bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating the Prognostic Variables for Overall Survival in Patients with Metastatic Renal Cell Carcinoma: A Meta-Analysis Of 29,366 Patients
Authors: Li Bruce , Sood Swati , Huynh Melissa J. , Power Nicholas E. 
Published: April 2024

Background:
Scoring systems are a method of risk assessment used to stratify patients with metastatic renal cell carcinoma (mRCC) and guide systemic therapy. The variables are weighed equally when calculating total score. However, the difference of even 1 positive predictor can change one's risk category and therapy.

Objective:
To compare the relative strength of association between predictive variables and overall survival (OS) in mRCC.

Methods:
A search of Medical Literature Analysis and Retrieval System Online (MEDLINE) and Embase was conducted. Clinical studies, retrospective and prospective, were included if the association of at least 1 predictor and OS in patients with mRCC receiving first-line systemic therapy was evaluated. Meta-analysis was performed to generate pooled hazard ratios (HRs) and 95% CIs for OS for predictors with ≥ 5 included studies. Sensitivity analysis identified outlier heterogeneity and publication bias.

Results:
Sixty-six studies containing 29,366 patients were included. Meta-analysis indicated lung metastases, bone metastases, thrombocytosis, time to systemic therapy < 1 year, liver metastases, hypercalcemia, anemia, elevated neutrophil-lymphocyte ratio, multiple metastatic sites, neutrophilia, poor Eastern Cooperative Oncology Group (ECOG) status, no previous nephrectomy, elevated lactate dehydrogenase, Fuhrman grade 3 or 4, central nervous system metastases, elevated C-reactive protein, and Karnofsky Performance Status < 80% were associated with significantly worse OS. The HRs varied from 1.34 to 2.76, representing heterogeneity in predictive strength. The effects of study heterogeneity and publication bias were minimal to moderate across all predictors.

Conclusions:
Based on the differences in pooled HRs, prognostic strength between the variables is likely not equivalent. Restructuring scoring models, through inclusion of other variables and usage of relative weighting, should be considered to improve accuracy of risk stratification.
Social Care Education and Training Among US Pediatric Emergency Medicine Fellowship Programs
Authors: Assaf Raymen Rammy , Assaf Ryan David , Doucet Hannah Barber , Graff Danielle 
Published: April 2024

Objective
The aim of the study is to assess the association of social determinants of health (SDOH) education and social needs training on pediatric emergency medicine (PEM) physician perception and practices of social care.

Methods
Data were derived from the 2021 National Social Care Practices Survey of PEM program directors (PDs) and fellows. Ordinal and binary logistic regression modeling were completed for educational/training factors and social care perspective and practice outcomes.

Results
A national sample of 44 PDs (49% response rate) and 109 fellows (28%) participated. A minority of fellows received SDOH education and social needs training during fellowship. Fellows and PDs with SDOH education had a 3.1 odds (95% confidence interval CI, 1.4–6.9) of screening for social needs, with 4.4 odds among fellows (95% CI, 1.2–20.7). Those with social needs training were more comfortable assessing social risk, with 2.4 odds overall (95% CI, 1.2–4.7) and 3.1 odds among fellows (95% CI, 1.4–6.7). They also had 2.4 odds overall (95% CI, 1.1–4.9) of screening for social needs, with a 2.9 odds among fellows (95% CI, 1.3–6.8).

Conclusions
Social care education and training appear to be associated with comfort assessing social risk and social needs screening tendency among both PEM PDs and fellows. Key areas for educational interventions are identified among PEM fellows, who are uniquely positioned as clinical leaders and patient advocates.
Severe Blepharoptosis Correction with the Fixation of Levator Complex and Conjoint Fascial Sheath
Authors: Liu Haipeng , Li Tenghai , Wang Shimeng , Zhang Wei , Li Tian , Liu Bingzhang , Zhang Jiaqi , Shao Ying , Zhang Duo 
Published: April 2024

Background:
The correction of severe blepharoptosis is one of the most challenging operations in plastic surgery. This study introduces a novel self-reinforced fixation technique combining the levator complex with conjoint fascial sheath for the correction of severe blepharoptosis and reviews the postoperative results over the preceding 12 years.

