bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systematic sequence engineering enhances the induction strength of the glucose-regulated GTH1 promoter of Komagataella phaffii
Authors: Flores-Villegas Mirelle , Rebnegger Corinna , Kowarz Viktoria , Prielhofer Roland , Mattanovich Diethard , Gasser Brigitte 
Published: October 2023

Abstract
The promoter of the high-affinity glucose transporter Gth1 (PGTH1) is tightly repressed on glucose and glycerol surplus, and strongly induced in glucose-limitation, thus enabling regulated methanol-free production processes in the yeast production host Komagataella phaffii. To further improve this promoter, an intertwined approach of nucleotide diversification through random and rational engineering was pursued. Random mutagenesis and fluorescence activated cell sorting of PGTH1 yielded five variants with enhanced induction strength. Reverse engineering of individual point mutations found in the improved variants identified two single point mutations with synergistic action. Sequential deletions revealed the key promoter segments for induction and repression properties, respectively. Combination of the single point mutations and the amplification of key promoter segments led to a library of novel promoter variants with up to 3-fold higher activity. Unexpectedly, the effect of gaining or losing a certain transcription factor binding site (TFBS) was highly dependent on its context within the promoter. Finally, the applicability of the novel promoter variants for biotechnological production was proven for the secretion of different recombinant model proteins in fed batch cultivation, where they clearly outperformed their ancestors. In addition to advancing the toolbox for recombinant protein production and metabolic engineering of K. phaffii, we discovered single nucleotide positions and correspondingly affected TFBS that distinguish between glycerol- and glucose-mediated repression of the native promoter.
Development of a novel tobramycin dependent riboswitch
Authors: Kraus Leon , Duchardt-Ferner Elke , Bräuchle Eric , Fürbacher Simon , Kelvin Daniel , Marx Hans , Boussebayle Adrien , Maurer Lisa-Marie , Bofill-Bosch Cristina , Wöhnert Jens , Suess Beatrix 
Published: October 2023

Abstract
We herein report the selection and characterization of a new riboswitch dependent on the aminoglycoside tobramycin. Its dynamic range rivals even the tetracycline dependent riboswitch to be the current best performing, synthetic riboswitch that controls translation initiation. The riboswitch was selected with RNA Capture-SELEX, a method that not only selects for binding but also for structural changes in aptamers on binding. This study demonstrates how this method can fundamentally reduce the labour required for the de novo identification of synthetic riboswitches. The initially selected riboswitch candidate harbours two distinct tobramycin binding sites with KDs of 1.1 nM and 2.4 μM, respectively, and can distinguish between tobramycin and the closely related compounds kanamycin A and B. Using detailed genetic and biochemical analyses and 1H NMR spectroscopy, the proposed secondary structure of the riboswitch was verified and the tobramycin binding sites were characterized. The two binding sites were found to be essentially non-overlapping, allowing for a separate investigation of their contribution to the activity of the riboswitch. We thereby found that only the high-affinity binding site was responsible for regulatory activity, which allowed us to engineer a riboswitch from only this site with a minimal sequence size of 33 nt and outstanding performance.
scQTLbase: an integrated human single-cell eQTL database
Authors: Ding Ruofan , Wang Qixuan , Gong Lihai , Zhang Ting , Zou Xudong , Xiong Kewei , Liao Qi , Plass Mireya , Li Lei 
Published: October 2023

Abstract
Genome-wide association studies (GWAS) have identified numerous genetic variants associated with diseases and traits. However, the functional interpretation of these variants remains challenging. Expression quantitative trait loci (eQTLs) have been widely used to identify mutations linked to disease, yet they explain only 20–50% of disease-related variants. Single-cell eQTLs (sc-eQTLs) studies provide an immense opportunity to identify new disease risk genes with expanded eQTL scales and transcriptional regulation at a much finer resolution. However, there is no comprehensive database dedicated to single-cell eQTLs that users can use to search, analyse and visualize them. Therefore, we developed the scQTLbase (http://bioinfo.szbl.ac.cn/scQTLbase), the first integrated human sc-eQTLs portal, featuring 304 datasets spanning 57 cell types and 95 cell states. It contains ∼16 million SNPs significantly associated with cell-type/state gene expression and ∼0.69 million disease-associated sc-eQTLs from 3 333 traits/diseases. In addition, scQTLbase offers sc-eQTL search, gene expression visualization in UMAP plots, a genome browser, and colocalization visualization based on the GWAS dataset of interest. scQTLbase provides a one-stop portal for sc-eQTLs that will significantly advance the discovery of disease susceptibility genes.
MultifacetedProtDB: a database of human proteins with multiple functions
Authors: Bertolini Elisa , Babbi Giulia , Savojardo Castrense , Martelli Pier Luigi , Casadio Rita 
Published: October 2023

