bluuebunny/crossref_metadata_2025 huggingface dataset:
The evolution of the coronal loop structure due to the phase mixing of high and low-frequency Alfvén waves
Authors: Callingham H , De Moortel I , Pagano P
Published: October 2024

Coronal loops are known to host Alfvén waves propagating in the corona from the lower layers of the solar atmosphere and because of their internal structure, phase mixing is likely to occur. The structure of the coronal loop could be significantly affected by the thermodynamic feedback of the heating generated by phase mixing. However, this phenomenon can be sensitive to the period of the propagating Alfvén waves due to how short period waves can be easily dissipated and the way long-period waves may accumulate considerable energy in resonating coronal loops. Using the Lare2d code, a coronal loop model of a field-aligned thermodynamic equilibrium and a cross-field background heating profile is created, with an additional forcing term added to drive Alfvén waves with coronal amplitudes between $5{\!-\!}30 \, \mathrm{km} \, \mathrm{s}^{-1}$. We show that high-frequency waves can generate heating corresponding to a ${\sim} 10~{{\ \rm per\ cent}}$ increase of the initial coronal shell temperature, chromospheric upflows of up to  $0.6 \, \mathrm{km} \, \mathrm{s}^{-1}$ and a coronal shell mass increase of ${\sim} 15~{{\ \rm per\ cent}}$. These changes are sufficient to alter and maintain a new coronal loop density structure, broadening the region where efficient phase mixing (and therefore heating) occurs. In contrast, low-frequency waves are unable to be effectively dissipated, resulting in minimal changes to the loop structure. We see little evidence of wave energy accumulation in the corona and are unable to conclude that the dissipation of low-frequency Alfvén waves can be an effective heating mechanism in coronal loops in the setup used in this study.
gutMGene v2.0: an updated comprehensive database for target genes of gut microbes and microbial metabolites
Authors: Qi Changlu , He Guoyou , Qian Kai , Guan Siyuan , Li Zhaohai , Liang Shuang , Liu Juntao , Ke Xianzhe , Zhang Sainan , Lu Minke , Cheng Liang , Zhang Xue
Published: October 2024

The gut microbiota is essential for various physiological functions in the host, primarily through the metabolites it produces. To support researchers in uncovering how gut microbiota contributes to host homeostasis, we launched the gutMGene database in 2022. In this updated version, we conducted an extensive review of previous papers and incorporated new papers to extract associations among gut microbes, their metabolites, and host genes, carefully classifying these as causal or correlational. Additionally, we performed metabolic reconstructions for representative gut microbial genomes from both human and mouse. gutMGene v2.0 features an upgraded web interface, providing users with improved accessibility and functionality. This upgraded version is freely available at http://bio-computing.hrbmu.edu.cn/gutmgene. We believe that this new version will greatly advance research in the gut microbiota field by offering a comprehensive resource.
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

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

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

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

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 >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

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

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

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.
Evaluation of durum and hard red spring wheat panels for sensitivity to necrotrophic effectors produced by Parastagonospora nodorum
Authors: Szabo-Hever Agnes , Running Katherine , Seneviratne Sudeshi , Singh Gurminder , Zhang Zengcui , Peters Haugrud Amanda , Maccaferri Marco , Tuberosa Roberto , Xu Steven S. , Friesen Timothy L. , Faris Justin D.
Published: October 2024