Methods:
This retrospective review included all patients who underwent self-reinforced fixation with or without conjoint fascial sheath at the authors’ center between 2010 and 2022. The clinical data of the 2 groups were collected and evaluated.

Results:
All patients were followed up for 6 months to 8 years postoperatively. The mean postoperative marginal reflex distance 1 and levator function increased significantly in both groups. Sufficient correction of ptosis was achieved in 32 (65.31%) and 84 (81.56%) eyelids in groups I and II, respectively. The mean eyelid lagophthalmos was 1.27 ± 0.91 mm and 0.85 ± 0.89 mm in groups I and II, respectively. The most common complication was undercorrection of ptosis, which was observed in 14 eyelids (28.57%) and 15 eyelids (14.56%) in groups I and II, respectively.

Conclusions:
The self-reinforced fixation technique was effective in correcting severe congenital ptosis in Chinese patients. The clinical effect was consistent in the long-term follow-up cases, and the recurrence rate was low. Thus, this technique can enhance the strength of the levator muscle and maintain appropriate elasticity of eye closure.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, III.
Reinnervated Serratus Free Flap for a Functional Outcome in Tongue Reconstruction: A Surgical Technique Video
Authors: Baujat Bertrand , Broustaut Nicolas , Dauzier Etienne , Tassart Marc , Wagner Isabelle , Atallah Sarah , Marhic Alix 
Published: April 2024

Summary:
The current benchmark for tongue reconstruction after excision of locally advanced tumors involves the use of free skin or fasciocutaneous flaps, such as the anterolateral thigh flap or forearm free flap. They facilitate the volumetric reconstruction of the tongue, leveraging passive mobility from the remaining native tongue tissue. The challenge in tongue reconstruction surgery remains achieving functional restoration through adequate volume and optimized mobility, using tissue that is both adapted and comparable to native tissue. Although the free serratus muscle flap has been described for various indications, its application in tongue reconstructions remains underexploited. In cases of locally advanced tumors affecting the mobile tongue, typically within the junctional area and without extension to the floor of the mouth or to the tip of the tongue, the serratus free flap has shown positive results. Reinnervation of the flap is achieved connecting the thoracodorsal nerve to the descending branch of the XII nerve. This technique facilitates functional tongue reconstruction, promoting rapid mucosal epithelialization and reinnervation, which, in turn, preserves muscle volume and sustains adequate trophicity without fibrosis. Regarding these considerations, the pure muscle serratus free flap emerges as a valuable and effective alternative in tongue reconstruction. There is a dearth of step-by-step operative technique descriptions for this indication in the literature. The authors present videos demonstrating the surgical technique, showcasing procedures as performed at Tenon Hospital (Paris, France).
Gut permeability is associated with lower insulin sensitivity in youth with perinatally acquired HIV
Authors: Dirajlal-Fargo Sahera , Yu Wendy , Jacobson Denise L. , Mirza Ayesha , Geffner Mitchell E. , Jao Jennifer , McComsey Grace A. ,   for the Pediatric HIV/AIDS Cohort Study (PHACS)
Published: April 2024

