bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Multi-institutional Analysis of a Textbook Outcome Among Patients Undergoing Microvascular Breast Reconstruction
Authors: Shammas Ronnie L. , Hassan Abbas M. , Sergesketter Amanda R. , Berlin Nicholas L. , Mirza Humza N. , Guzman Natalie M. , Naga Hani I. , Vingan Perri , Govande Janhavi G. , Silverstein Max L. , Momeni Arash , Sisk Geoffroy C. , Largo Rene D. , Momoh Adeyiza O. , Nelson Jonas A. , Matros Evan , Phillips Brett T. 
Published: June 2024

Background
Individual outcomes may not accurately reflect the quality of perioperative care. Textbook outcomes (TOs) are composite metrics that provide a comprehensive evaluation of hospital performance and surgical quality. This study aimed to investigate the prevalence and predictors of TOs in a multi-institutional cohort of patients who underwent breast reconstruction with deep inferior epigastric artery perforator flaps.

Methods
For autologous reconstruction, a TO was previously defined as a procedure without intraoperative complications, reoperation, infection requiring intravenous antibiotics, readmission, mortality, systemic complications, operative duration ≤12 hours for bilateral and ≤10 hours for unilateral/stacked reconstruction, and length of stay (LOS) ≤5 days. We investigated associations between patient-level factors and achieving a TO using multivariable regression analysis.

Results
Of 1000 patients, most (73.2%) met a TO. The most common reasons for deviation from a TO were reoperation (9.6%), prolonged operative time (9.5%), and prolonged LOS (9.2%). On univariate analysis, tobacco use, obesity, widowed/divorced marital status, and contralateral prophylactic mastectomy or bilateral reconstruction were associated with a lower likelihood of TOs (P < 0.05). After adjustment, bilateral prophylactic mastectomy (odds ratio [OR], 5.71; P = 0.029) and hormonal therapy (OR, 1.53; P = 0.050) were associated with a higher likelihood of TOs; higher body mass index (OR, 0.91; P = <0.001) was associated with a lower likelihood.

Conclusion
Approximately 30% of patients did not achieve a TO, and the likelihood of achieving a TO was influenced by patient and procedural factors. Future studies should investigate how this metric may be used to evaluate patient and hospital-level performance to improve the quality of care in reconstructive surgery.
The Fisher Subunit Anatomical Approach for Cleft Lip Revisions
Authors: Galarza Laura I. , Sudduth Jack D. , Rose Alexandra M. , Moss Clayton A. , Humphries Laura S. , Hoppe Ian C. 
Published: June 2024

Abstract
Many techniques exist to reapproximate a cleft lip but can leave unsatisfactory results with nonanatomic scars and a short upper lip, creating a need for revision. Many revisions focus on adjacent tissue transfers and realignment of landmarks, but in the senior authors' experience, recreating the defect and utilizing the Fisher repair for revision have led to aesthetically pleasing results and less noticeable scars. A database was collected that included all cleft lip revisions performed at a large, comprehensive children's hospital from October 2018 to July 2021. Inclusion criteria included any cleft patient with a cleft lip revision performed by two craniofacial surgeons. Data collected included sex, characteristics of the cleft lip, age at initial and index repair, type of initial repair, previous revisions, type of revision with any additional tissue rearrangement, and any nose repair. Sixty-five patients were included in the study for analysis. The type of initial repair was known in sixty-four cases (98%), and fifty-four were Millard repairs (83%). Twenty-two patients (33%) had a previous revision prior to their index revision. Sixty patients (92%) underwent the Fisher repair technique for their index revision and forty-six patients (70%) underwent nasal revision. In follow-up, all patients demonstrated an improvement in lip aesthetics. This study demonstrates a large subset of patients that have undergone cleft lip revision using the Fisher technique. In the senior surgeons' experience, the Fisher repair technique in the setting of cleft lip revision is an ideal way to address the shortcomings of historical repair techniques.
Targeted Muscle Reinnervation
Authors: Vonu Peter M. , Shekouhi Ramin , Crawford Kristina , Hones Keegan M. , Chim Harvey 
Published: June 2024

