bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alpha Defensin-1 Level Correlates with Periprosthetic Infection Severity following Implant-based Breast Reconstruction
Authors: Sobti Nikhil , Vishwanath Neel , Stead Thor , Rao Vinay , Soliman Luke , Breuing Karl , Kwan Daniel , Liu Paul , Schmidt Scott 
Published: January 2024

Background:
Accurate diagnosis of periprosthetic infections following breast reconstructions is paramount to reduce morbidity. Alpha defensin-1 (AD-1) is an antimicrobial peptide released by neutrophils. This study evaluates the relationship between quantitative AD-1 levels and infection severity in patients with suspected periprosthetic infection.

Methods:
Retrospective review was conducted of patients with prior breast implant reconstruction undergoing surgery for either suspected infection or prosthesis exchange and revision. The AD-1 level in periprosthetic fluid was sent for quantitative analysis. Association between AD-1 levels with outcomes, management, systemic markers of infection, and overall infection severity was evaluated.

Results:
Thirty-eight breasts were included. Infected breasts had higher AD-1 levels (3.91 versus 0.14, P < 0.01), greater odds of erythema [odds ratio (OR) 2.98 (1.53–5.82), P = 0.01], purulence [OR 2.84 (1.51–5.35), P = 0.01], fever [OR 1.84 (1.15–2.93), P = 0.01], threatened implant exposure [OR 2.97 (1.48–5.95), P < 0.01], and true implant exposure [OR 1.79 (1.04–3.08), P = 0.04]. Increasing AD-1 was an independent risk factor for washout (P < 0.01), and explant [OR 2.48 (1.47–4.2), P < 0.01]. AD-1 positively correlated with white blood cell count (β = 1.81 cells/µL, P < 0.01), and serum lactate (β = 0.19 meq/L, P < 0.04). Increasing AD-1 level was an independent predictor of infection severity (χ² = 22.77, P < 0.01).

Conclusions:
AD-1 levels correlate with infection severity, highlighting its potential both when clinical examination is ambiguous and when treatment response is being monitored. Although further evaluation is warranted, AD-1 may demonstrate utility in novel breast implant salvage algorithms.
The impact of perceived injustice on pain and psychological outcomes after traumatic injury: a longitudinal analysis
Authors: Trost Zina , Sturgeon John , Agtarap Stephanie , McMinn Kenleigh , McShan Evan , Boals Adriel , Arewasikporn Anne , Foreman Michael , Warren Ann Marie 
Published: January 2024

Abstract
Individuals' appraisals regarding the injustice of their pain or physical injury have emerged as a significant risk factor for worse physical and psychological outcomes. Injustice appraisals are defined by perceptions of external blame for pain or injury and viewing pain or injury as a source of irreparable loss. To date, research on the impact of injustice appraisal has been primarily cross sectional, and existing longitudinal studies have examined injustice appraisals at only 2 time points in the context of rehabilitation treatment. This study examined the trajectory of injustice appraisals in 171 patients admitted for traumatic injury at admission, as well as 3, 6, and 12 months after discharge and examined injustice appraisals as a potential moderator of recovery after injury. Findings can be summarized as follows: First, injustice perception was largely stable in the 12 months after hospital discharge. Second, elevated injustice perception was associated with decreased recovery in pain intensity and depressive symptomatology over the study period but did not moderate changes in pain catastrophizing or posttraumatic stress symptomatology over time. This study is the first naturalistic prospective analysis of injustice appraisal following trauma admission within the American healthcare system. Findings indicate that injustice appraisals do not naturally decrease in the aftermath of traumatic injury and may be a risk factor for poorer physical and psychological recovery. Future research should examine additional sociodemographic and psychosocial factors that may contribute to elevated injustice appraisal, as well as ways of addressing the potential deleterious impact of injustice appraisals in treatment settings.
Robot-assisted radical cystectomy with intracorporeal urinary diversion: an updated systematic review and meta-analysis of its differential effect on effectiveness and safety
Authors: Fu Shi , Shi HongJin , Fan Zhinan , Li Jinze , Luan Ting , Dong Haonan , Wang Jincheng , Chen Shuwen , Zhang Jinsong , Wang Jiansong , Ding Mingxia , Wang Haifeng 
Published: January 2024

Background:
Robot-assisted laparoscopic cystectomy with intracorporeal urinary diversion (iRARC) is increasingly being used in recent years. Whether iRARC offers advantages over open radical cystectomy (ORC) remains controversial. This study aimed to compare the difference of perioperative outcomes, oncological outcomes and complications between iRARC and ORC.

