recruited on a voluntary basis to watch a showcase session using a portable 3D imaging system allowing 3D images of skin lesions to be examined and digitally manipulated. After the session, participants filled in an anonymous questionnaire evaluating their perceptions.

Results
Of the 119 learners, most (&gt; 84%) strongly agreed/agreed that (i) they would have more confidence in the field of dermatology; (ii) their ability to describe skin lesions would increase; (iii) their understanding of common dermatological conditions would increase; (iv) 3D images allow a greater approximation to real-life encounters than 2D images; and (v) learning with this modality would be useful. Of the 20 faculty members, most (&gt; 84%) strongly agreed/agreed that (i) it is easier to teach with the aid of 3D images, and (ii) they would want access to 3D images during teaching sessions. Skin tumours were perceived to be learnt best via this modality in terms of showcasing topography (P &lt; 0.01) and close approximation to real-life (P &lt; 0.001). Overall, thematic analysis from qualitative analysis revealed that conditions learnt better with 3D images were those with surface changes and characteristic topography.

Conclusions
Our results show that the greatest utility of 3D images lies in conditions where lesions have skin surface changes in the form of protrusions or depressions, such as in skin tumours or ulcers. As such, 3D images can be useful teaching tools in dermatology, especially in conditions where appreciation of surface changes and topography is important.
Adalimumab Clearance, Rather Than Trough Level, May Have Greatest Relevance to Crohn’s Disease Therapeutic Outcomes Assessed Clinically and Endoscopically
Authors: Wright Emily K , Chaparro Maria , Gionchetti Paolo , Hamilton Amy L , Schulberg Julien , Gisbert Javier P , Chiara Valerii Maria , Rizzello Fernando , De Cruz Peter , Panetta John C , Everts-van der Wind Annelie , Kamm Michael A , Dervieux Thierry 
Published: August 2023

Abstract

Objective
We postulated that adalimumab [ADA] drug clearance [CL] may be a more critical determinant of therapeutic outcome than ADA concentration. This was tested in Crohn’s disease [CD] patients undergoing ADA maintenance treatment.

Methods
CD patients from four cohorts received ADA induction and started maintenance therapy. Therapeutic outcomes consisted of endoscopic remission [ER], sustained C-reactive protein [CRP] based clinical remission [defined as CRP levels below 3 mg/L in the absence of symptoms], and faecal calprotectin [FC] level below 100 µg/g. Serum albumin, ADA concentration, and anti-drug antibody status were determined using immunochemistry and homogeneous mobility shift assay, respectively. CL was determined using a nonlinear mixed effect model with Bayesian priors. Statistical analysis consisted of Mann–Whitney test and logistic regression with calculation of odds ratio. Repeated event analysis was conducted using a nonlinear mixed effect model.

Results
In 237 enrolled patients [median age 40 years, 45% females], median CL was lower in patients achieving ER as compared with those with persistent active endoscopic disease [median 0.247 L/day vs 0.326 L/day, respectively] [p &lt;0.01]. There was no significant difference in ADA concentration between patients in endoscopic remission compared with those with recurrence [median 9.3 µg/mL vs 11.7 µg/mL, respectively]. Sustained CRP-based clinical remission and FC levels below 100 µg/g were generally associated with lower CL and higher ADA concentration. Repeated event analysis confirmed those findings with better performances of CL than concentration in associating with ER and other outcomes.

Conclusion
Lower ADA clearance is associated with an improved clinical outcome for patients with Crohn’s disease and may be a superior pharmacokinetic measure than concentration.
Combining cardiopulmonary exercise testing with echocardiography: a multiparametric approach to the cardiovascular and cardiopulmonary systems
Authors: Del Punta Lavinia , De Biase Nicolò , Armenia Silvia , Di Fiore Valerio , Maremmani Davide , Gargani Luna , Mazzola Matteo , De Carlo Marco , Mengozzi Alessandro , Lomonaco Tommaso , Galeotti Gian Giacomo , Dini Frank L , Masi Stefano , Pugliese Nicola Riccardo 
Published: August 2023

Abstract
Exercise intolerance is a prominent feature of several cardiovascular conditions. However, the physical effort requires the intertwined adaptation of several factors, namely the cardiovascular system, the lungs, and peripheral muscles. Several abnormalities in each domain may be present in a given patient. Cardiopulmonary exercise testing (CPET) has been used to investigate metabolic and ventilatory alterations responsible for exercise intolerance but does not allow for direct evaluation of cardiovascular function. However, this can readily be obtained by concomitant exercise-stress echocardiography (ESE). The combined CPET-ESE approach allows for precise and thorough phenotyping of the pathophysiologic mechanisms underpinning exercise intolerance. Thus, it can be used to refine the diagnostic workup of patients with dyspnoea of unknown origin, as well as improve risk stratification and potentially guide the therapeutic approach in specific conditions, including left and right heart failure or valvular heart disease. However, given its hitherto sporadic use, both the conceptual and technical aspects of CPET-ESE are often poorly known by the clinician. Improving knowledge in this field could significantly aid in anticipating individual disease trajectories and tailoring treatment strategies accordingly. Therefore, we designed this review to revise the pathophysiologic correlates of exercise intolerance, the practical principles of the combined CPET-ESE examination, and its main applications according to current literature.
Real Exchange Rates and the Earnings of Immigrants
Authors: Dustmann Christian , Ku Hyejin , Surovtseva Tetyana 
Published: August 2023