BackgroundTargeted muscle reinnervation (TMR) has demonstrated efficacy in reducing neuroma and chronic pain. In this article, we investigated postoperative outcomes in our patient cohort, with a focus on the role of nonmodifiable factors such as patient age and gender.MethodsPatients who had extremity TMR from April 2018 to October 2022 were reviewed. Outcomes of interest included patient age, gender, cause and type of amputation, delayed versus immediate TMR, as well as postoperative improvement in pain as assessed by numerical rating score (NRS).ResultsA total of 40 patients underwent TMR on 47 limbs. Mean age was 46.2 ± 17.0 years. Delayed TMR (27, 57.4%) was most commonly performed, followed by immediate and delayed-immediate at 11 (23.4%) and 9 (19.1%), respectively. Amputation level was most commonly above-knee in 20 (42.6%) patients, followed by below-knee (12, 25.5%), transhumeral (8, 17.0%), transradial (6, 12.8%), and shoulder (1, 2.1%). The median time interval between amputation and TMR was 12 months. The median preoperative NRS assessing residual limb pain (RLP) for patients who underwent delayed TMR was 10. The median postoperative NRS assessing RLP for all patients was 0 (interquartile range25–75: 0–5) and significantly improved compared with preoperative NRS (P< 0.001). At the last follow-up for limbs that had delayed and delayed-immediate TMR (n = 36), 33 (91.7%) limbs had more than 50% resolution of RLP. There was a significant difference in median postoperative NRS by gender (4 in men and 0 in women) (P< 0.05). Postoperative median NRS also favored younger patients (0, <50 years compared with 4.5, >50 years) (P< 0.05). Multiple linear regression analysis showed that, of different variables analyzed, only male gender and older age were predictive of poorer postoperative outcomes.ConclusionTMR showed high efficacy in our cohort, with improved short-term outcomes in women and younger patients.
Vasoactive and Antifibrotic Properties of Cannabinoids and Applications to Vasospastic/Vaso-Occlusive Disorders
Authors: Li Gabrielle , Choi Janice , Stephens Kristen L. , DeGeorge Brent R. 
Published: June 2024

Background
Management of vasospastic and vaso-occlusive disorders is a complex challenge, with current treatments showing varied success. Cannabinoids have demonstrated both vasodilatory and antifibrotic properties, which present potential mechanisms for therapeutic relief. No existing review examines these effects in peripheral circulation in relation to vasospastic and vaso-occlusive disorders. This study aims to investigate vasodilatory and antifibrotic properties of cannabinoids in peripheral vasculature for application in vasospastic and vaso-occlusive disorders affecting the hand.

Methods
A systematic search was conducted by 2 independent reviewers across PubMed, Cochrane, Ovid MEDLINE, and CINAHL to identify studies in accordance with the determined inclusion/exclusion criteria. Information regarding study design, medication, dosage, and hemodynamic or antifibrotic effects were extracted. Descriptive statistics were used to summarize study findings as appropriate.

Results
A total of 584 articles were identified, and 32 were selected for inclusion. Studies were grouped by effect type: hemodynamic (n = 17, 53%) and antifibrotic (n = 15, 47%). Vasodilatory effects including reduced perfusion pressure, increased functional capillary density, inhibition of vessel contraction, and increased blood flow were reported in 82% of studies. Antifibrotic effects including reduced dermal thickening, reduced collagen synthesis, and reduced fibroblast migration were reported in 100% of studies.

Conclusion
Overall, cannabinoids were found to have vasodilatory and antifibrotic effects on peripheral circulation via both endothelium-dependent and independent mechanisms. Our review suggests the applicability of cannabis-based medicines for vasospastic and vaso-occlusive disorders affecting the hand (eg, Raynaud disease, Buerger disease). Future research should aim to assess the effectiveness of cannabis-based medicines for these conditions.
Methods of Evaluating EEG Reactivity in Adult Intensive Care Units: A Review
Authors: Hwang Jaeho , Cho Sung-Min , Geocadin Romergryko , Ritzl Eva K. 
Published: June 2024

Purpose:
EEG reactivity (EEG-R) has become widely used in intensive care units for diagnosing and prognosticating patients with disorders of consciousness. Despite efforts toward standardization, including the establishment of terminology for critical care EEG in 2012, the processes of testing and interpreting EEG-R remain inconsistent.

Methods:
A review was conducted on PubMed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Inclusion criteria consisted of articles published between January 2012, and November 2022, testing EEG-R on adult intensive care unit patients. Exclusion criteria included articles focused on highly specialized stimulation equipment or animal, basic science, or small case report studies. The Quality In Prognostic Studies tool was used to assess risk of bias.

