bluuebunny/crossref_metadata_2025_split huggingface dataset:
Health care impact of lower extremity amputations in diabetes mellitus derived from Dutch insurance claims; design of the retrospective cohort study; Dutch diabetes estimate—amputation initiative (DUDE-8)
Authors: Rosien Leonie , Geurten Rose J. , Bilo Henk J. G. , Ruwaard Dirk , Gans Rijk O. B. , Oskam Jacques , van Tilburg Chantal , Elissen Arianne M. J. , van Dijk Peter R. 
Published: October 2024

Introduction:
Many individuals with diabetes mellitus (DM) experience complications that significantly impact their quality of life and life expectancy. Foot complications, arising from neuropathy, macroangiopathy, and metabolic derangements, or a combination of these factors, are a major concern. The combination of these disorders increases the risk of developing diabetic foot ulcers (DFUs), which in turn can lead to lower extremity amputations (LEAs) if not promptly and adequately treated. Globally, 80% of all nontraumatic LEAs are due to DM, and most of these were preceded by a nonhealing DFU. Studies in the Netherlands have explored the incidence of LEA in the diabetic population, reporting a range from 78 to 704 per 100 000 person-years. The current design focuses on utilizing the available all-claims data to gain valuable insights into amputation rates among individuals with DM in the Netherlands during the years 2013–2019 and develop a more comprehensive understanding of the current Dutch situation.

Methods and analyses:
In the Netherlands, all amputations are performed in hospitals, allowing for comprehensive financial claims data. The current project focuses on utilizing the available all-claims data to gain insights into yearly LEA rates among individuals with and without DM in the Netherlands. Over the period 2013–2019, various predefined analyses will be performed, including costs and outcomes. Individuals will be matched based on age, gender, and, where applicable, socioeconomic status. Depending on the research questions, additional analyses will take place on epidemiology, healthcare use, costs, and mortality rates.
Is infracolic omentectomy necessary for early-stage (FIGO I–II) borderline ovarian tumors? A protocol for systematic review and meta-analysis
Authors: Reis Rosilene J. , Medeiros Lidia R. , Reis Ricardo , Zanon Jeferson R. , Avila Renata , Souza Mileide M. 
Published: October 2024

Background:
Borderline ovarian tumors (BOTs) are reported to account for 10%–20% of all ovarian tumors. Guidelines for the surgical management of BOTs include hysterectomy with bilateral salpingo-oophorectomy, peritoneal washings, omentectomy, and multiple peritoneal biopsies. However, when omentectomy is recommended, it is unclear whether removal of a normal-appearing omentum has a therapeutic benefit.

Methods:
We will search the following databases: the Cochrane Central Register of Controlled Trials (CENTRAL), the latest issue in the Cochrane Library, PubMed, EMBASE, LILACS, SCOPUS, Web of Science and Grey literature. Randomized controlled trials (RCTs) and non-randomized studies will be included if the patients are adults (≥18 years) with BOTs in stages I–II according to International Federation of Gynaecology and Obstetrics (FIGO). The methodological assessment will be carried out by two reviewers independently of each other using Cochrane risk-of-bias tool for randomized controlled trials (RoB 2), and the risk of bias in non-randomized studies (ROBINS-I) tool for non-randomized. The search strategy is constructed using the Boolean operators “OR” and “AND,” thorough search, a combination of medical subject heading and free-text terms will be employed. The Review Manager 5.4 will be used for the meta-analysis. For time‐to‐event data, we will use the hazard ratio with a 95% confidence interval (CI). For dichotomous outcomes, we will be used to calculate the risk ratio with a 95% CI. Continuous outcomes will be presented as the weighted mean difference or standardized mean difference with 95% CI.

Results:
This review will evaluate the effects of non-infracolic omentectomy on overall survival, progression-free survival, quality of life, recurrence index and adverse events in patients with BOTs.