Abstract
We relate origin-destination real price differences to immigrants’ reservation wages and their career trajectories, exploiting administrative data from Germany and the 2004 enlargement of the European Union. We find that immigrants who enter Germany when a unit of earnings from Germany allows for larger consumption at home settle for lower entry wages, but subsequently catch up to those arriving with less favourable exchange rates, through transition to better-paying occupations and firms. Similar patterns hold in the United States data. Our analysis offers one explanation for the widespread phenomenon of immigrants’ downgrading, with new implications for immigrant cohort effects and assimilation profiles.
Reference genomes for BALB/c Nude and NOD/SCID mouse models
Authors: Schmid-Siegert Emanuel , Qin Mengting , Tian Huan , Arpat Bulak , Chen Bonnie , Xenarios Ioannis 
Published: August 2023

Abstract
Mouse xenograft models play a vital role in tumor studies for research as well as for screening of drugs for the pharmaceutical industry. In particular, models with compromised immunity are favorable to increase the success of transplantation, such as, e.g. NOD/SCID and BALB/c Nude strains. The genomic sequence and alterations of many of these models still remain elusive and might hamper a model’s further optimization or proper adapted usage. This can be in respect to treatments (e.g. NOD/SCID sensitivity to radiation), experiments or analysis of derived sequencing data of such models. Here we present the genome assemblies for the NOD/SCID and BALB/c Nude strains to overcome this short-coming for the future and improve our understanding of these models in the process. We highlight as well first insights into observed genomic differences for these models compared to the C57BL/6 reference genome. Genome assemblies for both are close to full-chromosome representations and provided with liftover annotations from the GRCm39 reference genome.
Two independent DNA repair pathways cause mutagenesis in template switching deficient Saccharomyces cerevisiae
Authors: Jiang Yangyang Kate , Medley Eleanor A , Brown Grant W 
Published: August 2023

Abstract
Upon DNA replication stress, cells utilize the postreplication repair pathway to repair single-stranded DNA and maintain genome integrity. Postreplication repair is divided into 2 branches: error-prone translesion synthesis, signaled by proliferating cell nuclear antigen (PCNA) monoubiquitination, and error-free template switching, signaled by PCNA polyubiquitination. In Saccharomyces cerevisiae, Rad5 is involved in both branches of repair during DNA replication stress. When the PCNA polyubiquitination function of Rad5 s disrupted, Rad5 recruits translesion synthesis polymerases to stalled replication forks, resulting in mutagenic repair. Details of how mutagenic repair is carried out, as well as the relationship between Rad5-mediated mutagenic repair and the canonical PCNA-mediated mutagenic repair, remain to be understood. We find that Rad5-mediated mutagenic repair requires the translesion synthesis polymerase ζ but does not require other yeast translesion polymerase activities. Furthermore, we show that Rad5-mediated mutagenic repair is independent of PCNA binding by Rev1 and so is separable from canonical mutagenic repair. In the absence of error-free template switching, both modes of mutagenic repair contribute additively to replication stress response in a replication timing-independent manner. Cellular contexts where error-free template switching is compromised are not simply laboratory phenomena, as we find that a natural variant in RAD5 is defective in PCNA polyubiquitination and therefore defective in error-free repair, resulting in Rad5- and PCNA-mediated mutagenic repair. Our results highlight the importance of Rad5 in regulating spontaneous mutagenesis and genetic diversity in S. cerevisiae through different modes of postreplication repair.
Autophagy impairment and lifespan reduction caused by Atg1 RNAi or Atg18 RNAi expression in adult fruit flies (Drosophila melanogaster)
Authors: Bierlein Mariah , Charles Joseph , Polisuk-Balfour Trevor , Bretscher Heidi , Rice Micaela , Zvonar Jacklyn , Pohl Drake , Winslow Lindsey , Wasie Brennah , Deurloo Sara , Van Wert Jordan , Williams Britney , Ankney Gabrielle , Harmon Zachary , Dann Erica , Azuz Anna , Guzman-Vargas Alex , Kuhns Elizabeth , Neufeld Thomas P , O’Connor Michael B , Amissah Felix , Zhu Changqi C 
Published: August 2023