Septoria nodorum blotch is an important disease of both durum and hard red spring wheat (HRSW) worldwide. The disease is caused by the necrotrophic fungal pathogen Parastagonospora nodorum when compatible gene-for-gene interactions occur between pathogen-produced necrotrophic effectors (NEs) and corresponding host sensitivity genes. To date, nine sensitivity gene-NE interactions have been identified, but there is little information available regarding their overall frequency in durum and HRSW. Here, we infiltrated a global HRSW panel (HRSWP) and the Global Durum Panel (GDP) with P. nodorum NEs SnToxA, SnTox1, SnTox267, SnTox3, and SnTox5. Frequencies of sensitivity to SnTox1 and SnTox5 were higher in durum compared to HRSW and vice versa for SnTox267 and SnTox3. Strong associations for the known sensitivity loci Tsn1, Snn1, Snn2, Snn3, Snn5, and Snn7 along with potentially novel sensitivity loci on chromosome arms 7DS and 3BL associated with SnToxA and SnTox267, respectively, were identified in the HRSWP. In the GDP, Snn1, Snn3, and Snn5 were identified along with novel loci associated with sensitivity to SnTox267 on chromosome arms 2AS, 2AL, and 6AS and with SnTox5 sensitivity on 2BS and 7BL. These results reveal additional NE sensitivity loci beyond those previously described demonstrating a higher level of genetic complexity of the wheat-P. nodorum system than previously thought. Knowledge regarding the prevalence and genomic locations of SNB susceptibility genes in HRSW and durum will prove useful for developing efficient breeding strategies and improving varieties for SNB resistance.
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

The 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

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.
A Century of Surgical Quality: Origins, Evolution, and Future Directions
Authors: Hoyt David B. , Ko Clifford Y. , Opelka Frank G.
Published: October 2024

Over a century has passed since Ernst A. Codman’s pioneering call for surgeons to take open responsibility for patient care, a concept integral to the emergence and leadership of the American College of Surgeons (ACS). Codman’s End Result Idea, originating in the early 20th century, laid the groundwork for professional responsibility and accountability in surgical practice, catalyzing the formation of the ACS. His innovative use of the “end result” technique at Massachusetts General Hospital highlighted significant variability in surgical outcomes, spurring debates on specialization and accountability. The ACS, under John Bowman’s leadership, aimed to ensure optimal care through defined standards and verification mechanisms. Codman’s Bone Sarcoma Registry, initiated in 1920, marked an early attempt at quality assessment and improvement through data collection. Despite facing resistance, Codman’s vision laid the foundation for modern quality initiatives in surgical care. ACS programs, spanning trauma care to cancer treatment and beyond, have significantly enhanced patient outcomes while reducing costs. Looking forward, advancing surgical quality requires measuring quality, leveraging trusted data, embracing change management, fostering collaboration, and empowering specialists. The future of surgical care depends on collective efforts to uphold standards that ensure optimal care for all.
Improved Cardiac Rehabilitation Referral Rates following Coronary Artery Bypass Graft and Heart Valve Replacement in an Inner-City Veteran Population
Authors: Gopal Akash , Detroyer Ian , de Alcantara Lima Neiberg , Ramappa Preeti
Published: October 2024

Cardiac rehabilitation (CR) is underutilized due to various barriers, despite its known benefits in decreasing 5-year mortality after cardiac surgery. The authors initiated a quality improvement project to identify barriers and enhance CR referral rates and participation. The team conducted a retrospective review of cardiac surgery patients from 2015 to 2022 at the Detroit Veterans Affairs. Phase 1 covered 2015–2017 (preintervention), phase 2 was the intervention period, and phase 3 covered 2018–2022 (postintervention). Appropriate CR referral was defined as within 6 months postevent. Referral rates and 1-year post-op hospitalization were assessed. Group 1 (2015–2017) had 54 male patients, 44% Black, 89% hypertensive, with a 22% CR referral rate. Group 2 (2018–2022) had 98 male patients, 64% Caucasian, mean age 73 years, with a 36% CR referral rate postintervention (P = 0.0018). One-year hospitalization decreased from 26% to 13% (P = 0.20). CR is still an underutilized tool. Provider education and complete funding of CR can improve referral rates and participation.
Rapid Pleurodesis in Patients With Chronic Noninfectious Pleural Effusion
Authors: Pu Chan Yeu , Avendano Camilo A. , Durant Makayla , Ospina-Delgado Daniel , Burbano Alma V. , Swenson Kai E. , Beattie Jason , Parikh Mihir , Majid Adnan
Published: October 2024

Background:

Small cohort studies have shown rapid pleurodesis protocol's (RPP) effectiveness and capacity to expedite pleurodesis for malignant pleural effusion (MPE). This study intends to evaluate the effectiveness of the RPP in inducing pleurodesis in patients with pleural effusions from either malignant or benign etiologies.