Conclusion:
Our results will provide clear evidence to determine whether non-infracolic omentectomy is an effective and safe intervention for early stage (FIGO I–II) BOTs, thus benefiting patients, practitioners, and policy makers.
Plasma treatment is associated with decreased brain lesion and resuscitation requirements after traumatic brain injury in a swine model of prolonged damage-control resuscitation
Authors: Jin Guang , Liggett Marjorie R. , Ho Jessie W. , Dawood Zaiba Shafik , Chtraklin Kiril , Diaz Dariel , Alam Hasan B. 
Published: October 2024

BACKGROUND
Hemorrhage and traumatic brain injury (TBI) are the leading causes of death in trauma. Future military conflicts are likely to be in austere environments, where prolonged damage-control resuscitation (p-DCR) may be required for 72 hours before evacuation. Previous studies showed that early administration of fresh frozen plasma (FFP) during p-DCR can significantly decrease the volume of resuscitation required in models of hemorrhagic shock and also provide neuroprotection after TBI. In the current study, we hypothesized that the addition of FFP to p-DCR would decrease the resuscitation requirements and improve neurological outcomes in a large animal model of combined hemorrhagic shock and TBI.

METHODS
Yorkshire swine (40–45 kg; n = 10) were subjected to TBI (controlled cortical impact) and 40% blood volume hemorrhage. After 2 hours of shock, they were randomized to either: (1) p-DCR–normal saline or (2) p-DCR–FFP (250 mL). Prolonged damage-control resuscitation targeted a systolic blood pressure of 90% of baseline, in line with Tactical Combat Casualty Care principles. At 72 hours, animals were transfused 1 U of packed red blood cells, simulating evacuation to higher echelons of care. Brain lesion size, physiologic parameters, resuscitation fluid requirements, and neurological severity score were used to compare the clinical outcomes.

RESULTS
The p-DCR–FFP group required significantly less total volume (4,540.0 ± 151.7 mL vs. 974.0 ± 167.0 mL, p < 0.01) of resuscitation to maintain the target systolic blood pressure. Fresh frozen plasma–treated animals had significantly reduced brain lesion size (4,517.0 ± 180.0 mm3 vs. 2,477.0 ± 1,191.0 mm3, p < 0.01) and showed significantly decreased functional neurologic impairment.

CONCLUSION
In this exploratory study, treatment with FFP decreased resuscitation requirements, reduced brain lesion size, and improved neurological outcomes when added to prolonged DCR in a porcine model of combined hemorrhagic shock and TBI.
Metagenomic analysis during capecitabine therapy reveals microbial chemoprotective mechanisms and predicts drug toxicity in colorectal cancer patients
Authors: Hillege Lars E. , Trepka Kai R. , Ziemons Janine , Aarnoutse Romy , Guthrie Benjamin G. H. , de Vos-Geelen Judith , Iersel Liselot Valkenburg-van , van Hellemond Irene E.G. , Baars Arnold , Vestjens Johanna H.M.J. , Penders John , Deutschbauer Adam , Atreya Chloe E. , Kidder Wesley A. , Turnbaugh Peter J. , Smidt Marjolein L. 
Published: October 2024

AbstractPurposeUnpredictable chemotherapy side effects are a major barrier to successful treatment. Cell culture and mouse experiments indicate that the gut microbiota is influenced by and influences anti-cancer drugs. However, metagenomic data from patients paired to careful side effect monitoring remains limited. Herein, we focus on the oral fluoropyrimidine capecitabine (CAP). We investigate CAP-microbiome interactions through metagenomic sequencing of longitudinal stool sampling from a cohort of advanced colorectal cancer (CRC) patients.MethodsWe established a prospective cohort study including 56 patients with advanced CRC treated with CAP monotherapy across 4 centers in the Netherlands. Stool samples and clinical questionnaires were collected at baseline, during cycle 3, and post-treatment. Metagenomic sequencing to assess microbial community structure and gene abundance was paired with transposon mutagenesis, targeted gene deletion, and media supplementation experiments. An independent US cohort was used for model validation.ResultsCAP treatment significantly altered gut microbial composition and pathway abundance, enriching for menaquinol (vitamin K2) biosynthesis genes. Transposon library screens, targeted gene deletions, and media supplementation confirmed that menaquinol biosynthesis protectsEscherichia colifrom drug toxicity. Microbial menaquinol biosynthesis genes were associated with decreased peripheral sensory neuropathy. Machine learning models trained in this cohort predicted hand-foot syndrome and dose reductions in an independent cohort.ConclusionThese results suggest treatment-associated increases in microbial vitamin biosynthesis serve a chemoprotective role for bacterial and host cells, with implications for toxicities outside the gastrointestinal tract. We provide aproof-of-conceptfor the use of microbiome profiling and machine learning to predict drug toxicities across independent cohorts. These observations provide a foundation for future human intervention studies, more in-depth mechanistic dissection in preclinical models, and extension to other cancer treatments.
Antibiotic-Mediated Plasmonic Resonance on a Novel Nanopillar Metasurface Array
Authors: Waitkus Jacob , Park JaeWoo , Ndukaife Theodore , Yang Sui , Du Ke 
Published: October 2024

