bluuebunny/crossref_metadata_2025_split huggingface dataset:
A bacterial transcription activator dedicated to the expression of the enzyme catalyzing the first committed step in fatty acid biosynthesis
Authors: Xu Yuanyou , Lin Zihan , Hou Jiyuan , Ye Kai , Han Sirui , Liang Yuxuan , Liang Huihui , Wu Shihua , Tao Yizhi J , Gao Haichun 
Published: October 2024

Abstract
Acetyl-CoA carboxylase (ACCase) catalyzes the first committed and rate-limiting step of de novo fatty acid synthesis (FAS). Although this step is tightly regulated, regulators that specifically control transcription of the ACCase genes remain elusive. In this study, we identified LysR-type transcriptional regulator AccR as a dedicated activator for the transcription of accS, a gene encoding a multiple-domain ACCase in Shewanella oneidensis. We showed that AccR interacts with the accS promoter in vivo in response to changes in acetyl-CoA levels and in vitro. Analysis of the crystal structure of the effector-binding domain (EBD) of AccR identified two potential ligand-binding pockets, one of which is likely to bind acetyl-CoA as a ligand based on results from molecular docking, direct binding assay and mutational analysis of the residues predicted to interact with acetyl-CoA. Despite this, the interaction between AccR and acetyl-CoA alone appears unstable, implying that an additional yet unknown ligand is required for activation of AccR. Furthermore, we showed that AccR is acetylated, but the modification may not be critical for sensing acetyl-CoA. Overall, our data substantiate the existence of a dedicated transcriptional regulator for ACCases, expanding our current understanding of the regulation of FAS.
mVOC 4.0: a database of microbial volatiles
Authors: Kemmler Emanuel , Lemfack Marie Chantal , Goede Andrean , Gallo Kathleen , Toguem Serge M T , Ahmed Waqar , Millberg Iris , Preissner Saskia , Piechulla Birgit , Preissner Robert 
Published: October 2024

Abstract
Metabolomic microbiome research has become an important topic for understanding agricultural, ecological as well as health correlations. Only the determination of both the non-volatile and the volatile organic compound (mVOC) production by microorganisms allows a holistic view for understanding the complete potential of metabolomes and metabolic capabilities of bacteria. In the recent past, more and more bacterial headspaces and culture media were analyzed, leading to an accumulation of about 3500 mVOCs in the updated mVOC 4.0 database, including compounds synthesized by the newly discovered non-canonical terpene pathway. Approximately 10% of all mVOCs can be assigned with a biological function, some mVOCs have the potential to impact agriculture in the future (e.g. eco-friendly pesticides) or animal and human health care. mVOC 4.0 offers various options for exploring extensively annotated mVOC data from different perspectives, including improved mass spectrometry matching. The mVOC 4.0 database includes literature searches with additional relevant keywords, making it the most up-to-date and comprehensive publicly available mVOC platform at: http://bioinformatics.charite.de/mvoc.
Uncoupling FRUITFULL’s functions through modification of a protein motif identified by co-ortholog analysis
Authors: Thoris Kai , Correa Marrero Miguel , Fiers Martijn , Lai Xuelei , Zahn Iris E , Jiang Xiaobing , Mekken Mark , Busscher Stefan , Jansma Stuart , Nanao Max , de Ridder Dick , van Dijk Aalt D J , Angenent Gerco C , Immink Richard G H , Zubieta Chloe , Bemer Marian 
Published: October 2024

Abstract
Many plant transcription factors (TFs) are multifunctional and regulate growth and development in more than one tissue. These TFs can generally associate with different protein partners depending on the tissue type, thereby regulating tissue-specific target gene sets. However, how interaction specificity is ensured is still largely unclear. Here, we examine protein–protein interaction specificity using subfunctionalized co-orthologs of the FRUITFULL (FUL) subfamily of MADS-domain TFs. In Arabidopsis, FUL is multifunctional, playing important roles in flowering and fruiting, whereas these functions have partially been divided in the tomato co-orthologs FUL1 and FUL2. By linking protein sequence and function, we discovered a key amino acid motif that determines interaction specificity of MADS-domain TFs, which in Arabidopsis FUL determines the interaction with AGAMOUS and SEPALLATA proteins, linked to the regulation of a subset of targets. This insight offers great opportunities to dissect the biological functions of multifunctional MADS TFs.
RepeatsDB in 2025: expanding annotations of structured tandem repeats proteins on AlphaFoldDB
Authors: Clementel Damiano , Arrías Paula Nazarena , Mozaffari Soroush , Osmanli Zarifa , Castro Ximena Aixa ,   RepeatsDB curators, Borucki Estefanía Lorena , Cabrera Maia , Chinestrad Patricio , Czarnowski Ian , Lombardo Jose Francisco , Menna Pablo Lorenzano , Mogro Ezequiel Gerardo , Padilla Franzotti Carla Luciana , Santillan Julia Yamila , Ferrari Carlo , Kajava Andrey V , Tosatto Silvio C E , Monzon Alexander Miguel 
Published: October 2024