Methods:

In this single-center, retrospective cohort study spanning 2 decades, we assessed patients with recurrent symptomatic chronic noninfectious pleural effusion, both benign and malignant. Post-RPP, chest tubes were removed when fluid output dropped below 150 mL/d, and patients were discharged with daily indwelling pleural catheter (IPC) drainage. Exclusion criteria included nonexpandable lung and active pleural infection. Treatment success was defined as IPC removal on reduced output (<50 mL) on 3 consecutive drainages and radiologic effusion resolution. Recurrence was defined as the occurrence of pleural effusion requiring additional pleural procedures postsuccess. Duration outcome was expressed as median with IPC placement as time zero.

Results:

Of the 210 patients studied, 72% had MPE, and 28% had benign effusions. The median hospital stay was 4 days post-RPP. Treatment was successful in 177 (84%) patients within a median of 12 days, with no significant differences between MPE and benign cases. Nine patients (5%) experienced recurrence within a median of 152 days. Complications included hemothorax in 4 (1.9%) and empyema in 2 (1%). The thirty-day mortality rate was 9%, with a median survival time of 245 days postprocedure.

Conclusion:

The RPP combines the benefit of chemical pleurodesis and IPC and appears to be a reasonable option for patients with recurrent and symptomatic pleural effusion.
Correlation between gut microbiota and pancreatitis: a bidirectional Mendelian randomization
Authors: Nan Boyuan , Jin Luyuan , Wang Tianze , Long Chao , Zhao Hao , Wang Chunhui , Zhang Wei
Published: October 2024

Objective

The causative role of gut microbiota in pancreatitis remains unknown. This study aimed to investigate potential causal associations between gut microbiota and pancreatitis, using bidirectional Mendelian randomization (MR) analysis.

Methods

We analyzed genome-wide association study (GWAS) summary statistics for gut microbiota (211 taxa from gut microbiota, n = 18 340) and two types of pancreatitis, namely acute pancreatitis (AP, 5509 cases and 301 383 controls) and chronic pancreatitis (CP, 3002 cases and 301 383 controls). A reverse MR analysis was also performed to assess the possibility of reverse causation.

Results

Nine features (one family + eight genera) showed a causal association with AP. According to inverse-variance weighted (IVW) estimates, phylum Firmicutes (P = 4.10 × 10−2), genus Erysipelatoclostridium (P = 4.80 × 10−2), genus Flavonifractor (P = 4.10 × 10−2), genus Methanobrevibacter (P = 3.40 × 10−2), and genus Prevotella9 (P = 4.60 × 10−2) were found to have a protective effect on AP. Additionally, genus Eubacteriumeligensgroup (P = 4.10 × 10−2), genus Eubacteriumfissicatenagroup (P = 4.00 × 10−3), genus Coprococcus3 (P = 4.10 × 10−2), and genus Haemophilus (P = 4.60 × 10−2) exhibited a positive correlation with AP. Four features (two families + two genera) were causally associated with CP. IVW results also confirmed that family Clostridiaceae1 (P = 3.30 × 10−2), genus LachnospiraceaeFCS020group (P = 4.60 × 10−2), and genus Prevotella9 (P = 1.90 × 10−2) were protective factors for CP, whereas the presence of family Victivallaceae (P = 2.60 × 10−2) correlated with CP risk. No causal effects of pancreatitis (AP or CP) on these gut microbiota taxa were found in the reverse MR analysis.