Results:
One hundred and five articles were identified, with 26 variables collected for each. EEG-R testing varied greatly, including the number of stimuli (range: 1–8; 26 total described), stimulus length (range: 2–30 seconds), length between stimuli (range: 10 seconds–5 minutes), frequency of stimulus application (range: 1–9), frequency of EEG-R testing (range: 1–3 times daily), EEG electrodes (range: 4–64), personnel testing EEG-R (range: neurophysiologists to nonexperts), and sedation protocols (range: discontinuing all sedation to no attempt). EEG-R interpretation widely varied, including EEG-R definitions and grading scales, personnel interpreting EEG-R (range: EEG specialists to nonneurologists), use of quantitative methods, EEG filters, and time to detect EEG-R poststimulation (range: 1–30 seconds).

Conclusions:
This study demonstrates the persistent heterogeneity of testing and interpreting EEG-R over the past decade, and contributing components were identified. Further many institutional efforts must be made toward standardization, focusing on the reproducibility and unification of these methods, and detailed documentation in the published literature.
Cytoprotective and Neuroinductive Effects of Thiol-Containing Simple Signaling Molecules
Authors: Dahlgren Kylie J. , Hemmerla August J. , Moore Marissa A. , Calle Daniela , Ulery Bret D. 
Published: June 2024

ABSTRACTAround 20 million Americans, mostly young adults, have suffered from a peripheral nerve injury due to trauma or a medical condition. However, prevailing treatments, including those that employ exogenous growth factors, often exhibit drawbacks outweighing their benefits, highlighting the need for novel solutions. Non-complex agents that govern bioactivity, termed simple signaling molecules (SSMs), offer an exciting alternative when compared to traditional approaches due to their small size, ready availability, and influence on cellular pathways. This study explores the cytoprotective and neuroinductive effects of three thiol-containing SSMs: hydrogen sulfide (H2S), n-acetyl cysteine (NAC), and glutathione (GSH). Neural stem cells (NE-4Cs) were exposed to toxic levels of hydrogen peroxide (H2O2) while supplemented with different concentrations of H2S, NAC, or GSH to assess their cytoprotective effects. To study the neuroinductivity of H2S, NAC, and GSH with NE-4Cs, immunofluorescence microscopy for an early neuronal marker, β3-tubulin, was employed to determine stem cell neural differentiation. Significant cytoprotection was found for NAC (2 - 8 mM) and GSH (2 - 12 mM), while H2S showed limited protective effects. Interestingly, the opposite result was observed for neuroinductivity as only H2S (7.75 - 125 μM) achieved a desirable effect while NAC and GSH had minimal impact on neural differentiation. This research establishes therapeutic concentration ranges of H2S, NAC, and GSH for future drug delivery systems targeting neural regeneration, especially for peripheral nerve injuries.LAY SUMMARYApproximately 20 million Americans, mainly young adults, suffer from peripheral nerve injuries, necessitating new effective treatments. Currently emerging approaches, including growth factor-based therapies, unfortunately face considerable limitations. This study explores the potential of simple signaling molecules (SSMs) - small, readily available agents - specifically hydrogen sulfide (H2S), n-acetyl cysteine (NAC), and glutathione (GSH) for their potential to be used to address issues underlying peripheral nerve injuries. Our findings reveal NAC and GSH have cytoprotective effects, whereas H2S is neuroinductive. This research identifies optimal concentrations for future drug delivery targeting neural regeneration, especially beneficial for peripheral nerve injuries.FUTURE WORKSUpcoming investigation will concentrate on exploiting the potential of novel SSM-releasing monomers within degradable polymeric systems. This involves defining therapeutic windows and optimizing polymer chemistry to induce desired cytoprotective and neuroinductive effects in neural stem cells, crucial for peripheral nerve injury repair. Emphasizing controlled release, this approach holds promise for developing advanced therapeutic strategies utilizing H2S, NAC, and/or GSH in nerve guidance conduits.GRAPHICAL ABSTRACT
Effect of cyclic loading on the ultimate tensile strength of small metallic suture anchors used for attaching artificial tendons in rabbits
Authors: Fidelis Obinna P. , Mulon Pierre-Yves , Anderson David E. , Crouch Dustin L. 
Published: June 2024