Abstract
MultifacetedProtDB is a database of multifunctional human proteins deriving information from other databases, including UniProt, GeneCards, Human Protein Atlas (HPA), Human Phenotype Ontology (HPO) and MONDO. It collects under the label ‘multifaceted’ multitasking proteins addressed in literature as pleiotropic, multidomain, promiscuous (in relation to enzymes catalysing multiple substrates) and moonlighting (with two or more molecular functions), and difficult to be retrieved with a direct search in existing non-specific databases. The study of multifunctional proteins is an expanding research area aiming to elucidate the complexities of biological processes, particularly in humans, where multifunctional proteins play roles in various processes, including signal transduction, metabolism, gene regulation and cellular communication, and are often involved in disease insurgence and progression. The webserver allows searching by gene, protein and any associated structural and functional information, like available structures from PDB, structural models and interactors, using multiple filters. Protein entries are supplemented with comprehensive annotations including EC number, GO terms (biological pathways, molecular functions, and cellular components), pathways from Reactome, subcellular localization from UniProt, tissue and cell type expression from HPA, and associated diseases following MONDO, Orphanet and OMIM classification. MultiFacetedProtDB is freely available as a web server at: https://multifacetedprotdb.biocomp.unibo.it/.
Compartmentalization of androgen receptors at endogenous genes in living cells
Authors: Yavuz Selçuk , Kabbech Hélène , van Staalduinen Jente , Linder Simon , van Cappellen Wiggert A , Nigg Alex L , Abraham Tsion E , Slotman Johan A , Quevedo Marti , Poot Raymond A , Zwart Wilbert , van Royen Martin E , Grosveld Frank G , Smal Ihor , Houtsmuller Adriaan B 
Published: October 2023

AbstractA wide range of nuclear proteins are involved in the spatio-temporal organization of the genome through diverse biological processes such as gene transcription and DNA replication. Upon stimulation by testosterone and translocation to the nucleus, multiple androgen receptors (ARs) accumulate in microscopically discernable foci which are irregularly distributed in the nucleus. Here, we investigated the formation and physical nature of these foci, by combining novel fluorescent labeling techniques to visualize a defined chromatin locus of AR-regulated genes—PTPRN2 or BANP—simultaneously with either AR foci or individual AR molecules. Quantitative colocalization analysis showed evidence of AR foci formation induced by R1881 at both PTPRN2 and BANP loci. Furthermore, single-particle tracking (SPT) revealed three distinct subdiffusive fractional Brownian motion (fBm) states: immobilized ARs were observed near the labeled genes likely as a consequence of DNA-binding, while the intermediate confined state showed a similar spatial behavior but with larger displacements, suggesting compartmentalization by liquid–liquid phase separation (LLPS), while freely mobile ARs were diffusing in the nuclear environment. All together, we show for the first time in living cells the presence of AR-regulated genes in AR foci.
Oral Nicotine Gum Discussions on Twitter: Content Analysis
Authors: Galimov Artur , Kirkpatrick Matthew G , Vassey Julia , Galstyan Ellen , Smith Ashley , Allem Jon-Patrick , Unger Jennifer B 
Published: October 2023

Abstract

Background
Oral nicotine gum such as LUCY, which comes in colorful packaging, mimicking traditional chewing gum, is becoming popular. Many brands of gum have not been approved by the FDA for smoking cessation. This study examined public discourse about, including sentiment toward, oral nicotine gum on Twitter.

Methods
We used Twitter’s Streaming Application Programming Interface to collect data from January 1, 2021, to December 21, 2021, using “nicotine gum” and/or “#nicotinegum” search terms (N = 19 171 unique tweets were collected). We used an inductive approach to become familiar with the data, generated a codebook, and conducted a content analysis on (n = 2152) tweets.

