bluuebunny/crossref_metadata_2025_split huggingface dataset:
Order Set Usage is Associated With Lower Hospital Mortality in Patients With Sepsis
Authors: Dale Christopher R. , Schoepflin Sanders Shelley , Chang Shu Ching , Pandhair Omar , Diggs Naomi G. , Woodruff Whitney , Selander David N. , Mark Nicholas M. , Nurse Sarah , Sullivan Mark , Mezaraups Liga , O’Mahony D. Shane 
Published: May 2023

IMPORTANCE:
The Surviving Sepsis Campaign recommends standard operating procedures for patients with sepsis. Real-world evidence about sepsis order set implementation is limited.

OBJECTIVES:
To estimate the effect of sepsis order set usage on hospital mortality.

DESIGN:
Retrospective cohort study.

SETTING AND PARTICIPANTS:
Fifty-four acute care hospitals in the United States from December 1, 2020 to November 30, 2022 involving 104,662 patients hospitalized for sepsis.

MAIN OUTCOMES AND MEASURES:
Hospital mortality.

RESULTS:
The sepsis order set was used in 58,091 (55.5%) patients with sepsis. Initial mean sequential organ failure assessment score was 0.3 lower in patients for whom the order set was used than in those for whom it was not used (2.9 sd [2.8] vs 3.2 [3.1], p < 0.01). In bivariate analysis, hospital mortality was 6.3% lower in patients for whom the sepsis order set was used (9.7% vs 16.0%, p < 0.01), median time from emergency department triage to antibiotics was 54 minutes less (125 interquartile range [IQR, 68–221] vs 179 [98–379], p < 0.01), and median total time hypotensive was 2.1 hours less (5.5 IQR [2.0–15.0] vs 7.6 [2.5–21.8], p < 0.01) and septic shock was 3.2% less common (22.0% vs 25.4%, p < 0.01). Order set use was associated with 1.1 fewer median days of hospitalization (4.9 [2.8–9.0] vs 6.0 [3.2–12.1], p < 0.01), and 6.6% more patients discharged to home (61.4% vs 54.8%, p < 0.01). In the multivariable model, sepsis order set use was independently associated with lower hospital mortality (odds ratio 0.70; 95% CI, 0.66–0.73).

CONCLUSIONS AND RELEVANCE:
In a cohort of patients hospitalized with sepsis, order set use was independently associated with lower hospital mortality. Order sets can impact large-scale quality improvement efforts.
Risk analysis of subsequent therapies after first-line chemotherapy in advanced testicular cancer patients
Authors: Yen Tsung-Han , Wang Shian-Shiang , Yang Cheng-Kuang , Lu Kevin , Chen Chuan-Shu , Cheng Chen-Li , Hung Sheng-Chun , Chiu Kun-Yuan , Chen Chun Pen , Yang Chi-Rei , Li Jian-Ri 
Published: May 2023

Background:
Testicular cancer is the most common solid cancer diagnosed among young men. Despite good response to chemotherapy and a high survival rate, subsequent salvage therapies may still be required for some patients in advanced stages. The predictive and prognostic markers are crucial unmet needs.

Methods:
We retrospectively analyzed advanced testicular cancer patients who had received first-line chemotherapy between January 2002 and December 2020. The associations between baseline characteristics and clinical outcomes were evaluated.

Results:
Of the 68 included patients, the median age was 29 years. Among them, 40 patients received only first-line chemotherapy while the remaining 28 received subsequent chemotherapy or surgeries. Data reveal that 82.5% (33/40) of the patients in the chemotherapy-only group were recorded as a good prognostic risk using the International Germ Cell Cancer Collaborative Group classification when compared with 35.7% (10/28) in the second-line therapy group. In the chemotherapy-only group, 53.8% of patients were presented with lymph node metastasis compared with 78.6% in the second-line therapy group (p = 0.068). Fifteen percent of patients (6/40) were recorded as S stage 2–3 in the chemotherapy-only group, whereas 85.2% (23/28) were recorded as such in the second-line therapy group (p < 0.001). The 5-year overall survival estimation was 92.9% in the chemotherapy-only group and 77.3% in the second-line therapy group. Univariate analysis for overall survival revealed that those patients at the S 2–3 stage and those receiving second-line therapies showed a trend of having an increased death risk (hazard ratio [HR] = 8.26, 95% confidence interval (CI), 0.99-68.67, p = 0.051; HR = 7.76, 95% CI, 0.93-64.99, p = 0.059, respectively). The S 2–3 stage was also independently associated with the risk of subsequent therapy (HR = 33.13; 95% CI, 2.55-430.64, p = 0.007).