Abstract
Autophagy, an autophagosome and lysosome-based eukaryotic cellular degradation system, has previously been implicated in lifespan regulation in different animal models. In this report, we show that expression of the RNAi transgenes targeting the transcripts of the key autophagy genes Atg1 or Atg18 in adult fly muscle or glia does not affect the overall levels of autophagosomes in those tissues and does not change the lifespan of the tested flies but the lifespan reduction phenotype has become apparent when Atg1 RNAi or Atg18 RNAi is expressed ubiquitously in adult flies or after autophagy is eradicated through the knockdown of Atg1 or Atg18 in adult fly adipocytes. Lifespan reduction was also observed when Atg1 or Atg18 was knocked down in adult fly enteroblasts and midgut stem cells. Overexpression of wild-type Atg1 in adult fly muscle or adipocytes reduces the lifespan and causes accumulation of high levels of ubiquitinated protein aggregates in muscles. Our research data have highlighted the important functions of the key autophagy genes in adult fly adipocytes, enteroblasts, and midgut stem cells and their undetermined roles in adult fly muscle and glia for lifespan regulation.
Biochemical characterization of a new ulvan lyase and its applicability in utilization of ulvan and preparation of ulva oligosaccharides
Authors: Li Chen , Tang Tiancheng , Jiang Jinju , Yao Zhong , Zhu Benwei 
Published: August 2023

Abstract
Ulva is globally distributed specie and has a high economic value. Ulvan is one of the main active substances in Ulva, which has a variety of biological properties. Ulvan lyase degrades ulvan through a β-elimination mechanism which cleaves the β-glycosidic bond between Rha3S and GlcA or IdoA. The complex monosaccharide composition of ulvan makes it promising for use in food and pharmaceutical applications. This thesis explores a putative ulvan lyase from Alteromonas sp. KUL_42. We expressed and purified the protein, performed a series of characterizations and signal peptide had been removed. The results showed that the protein molecular weight of ULA-2 was 53.97 kDa, and it had the highest catalytic activity at 45 °C and pH 8.0 in Tris–HCl buffer. The Km and Vmax values were 2.24 mg · mL−1 and 2.048 μmol · min−1 · mL−1, respectively. The activity of ULA-2 was able to maintain more than 80% at 20 ~ 30 °C. ESI-MS analysis showed that the primary end-products were mainly disaccharides to tetrasaccharides. The study of ULA-2 enriches the ulvan lyase library, promotes the development and high-value utilization of Ulva resources, and facilitates further research applications of ulvan lyase in ulva oligosaccharides.
Cytokine signaling in chimeric antigen receptor T-cell therapy
Authors: Kagoya Yuki 
Published: August 2023

Abstract
Adoptive immunotherapy using chimeric antigen-receptor (CAR)-engineered T cells can induce robust antitumor responses against hematologic malignancies. However, its efficacy is not durable in the majority of the patients, warranting further improvement of T-cell functions. Cytokine signaling is one of the key cascades regulating T-cell survival and effector functions. In addition to cytokines that use the common γ chain as a receptor subunit, multiple cytokines regulate T-cell functions directly or indirectly. Modulating cytokine signaling in CAR-T cells by genetic engineering is one promising strategy to augment their therapeutic efficacy. These strategies include ectopic expression of cytokines, cytokine receptors, and synthetic molecules that mimic endogenous cytokine signaling. Alternatively, autocrine IL-2 signaling can be augmented through reprogramming of CAR-T cell properties through transcriptional and epigenetic modification. On the other hand, cytokine production by CAR-T cells triggers systemic inflammatory responses, which mainly manifest as adverse events such as cytokine-release syndrome (CRS) and neurotoxicity. In addition to inhibiting direct inflammatory mediators such as IL-6 and IL-1 released from activated macrophages, suppression of T-cell-derived cytokines associated with the priming of macrophages can be accomplished through genetic modification of CAR-T cells. In this review, I will outline recently developed synthetic biology approaches to exploit cytokine signaling to enhance CAR-T cell functions. I will also discuss therapeutic target molecules to prevent or alleviate CAR-T cell-related toxicities.
Embedding research study recruitment within the patient portal preCheck-in
Authors: Leuchter Richard K , Ma Suzette , Bell Douglas S , Hays Ron D , Vidorreta Fernando Javier Sanz , Binder Sandra L , Sarkisian Catherine A 
Published: August 2023

Abstract

Objective
Patient portals are increasingly used to recruit patients in research studies, but communication response rates remain low without tactics such as financial incentives or manual outreach. We evaluated a new method of study enrollment by embedding a study information sheet and HIPAA authorization form (HAF) into the patient portal preCheck-in (where patients report basic information like allergies).

Materials and Methods
Eligible patients who enrolled received an after-visit patient-reported outcomes survey through the patient portal. No additional recruitment/messaging efforts were made.

Results
A total of 386 of 843 patients completed preCheck-in, 308 of whom signed the HAF and enrolled in the study (37% enrollment rate). Of 93 patients who were eligible to receive the after-visit survey, 45 completed it (48% completion rate).

Conclusion
Enrollment and survey completion rates were higher than what is typically seen with recruitment by patient portal messaging, suggesting that preCheck-in recruitment can enhance research study recruitment and warrants further investigation.