Results
Cessation (n = 716, 33.3%), personal experience (n = 370, 17.2%), and addiction to gum (n = 135, 6.3%) were the most prevalent themes. Cessation tweets primarily discussed cigarette smoking cessation (n = 418, 58.4% of cessation tweets) and successful cessation experiences (n = 155, 21.6%). Other identified themes pertained to using nicotine gum for cognitive enhancement or catching a “buzz” (n = 102, 4.7%), marketing (n = 98, 4.6%), using nicotine gum with other substances (n = 90, 4.2%), and adverse effects (n = 63, 2.9%). Sentiment analysis results revealed that 675 (44.2%) tweets were categorized as neutral, 605 (39.6%) tweets were classified as positive, and 248 tweets (16.2%) were negative.

Conclusions
About one-third of tweets in our corpus mentioned nicotine gum in the context of smoking cessation. Most nicotine gum-related posts conveyed positive and neutral sentiments. Future studies should consider adding novel nicotine gum-specific search terms as well as exploring other social media platforms to gain more insights about these products.

Implications
Our findings suggest that Twitter has the potential to track and facilitate conversations between those seeking cigarette cessation advice and those who have successfully quit tobacco by using nicotine gum. Monitoring of promotional content from nicotine gum companies is needed to ensure these products are not appealing to youth and nonusers of tobacco.
Systematic review: exploring outcomes of commercial and homemade blenderized tube-feeding regimens on feeding tolerance in pediatric patients
Authors: Velly Miguel Mariana , Haubrick Kevin 
Published: October 2023

Abstract

Context
Increasing numbers of patients and caregivers are requesting transition to blenderized tube feeding. There is a lack of systematic reviews addressing the outcomes of blenderized tube feeding.

Objective
The aim was to evaluate the association of blenderized tube feeding on feeding tolerance in enterally fed pediatric patients.

Data Sources
A literature search for articles from 2012–2022 using PubMed, Medline, Embase, and CINAHL yielded 78 articles.

Data Extraction
A description and evaluation of the study’s sample, purpose, and results were summarized for 9 studies using the Academy of Nutrition and Dietetics Evidence Analysis Library Worksheet.

Data Analysis
Nine studies were evaluated using the Evidence Analysis Library Quality Criteria checklist.

Conclusions
Studies demonstrated an improvement in vomiting (n = 7), gagging/retching and heartburn (n = 6), abdominal pain/upset and distension (n = 3), and diarrhea (n = 6) with blenderized tube feeding. The outcomes of blenderized tube feeding on gas (n = 5) and constipation (n = 9) are variable and remain unclear.

Systematic Review Registration
PROSPERO registration no. CRD42022369247.
The Benefit of Exercise in Patients With Cancer Who Are Receiving Chemotherapy: A Systematic Review and Network Meta-Analysis
Authors: Herranz-Gómez Aida , Suso-Martí Luis , Varangot-Reille Clovis , Barrachina-Gauchia Laia , Casaña José , López-Bueno Laura , Calatayud Joaquín , Cuenca-Martínez Ferran 
Published: October 2023

Abstract

Objective
This study aimed to determine which therapeutic exercise-based intervention is most effective in improving cardiorespiratory fitness (CRF) in patients with cancer receiving chemotherapy.

Methods
The authors conducted a systematic review with network meta-analysis in MEDLINE (PubMed), Embase, Cumulative Index to Nursing and Allied Health Literature, Scopus, SPORTDiscus, and Web of Science. The authors employed the Physiotherapy Evidence Database and the Revised Cochrane Risk of Bias Tool for Randomized Trials to assess the methodological quality and risk of bias, respectively.

Results
A total of 27 studies were included. Data were pooled using a random-effects model. Adding aerobic training (moderate to high intensity), with or without resistance training, to usual care versus usual care was statistically significant, with a small beneficial effect (aerobic training: standardized mean difference = 0.46; 95% CI= 0.17 to 0.75; aerobic and resistance training: standardized mean difference = 0.26; 95% CI = 0.00 to 0.52) for peak oxygen consumption at the postintervention assessment.

Conclusion
Therapeutic exercise-based interventions to improve short-term CRF in patients with cancer receiving chemotherapy should include moderate- to high-intensity aerobic exercise, with or without resistance training.