Abstract
RepeatsDB (URL: https://repeatsdb.org) stands as a key resource for the classification and annotation of Structured Tandem Repeat Proteins (STRPs), incorporating data from both the Protein Data Bank (PDB) and AlphaFoldDB. This latest release features substantial advancements, including annotations for over 34 000 unique protein sequences from &gt;2000 organisms, representing a fifteenfold increase in coverage. Leveraging state-of-the-art structural alignment tools, RepeatsDB now offers faster and more precise detection of STRPs across both experimental and predicted structures. Key improvements also include a redesigned user interface and enhanced web server, providing an intuitive browsing experience with improved data searchability and accessibility. A new statistics page allows users to explore database metrics based on repeat classifications, while API enhancements support scalability to manage the growing volume of data. These advancements not only refine the understanding of STRPs but also streamline annotation processes, further strengthening RepeatsDB’s role in advancing our understanding of STRP functions.
Do-It-Yourself Flavored Capsule Cigarettes: Exploiting Potential Regulatory Loopholes?
Authors: Dobbs Page D , Soule Eric K , Mahoney Margaret , Tabassum Mufazzela , Burgess Nia , Henriksen Lisa 
Published: October 2024

Abstract

Introduction
Capsule cigarettes allow users to crush liquid-filled capsules to release flavors into cigarettes’ filters. New devices are emerging across the globe that allow people who smoke to circumvent tobacco flavor restrictions via injectable capsules. This study examined TikTok videos marketing flavored capsule injector devices.

Methods
TikTok videos (n = 832) posted worldwide between July 6, 2021, and December 28, 2023, that used hashtags #injectorflavor, #flavourclickball, #flavorball, and #injectorballcigarette were collected using a TikTok application programing interface. A codebook was developed using a systematic iterative approach, identifying six codes: flavor capsules, promotes flavors (i.e., fruit, mint or menthol flavors, nonalcoholic drinks, alcoholic drinks), demonstrates how to use or refill large injector devices, demonstrates how to use small convenient devices, includes music (any or English language). Two independent coders annotated all videos.

Results
Overall, 88.3% (n = 735) of the videos displayed flavor capsules and had been viewed more than 72 million times. Half (51.6%) of the videos demonstrated how to use large box-shaped devices to inject capsules into the filter of a cigarette, and 15.0% of the videos showed how to do this with smaller, more convenient devices. Flavors including fruit (35.5%), menthol/mint (27.8%), nonalcoholic drinks (21.9%), and alcoholic drinks (11.6%) were used to promote these capsules. Most videos (85.6%) were uploaded by sellers on “TikTok shop.”

Discussion
TikTok accounts are promoting injectable capsule devices that circumvent flavored tobacco sales restrictions. Policy makers, tobacco control advocates, and public health practitioners should be aware of such marketing to inform regulation and develop prevention strategies.

Implications
Our findings identified an emerging product that can encourage circumvention of flavor restriction policies. Regulators, policy makers, public health practitioners, researchers, and advocates should be aware of such products to inform regulation and develop prevention strategies. Given the potential for these products to reduce the intended effects of flavored tobacco sales restrictions, policy makers must be poised to address materials that consumers use to create their own flavored tobacco products, including flavor capsules designed to be inserted into cigarettes.
Neuromorphic neuromodulation: Towards the next generation of closed-loop neurostimulation
Authors: Herbozo Contreras Luis Fernando , Truong Nhan Duy , Eshraghian Jason K , Xu Zhangyu , Huang Zhaojing , Bersani–Veroni Thomas Vincenzo , Aguilar Isabelle , Leung Wing Hang , Nikpour Armin , Kavehei Omid 
Published: October 2024

