bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-wide screen and multi-omics analysis reveal OGT1 participate in the biosynthesis of safflower flavonoid glycosides
Authors: Xian Bin , Zhou Yanxun , Hu Yueying , Peng Yanni , Song Xiaominting , Xi Ziqing , Li Yuhang , Yan Jie , Ren Chaoxiang , Pei Jin , Chen Jiang 
Published: September 2024

Abstract
Safflower, an economic crop, is renowned for its flowers, which are widely used in medicines for treating cardiovascular and cerebrovascular diseases and in dyes for food and industry. The utility of safflower depends on its flavonoid glycosides. Therefore, the biosynthesis of safflower flavonoid glycosides has been a focus of attention, but the present mechanisms remain poorly understood. This study aims to identify functional genes associated with flavonoid glycoside biosynthesis in safflower through a comprehensive approach that integrates whole-genome screen and multi-omics correlation studies. CYP and UGT are two crucial genes families involved in flavonoid glycoside biosynthesis. We have screened 264 CYP genes and 140 UGT genes in the genome of safflower and conducted analyzes including phylogenetic relationships, conserved motifs, gene structures, cis-acting elements, and chromosome mapping, which provided extensive and comprehensive data on the CYP and UGT gene families. Integration of phenotype and metabolic data from safflower different tissues helped narrow down the screening by confirming that HSYA is synthesized only in flowers. Based on the gene expression patterns and phylogenetic analysis, CtOGT1 was ultimately identified, which could catalyze the generation of glycosides using various flavonoid substrates and exhibited strong substrate affinity. Moreover, molecular docking studies elucidated CtOGT1’s highly active intrinsic mechanism. In conclusion, this study effectively identified genes responsible for flavonoid glycoside biosynthesis in safflower through the integration of whole-genome screen and multi-omics analysis, established a comprehensive foundation of data, methodology, and experimental evidence for further elucidating the pathways of safflower flavonoid glycoside biosynthesis.
Decoding the genetic basis of secretory tissues in plants
Authors: Han Yuepeng 
Published: September 2024

Abstract
Although plant secretory tissues play important roles in host defense against herbivores and pathogens and the attraction of insect pollinators, their genetic control remains elusive. Here, it is focused that current progress has been made in the genetic regulatory mechanisms underpinning secretory tissue development in land plants. C1HDZ transcription factors (TFs) are found to play crucial roles in the regulation of internal secretory tissues in liverworts and Citrus as well as external secretory tissues in peach. C1HDZ TFs regulate secretory tissue development via synergistic interaction with AP2/ERF and MYC TFs. Thus, a set of genes are speculated to be recruited convergently for the formation of secretory tissues in land plants.
Sign Changes of the Error Term in the Piltz Divisor Problem
Authors: Baluyot Siegfred , Castillo Cruz 
Published: September 2024

Abstract
We study the function $\Delta _{k}(x):=\sum _{n\leq x} d_{k}(n) - \mbox{Res}_{s=1} ( \zeta ^{k}(s) x^{s}/s )$, where $k\geq 3$ is an integer, $d_{k}(n)$ is the $k$-fold divisor function, and $\zeta (s)$ is the Riemann zeta-function. For a large parameter $X$, we show that if the Lindelöf hypothesis (LH) is true, then there exist at least $X^{\frac{1}{k(k-1)}-\varepsilon }$ disjoint subintervals of $[X,2X]$, each of length $X^{1-\frac{1}{k}-\varepsilon }$, such that $|\Delta _{k}(x)|\gg x^{\frac{1}{2}-\frac{1}{2k}}$ for all $x$ in the subinterval. In particular, $\Delta _{k}(x)$ does not change sign in any of these subintervals. If the Riemann hypothesis (RH) is true, then we can improve the length of the subintervals to $\gg X^{1-\frac{1}{k}} (\log X)^{-k^{2}-2}$. These results may be viewed as higher-degree analogues of theorems of Heath-Brown and Tsang, who studied the case $k=2$, and Cao, Tanigawa, and Zhai, who studied the case $k=3$. The first main ingredient of our proofs is a bound for the second moment of $\Delta _{k}(x+h)-\Delta _{k}(x)$. We prove this bound using a method of Selberg and a general lemma due to Saffari and Vaughan. The second main ingredient is a bound for the fourth moment of $\Delta _{k}(x)$, which we obtain by combining a method of Tsang with a technique of Lester.
Modernizing behavioral parent training program for ADHD with mHealth strategies, telehealth groups, and health behavior curriculum: a randomized pilot trial
Authors: Tandon Pooja S , Gabert Tess , Kuhn Michelle , Tran Nguyen , Ola Cindy , Sullivan Erin , Zhou Chuan , Stein Mark , Mendoza Jason A , Sasser Tyler , Gonzalez Erin 
Published: September 2024