Impact
It is important to improve CRF in the oncological population due to its relationship with mortality. The results showed the benefit of exercise to improve cardiorespiratory fitness in the oncology population receiving chemotherapy treatment.
A Retrieved-Context Theory of Financial Decisions
Authors: Wachter Jessica A , Kahana Michael Jacob 
Published: October 2023

Abstract
Studies of human memory indicate that features of an event evoke memories of prior associated contextual states, which in turn become associated with the current event’s features. This retrieved-context mechanism allows the remote past to influence the present, even as agents gradually update their beliefs about their environment. We apply a version of retrieved-context theory, drawn from the literature on human memory, to explain three types of evidence in the financial economics literature: the role of early life experience in shaping investment choices, occurrence of financial crises, and the effect of fear on asset allocation. These applications suggest a recasting of neoclassical rational expectations in terms of beliefs as governed by principles of human memory.
Incidence and predictors of demyelinating disease in spondyloarthritis: data from a longitudinal cohort study
Authors: Remalante-Rayco Patricia , Espiritu Adrian I , Daghistani Yassir , Chim Tina , Atenafu Eshetu , Keshavarzi Sareh , Jha Mayank , Gladman Dafna D , Oh Jiwon , Haroon Nigil , Inman Robert D 
Published: October 2023

Abstract

Objectives
The objectives of this study were to investigate the incidence of demyelinating disease (DD) among SpA patients and to identify risk factors that predict DD in this patient population.

Methods
Axial SpA (axSpA) and PsA patients were identified from a longitudinal cohort database. Each group was analysed according to the presence or absence of DD. Incidence rates (IRs) of DD were obtained, with competing risk analysis. Cox regression analysis (with Fine and Gray’s method) was used to evaluate predictors of DD development.

Results
Among 2260 patients with follow-up data, we identified 18 DD events, corresponding to an average IR of 31 per 100 000 persons per year for SpA. The IR of DD at 20 years was higher in axSpA than in PsA (1.30% vs 0.13%, P = 0.01). The risk factors retained in the best predictive model for DD development included ever- (vs never-) smoking [hazard ratio (HR) 2.918, 95% CI 1.037–8.214, P = 0.0426], axSpA (vs PsA) (HR 8.790, 95% CI 1.242–62.182, P = 0.0294) and presence (vs absence) of IBD (HR 5.698, 95% CI 2.083–15.589, P = 0.0007). History of TNF-α inhibitor therapy was not a predictor of DD.

Conclusion
The overall incidence of DD in this SpA cohort was low. Incident DD was higher in axSpA than in PsA. A diagnosis of axSpA, the presence of IBD, and ever-smoking predicted the development of DD. History of TNF-α inhibitor use was not found to be a predictor of DD in this cohort.
Hepatocyte-specific deletion of small heterodimer partner protects mice against acetaminophen-induced hepatotoxicity via activation of Nrf2
Authors: Ghosh Priyanka , Magee Nancy , Akakpo Jephte Y , Ahamed Forkan , Eppler Natalie , Jones Elizabeth , Yu Yifan , He Lily , Lebofsky Margitta , Dai Hongyan , Jaeschke Hartmut , Ding Wen-Xing , Zhang Yuxia 
Published: October 2023

Abstract
Acetaminophen (APAP) overdose stands as the primary cause of acute liver failure in the United States. APAP hepatotoxicity involves hepatic glutathione (GSH) depletion and mitochondrial damage. To counteract the toxicity of APAP, the nuclear factor erythroid 2 like 2 (Nrf2) activates the expression of genes responsible for drug detoxification and GSH synthesis. In this study, we present evidence that the elimination of hepatocyte small heterodimer partner, a critical transcriptional repressor for liver metabolism, results in Nrf2 activation and protects mice from APAP-induced acute liver injury. Initial investigations conducted on wildtype (WT) mice revealed a swift downregulation of Shp mRNA within the first 24 h after APAP administration. Subsequent treatment of hepatocyte-specific Shp knockout (ShpHep−/−) mice with 300 mg/kg APAP for 2 h exhibited comparable bioactivation of APAP with that observed in the WT controls. However, a significant reduction in liver injury was observed in ShpHep−/− after APAP treatment for 6 and 24 h. The decreased liver injury correlated with a faster recovery of GSH, attributable to heightened expression of Nrf2 target genes involved in APAP detoxification and GSH synthesis. Moreover, in vitro studies revealed that SHP protein interacted with NRF2 protein, inhibiting the transcription of Nrf2 target genes. These findings hold relevance for humans, as overexpression of SHP hindered APAP-induced NRF2 activation in primary human hepatocytes. In conclusion, our studies have unveiled a novel regulatory axis involving SHP and NRF2 in APAP-induced acute liver injury, emphasizing SHP as a promising therapeutic target in APAP overdose-induced hepatotoxicity.
Indocyanine Green Lymphography in Conservative Lymphedema Therapy: A Scoping Review
Authors: Trevethan Megan , Patterson Freyr , Doig Emmah , Pigott Amanda 
Published: October 2023