Conclusion

This study confirms a potential causal relationship between gut microbiota and pancreatitis, highlighting the gut microbiota-pancreas axis in the pathogenesis of pancreatitis.
Predictive value of early-stage postoperative albumin–bilirubin grade on the overall survival of hepatocellular carcinoma patients undergoing resection
Authors: Pan Zheng , Ye Yan-Shuo , Wang Zhan-Peng , Li Wei
Published: October 2024

Objectives

The albumin–bilirubin (ALBI) and ΔALBI grades have attracted substantial attention for their ability to predict the overall survival (OS) of patients with hepatocellular carcinoma (HCC). This retrospective study aimed to evaluate the predictive value of the ALBI grade at different time points for the OS of patients with HCC who underwent surgical resection.

Methods

The clinical data of patients with HCC who underwent radical resection in our hospital were collected and analyzed. The survival rate was analyzed using the Kaplan–Meier method and log-rank test. The risk factors influencing OS were identified via univariate and multivariate Cox regression analyses.

Results

A total of 104 patients with HCC were included in this study. The 1-, 3-, and 5-year OS rates of these patients were 91.3%, 64.0%, and 60.2%, respectively. The OS rates were significantly higher in patients with early-stage postoperative ALBI grade 2 than in those with grade 3 (P < 0.001); however, the preoperative ALBI grade, later-stage postoperative ALBI grade, ΔALBI grade (early stage), or ΔALBI grade (later stage) did not affect the OS rate. Furthermore, resection of ≥3 Couinaud liver segments [hazard ratio (HR) = 4.74; 95% confidence interval (CI), 2.32–9.67; P < 0.001], occurrence of postoperative complications (HR = 2.95; 95% CI, 1.38–6.31; P = 0.005), and early-stage postoperative ALBI grade 3 (HR = 2.50; 95% CI, 1.18–5.31; P = 0.02) were identified as independent risk factors for the OS of patients with HCC.

Conclusion

Early-stage postoperative ALBI grade can be used to predict the OS of patients with HCC who have undergone radical hepatectomy. Early-stage postoperative ALBI grade 3, resection of ≥3 Couinaud liver segments, and occurrence of postoperative complications are independent risk factors affecting the OS of these patients.
Investigating the Risk Factors Associated With Acute Neurologic Dysfunction in Pediatric Hyperglycemic Emergencies on Transport
Authors: Scollay Grant , Cantor Zach , Fraser Douglas D. , MacDonald Russell , McGahern Candice , Reddy Deepti , Webster Richard J. , Alnaji Fuad
Published: October 2024

Objective

This study aims to identify key characteristics of hyperglycemic emergencies in pediatric patients and those at risk for acute neurologic dysfunction during transport.

Methods

We conducted a retrospective chart review of pediatric patients during interfacility transport by Ornge, Ontario's critical care transport service, from January 1, 2009, to December 31, 2019. Data were extracted from electronic patient care records and included demographic, clinical, and transport-specific variables. Two multiple logistic regression models were utilized to analyze associations between predictor variables and neurologic dysfunction (GCS, <14).

Results

Of the 399 patients included, 24% (n = 95) had a GCS score of <14. Patients with a GCS score of <14 were more acidotic compared with those with a GCS score of ≥14 (median pH, 6.9 [IQR, 6.8–7.1] vs median, pH 7.0 [IQR, 1.0–7.2]; P < 0.001). Higher median corrected sodium for glucose values were observed in patients with a GCS score of <14 compared to those with a GCS score of ≥14 (145.7 mmol/L [IQR, 140.6–149.9 mmol/L] vs 141.7 mmol/L [IQR, 138.3–146.4 mmol/L]; P < 0.001). Multiple logistic regression identified younger age (aOR, 0.91; 95% CI, 0.84–0.98; P = 0.01), severe acidosis (pH <7.10; aOR, 3.56; 95% CI, 1.33–11.62; P = 0.02), and higher creatinine (aOR, 1.01; 95% CI, 1.01–1.02; P < 0.001) as risk factors for acute neurologic dysfunction.