Abstract
Neuromodulation techniques have emerged as promising approaches for treating a wide range of neurological disorders, precisely delivering electrical stimulation to modulate abnormal neuronal activity. While leveraging the unique capabilities of AI holds immense potential for responsive neurostimulation, it appears as an extremely challenging proposition where real-time (low-latency) processing, low-power consumption, and heat constraints are limiting factors. The use of sophisticated AI-driven models for personalized neurostimulation depends on the back-telemetry of data to external systems (e.g. cloud-based medical mesosystems and ecosystems). While this can be a solution, integrating continuous learning within implantable neuromodulation devices for several applications, such as seizure prediction in epilepsy, is an open question. We believe neuromorphic architectures hold an outstanding potential to open new avenues for sophisticated on-chip analysis of neural signals and AI-driven personalized treatments. With more than three orders of magnitude reduction in the total data required for data processing and feature extraction, the high power- and memory-efficiency of neuromorphic computing to hardware-firmware co-design can be considered as the solution-in-the-making to resource-constraint implantable neuromodulation systems. This perspective introduces the concept of Neuromorphic Neuromodulation, a new breed of closed-loop responsive feedback system. It highlights its potential to revolutionize implantable brain–machine microsystems for patient-specific treatment.
Application of an implementation premortem: A novel qualitative approach leveraging prospective hindsight to enhance barbershop health interventions for Black men
Authors: Wippold Guillermo M , Wong Dylan , Garcia Kaylyn A , Crichlow Zion , Frary Sarah Grace , Mote Thrisha , Griffith Derek M 
Published: October 2024

Abstract
Barbershop-based efforts to promote health among Black men have been uniquely successful. Despite the success of these efforts, the emphasis on outcomes as opposed to how these outcomes can be achieved has created a gap in the literature. The present study addresses this gap by describing implementation-related program priorities that Black men identify for barbershop-based interventions. Twenty-three Black men participated in implementation premortem activities. Participants were: (i) given details about a barbershop-based health promotion effort, (ii) told that the effort had failed, and (iii) were asked to identify potential sources of program failure and strategies to overcome those challenges. The frequency of program priorities was calculated based on the Exploration, Preparation, Implementation, and Sustainment (EPIS) Framework, and focus group data were analyzed using an inductive thematic qualitative data analytic approach. Data analyses occurred in three phases: (i) excerpts were grouped by Phase, Domain, and Construct of the EPIS Framework; (ii) themes within each excerpt were then identified using an inductive approach; and (iii) themes were organized into conceptually similar and parsimonious categories. Participants suggested that the biggest source of program failure was that more attention needed to be paid to Program Fit during the Implementation Phase. Participants reported concerns with the accessibility and convenience of the effort. Additional participant concerns included economic issues, community ownership, climate, staffing processes, cultural sensitivity, engagement, and trust. The implementation of health promotion programs for Black men should pay particular attention to how the intervention fits the needs, lives, and contexts of potential participants.
The in vivo effects of knockdown of long non‐coding RNA XIST on fibroid growth and gene expression
Authors: Chuang Tsai‐Der , Ton Nhu , Rysling Shawn , Khorram Omid 
Published: October 2024