AbstractThis study demonstrates a silicon nanopillar metasurface coupled with localized surface plasmon resonance (LSPR) mediated by the presence of cephalexin antibiotics in solution for biosensing applications. A facile fabrication process was developed to create the metasurface on silicon wafers with a unique resonance signature. The resulting metasurface consists of periodic nanopillars approximately 180 nm in diameter, 210 nm deep, and with a controlled edge-to-edge separation of 200 nm. These dimensions were chosen based on a finite element method simulation that was used to investigate the ideal parameters to produce the desired resonance effect in the metasurface reflection spectra. Optimization of the nanopillar surface properties and the sidewall angle allowed for replication of the simulations. This metasurface was coupled with BSA-coated gold nanospheres (BSANS) to mediate the redshift of peak resonance wavelength values, occurring only in the presence of the antibiotic linker. The device fabricated herein exhibits a significant 22 nm wavelength shift resulting from changes to the local refractive index in the presence of the BSANS-antibiotic coupling. Further enhancement of the binding events is promoted by the LSPR hot spots formed between the nanoparticles and the metasurface allowing for sensitive and real-time detection.
Noninvasive Assessment of Temporal Dynamics in Sympathetic and Parasympathetic Baroreflex Responses
Authors: Suarez-Roca Heberto , Mamoun Negmeldeen , Mathew Joseph P , Bortsov Andrey V 
Published: October 2024

ABSTRACTBackgroundThe baroreflex system is crucial for cardiovascular regulation and autonomic homeostasis. A comprehensive assessment requires understanding the simultaneous temporal dynamics of its multiple functional branches, which traditional methods often overlook.ObjectiveTo develop and validate a noninvasive method for simultaneously assessing the temporal dynamics of sympathetic and parasympathetic baroreflexes using pulse contour analysis and the sequence method.MethodsBeat-to-beat blood pressure and ECG recordings were analyzed from 55 preoperative cardiothoracic surgery patients in the supine position and 21 subjects from the EUROBAVAR dataset in both supine and standing positions. Systolic arterial pressure (SAP), interbeat interval (IBI), cardiac output (CO), myocardial contraction (dP/dtmax), and systemic vascular resistance (SVR) were estimated using pulse contour analysis. Baroreflex sensitivity (BRS) was calculated via the sequence method and correlated with hemodynamic and heart rate variability (HRV) parameters.ResultsParasympathetic BRS for IBI was correlated with the root mean square of successive differences of ECG RR intervals (RMSSD-HRV) at 0-beat delay. Sympathetic BRS for SVR strongly correlated with SVR, CO, and RMSSD-HRV, particularly at 3-beat delay, and was uniquely associated with SAP at 1-beat delay. Sympathetic BRS for dP/dtmaxcorrelated with dP/dtmaxat 1-beat delay. In contrast, BRS for CO correlated with CO and SVR at 0- and 3-beat delays. Postural changes mainly affected parasympathetically-mediated BRS for IBI and, to a lesser extent, the sympathetic vascular and myocardial branches.ConclusionsThis method effectively captures multiple baroreflex responses and their temporal dynamics, revealing distinct autonomic mechanisms and the impact of postural changes. Further validation is warranted.
A European clinical practice guideline on pain, agitation, delirium, and iatrogenic withdrawal syndrome management in critically ill children: A protocol
Authors: MacDonald Ibo , Cavin-Trombert Alexia , Jaques Cécile , Amigoni Angela , Ramelet Anne-Sylvie 
Published: October 2024