Methods:
The PubMed, Embase, Cochrane Library, Web of Science and CNKI databases were searched in July 2023 according to the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses) statement. Studies were identified to be eligible if they compared perioperative outcomes, oncological outcomes and complications in patients who underwent iRARC with ORC.

Results:
Twenty-two studies involving 7020 patients were included. Compared to ORC, iRARC was superior for estimated blood loss [estimated blood loss (EBL) weighted mean difference (WMD): −555.52; 95% CI, −681.64 to −429.39; P<0.001], blood transfusion rate [odds ratio (OR): 0.16; 95% CI, 0.09–0.28; P<0.001], length of hospital stay [length of hospital stay (LOS) WMD: −2.05; 95% CI, −2.93 to −1.17; P<0.001], Clavien–Dindo grades ≥III complication rate [30 days: OR: 0.57; 95% CI 0.44–0.75; P<0.001; 90 days: OR: 0.71; 95% CI 0.60–0.84; P<0.001], and positive surgical margin [positive surgical margin (PSM) OR: 0.65; 95% CI 0.49–0.85; P=0.002]. However, iRARC had a longer operative time [operative time (OT) WMD: 68.54; 95% CI 47.41–89.67; P<0.001] and a higher rate of ureteroenteric stricture [ureteroenteric stricture (UES) OR: 1.56; 95% CI 1.16–2.11; P=0.003]. Time to flatus, time to bowel, time to regular diet, readmission rate, Clavien–Dindo grades less than III complication rate for iRARC were similar to that for ORC. Interestingly, the results of subgroup analysis revealed no difference in EBL between iRARC and ORC when the diversion type was neobladder. When the ileal conduit was selected as the diversion type, the LOS was similar in both procedures.

Conclusion:
Robot-assisted laparoscopic cystectomy with intracorporeal urinary diversion appears to be superior to open radical cystectomy in terms of effectiveness and safety. However, attention should be paid to the occurrence of ureteroenteric stricture during follow-up.
Fatal Case of Exercise Collapse Associated with Sickle Cell Trait with Novel Underlying LAMA2 Mutation
Authors: Jaramillo Couger Jimenez , Gibbons Thomas , Rose Rachel , Walsh John 
Published: January 2024

AbstractSickle cell trait is typically thought to be an asymptomatic carrier state, but it is rarely associated with exertional rhabdomyolysis in cases termed Exercise Collapse Associated with Sickle Cell Trait (ECAST). In a subset of these cases, underlying disease contributes to the development and/or severity of the ensuing medical complications. We describe the first ever case of ECAST reported in a previously asymptomatic, multiply deployed, highly physically active service member with an underlying heterozygousLAMA2mutation. Moreover, the mutation identified via whole exome sequencing is a novel, likely pathogenic variant that has yet to be described in the literature.
Development and validation of a nomogram prognostic model for small cell lung cancer optimized by age and metastatic pattern
Authors: Guo Hanfei , Tuerxun Halahati , Li Wenqian , He Hua , Yang Wang , Bai Yuansong , Li Yarong , Yang Yu , Li Lingyu , Cui Jiuwei 
Published: January 2024

Background:
The objective of this study is to establish and validate a novel nomogram by optimizing the eighth edition of the TNM classification by adding age and metastatic pattern.

Methods:
Clinical data of 1085 patients with small cell lung cancer (SCLC) from a Chinese multi-institutional registry were subjected to bootstrap external validation based on a prognostic nomogram built by integrating significant prognostic factors for survival from 21,707 cases from the Surveillance, Epidemiology, and End Results (SEER) database (training cohort). Kaplan–Meier survival analyses and concordance index (c-index) were used to test the application of the risk stratification system.

Results:
Both cohorts exhibited significant mortality increases with age (SEER hazard ratio [HR], 1.319; China HR, 1.237; both P < 0.001). The patterns of organ metastasis, liver (HR = 3.219), lung (HR = 1.750), brain (HR = 1.509), and bone (HR = 2.614), had significantly disparate prognoses. The nomogram based on the TNM classification of lung cancer was optimized by age and organ metastatic pattern, with an improvement in the C-index (from 0.617 to 0.661 in the training cohort and from 0.620 to 0.668 in the external validation cohort).