Abstract

Objective
Parent behavior management training (BMT) is an evidence-based yet underutilized tool to treat children with ADHD and address related health disparities. This pilot study investigated the acceptability and feasibility of a novel, health behavior-, and technology-adapted BMT (LEAP) vs. standard BMT.

Methods
The weekly 9-session LEAP telemedicine group program is based on a standard BMT curriculum enhanced with strategies for supporting optimal child sleep, problematic media use (PMU), and physical activity, including wrist-worn activity trackers. Children ages 6–10 years with ADHD and their caregivers were randomized to LEAP or standard BMT. Acceptability and feasibility were tracked. Caregivers completed standardized measures, and children wore hip-worn accelerometers for 1 week at baseline, postintervention (10 weeks), and follow-up (20 weeks).

Results
84 parent/child dyads were randomized to LEAP or standard BMT, with high and comparable acceptability and feasibility. Both treatment groups demonstrated decreased ADHD symptoms and improved executive functions postintervention (p &lt; .0001), maintained at follow-up. Average accelerometer-measured MVPA decreased and sleep duration remained unchanged, while PMU and bedtime resistance improved for both groups.

Conclusions
LEAP is highly feasible and acceptable, and yielded similar initial clinical and health behavior improvements to standard BMT. Innovative and targeted supports are needed to promote healthy behaviors in children with ADHD.
Integrating testing volume into bandit algorithms for infectious disease surveillance
Authors: Warren Joshua L , Prunas Ottavia , Paltiel A David , Thornhill Thomas , Gonsalves Gregg S 
Published: September 2024

Abstract
Mobile testing services provide opportunities for active surveillance of infectious diseases for hard-to-reach and/or high-risk individuals who do not know their disease status. Identifying as many infected individuals as possible is important for mitigating disease transmission. Recently, multi-armed bandit sampling approaches have been adapted and applied in this setting to maximize the cumulative number of positive tests collected over time. However, these algorithms have not considered the possibility of variability in the number of tests administered across testing sites. What impact this variability has on the ability of these approaches to maximize yield is currently unknown. Therefore, we investigate this question by extending existing sampling frameworks to directly account for variability in testing volume while also maintaining the computational tractability of the previous methods. Through a simulation study based on human immunodeficiency virus infection characteristics in the Republic of the Congo (Congo-Brazzaville) as well as an application to COVID-19 testing data in Connecticut, we find improved long- and short-term performances of the new methods compared to several existing approaches. Based on these findings and the ease of computation, we recommend use of the newly developed methods for active surveillance of infectious diseases when variability in testing volume may be present.
Gene silencing in broomrapes and other parasitic plants of the Orobanchaceae family: mechanisms, considerations, and future directions
Authors: Zainali Nariman , Alizadeh Houshang , Delavault Philippe 
Published: September 2024

Abstract
Holoparasites of the Orobanchaceae family are devastating pests causing severe damage to many crop species, and are nearly impossible to control with conventional methods. During the past few decades, RNAi has been seen as a promising approach to control various crop pests. The exchange of small RNAs (sRNAs) between crops and parasitic plants has been documented, indicating potential for the development of methods to protect them via the delivery of the sRNAs to parasites, a method called host-induced gene silencing (HIGS). Here we describe various approaches used for gene silencing in plants and suggest solutions to improve the long-distance movement of the silencing triggers to increase the efficiency of HIGS in parasitic plants. We also investigate the important biological processes during the life cycle of the parasites, with a focus on broomrape species, providing several appropriate target genes that can be used, in particular, in multiplex gene silencing experiments. We also touch on how the application of nanoparticles can improve the stability and delivery of the silencing triggers, highlighting its potential for control of parasitic plants. Finally, suggestions for further research and possible directions for RNAi in parasitic plants are provided.
A Systematic Review of the Effect of Gene–Lifestyle Interactions on Metabolic-Disease-Related Traits in South Asian Populations
Authors: Bineid Manahil M , Ventura Eduard F , Samidoust Aryan , Radha Venkatesan , Anjana Ranjit Mohan , Sudha Vasudevan , Walton Gemma E , Mohan Viswanathan , Vimaleswaran Karani Santhanakrishnan 
Published: September 2024

Abstract

Context
Recent data from the South Asian subregion have raised concern about the dramatic increase in the prevalence of metabolic diseases, which are influenced by genetic and lifestyle factors.