AbstractBackgroundSuture anchor failures can lead to revision surgeries which are costly and burdensome for patients. The durability of musculoskeletal reconstructions is therefore partly affected by the design of the suture anchors.PurposeThe purpose of the study was to quantify the strength of different suture anchors whose sizes are suitable for attaching artificial Achilles and tibialis cranialis tendons in a rabbit model, as well as determine the effect of cyclic loading on the anchoring strength.MethodFour anchors (two with embedded eyelet and two with raised eyelet, n=5 per group) were tested with cyclical loading (1000 cycles and 4.5 mm/sec) and without cycling, to inform the failure loads and mode of failure of the suture anchors. An eyebolt screw with smooth eyelet was used as a control for the test groups.ResultsAll samples in all groups completed 1000 cycles and failed via suture breakage in both test conditions. All anchors had failure loads exceeding the peak Achilles tendon force in rabbits during hopping gait. The data analysis showed an effect of anchor type on the maximum tensile force at failure (Fmax) in all suture categories but not an effect of loading condition. Also, the Anika anchor had a significantly less adverse effect on suture strength compared to Arthrex anchor (p=0.015), IMEX anchor (p=0.004) and Jorvet anchor (p<0.001). We observed a greater percentage of failure at the mid-section for the anchors with the raised eyelets compared to the anchors with embedded eyelets, which all failed at the knot.ConclusionAnchors with embedded eyelets had clinically preferred mode of failure with less adverse effects on suture and, may be more reliable than anchors with raised eyelets for attaching artificial Achilles and tibialis cranialis tendons in rabbits.
Anticipating Protein Evolution with Successor Sequence Predictor
Authors: Khan Rayyan Tariq , Kohout Pavel , Musil Milos , Rosinska Monika , Damborsky Jiri , Mazurenko Stanislav , Bednar David 
Published: June 2024

AbstractThe quest to predict and understand protein evolution has been hindered by limitations on both the theoretical and the experimental fronts. Most existing theoretical models of evolution are descriptive, rather than predictive, leaving the final modifications in the hands of researchers. Existing experimental techniques to help probe the evolutionary sequence space of proteins, such as directed evolution, are resource-intensive and require specialised skills. We present the Successor Sequence Predictor (SSP) as an innovative solution. Successor Sequence Predictor is anin silicomethod that mimics laboratory-based protein evolution by reconstructing a protein’s evolutionary history and suggesting future amino acid substitutions based on trends observed in that history through carefully selected physicochemical descriptors. This approach enhances specialised proteins by predicting mutations that improve desired properties, such as thermostability, activity, and solubility. Successor Sequence Predictor can thus be used as a general protein engineering tool to develop practically useful proteins. The code of the Successor Sequence Predictor is provided, and the design of mutations will be also possible via an easy-to-use web serverhttps://loschmidt.chemi.muni.cz/fireprotasr/.Graphical AbstractTracing Evolution’s Pathway to the Future
Engineering ERα degraders with pleiotropic ubiquitin ligase ligands maximizes therapeutic efficacy by co-opting distinct effector ligases
Authors: Shemorry Anna , Besten Willem den , Mulvihill Melinda M. , Essenburg Curt J. , Blaquiere Nicole , Kleinheinz Tracy , Villemure Elisia , Peale Frank , Deshmukh Gauri , Maddalo Danilo , Levy Elizabeth , Yu Kebing , Tovar Elizabeth A. , Wolfrum Emily , Blake Robert A. , Nagapudi Karthik , Forrest William F. , Staben Steven T. , Graveel Carrie R. , Fairbrother Wayne J. , Wertz Ingrid E. 
Published: June 2024