Conclusion:
Our real-world data show the predictive role of serum tumor marker stage 2–3 to be associated with any subsequent therapies after first-line chemotherapy. This can facilitate clinical decision making during the testicular cancer treatment process.
Neovaginoplasty With Nile Tilapia Skin: Cytological and Microbiota Evaluation
Authors: Teófilo Cristiana Rodrigues , Peixoto Raquel Autran Coelho , Eleutério Renata Mirian Nunes , Lima Junior Edmar Maciel , de Moraes Filho Manoel Odorico , Bezerra Leonardo Robson Pinheiro Sobreira , Bruno Zenilda Vieira 
Published: May 2023

Objectives
To study the clinical, cytological, and vaginal microbiota findings in patients with Mayer-Rokitansky-Küster-Hauser syndrome who underwent neovaginoplasty using Nile tilapia fish skin.

Methods
This is a cross-sectional study with 7 cisgender women with Mayer-Rokitansky-Küster-Hauser syndrome who had previously undergone neovagina reconstruction using Nile tilapia fish skin at a university hospital. Local institutional review board approval and written permission from the patient were obtained. Between August 2019 and November 2021, within 12 to 24 months after surgery, vaginal specimens were obtained for conventional oncotic and hormonal cytology, and for Gram staining. The Nugent scores were calculated. Colposcopy was also performed.

Results
Squamous cells without atypia were found in all patients. Five patients had intermediate vaginal microbiota (Nugent score of 4), which was determined by the presence of few lactobacilli on Gram staining. In hormonal cytology, 4 patients presented with findings compatible with menacme. No colposcopic change was observed. When postsurgical dilation was performed correctly, a mean vaginal length of 8.3 cm was maintained after 1 year of follow-up.

Conclusions
Squamous cells without atypia were present in neovaginas with Nile tilapia fish skin. Most vaginal contents revealed intermediate microbiota and hormonal results compatible with menacme. Studies with a greater number of patients are necessary for a more comprehensive understanding of the microbiome in neovaginas with this new technique, thereby providing support for the treatment and prevention of associated pathologies.
“Anatomy of the superficial radial nerve and its target nerves for targeted muscle reinnervation: an anatomical cadaver study”
Authors: Langeveld Mirte , Bruin Luca L. , Hundepool Caroline A. , Power Dominic , Duraku Liron S. , Zuidam J. Michiel 
Published: May 2023

Background:
Targeted muscle reinnervation (TMR) is a surgical procedure for treating symptomatic neuroma, in which the neuroma is removed and the proximal nerve stump is coapted to a donor motor branch innervating a nearby muscle. This study aimed to identify optimal motor targets for TMR of the Superficial Radial Nerve (SRN).

Methods:
Seven cadaveric upper limbs were dissected to describe the course of the SRN in the forearm and motor nerve supply – number, length, diameter, and entry points in muscle of motor branches - for potential recipient muscles.

Results:
The radial nerve provided three (3/6), two (2/6) or one (1/6) motor branches to the brachioradialis (BR) muscle, entering the muscle 21.7±17.9 to 10.8±15 mm proximal to the lateral epicondyle. One (1/7), two (3/7), three (2/7) or four (1/7) motor branches innervated the extensor carpi radialis longus (ERCL) muscle, with entry points 13.9±16.2 to 26.3±14.9 mm distal from the lateral epicondyle. In all specimens the posterior interosseous nerve gave off one motor branch to the extensor carpi radialis brevis (ECRB), which divided in two or three secondary branches. The distal anterior interosseus nerve (AIN) was assessed as potential recipient for TMR coaptation and had a freely transferable length of 56.4±12.7 mm.

Conclusions:
When considering TMR for neuromas of the SRN in the distal third of the forearm and hand, the distal AIN is a suitable donor target. For neuromas of the SRN in the proximal two thirds of the forearm, the motor branches to the ERCL, ERCB, and BR are potential donor targets.
Comparing Trends in Medicare Reimbursement and Inflation within Plastic Surgery Subspecialties”
Authors: Stoffel Victoria , Shim Jalene Y , Pacella Salvatore J. , Gosman Amanda A , Reid Chris M 
Published: May 2023