Conclusion:
This model provides useful quantitative tool for physicians to make critical diagnostic and treatment decisions for patients with SCLC.
Prospective Evaluation of Circulating Tumor DNA using Next Generation Sequencing as a Biomarker during Neoadjuvant Chemotherapy in Localized Pancreatic Cancer
Authors: Shah Dhavan , Wells Amy , Cox Madison , Dawravoo Kevin , Abad John , D’Souza Arlene , Suh Grace , Bayer Robert , Chaudhry Sohail , Zhang Qiang , Cristofanilli Massimo , Bentrem David , Chawla Akhil 
Published: January 2024

Objective:
In this prospective study, we aim to characterize the prognostic value of circulating tumor DNA (ctDNA) by next-generation-sequencing (NGS) in patients undergoing neoadjuvant chemotherapy (NAC) for pancreatic ductal adenocarcinoma (PDAC).

Summary Background Data:
Circulating tumor DNA is a promising blood-based biomarker that is prognostic in several malignancies. Detection of ctDNA by NGS may provide insights regarding the mutational profiles in PDAC to help guide clinical decisions for patients in a potentially curative setting. However, the utility of ctDNA as a biomarker in localized PDAC remains unclear.

Methods:
Patients with localized PDAC were enrolled in a prospective study at Northwestern Medicine between October 2020 and October 2022. Blood samples were collected to perform targeted tumor agnostic NGS utilizing the Tempus x|F 105 gene panel at three timepoints: pre-therapy (at diagnosis), post-NAC, and after local therapy, including surgery. The relationship between ctDNA detection and CA19-9, and the prognostic significance of ctDNA detection were analyzed.

Results:
56 patients were included in the analysis. ctDNA was detectable in 48% at diagnosis, 33% post-NAC, and 41% after local therapy. After completion of NAC, patients with detectable ctDNA had higher CA19-9 levels versus those without (78.4 vs. 30.0, P=0.02). The presence of baseline ctDNA was associated with a CA19-9 response; those without ctDNA had a significant CA19-9 response following NAC (109.0 U/mL vs. 31.5 U/mL; P=0.01), while those with ctDNA present at diagnosis did not (198.1 U/mL vs. 113.8 U/mL; P=0.77). In patients treated with NAC, the presence of KRAS ctDNA at diagnosis was associated with and independently predicted worse progression-free-survival.

Conclusion:
This report demonstrates the prognostic value of ctDNA analysis with NGS in localized PDAC. NGS ctDNA is a biomarker of treatment response to NAC. KRAS ctDNA at diagnosis independently predicts worse survival in patients treated with NAC.
Comparative chemical characters of Ziziphi Spinosae Semen from geographical origins of China
Authors: Wang Pengwang , Sha Miao , Zhang Weimei , Tian Hongyue , Liang Xu , Tian Wei , Xu Bo , Chang Guanglu , Li Xia , Gao Wenyuan 
Published: January 2024

Abstract

Background
Ziziphi Spinosae Semen (ZSS) contains a wide range of active components. Because existing methods cannot fully evaluate these components, a new quantitative method needs to be established for component characterization.

Objective
Ziziphi Spinosae Semen has gained increasing attention in recent years, primarily as a medicinal and edible plant. The content determination of ZSS is not specified in the Chinese Pharmacopeia (2020 edition). Environmental conditions in different production areas can influence the quality of ZSS. This study aims to identify ZSS collected from various geographical origins in China.

Materials and methods
High-performance liquid chromatography (HPLC) fingerprints were established using optimized HPLC-photo-diode array methods. Subsequently, similarity analysis and quantification of ZSS from different sources were conducted. Metabolites of ZSS were identified and evaluated using the UHPLC-Q Exactive HF Orbitrap MS system. Principal component analysis, hierarchical cluster analysis, and orthogonal partial least squares discriminant analysis were performed based on all peak areas.

Results
In this study, the components of ZSS against insomnia were screened through network pharmacology. As revealed by the results of protein-protein interaction network analysis, Gene Ontology analysis, and Kyoto Encyclopedia of Genes and Genomes pathway analysis, 14 core components, 10 core targets, and 25 pathways were identified. Thirty-four batches of ZSS fingerprints were established through the HPLC method, which identified 12 characteristic peaks, with 6 being qualitatively identified. An identification method for assessing differences in the chemical composition of ZSS from different origins was developed by using UHPLC-Q Exactive HF Orbitrap MS. Differential markers from various origins were screened and identified. Through multiple analyses such as principal component analysis and orthogonal partial least squares discriminant analysis, it was concluded that there were differences in ZSS metabolites from Hebei, Shandong, and Shaanxi provinces. Seventeen differential metabolites of different origins were identified.