Conclusions

Our findings reveal associations between acute neurologic dysfunction, younger age, severe acidosis, and elevated corrected sodium for glucose values in pediatric hyperglycemic emergencies during transport. Education and adherence to guidelines are recommended to improve outcomes in this population.
Local Supports to Break the Cycle: A Description of Intersectional Interventions to Address Adverse Childhood Experiences and Drug Overdose
Authors: Myrick Amie C. , Adams Camille A. , Cremer Laura J. , Filion Nicole , Haddad Stephanie , Snyder Caroline , Wisdom April
Published: October 2024

Context:

Adverse childhood experiences (ACEs), substance use disorders (SUDs), and overdose are interconnected issues impacting individuals and communities at multiple levels of the social ecology and across generations. Few studies describe approaches that intentionally and simultaneously address these issues.

Program:

This paper examines activities of 15 sites across the country that were designed to simultaneously prevent ACEs, SUD, and overdose. This paper describes the work at the intersection as well as gaps and opportunities. Describing ways to implement intersectional programming may assist other organizations in taking similar steps in their communities.

Implementation:

From December 2020 through July 15, 2023, funded sites received technical assistance from the National Association of County and City Health Officials and the Centers for Disease Control and Prevention for 18 months to support the implementation, adaptation, and/or expansion of evidence-based programs to address ACEs, SUD, and overdose.

Evaluation:

Activities were coded to identify intersectional interventions that addressed ACEs, SUD, and overdose. Most of the ACEs prevention strategies and overdose prevention priority areas/guiding principles from which communities could choose were represented. Most activities were implemented with caregivers and families and addressed ACEs through interventions to lessen harm or to promote social norms. Primary prevention and coordination of resources were the most used overdose prevention priority area/guiding principle.

Discussion:

It is possible to address the intersection of ACEs, SUD, and overdose on a local level. Opportunities to further address the intersection include incorporating more secondary and tertiary prevention strategies, expanding economic supports, and increasing the work focused on equity.
Multisensory sensitivity in relation to pain: a scoping review of terminology and assessment
Authors: Dunne Harper , Frey-Law Laura A.
Published: October 2024

Chronic pain is a debilitating health problem affecting 20 million Americans annually. Most patients with chronic pain report negative impacts on daily function and quality of life, which can result in devastating emotional and financial stress. Although the causes of chronic pain remain elusive, there is increasing interest in sensitivity to everyday sensory stimuli as it relates to chronic pain, potentially serving as an indirect marker of altered central nervous system sensory processing. However, sensitivity to multiple sensory inputs, eg, bright lights, certain fabrics, loud noises, etc, is described using multiple terminologies. The lack of a common vocabulary makes it difficult to find and summarize related discoveries, potentially inhibiting scientific progress. Thus, the purpose of this scoping review was to identify and characterize the terminology used in publications assessing some form of multisensory sensitivity as it relates to pain (eg, a pain cohort or pain sensitivity). Our review of 6 databases (PubMed, Scopus, Embase, CINAHL, PsycINFO+, and Cochrane) comprehensively cataloged peer-reviewed studies published through March 2023 in this domain. Of 12,841 possible studies identified, 92 met all inclusion criteria, with over 80% being published in the last decade. A wide range of terminology has been used for this construct, likely in part a result of the many different professional disciplines represented. These results provide valuable insights for future development of a standardized vocabulary and serve as a resource to aid future investigators of multisensory sensitivity and pain in their study design.
Internal regulation between constitutively expressed T cell co-inhibitory receptors BTLA and CD5 and tolerance in recent thymic emigrants
Authors: Adegoke Adeolu O. , Thangavelu Govindarajan , Chou Ting-Fang , Petersen Marcos I. , Kakugawa Kiyokazu , May Julia F. , Joannou Kevin , Wang Qingyang , Ellestad Kristofor K. , Boon Louis , Bretscher Peter A. , Cheroutre Hilde , Kronenberg Mitchell , Baldwin Troy A. , Anderson Colin C.
Published: October 2024