AbstractIntroductionIn pediatric intensive care units, pain, sedation, delirium, and iatrogenic withdrawal syndrome must be managed as interrelated conditions. Existing clinical practice guidelines have some methodological limitations and are not readily transferrable to the European context without adaptation. This protocol describes the methods for developing a high-quality, and the first patient- and family-informed European guideline for managing pain, sedation, delirium and iatrogenic withdrawal syndrome.MethodsThe guideline will be developed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) - ADOLOPEMENT approach, engaging clinical experts and patients and families in the development process. It will consist of seven phases: 1) Set-up – establishing three groups for guideline development: i) steering committee, ii) development panel (experts and patient/family partners from across Europe), and iii) patient and family advisory panel, and scoping to determine population, conditions, purpose, and users of the guideline; 2) Preparation – voting on summary recommendations, prioritizing research questions and outcomes, and matching research questions with existing recommendations; 3) Search and retrieval of evidence – using three search approaches to develop search strategies to find evidence, conducting individualized searches for each summary recommendation and new research question, selecting evidence, study appraisal, and initial data extraction; 4) Evidence synthesis – summarizing evidence in evidence profiles and summary of evidence tables, and conducting panel surveys of current practice when evidence is absent; 5) Development – drafting recommendations, voting on and approving them, and developing accompanying materials; 6) Review – conducting internal, society-level, and external international expert reviews; and 7) Issue – publishing the guideline.DiscussionThis protocol ensures a transparent process follows the GRADE approach for guideline development, leading to a high-quality, trustworthy, and credible guideline for managing pain, sedation, delirium and iatrogenic withdrawal syndrome in critically ill children. Tailored to the European context for healthcare professionals.Registration:Practice guideline REgistration for transPAREncy (PREPARE) registration number PREPARE-2024CN859
Cross-species vs species-specific models for protein melting temperature prediction
Authors: López Sebastián García , Salomon Jesper , Boomsma Wouter 
Published: October 2024

AbstractProtein melting temperatures are important proxies for stability, and frequently probed in protein engineering campaigns, including enzyme discovery, protein optimization, and de novo protein design. With the emergence of large datasets of melting temperatures for diverse natural proteins, it has become possible to train models to predict this quantity, and the literature has reported impressive performance values in terms of Spearman rho. The high correlation scores suggest that it should be possible to reliably predict melting temperature changes in engineered variants, to design de novo thermostable proteins, and identifying naturally thermostable proteins. However, in practice, results in this setting are often disappointing. In this paper, we explore the discrepancy between these two settings. We show that Spearman rho over cross-species data gives an overly optimistic impression of prediction performance, and that models trained on species-specific data often outperform larger cross-species models. Finally, we explore a number of strategies for improving performance, demonstrating a performance boost of 1.5 degree RMSE with fairly simple means.
Invasive mammals disrupt native dung beetle community coexistence
Authors: Akashi Ryo , Yamaguchi Ryo , Nakaoka Shinji 
Published: October 2024

AbstractBiological invasions are among the major drivers of biodiversity and are increasing worldwide. Among the invasive species, mammals have a particularly profound impact on native ecosystems. As primary decomposers of mammalian feces, dung beetles are critical in ecosystem functioning, and their community structure is closely linked to their services. However, the introduction of invasive mammals threatens these beetles and potentially disrupts their ecosystem services. Therefore, it is necessary to understand the resulting changes in communities. We developed a novel population dynamics model focusing on the interactions among mammals, feces, and dung beetles. Our results indicate that such invasions increase the risk of extinction of specialist dung beetles that cannot utilize the feces of invasive mammals. The risk of extinction is particularly high when generalist dung beetles show a preference for native feces, leading to intensified interspecific competition for resources. Additionally, the extinction risk of specialist dung beetles increases when invasive mammals display irruptive population dynamics. In conclusion, our findings demonstrated that non-native mammalian invasions disrupt the coexistence of native dung beetle communities, potentially leading to losses in biodiversity and ecosystem function. These risks should be considered in future empirical studies to evaluate the impact of invasive mammals on dung beetle communities.
Green synthesized silver nanoparticles fromMoringa: Potential for preventative treatment of SARS-CoV-2 contaminated water
Authors: Bello Adebayo J. , Ebunoluwa Omorilewa B. , Ayorinde Rukayat O. , Onyepeju Nneka , Shaibu Joseph O. , Adewole Adeniyi R. , Adewole Abeebat O. , Adedeji Olusegun , Akinnusi Ololade O. , Oladapo Olajumoke B. , Popoola Temitope S. , Arotiba Oluwamodupe M. , Minari Joseph B. , Adams Luqman A. , Okpuzor Joy , Shittu Mujeeb O. 
Published: October 2024