AbstractThe role of long non‐coding RNAs in fibroid pathogenesis remains largely unexplored. In a previous study, we found elevated XIST (X‐inactive specific transcript) levels in fibroids, which sponged miR‐29c and miR‐200c, leading to the overexpression of their target genes. This study aimed to assess the therapeutic potential of XIST downregulation in fibroid treatment. Ovariectomized SCID (severe combined immunodeficiency) mice were implanted with fibroid tumors transduced with XIST siRNA or a control via lentivirus. After 1 month, animals were sacrificed and the xenografts were removed for further analysis. XIST knockdown reduced tumor weight by 15% and increased miR‐29c and miR‐200c expression by 3.9‐fold and 2.2‐fold, respectively. The mRNA expression of miR‐29c targets (COL3A1, TGF‐β3, CDK2, SPARC) and miR‐200c targets (CDK2, FN1, TDO2), as well as PRL, E2F1, and EZH2, was significantly decreased. Protein abundance of collagen, COL3A1, FN1, CDK2, SPARC, and EZH2 was also reduced. IHC analysis of xenograft sections using the markers of Ki67 for cell proliferation and cleaved caspase 3 for apoptosis showed decreased cell proliferation and no changes in apoptosis in the XIST knockdown xenografts. This analysis also revealed decreased collagen and E2F1 staining nuclei in the XIST knockdown xenografts. These results indicate that downregulation of XIST in fibroids has beneficial therapeutic effects, by reducing tumor growth and the expression of genes involved in cell proliferation, inflammation, and extracellular matrix regulation.
Are They Prepared? Comparing Intern Milestone Performance of Accelerated 3-Year and 4-Year Medical Graduates
Authors: Santen Sally A. , Yingling Sandra , Hogan Sean O. , Vitto Christina M. , Traba Christin M. , Strano-Paul Lisa , Robinson Alex N. , Reboli Annette C. , Leong Shou Ling , Jones Betsy G. , Gonzalez-Flores Alicia , Grinnell Megan E. , Dodson Lisa G. , Coe Catherine L. , Cangiarella Joan , Bruce Ericka L. , Richardson Judee , Hunsaker Matthew L. , Holmboe Eric S. , Park Yoon Soo 
Published: October 2024

Abstract

Purpose
Accelerated 3-year programs (A3YPs) at medical schools were developed to address student debt and mitigate workforce shortage issues. This study investigated whether medical school length (3 vs 4 years) was associated with early residency performance. The primary research question was as follows: Are the Accreditation Council for Graduate Medical Education Milestones (MS) attained by A3YP graduates comparable to graduates of traditional 4-year programs (T4YPs) at 6 and 12 months into internship?

Method
The MS data from students entering U.S. medical schools in 2021 and 2022 from the 6 largest specialties were used: emergency medicine, family medicine, internal medicine, general surgery, psychiatry, and pediatrics. Three-year and 4-year graduates were matched for analysis (2,899 matched learners: 182 in A3YPs and 2,717 in T4YPs). The study used a noninferiority study design to examine data trends between the study cohort (A3YP) and control cohort (T4YP). To account for medical school and residency program effects, the authors used cross-classified random-effects regression to account for clustering and estimate group differences.

Results
The mean Harmonized MS ratings for the midyear and end-year reporting periods showed no significant differences between the A3YP and T4YP groups (mean [SE] cross-classified coefficient = 0.01 [0.02], P = .77). Mean MS ratings across internal medicine MS for the midyear and end-year reporting periods showed no significant differences between the A3YP and T4YP groups (mean [SE] cross-classified coefficient = −0.03 [0.03], P = .31). Similarly, for family medicine, there were no statistically significant differences between the A3YP and T4YP groups (mean [SE] cross-classified coefficient = 0.01 [0.02], P = .96).

Conclusions
For the specialties studied, there were no significant differences in MS performance between 3-year and 4-year graduates at 6 and 12 months into internship. These results support comparable efficacy of A3YPs in preparing medical students for residency.
Ultrasound-Guided Double-Point Versus Single-Point Serratus Anterior Plane Block for Modified Radical Mastectomy
Authors: Xu Jianghui , Ling Dandan , Xu Qianyun , Sun Pengfei , Wei Shiyou , Gao Lingling , Lou Feifei , Zhang Jun 
Published: October 2024

Objectives:
The double-point serratus anterior plane block (SAPB) covers more area, including the axilla, than the single-point approach, potentially offering better pain relief after modified radical mastectomy (MRM). The objective of this study were to evaluate the clinical outcomes of these 2 procedures for patients treated with MRMs.

Methods:
Sixty women were randomly assigned to double- or single-point groups. Double-point received SAPB at the third and fifth ribs, single-point at the fifth rib. The primary outcome includes pain numeric rating scale (NRS) at rest and movement 24 hours postsurgery. The secondary outcomes are axilla comfort NRS, recovery quality, and adverse events.