Conclusions
This study confirmed that ZSS played a synergistic role in improving insomnia through multiple components, targets, and pathways. The content of all 5 components was high, except for jujuboside B. In addition, 6 compounds in ZSS extracts from different origins differed in content, indicating that different growth environments might impact the quality of ZSS.
Automated Synthesis of Wireframe DNA Nanotubes
Authors: Islas Patricia , Platnich Casey M. , Gidi Yasser , Karimi Ryan , Ginot Lorianne , Cosa Gonzalo , Sleiman Hanadi F. 
Published: January 2024

ABSTRACTDNA nanotechnology has revolutionized our ability to position matter at the nanoscale, but the preparation of DNA-based architectures remains laborious. To facilitate the formation of custom structures, we report a fully automated method to produce sequence- and size-defined DNA nanotubes. By programming the sequential addition of desired building blocks, rigid DX-tile-based DNA nanotubes (and flexible wireframe DNA structures) are attained, where the total number of possible constructs increases as a power function of the number of different units available. Using single-molecule fluorescence imaging, the kinetics and yield of each synthetic step can be quantitatively determined, revealing differences in self-assembly dynamics as the nanotube is built up from the solid support and providing new insights into DNA self-assembly. The exploitation of automation for both assembly and analysis (tthrough anad-hocdeveloped K-means clustering algorithm) facilitates a workflow wherein the synthesis parameters may be iteratively improved upon, demonstrating how a single-molecule ‘assembly-analysis-optimization’ sequence can be used to generate complex, non-covalent materials in good yield. The presented synthetic strategy is generalizable, making use of equipment already available in most standard laboratories and represents the first fully automated supramolecular assembly on a solid support.
Biologically Driven In Vivo Occlusion Design Provides a Reliable Experimental Glaucoma Model
Authors: Hong Eunji , Tian Feng , Glynn Christopher , Tsekov Sophia , Huang Sizhe , Zhou Songlin , He Zhigang , Rao Siyuan , Wang Qianbin 
Published: January 2024

AbstractFluid flow transport through the trabecular meshwork tissues is a major regulator of intraocular pressure (IOP) modulation in healthy and glaucomatous individuals. Microbead occlusion models of ocular hypertension regulate aqueous humor drainage to induce high IOP to allow for in vivo study of pressure-related glaucomatous pathology. However, the reliability and application of current injectable microbeads are hindered by inadequate design of the beads-tissue interfaces to maintain a stable IOP elevation over the long term. Considering the graded, porous architecture and fluid transport of the trabecular meshwork, we developed a tailored, injectable “viscobeads” technique, which induced a sustained elevation of IOP for at least 8 weeks. These composite viscobeads contain a non-degradable polystyrene (PS) core for structural support and a biodegradable polylactic-co-glycolic acid (PLGA) viscoelastic surface. This approach enhances the obstruction of aqueous humor drainage through heterogeneous sizes of trabecular meshwork fenestrations and reliably modulates the magnitude and duration of ocular hypertension. In a mouse model, a single viscobeads injection resulted in sustained IOP elevation (average 21.4±1.39 mm Hg), leading to a 34% retinal ganglion cell (RGC) loss by 56 days. In an earlier stage of glaucoma progression, we conducted non-invasive electroretinography (ERG) recording and revealed glaucomatous progression by analyzing high-frequency oscillatory potentials. To further explore the application of the viscobeads glaucoma models, we assayed a series of genes through adeno-associated virus (AAV)-mediated screening in mice and assessed the impact of genetic manipulation on RGC survivals. CRISPR mediated disruption of the genes, PTEN, ATF3 and CHOP enhanced RGC survival while LIN 28 disruption negatively impacted RGC survival. This biologically driven viscobeads design provides an accessible approach to investigate chronic intraocular hypertension and glaucoma-like neurodegeneration and ultimately tenders the opportunity to evaluate genetic and pharmacological therapeutics.
A Multiomics, Spatiotemporal, and Single Cell Atlas for Mapping Cell-Type-Specific Dysregulation at the Maternal-Fetal Interface
Authors: Wang Cheng , Zhou Yan , Wang Yuejun Jessie , Guha Tuhin Kumar , Luo Zhida , McIntyre Tara I. , Schwab Marisa E. , Davidson Brittany R. , Reeder Gabriella C. , Wong Ronald J. , England Sarah , Gonzalez Juan M. , Blelloch Robert , Combes Alexis J. , Giudice Linda C. , Erlebacher Adrian , MacKenzie Tippi C. , Stevenson David K. , Shaw Gary M. , Snyder Michael P. , Fisher Susan J. , Winn Virginia D. , Li Jingjing 
Published: January 2024