Objective
The aim of this systematic review was to summarize the contemporary evidence for the effect of gene–lifestyle interactions on metabolic outcomes in this population.

Data sources
PubMed, Web of Science, and SCOPUS databases were searched up until March 2023 for observational and intervention studies investigating the interaction between genetic variants and lifestyle factors such as diet and physical activity on obesity and type 2 diabetes traits.

Data extraction
Of the 14 783 publications extracted, 15 were deemed eligible for inclusion in this study. Data extraction was carried out independently by 3 investigators. The quality of the included studies was assessed using the Appraisal Tool for Cross-Sectional Studies (AXIS), the Risk Of Bias In Non-randomized Studies—of Interventions (ROBINS-I), and the methodological quality score for nutrigenetics studies.

Data analysis
Using a narrative synthesis approach, the findings were presented in textual and tabular format. Together, studies from India (n = 8), Pakistan (n = 3), Sri Lanka (n = 1), and the South Asian diaspora in Singapore and Canada (n = 3) reported 543 gene–lifestyle interactions, of which 132 (∼24%) were statistically significant. These results were related to the effects of the interaction of genetic factors with physical inactivity, poor sleep habits, smoking, and dietary intake of carbohydrates, protein, and fat on the risk of metabolic disease in this population.

Conclusions
The findings of this systematic review provide evidence of gene–lifestyle interactions impacting metabolic traits within the South Asian population. However, the lack of replication and correction for multiple testing and the small sample size of the included studies may limit the conclusiveness of the evidence. Note, this paper is part of the Nutrition Reviews Special Collection on Precision Nutrition.

Systematic Review Registration
PROSPERO registration No. CRD42023402408.
Some Polyphenolic Compounds as Potential Therapeutic Agents in Cervical Cancer: The Most Recent Advances and Future Prospects
Authors: Sanlier Nazlı Tunca , Saçinti Koray Görkem , Türkoğlu İnci , Sanlier Nevin 
Published: September 2024

Abstract
The leading causes of cancer include gradual changes in regulatory proteins, dysregulated cell-signaling pathways, dysfunction of apoptosis, and oxidative stress. Consuming polyphenols from food sources has been proven to have strong connections with ameliorating specific physiological biomarkers along with other elements concerning cancer. Recent studies have focused on polyphenols’ molecular mechanisms of action and anticancer and chemopreventive properties and effects in the treatment of different types of cancer. Polyphenols participate in the regulation of numerous cellular mechanisms alongside signaling pathways through their effects on inflammation, cellular proliferation, apoptosis, and partially via epigenetic alterations in cervical cancer. A number of animal models and cell and human studies have indicated the use of polyphenols to be safe and tolerable. Thus, it would be fair to state that, with their advantages vis-à-vis lack of toxicity, cost, and access, and with the positive clinical results, polyphenols have a potential to make a difference in cancer treatment. The present review examined the chemical and physical properties, analogs, metabolites, and mechanisms of physiological activities of various polyphenols and how they may affect the incidence rate and management of cervical cancer. Therefore, this review constitutes a starting point to examine the potential applications for cervical cancer.
RAPID ALKALINIZATION FACTOR 22 is a key modulator of the root hair growth responses to fungal ethylene emissions in Arabidopsis
Authors: Morcillo Rafael Jorge León , Leal-López Jesús , Férez-Gómez Alberto , López-Serrano Lidia , Baroja-Fernández Edurne , Gámez-Arcas Samuel , Tortosa Germán , López Leonel E , Estevez José Manuel , Doblas Verónica G , Frías-España Laura , García-Pedrajas María Dolores , Sarmiento-Villamil Jorge , Pozueta-Romero Javier 
Published: September 2024