AbstractBiogenic silver nanoparticles have been reported as good antimicrobial candidates. Thus, this study investigated the antiviral activity of silver nanoparticles synthesized against SARS-CoV-2. The silver nanoparticle was biosynthesized using leave extracts ofMoringa oleifera(AgNPmo) and characterized using UV-Vis spectroscopy, Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy, and X-ray diffractometry (XRD). The AgNPmo was first tested on clinical bacterial isolates,Pseudomonas aeruginosa(ATTC 154423) andStaphylococcus aureus(ATTC 209233), to ascertain its antimicrobial potential. In-vitro studies were also conducted to determine the cytotoxicity effect of AgNPmo on Vero cells. The efficacy and concentration of AgNPmo against SARS-CoV-2 were evaluated using a qPCR assay in a dose-dependent manner. The results demonstrated the successful biosynthesis and characterization of AgNPmo and its efficacy against the bacterial isolates. The AgNPmo showed low toxicity on the Vero cells. The IC50from the cytotoxicity assay demonstrated the antiviral activity of the AgNPmo on the SARS-CoV-2 virus, leading to an increase in the Cycle threshold values, notably at 48 hours of incubation and at low concentrations. The results showed that the biogenic AgNPmo synthesized was cost-effective and showed both antimicrobial and antiviral potentials. These findings suggest that the nanoparticles could be a promising alternative for combating SARS-CoV-2, especially for water purification and preventing transmission.
Real-time high-resolution microscopy reveals how single-cell lysis shapes biofilm matrix morphogenesis
Authors: Squyres Georgia R. , Newman Dianne K. 
Published: October 2024

SummaryDuring development, multiscale patterning requires that cells organize their behavior in space and time. Bacteria in biofilms must similarly dynamically pattern their behavior with a simpler toolkit. Like in eukaryotes, morphogenesis of the extracellular matrix is essential for biofilm development, but how it is patterned has remained unclear. Here, we explain how the architecture of eDNA, a key matrix component, is controlled by single cell lysis events duringPseudomonas aeruginosabiofilm development. We extend single-cell imaging methods to capture complete biofilm development, characterizing the stages of biofilm development and visualizing eDNA matrix morphogenesis. Mapping the spatiotemporal distribution of single cell lysis events reveals that cell lysis is restricted to a specific biofilm zone. Simulations indicate that this patterning couples cell lysis to growth, more uniformly distributing eDNA throughout the biofilm. Finally, we find that patterning of cell lysis is organized by nutrient gradients that act as positioning cues.
A systematic review of aperiodic neural activity in clinical investigations
Authors: Donoghue Thomas 
Published: October 2024

AbstractIn the study of neuro-electrophysiological recordings, aperiodic neural activity – activity with no characteristic frequency – has increasingly become a common feature of study. This interest has rapidly extended to clinical work, with many reports investigating aperiodic activity from patients from a broad range of clinical disorders. This work typically seeks to evaluate aperiodic activity as a putative biomarker relating to diagnosis or treatment response, and/or as a potential marker of underlying physiological activity. There is thus far no clear consensus on if and how aperiodic neural activity relates to clinical disorders, nor on the best practices for how to study it in clinical research. To address this, this systematic literature review, following PRISMA guidelines, examines reports of aperiodic activity in electrophysiological recordings with human patients with psychiatric and/or neurological disorders, finding 143 reports across 35 distinct disorders. Reports within and across disorders are summarized to evaluate current findings and examine what can be learned as pertains to the analysis, interpretations, and overall utility of aperiodic neural activity in clinical investigations. Aperiodic activity is commonly reported to relate to clinical diagnoses, with 31 of 35 disorders reporting a significant effect in diagnostic and/or treatment related studies. However, there is variation in the consistency of results across disorders, with the heterogeneity of patient groups, disease etiologies, and treatment status arising as common themes across different disorders. Overall, the current variability of results, potentially confounding covariates, and limitations in current understanding of aperiodic activity suggests further work is needed before aperiodic activity can be established as a potential biomarker and/or marker of underlying pathological physiology. Finally, a series of recommendations are proposed, based on the findings, limitations, and key discussion topics of the current literature to assist with guiding productive future work on the clinical utility of studying aperiodic neural activity.Project RepositoryThe project repository contains code & data related to this project:https://github.com/TomDonoghue/AperiodicClinical