BackgroundOver the past decade across multiple surgical specialties, Medicare reimbursement rates have remained stagnant failing to keep pace with inflation. An internal comparison of subspecialties within plastic surgery has not yet been attempted. The goal of this study is to investigate the trends in reimbursement from 2010 to 2020 and compare across the subspecialties of plastic surgery.MethodsThe Physician/Supplier Procedure Summary (PSPS) was used to extract the annual case volume for the top 80% most-billed CPT codes within plastic surgery. Codes were defined into the following subspecialties: microsurgery, craniofacial surgery, breast surgery, hand surgery, and general plastic surgery. The Medicare physician reimbursement was weighted by case volume. The growth rate and compound annual growth rate (CAGR) were calculated and compared against an inflation-adjusted reimbursement value.ResultsOn average, inflation-adjusted growth in reimbursement for the procedures analyzed in this study was (-13.5%). The largest decrease in growth rate was within the field of Microsurgery (-19.2%), followed by Craniofacial surgery (-17.6%). These subspecialties also had the lowest CAGR (-2.11% and -1.91%, respectively). For case volumes, Microsurgery increased case volumes by an average of 3% per year, while craniofacial surgery increased case volumes by an average of 5% per year.ConclusionAfter adjusting for inflation, all subspecialties had a decrease in growth rate. This was particularly evident in the fields of craniofacial surgery and microsurgery. Consequently, practice patterns and patient access may be negatively affected. Further advocacy and physician participation in reimbursement rate negotiation may be essential to adjust for variance and inflation.
“ ” Codes
Authors: Zhou Feng , Gong Lunli , Zhang Jun , Wang Guobao , Khan Aawrish , Gao Qiuni , Qi Lili , Cui Haiyan 
Published: May 2023

Abstract
We have summarized a simple and effective method of filler injection for facial rejuvenation in Chinese patients and named it “ ” Codes. It is simple and easy to operate, which worth clinical promotion and application.
Evaluation of Blepharoptosis in Patients With Refractory Blepharospasm by VISA—Video Recordings, Idiosyncratic Expressions, Sensory Tricks, and Ancillary Procedures
Authors: Lai Chung-Sheng , Ramachandran Savitha , Lee Chia-Chen , Lai Ya-Wei , Chang Yang-Pei , Huang Shu-Hung 
Published: May 2023

Background
How to evaluate blepharoptosis concomitantly presented with refractory and uncontrollable blepharospasm? To date, there is a paucity of publications on the ideal evaluation methods. An innovative method—video recordings, idiosyncratic facial expressions, sensory tricks, and ancillary procedures (VISA)—is developed for preoperative evaluation, and the surgical outcomes are demonstrated.

Methods
A retrospective study using VISA for blepharoptosis evaluation was conducted on 51 patients with refractory blepharospasm. Based on the evaluation, patients underwent blepharoptosis correction simultaneously besides the selective myectomy and myotomy in situ of the eyelid protractors for blepharospasm. Preoperative and postoperative palpebral fissure height, margin reflex distance 1, ptosis severity, and levator function were assessed to identify the effectiveness of VISA. All the procedures were performed by the senior author C.-S.L.

Results
There were 42 patients diagnosed with essential blepharospasm and 9 patients with Meige syndrome. Forty-one patients (82/102 eyelids [80.4%]) had concomitant blepharoptosis and blepharospasm. Ptosis severity was mild in 21 eyelids (25.6%), moderate in 12 eyelids (14.6%), and severe in 49 eyelids (59.8%). Preoperative/postoperative (6 months) values of palpebral fissure height, margin reflex distance 1, and levator function were 4.70 ± 2.45 mm/8.35 ± 1.33 mm (P < 0.05), −0.30 ± 3.19 mm/3.73 ± 1.05 mm (P < 0.05), and 13.07 ± 2.56 mm/13.68 ± 2.34 mm (P < 0.05), respectively. Undercorrection and revision rate reported 9.8% and 3.7%, individually.