Abstract
In Arabidopsis (Arabidopsis thaliana (L.) Heynh), exposure to volatile compounds (VCs) emitted by Penicillium aurantiogriseum promotes root hair (RH) proliferation and hyper-elongation through mechanisms involving ethylene, auxin, and photosynthesis signaling. In addition, this treatment enhances the levels of the small signaling peptide RAPID ALKALINIZATION FACTOR 22 (RALF22). Here, we used genetics to address the role of RALF22 in fungal VC-promoted RH growth and to identify the bioactive fungal VC. We found that RHs of ralf22 and feronia (fer-4) plants impaired in the expression of RALF22 and its receptor FERONIA, respectively, responded weakly to fungal VCs. Unlike in wild-type roots, fungal VC exposure did not enhance RALF22 transcript levels in roots of fer-4 and ethylene- and auxin-insensitive mutants. In ralf22 and fer-4 roots, this treatment did not enhance the levels of ERS2 transcripts encoding one member of the ethylene receptor family and those of some RH-related genes. RHs of ers2-1 and the rsl2rsl4 double mutants impaired in the expression of ERS2 and the ethylene- and auxin-responsive ROOT HAIR DEFECTIVE 6-LIKE 2 and 4 transcription factors, respectively, weakly responded to fungal VCs. Moreover, roots of plants defective in photosynthetic responsiveness to VCs exhibited weak RALF22 expression and RH growth responses to fungal VCs. VCs of ΔefeA strains of P. aurantiogriseum cultures impaired in ethylene synthesis weakly promoted RH proliferation and elongation in exposed plants. We conclude that RALF22 simultaneously functions as a transcriptionally regulated signaling molecule that participates in the ethylene, auxin, and photosynthesis signaling-mediated RH growth response to fungal ethylene emissions and regulation of ethylene perception in RHs.
Validation of a Clinical Teaching Competency Framework for Physical Therapists: A Mixed-Methods Approach
Authors: Sharp Amanda , Bilyeu Catherine , Wengrovius Carissa , Myers Katherine 
Published: September 2024

Abstract

Objective
A competency framework for clinical teaching in physical therapy was established in a recent study. Validation of competency frameworks requires multiple steps, including consideration of end-user perceptions of value and utility. The purpose of this study was to further validate the Clinical Teaching Competency Framework by gathering input specifically from clinical education faculty.

Methods
This study used an explanatory sequential mixed-methods approach to seek input from clinical instructors (CIs) and site coordinators of clinical education (SCCE) from diverse practice areas and geographic regions. A survey invited participation from active clinical education faculty, and survey respondents were invited to participate in a focus group. Two focus groups were held via Zoom.

Results
Survey responses from those holding roles of CI (59.3%), SCCE (11.3%), and CI/SCCE (29.4%) indicated support for the competency framework, including perceived value to their role (93.1%) and improvement in the quality of clinical education (94.1%). Concern regarding the ease of utilization of the framework was indicated by 24% of respondents. There were no statistically significant differences in responses based on role or credentials. The focus groups resulted in an overarching theme of collective impact, with 4 subthemes: assessment, CI development, implementation, and guidelines.

Conclusion
Clinical education faculty perceive value and utility in the Clinical Teaching Competency Framework. Implementation of the framework should be collaborative and consistent across academic and clinical education programs.

Impact
This study moves the profession one step closer to the use of a competency framework specifically targeted at clinical teaching in physical therapy. Clinical education faculty will be primary users of a competency framework, and buy-in from this user group is key to implementation. Continued efforts to validate this framework contribute to addressing the need for CI development and support in delivering excellence in clinical education.
Safety of rTMS for Schizophrenia: A Systematic Review and Meta-analysis
Authors: Blyth Sophia H , Cruz Bosch Claudia , Raffoul Julian J , Chesley Jordyn , Johnson Benjamin , Borodge Darara , Sagarwala Raza , Masters Ross , Brady Roscoe O , Vandekar Simon , Ward Heather Burrell 
Published: September 2024

Abstract

Background and Hypothesis
Current treatments for schizophrenia are only partially effective, and there are no medications for negative symptoms or cognitive impairment. Neuromodulation, such as repetitive transcranial magnetic stimulation (rTMS), has potential as a novel intervention for schizophrenia. Prior to clinical use, rTMS should have demonstrated safety in a large schizophrenia population. However, the safety profile of rTMS in schizophrenia is not well characterized, and regulatory agencies have expressed concern about safety in this population.