AbstractThe placenta, the first organ to functionally mature, undergoes disordered development in many pregnancy complications. Molecular investigations have been hampered by the extreme cellular heterogeneity of the placenta, and this complexity is further exaggerated at the maternal-fetal interface where maternal and fetal cells co-mingle. We generated the paired single nucleus epigenomes and transcriptome for each of ∼200,000 cells at the human maternal-fetal interface from early pregnancy to term. These data identified cell-type-specific transcriptional regulatory programs and uncovered key transcription factors driving the lineage differentiation of placental cytotrophoblasts. Integrating spatial single cell proteomics profiling, we localized the observed cell typesin situ, and characterized the dynamic stages and distinct features of endothelial cells of maternal spiral arteries remodeled by extravillous cytotrophoblasts. Integrative analyses of the single cell data across gestation enabled fine-mapping of the developmental trajectories of cytotrophoblasts and decidual stromal cells, and defining the signature molecular profiles of known and novel cell (sub)types. To demonstrate clinical value, we integrated the reference single cell data with large-scale population genomes from pregnancy complications and identified the most vulnerable maternal and fetal cell types in preeclampsia, preterm birth, and miscarriage. This study presents the most comprehensive placental and decidual single cell resource across gestation to date, reveals new insights into the drivers of normal human placentation, and uncovers the cellular basis of dysfunction associated with common pregnancy complications.
Application of Elevated Atmospheric Pressure and Hypoxia Enhance Pluripotency and Stem Cell Differentiation
Authors: Pappalardo Zachary , Downie Bryan , Adams Bruce A. , Lim James 
Published: January 2024

SummaryPhysical forces regulate stem cell differentiation in-vivo, however few simple and precise methods exist to better understand this biology in-vitro. Here we describe the use of a novel bioreactor that enables addition of physical force in the form of elevated atmospheric pressure during reprogramming of human fibroblasts and culture of human induced pluripotent stem cell (iPSC) and neural stem cell (NSC) lines. We demonstrate that elevated atmospheric pressure and hypoxia can positively regulate reprogramming of human fibroblasts to iPSCs across multiple donors. Prolonged culture of iPSCs in elevated atmospheric pressure (+ 2 PSI) and 15% oxygen exhibited progressive differentiation with concomitant metabolic and epigenetic gene expression changes. Furthermore, elevated atmospheric pressure positively regulates differentiation of iPSCs to neural-ectodermal and hematopoietic lineages when combined with appropriate soluble factors and oxygen concentration. In summary, these results demonstrate the significance of applied atmospheric pressure for stem cell applications and warrants further investigation.
Aging and injury drive neuronal senescence in the dorsal root ganglia
Authors: Donovan Lauren J. , Brewer Chelsie L. , Bond Sabrina F. , Lopez Aleishai Pena , Hansen Linus H. , Jordan Claire E. , González Oscar C. , de Lecea Luis , Kauer Julie A. , Tawfik Vivianne L. 
Published: January 2024

ABSTRACTAging negatively impacts central nervous system function; however, the cellular impact of aging in the peripheral nervous system remains poorly understood. Aged individuals are more likely to experience increased pain and slower recovery after trauma. Such injury can damage vulnerable peripheral axons of dorsal root ganglion (DRG) neurons resulting in somatosensory dysfunction. One cellular mechanism common to both aging and injury is cellular senescence, a complex cell state that can contribute to the aged pro-inflammatory environment. We uncovered, for the first time, DRG neuron senescence in the context of aging and pain-inducing peripheral nerve injury in young and aged mice. Aged DRG neurons displayed multiple markers of senescence (SA-β-gal, p21, p16, IL6) when compared to young DRG neurons. Peripheral nerve injury triggered a further accumulation of senescent DRG neurons over time post-injury in young and aged DRG. These senescent neurons were dynamic and heterogeneous in their expression of senescence markers, p16, p21, and senescence-associated secretory phenotype (SASP) expression of IL6, which was influenced by age. An electrophysiological characterization of senescence marker-expressing neurons revealed high-firing and nociceptor-like phenotypes within these populations. In addition, we observed improvement in nociceptive behaviors in young and aged nerve-injured mice after treatment with a senolytic agent that eliminates senescent cells. Finally, we confirmed in human post-mortem DRG samples that neuronal senescence is present and increases with age. Overall, we describe a susceptibility of the peripheral nervous system to neuronal senescence with age or injury that may be a targetable mechanism to treat sensory dysfunction, such as chronic pain, particularly in aged populations.