Conclusions
VISA approach overcomes the difficulty of blepharoptosis assessment in patients with refractory blepharospasm. It provides useful preoperative information required for adequate blepharoptosis correction in blepharospasm surgery and yielded desirable outcomes.
Laser patterning bioprinting using a light sheet-based system equipped with light sheet imaging produces long-term viable skin constructs
Authors: Hafa Levin , Breideband Louise , Posada Lucas Ramirez , Torras Núria , Martinez Elena , Stelzer Ernst H.K. , Pampaloni Francesco 
Published: May 2023

AbstractThis research introduces a new 3D bioprinter that incorporates live imaging of the bioprinted tissue with high resolution and high-speed capabilities. The printer employs a light sheet-based system to photocrosslink polymers into hydrogels at a printing speed of up to 0.66 mm³/s with a resolution of 15.7 µm. A significant advancement of this bioprinter is its ability to track cells and bioink during crosslinking, which enables real- time evaluation of the 3D-bioprinted structure’s quality. Fibroblast cells were encapsulated using this method, and the viability was evaluated directly after bioprinting and seven days after encapsulation, which was found to be high (83% ± 4.34%). Furthermore, a full- thickness skin construct was bioprinted and maintained in culture for 6 weeks, demonstrating the long-term viability and physiological relevance of the bioprinted tissue. The usage of solid-state laser beam scanning devices could enhance bioprinting’s speed and precision. This fast and accurate light-based bioprinter offers a promising platform for generating customizable 3D-printed structures with viable long-term cultures.TeaserA novel bioprinter with live imaging capability using light sheet microscopy produces viable long-term cultures with high-resolution structures.Graphical abstractGeneral workflow of bioprinting skin constructs using light sheet bioprinting.
Multi-omics data analysis supporting inheritance of acquired traits in humans
Authors: Sharma Abhay 
Published: May 2023

AbstractExperimental evidence supports presence of germline mediated nongenetic inheritance in animals including mammalian models. Observational and molecular epidemiological studies also suggest existence of environmental exposure induced germline inheritance in humans. Considering the obvious difficulties in conducting prospective cross-generational human studies, integrative analysis of available multi-omics data may seem to offer a valuable approach for assessing biological plausibility of inheritance of acquired traits in the species. To that end, the concept has mainly been tested here that, under the assumption of inheritance, human exposure to an environmental factor, if known to induce paternal inheritance in mammalian models and to act through molecular pathways conserved across species, would induce correlated changes in sperm epigenome and somatic transcriptome in the exposed subjects. The test is based on physical exercise, a physiologically relevant factor for which multiple datasets of human sperm DNA methylome and somatic transcriptome from interventional pre-post cohort studies, that minimizes inter-individual variability, were available. Existing somatic transcriptome datasets from animal model studies on exercise have been used for comparison. To control the analysis, bariatric surgery, for which exercise matched human datasets existed, have been used. The hypothesis testing involves gene set overrepresentation, comparison between directionality of epigenome and coding transcriptome changes, gene ontology enrichment, and epigenome and non-coding transcriptome interaction. Remarkably, the results show that, in humans, exercise induced DNA methylation changes in sperm specifically represent transcriptional response to exercise in soma. This germline epigenomic encoding of acquired transcriptome changes in soma clearly supports biological plausibility of epigenetic inheritance in humans.
TERSE: Efficient compression of the diffraction data
Authors: Matinyan Senik , Abrahams Jan Pieter 
Published: May 2023

AbstractHigh-throughput data collection in crystallography poses significant challenges in handling massive amounts of data. Here, we present TERSE, a novel lossless compression algorithm specifically designed for diffraction data. We compare TERSE with the established lossless compression algorithms implemented in gzip, CBF, and HDF5, in terms of compression efficiency and speed, using continuous rotation electron diffraction data of an inorganic compound. Our results show that TERSE outperforms these algorithms by achieving a higher data compression at a speed that is at least an order of magnitude faster. TERSE files are byte-order independent and the algorithm can be readily implemented in hardware. By providing a tailored solution for diffraction data, TERSE facilitates more efficient data analysis and interpretation while mitigating storage and transmission concerns. TERSE C++20 compression/decompression code and an ImageJ/Fiji java plugin for reading TERSE files are open-sourced on GitHub under the permissive MIT license.SynopsisWe present a fast and lossless algorithm for compressing diffraction data, achieving up to 85% reduction in file size while processing up to 2000 512×512 frames per second. This breakthrough in compression technology is a significant step towards more efficient analysis and storage of large diffraction datasets.
Crosstalk between the glucocorticoid and mineralocorticoid receptor boosts glucocorticoid-induced killing of multiple myeloma cells
Authors: Clarisse Dorien , Prekovic Stefan , Vlummens Philip , Staessens Eleni , Van Wesemael Karlien , Thommis Jonathan , Fijalkowska Daria , Acke Guillaume , Zwart Wilbert , Beck Ilse M. , Offner Fritz , De Bosscher Karolien 
Published: May 2023