Background:
There is great potential but seemingly limited use of indocyanine green (ICG) lymphography to influence conservative lymphedema therapy clinical practice. This scoping review aimed to map existing evidence for ICG lymphography relating to conservative lymphedema therapy.

Methods:
A 6-staged scoping review framework of Arksey and O'Malley was used to guide the study. Protocol development included key stakeholder consultation. Searches were conducted in 5 databases with specialist librarian support. A 2-phase selection process undertaken by 2 researchers identified studies for inclusion. Conflicts were resolved by consensus. A subsequent 3-phase data extraction and quality appraisal process occurred. Key findings were presented in a descriptive numerical summary.

Results:
A total of 6316 records were identified, yielding 162 articles for inclusion. Categorization was made according to article type and purpose of ICG lymphography including lymphedema assessment (diagnosis and staging) and/or conservative therapy. Seventy-six empirical research articles with detailed reference to ICG lymphography were explored further.

Conclusion:
Current published research about ICG lymphography in conservative lymphedema therapy describes support for its use in lymphedema diagnosis, and proposes staging systems for lymphedema severity. Despite existing work, further exploration of effect on conservative therapy planning, clinical, and patient outcomes is necessary to consider future translation to clinical practice.
Risk Factors of Postoperative Coronal Balance Transition in Degenerative Lumbar Scoliosis
Authors: Ding Linyao , Sun Zhuoran , Li Weishi , Zeng Yan , Chen Ze , Qiu Weipeng , Hou Xiangyu , Yuan Lei 
Published: October 2023

Study Design.
Retrospective radiographic study.

Objective.
To determine the potential risk factors influencing the transition of postoperative coronal balance in degenerative lumbar scoliosis (DLS) patients.

Summary of Background Data.
As time passes after surgery, the spinal sequence of DLS patients may dynamically shift from coronal balance to imbalance, causing clinical symptoms. However, the transition of postoperative coronal balance and its risk factors have not been effectively investigated.

Materials and Methods.
We included 156 DLS patients. The cohort was divided into immediate postoperative coronal balance with follow-up balance (N=73) and follow-up imbalance (N=21), immediate postoperative coronal imbalance (CIB) with follow-up balance (N=23), and follow-up imbalance (N=39). Parameters included age, sex, classification of coronal balance, coronal balance distance, fusion of L5 or S1, location of apical vertebra, apical vertebral translation (AVT), Cobb angle of the main curve and lumbar-sacral curve, tilt and direction of L4/5, tilt and direction of upper instrumented vertebra (UIV), and Cobb angle of T1-UIV. Statistical testing was performed using chi-square/Fisher exact test, t tests or nonparametric tests, correlation testing, and stepwise logistic regression.

Results.
We identified a significant difference in preoperative AVT, preoperative Cobb angle, and immediate postoperative UIV tilt between patients with and without follow-up balance. Logistic regression analysis demonstrated factors associated with follow-up CIB included preoperative AVT (P=0.015), preoperative Cobb angle (P=0.002), and tilt of immediate postoperative UIV (P=0.018). Factors associated with immediate postoperative CIB in patients with follow-up coronal balance were sex, correction ratio of the main curve, and direction of L4. Logistic regression analysis further identified a correction ratio of main curve ≤0.7 (P=0.009) as an important predictive factor.

Conclusion.
Patients with immediate postoperative coronal balance and higher preoperative AVT, preoperative Cobb angle, and tilt of immediate postoperative UIV were more likely to experience follow-up CIB. A correction ratio of the main curve ≤0.7 was an independent predictor of follow-up CIB.

Level of Evidence.
3.