Immunologic self-tolerance involves signals from co-inhibitory receptors. Several T cell co-inhibitors, including PD-1, are expressed upon activation, whereas CD5 and BTLA are expressed constitutively. The relationship between constitutively expressed co-inhibitors and when they are needed is unknown. Deletion of
Btla
demonstrated BTLA regulates CD5 expression. Loss of BTLA signals, but not signalling by its ligand, HVEM, leads to increased CD5 expression. Higher CD5 expression set during thymic selection is associated with increased self-recognition, suggesting that BTLA might be needed early to establish self-tolerance. We found that BTLA and PD-1 were needed post-thymic selection in recent thymic emigrants (RTE). RTE lacking BTLA caused a CD4 T cell and MHC class II dependent multi-organ autoimmune disease. Together, our findings identify a negative regulatory pathway between two constitutively expressed co-inhibitors, calibrating their expression. Expression of constitutive and induced co-inhibitory receptors is needed early to establish tolerance in the periphery for RTE.
A new sauropod dinosaur hindlimb from the Lower Cretaceous Wessex Formation, Isle of Wight, UK
Authors: Higgins Robert R. , Mannion Philip D. , Barrett Paul M. , Upchurch Paul
Published: October 2024

The Barremian-aged Wessex Formation of the Isle of Wight, UK, offers a globally significant glimpse into the sauropod dinosaur faunas of the early Cretaceous. These deposits have yielded specimens of several neosauropod lineages, such as rebbachisaurids, titanosauriforms (including some of the earliest titanosaur remains), and possible flagellicaudatans. Here, we report an undescribed sauropod partial hindlimb from the Wessex Formation (NHMUK PV R16500) and analyse its phylogenetic affinities. This hindlimb preserves the left tibia, astragalus and pes, lacking only a few phalanges. NHMUK PV R16500 can be diagnosed based on two autapomorphies: an unusually high distal end to midshaft transverse width ratio in metatarsals III and IV, and the presence of small bump-like projections located in the centre of the proximal articular surfaces of the unguals of pedal digits I and II. The phylogenetic affinities of NHMUK PV R16500 are uncertain: although our analyses recover it as an early-branching somphospondylan, a single character change moves it to close to Flagellicaudata when extended implied weighting is applied. The possibility of flagellicaudatan affinities for NHMUK PV R16500 implies a potential ghost lineage that survived the Jurassic/Cretaceous boundary; however, we present evidence that the somphospondylan position is more probable and should be preferred.
A mathematical model for pancreatic cancer during intraepithelial neoplasia
Authors: Briones-Andrade Joshua , Ramírez-Santiago Guillermo , Romero-Arias J. Roberto
Published: October 2024

Cancer is the result of complex interactions of intrinsic and extrinsic cell processes, which promote sustained proliferation, resistance to apoptosis, reprogramming and reorganization. The evolution of any type of cancer emerges from the role of the microenvironmental conditions and their impact of some molecular complexes on certain signalling pathways. The understanding of the early onset of cancer requires a multiscale analysis of the cellular microenvironment. In this paper, we analyse a qualitative multiscale model of pancreatic adenocarcinoma by modelling the cellular microenvironment through elastic cell interactions and their intercellular communication mechanisms, such as growth factors and cytokines. We focus on the low-grade dysplasia (PanIN 1) and moderate dysplasia (PanIN 2) stages of pancreatic adenocarcinoma. To this end, we propose a gene-regulatory network associated with the processes of proliferation and apoptosis of pancreatic cells and its kinetics in terms of delayed differential equations to mimic cell development. Likewise, we couple the cell cycle with the spatial distribution of cells and the transport of growth factors to show that the adenocarcinoma evolution is triggered by inflammatory processes. We show that the oncogene RAS may be an important target for developing anti-inflammatory strategies that limit the emergence of more aggressive adenocarcinomas.