Results:
At 24 hours postsurgery, the double-point group compared with the single-point group showed movement pain NRS of 3 (2 to 3) versus 3 (3 to 4) (P=0.011) and rest pain NRS of 1 (1 to 1) versus 2 (1 to 3) (P=0.037). The difference between them did not exceed the minimum clindically important difference (MCID). The axillary comfort NRS in the double-point group was lower than the single-point group at 6 and 12 hours postsurgery, at 1 (1 to 2) versus 2 (2 to 4) (P=0.001) and 1 (1 to 2) versus 2 (2 to 4) (P=0.01), respectively, but there were no statistically significant differences at 24 and 48 hours postsurgery. At 48 hours postsurgery, pain scores and opioid use were similar in both groups. Recovery scores, rescue analgesia timing, adverse events, and hospital stay length were similar in both groups.

Discussion:
Double-point SAPB offers wider anesthetic spread but shows no significant clinical advantage in pain or axillary comfort over single-point SAPB after MRM.
The Effect of PD-1/PD-L1 Inhibitor and Statin Combination Therapy on Overall Survival and Gastrointestinal Toxicity
Authors: Shah Jay , Caleb Urias Rivera Andres , Lee Irene Jeong-Ah , Takigawa Kei , Mathew Antony , Wu Deanna , Lu Eric , Shatila Malek , Thomas Anusha S. , Zhang Hao Chi , Altan Mehmet , Zhao Dan , Xiao Qinghuan , Wang Yinghong 
Published: October 2024

Objectives:
Immune checkpoint inhibitors (ICIs), such as programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors, have been approved to treat a variety of cancers. Recently, studies have suggested that ICIs and statins are synergistic. However, the addition of statins to ICI therapy may increase the risk of gastrointestinal immune-related adverse events (irAEs). We investigated the effect of combination therapy with PD-1 and/or L1 inhibitors and statins on overall survival and gastrointestinal irAEs.

Methods:
We reviewed the charts of patients with select cancers who received PD-1 and/or PD-L1 inhibitors and statins. The incidence of gastrointestinal irAEs and overall survival were compared with that in a matched control group of patients who received PD-1 and/or PD-L1 inhibitors without statins.

Results:
Of the 823 patients in the statin group, 707 received PD-1 inhibitors, 86 received PD-L1 inhibitors, and 30 received both. Patients taking any statins (10.8%) and those taking high-intensity statins (15.8%) had higher rates of gastrointestinal irAEs than patients not taking statins (8.7%; P=0.046 and 0.006, respectively). Compared with the nonstatin treatments, statin use was associated with improved overall survival for patients taking PD-1 inhibitors (P<0.001) and for patients with (P=0.021) and without (P<0.001) gastrointestinal irAEs.

Conclusions:
Synergism of statins with PD-1 and PD-L1 inhibitors continues to be a developing field of interest. Our data demonstrate the survival benefit of combination therapy with PD-1 and/or PD-L1 inhibitors and statins, warranting further investigation.
Donor Tissue Preservation Time Impact on Keratolimbal Allograft Outcomes
Authors: Porter Robert J. , Peretz Daniel , Alsarhani Waleed K. , Chan Clara C. , Cheung Albert Y. , Holland Edward J. 
Published: October 2024

Purpose:
This study sought to determine the effect of donor preservation time and other donor tissue factors on the clinical outcomes of keratolimbal allograft (KLAL) transplantation.

Methods:
In this retrospective chart review of patients who underwent KLAL transplantation, electronic health records were reviewed for relevant patient ocular and surgical history. Donor tissue factors were collected from donor reports. The primary outcome measure was time to epithelialization. Exclusion criteria included prior ocular surface stem cell transplantation, loss to follow-up, missing data from medical records, indication for surgery other than limbal stem cell deficiency, and early removal of KLAL tissue. Regression analysis was performed to compare time to epithelialization and donor tissue factors. Subgroup analysis was performed using the Student t test to evaluate the impact of donor preservation time on time to epithelialization.

Results:
A total of 154 eyes were identified of which 122 were included for analysis. The mean time to epithelialization was 55 days and median was 35 days. No donor tissue factors were found to affect total time to corneal epithelialization. Subgroup analysis comparing the effect of different total preservation times on time to epithelialization did not reveal any statistically significant associations.

Conclusions:
No relationship was found between time to donor tissue preservation and time to epithelialization after KLAL surgery. It appears that limbal stem cells can be safely stored for up to 9 days in corneal storage solution in hypothermic temperatures without clinical consequences.