Study Design
We conducted a systematic review with meta-analysis of rTMS studies in schizophrenia. We searched PubMed, the Cochrane Library, PsycINFO, and Science Citation Index Expanded for rTMS studies in schizophrenia that reported adverse effects. We extracted the number of participants who experienced an adverse effect and calculated the prevalence of each adverse effect for active or sham rTMS. We tested the difference between the prevalence of events in the active and sham conditions. We assessed risk of bias using the Cochrane Handbook.

Study Results
The initial search identified 1472 studies. After screening, 261 full-text studies were assessed, and 126 met inclusion criteria (N = 4122 total subjects). The prevalence of headache or scalp pain, dizziness or syncope, facial twitching, and nausea was higher for active rTMS compared to sham (P &lt; .05). The prevalence of all other adverse effects, including seizure, was not different between active and sham rTMS.

Conclusions
rTMS is safe and well tolerated for people with schizophrenia. Individuals with schizophrenia are not at increased risk for adverse effects, including seizure, compared to the general population.
A p21 reporter iPSC line for evaluating CRISPR-Cas9 and vector-induced stress responses
Authors: Sun Yi-Dan , Li Guo-Hua , Zhang Feng , Cheng Tao , Zhang Jian-Ping , Zhang Xiao-Bing 
Published: September 2024

Abstract
CRISPR-Cas9 editing triggers activation of the TP53-p21 pathway, but the impacts of different editing components and delivery methods have not been fully explored. In this study, we introduce a p21-mNeonGreen reporter iPSC line to monitor TP53-p21 pathway activation. This reporter enables dynamic tracking of p21 expression via flow cytometry, revealing a strong correlation between p21 expression and indel frequencies, and highlighting its utility in guide RNA screening. Our findings show that p21 activation is significantly more pronounced with double-stranded oligodeoxynucleotides (ODNs) or adeno-associated viral vectors (AAVs) compared to their single-stranded counterparts. Lentiviral vectors (LVs) and integrase-defective lentiviral vectors induce notably lower p21 expression than AAVs, suggesting their suitability for gene therapy in sensitive cells such as hematopoietic stem cells or immune cells. Additionally, specific viral promoters like SFFV significantly amplify p21 activation, emphasizing the critical role of promoter selection in vector development. Thus, the p21-mNeonGreen reporter iPSC line is a valuable tool for assessing the potential adverse effects of gene editing methodologies and vectors.
Highlights Established a p21-mNeonGreen reporter iPSC line to track activation of the TP53-p21 pathway.
Found a direct correlation between p21-mNeonGreen expression and indel frequencies, aiding in gRNA screening.
Showed that LVs are preferable over AAVs for certain cells due to lower p21 activation, with viral promoter choice impacting p21 response.
Mesenchymal stromal cell transplantation ameliorates fibrosis and microRNA dysregulation in skeletal muscle ischemia
Authors: Sanz-Nogués Clara , Keane Alan J , Creane Michael , Hynes Sean O , Chen Xizhe , Lyons Caomhán J , Horan Emma , Elliman Stephen J , Goljanek-Whysall Katarzyna , O’Brien Timothy 
Published: September 2024

Abstract
Peripheral arterial disease (PAD) is associated with lower-extremity muscle wasting. Hallmark features of PAD-associated skeletal muscle pathology include loss of skeletal muscle mass, reduced strength and physical performance, increased inflammation, fibrosis, and adipocyte infiltration. At the molecular level, skeletal muscle ischemia has also been associated with gene and microRNA (miRNA) dysregulation. Mesenchymal stromal cells (MSCs) have been shown to enhance muscle regeneration and improve muscle function in various skeletal muscle injuries. This study aimed to evaluate the effects of intramuscularly delivered human umbilical cord-derived MSCs (hUC-MSCs) on skeletal muscle ischemia. Herein, we report an hUC-MSC-mediated amelioration of ischemia-induced skeletal muscle atrophy and function via enhancement of myofiber regeneration, reduction of tissue inflammation, adipocyte accumulation, and tissue fibrosis. These changes were observed in the absence of cell-mediated enhancement of blood flow recovery as measured by laser Doppler imaging. Furthermore, reduced tissue fibrosis in the hUC-MSC-treated group was associated with upregulation of miR-1, miR-133a, and miR-29b and downregulation of targeted pro-fibrotic genes such as Col1a1 and Fn1. Our results support the use of hUC-MSCs as a novel approach to reduce fibrosis and promote skeletal muscle regeneration after ischemic injury in patients with PAD.