SummaryProximity-inducing compounds that modulate target protein homeostasis are an emerging therapeutic strategy [1]. While the inherent complexity of these bifunctional compounds poses challenges for rational design and bioavailability, their composition also provides opportunities to co-opt specific cellular proteins to maximize therapeutic impact. Here, we systematically evaluate the cellular efficacy, biophysical mechanisms, and therapeutic benefits of a series of bifunctional degrader compounds, that are all engineered with the Estrogen Receptor-alpha (ERα)-inhibitor endoxifen linked to different bioactive ubiquitin ligase ligands. Bifunctional ERα degraders that incorporate CRL4-CRBN-binding ligands promoted the most potent ERα degradation, whereas those incorporating either CRL2-VHL- or IAP-binding ligands maximized the depth of ERα degradation. Notably, ERα degraders containing pan-IAP antagonist ligands significantly decreased the proliferation of ERα-dependent cells relative to clinical-stage ERα-degraders, including the SERDs fulvestrant and GDC-9545 and the bifunctional degrader ARV-471. Mechanistic studies revealed that pan-IAP antagonist-based ERα degraders uniquely promote TNFα-dependent cell death, unlike the clinical-stage comparators. Remarkably, the pan-IAP antagonist-ERα-degraders co-opt distinct effector ligases to achieve dual therapeutic effects: they harness XIAP within tumor cells to promote ERα degradation, and activate cIAP1/2 within tumor and immune cells to induce TNFα that drives tumor cell death. Our studies demonstrate a broader concept that co-opting the discrete functions of a selected set of cellular effectors, while simultaneously modulating therapeutic target protein homeostasis, are dual strategies that can be leveraged to maximize the efficacy of induced proximity therapeutics.
A robust protocol for the systematic collection and expansion of cells from ER+breast cancer tumors and their matching tumor-adjacent tissues
Authors: Topolnitska Diana , Moreno Camila Lopez , Paiva Alen , Buchel Edward , Safneck Janice , Raouf Afshin 
Published: June 2024

AbstractTherapy resistance and tumor recurrence are major challenges in the clinical management of breast cancer. Current data indicates that the breast tumor microenvironment (TME) and the tumor immune microenvironment (TIME) are important modulators of breast cancer cell response to chemotherapies and the development of therapy resistance. To this end, the ability to recreate the tumor microenvironment in the laboratory using autologous primary cells that make up the breast TME has become an indispensable tool for cancer researchers as it allows the study of tumor immunobiology in the context of therapy resistance. Moreover, the clinical relevance of data obtained from single cell transcriptomics and proteomics platforms would be greatly improved if primary autologous tumor cells were used. In this article, we report a robust and efficient workflow to obtain autologous cancer cells, cancer-associated fibroblasts, and tumor-infiltrating immune cells from primary human breast cancer tumors obtained from mastectomy procedures. As well, we show that this protocol can be used to obtain normal-like epithelial cells, fibroblasts, and immune cells from the matching tumor-adjacent breast tissue samples. Also, a robust methodology to expand each of these primary cell typesin vitrois presented that allows the maintenance of the primary tumor cell phenotype. The availability of a large number of autologous primary human breast tumor cells and their matching tumor-adjacent tissues will facilitate the study of differential and cancer cell-specific gene expression patterns that will further our understanding of how the TME and TIME influence therapy resistance in the breast tumor context.
Internet search algorithms: use of metadata, literacy and algorithmic education in the human–computer interaction
Authors: Barragán-Perea Efraín Alfredo , Tarango Javier 
Published: June 2024

Purpose
This paper aims to identify alternatives for citizens to get out of the bubble when interacting with the information provided by the internet through search engines. This situation arises because there is extensive ignorance about the way search engines operate and the way advanced search algorithms operate, both situations based on the specific segmentation of the public, which creates difficulties in obtaining vast information that allows the contrast and development of diverse perspectives, which do not necessarily lead to the use of critical thinking.

Design/methodology/approach
To achieve this contribution, a documentary-type investigation was carried out based on the review of the scientific literature on the subject, and the nature of this investigation, due to its purpose, being descriptive. The study takes as document selection criteria those original articles whose content relevance is linked to the purposes of this research proposal, published in scientific databases (SciELO, RedAlyC, Dialnet, ScienceDirect, WoS and Scopus) mostly between the years 2018 and 2023, in Spanish and English, that described the impact of bubble filters on full access to information and data privacy, for which the topics were addressed: internet search algorithms, bubble filters, search engines, privacy policies in search engines and management of personal data.

Findings
At the beginning, this paper clarifies the concepts of search algorithms on the Internet, bubble filters, search engines and privacy policies in search engines, which made it possible to identify alternatives that would allow the user to face the silent reality of the algorithms and avoid the bias in the information that the algorithm provides, in addition, the need to generate algorithmic literacy mechanisms, training in the use of metasearch engines and education in algorithms is proposed, with which citizens can exercise critical thinking in the way they interact on the internet.

Research limitations/implications
This is a theoretical proposal, in which various inferences are made from theoretical knowledge without fieldwork.

Originality/value
It is considered a document of important value in the training processes of librarians and information professionals in the training of users and in the ways of interaction with technology.