AbstractThe glucocorticoid receptor (GR) is a crucial drug target in multiple myeloma as its activation with glucocorticoids effectively triggers myeloma cell death. However, as high-dose glucocorticoids are also associated with deleterious side effects, novel approaches are urgently needed to improve GR action in myeloma. Here we reveal a functional crosstalk between GR and the mineralocorticoid receptor (MR) that culminates in improved myeloma cell killing. We show that the GR agonist Dexamethasone (Dex) downregulates MR levels in a GR-dependent way in myeloma cells. Co-treatment of Dex with the MR antagonist Spironolactone (Spi) enhances Dex-induced cell killing in primary, newly diagnosed GC-sensitive myeloma cells. In a relapsed GC-resistant setting, Spi alone induces distinct myeloma cell killing. On a mechanistic level, we find that a GR-MR crosstalk likely arises from an endogenous interaction between GR and MR in myeloma cells. Quantitative dimerization assays show that Spi reduces Dex-induced GR-MR heterodimerization and completely abolishes Dex-induced MR-MR homodimerization, while leaving GR-GR homodimerization intact. Unbiased transcriptomics analyses reveal that c-myc and many of its target genes are downregulated most by combined Dex-Spi treatment. Proteomics analyses further identify that several metabolic hallmarks are modulated most by this combination treatment. Finally, we identified a subset of Dex-Spi downregulated genes and proteins that may predict prognosis in the CoMMpass myeloma patient cohort. Our study demonstrates that GR-MR crosstalk is therapeutically relevant in myeloma as it provides novel strategies for glucocorticoid-based dose-reduction.
Predicting T Cell Receptor Functionality against Mutant Epitopes
Authors: Dorigatti Emilio , Drost Felix , Straub Adrian , Hilgendorf Philipp , Wagner Karolin I. , Bischl Bernd , Busch Dirk H. , Schober Kilian , Schubert Benjamin 
Published: May 2023

AbstractCancer cells or pathogens can escape recognition by T cell receptors (TCRs) through mutations of immunogenic epitopes. TCR cross-reactivity, i.e., recognition of multiple epitopes with sequence similarities, can be a factor to counteract such mutational escape. However, cross-reactivity of cell-based immunotherapies may also cause severe side effects when self-antigens are targeted. Therefore, the ability to predict the effect of mutations in the epitope sequence on T cell functionalityin silicowould greatly benefit the safety and effectiveness of newly-developed immunotherapies and vaccines. We here present “Predicting T cell Epitope-specific Activation against Mutant versions” (P-TEAM), a Random Forest-based model which predicts the effect of point mutations of an epitope on T cell functionality. We first trained and tested P-TEAM on a comprehensive dataset of 36 unique murine TCRs in response to systematic single-amino acid mutations of their target epitope (representing 5.472 unique TCR-epitope interactions). The model was able to classify T cell reactivities, corresponding toin vivorecruitment of T cells, and quantitatively predict T cell functionalities for unobserved single-point mutated altered peptide ligands (APLs), or even unseen TCRs, with consistently high performance. Further, we present an active learning framework to guide experimental design for assessing TCR functionality against novel epitopes, minimizing primary data acquisition costs. Finally, we applied P-TEAM to a novel dataset of 7 human TCRs reactive to the tumor neoantigen VPSVWRSSL. We observed a similarly robust performance for these human TCRs as for the murine TCRs recognizing SIINFEKL, thus providing evidence that our approach is applicable to therapeutically relevant TCRs as well as across species. Overall, P-TEAM provides an effective computational tool to study T cell responses against mutated epitopes.
Robust higher-order multiplexing in digital PCR by color-combination
Authors: Santos-Barriopedro Irene , Ursuegui Sylvain , Fradet Etienne , Dangla Rémi 
Published: May 2023

AbstractThere is a growing need in molecular biology to interrogate samples for higher number of biomarkers, beyond the 2 to 5 biomarkers typically addressable with standard PCR technologies. Here, we demonstrate a novel approach to increase the level of multiplexing in digital PCR up to 15-plex by detecting each target with 2 distinct fluorophores with a 6-color digital PCR system, a method called digital PCR by color combination. We provide a statistical framework to interpret digital PCR data by color combination, predicting that high-plexed assays by color combination can, in theory, have the same precision and sensitivity as corresponding single-plex assays. We verified the statistical framework and confirmed the sensitivity prediction experimentally on a 15-plex assay and an 11-plex assay. These results establish the technical framework for future high-plex assays addressing a variety of applications and utilities, such as infectious disease syndromic panels or tumor mutation profiling panels.