The relationships between alterations in the intestinal barrier, and bacterial translocation with the development of metabolic complications in youth with perinatally acquired HIV (YPHIV) have not been investigated.
The PHACS Adolescent Master Protocol enrolled YPHIV across 15 U.S. sites, including Puerto Rico, from 2007 to 2009. For this analysis, we included YPHIV with HIV viral load 1000 c/ml or less, with at least one measurement of homeostatic assessment of insulin resistance (HOMA-IR) or nonhigh density lipoprotein (non-HDLc) between baseline and year 3 and plasma levels of intestinal fatty-acid binding protein (I-FABP), lipopolysaccharide-binding protein (LBP), and zonulin levels at baseline. We fit linear regression models using generalized estimating equations to assess the association of baseline log10 gut markers with log10 HOMA-IR and non-HDLc at all timepoints.
HOMA-IR or non-HDLc was measured in 237, 189, and 170 PHIV at baseline, Yr2, and Yr3, respectively. At baseline, median age (Q1, Q3) was 12 years (10, 14), CD4+ cell count was 762 cells/μl (574, 984); 90% had HIV RNA less than 400 c/ml. For every 10-fold higher baseline I-FABP, HOMA-IR dropped 0.85-fold at baseline and Yr2. For a 10-fold higher baseline zonulin, there was a 1.35-fold increase in HOMA-IR at baseline, 1.23-fold increase in HOMA-IR at Yr2, and 1.20-fold increase in HOMA-IR at Yr3 in adjusted models. For a 10-fold higher baseline LBP, there was a 1.23-fold increase in HOMA-IR at baseline in the unadjusted model, but this was slightly attenuated in the adjusted model. Zonulin was associated with non-HDLc at baseline, but not for the other time points.
Despite viral suppression, intestinal damage may influence downstream insulin sensitivity in YPHIV.
Kaposi sarcoma herpesvirus viral load in bronchoalveolar lavage as a diagnostic marker for pulmonary Kaposi sarcoma
Authors: Saberian Chantal , Lurain Kathryn , Hill Lindsay K. , Marshall Vickie , Castro Elena M. Cornejo , Labo Nazzarena , Miley Wendell , Moore Kyle , Roshan Romin , Ruggerio Margie , Ryan Kerry , Widell Anaida , Ekwede Irene , Mangusan Ralph , Rupert Adam , Barochia Amisha , Whitby Denise , Yarchoan Robert , Ramaswami Ramya 
Published: April 2024

Objective:
Kaposi sarcoma is a vascular tumor that affects the pulmonary system. However, the diagnosis of airway lesions suggestive of pulmonary Kaposi sarcoma (pKS) is reliant on bronchoscopic visualization. We evaluated the role of Kaposi sarcoma herpesvirus (KSHV) viral load in bronchoalveolar lavage (BAL) as a diagnostic biomarker in patients with bronchoscopic evidence of pKS and evaluated inflammatory cytokine profiles in BAL and blood samples.

Design:
In this retrospective study, we evaluated KSHV viral load and cytokine profiles within BAL and blood samples in patients who underwent bronchoscopy for suspected pKS between 2016 and 2021.

Methods:
KSHV viral load and cytokine profiles were obtained from both the circulation and BAL samples collected at the time of bronchoscopy to evaluate compartment-specific characteristics. BAL was centrifuged and stored as cell pellets and KSHV viral load was measured using primers for the KSHV K6 gene regions.

Results:
We evaluated 38 BAL samples from 32 patients (30 with HIV co-infection) of whom 23 had pKS. In patients with airway lesions suggestive of pKS, there was higher KSHV viral load (median 3188 vs. 0 copies/106 cell equivalent; P = 0.0047). A BAL KSHV viral load cutoff of 526 copies/106 cells had a sensitivity of 72% and specificity of 89% in determining lesions consistent with pKS. Those with pKS also had higher IL-1β and IL-8 levels in BAL. The 3-year survival rate for pKS patients was 55%.

Conclusion:
KSHV viral load in BAL shows potential for aiding in pKS diagnosis. Patients with pKS also have evidence of cytokine dysregulation in BAL.
Outcomes of Dermal Regeneration Templates in Irradiated and Nonirradiated Scalp Defects
Authors: Yang Alan Z. , Shelton Eva , Katave Coral , Fruge Seth , Talbot Simon G. , Eberlin Kyle R. , Orgill Dennis P. , Ranganathan Kavitha L. 
Published: April 2024

Objectives:
Dermal regeneration templates (DRTs) are frequently used to treat scalp defects. The aim was to compare the time course of healing for DRTs in scalp defects with and without preoperative radiation.

Methods:
The authors conducted a retrospective cohort study of DRT-based scalp reconstruction at 2 academic medical centers between 2013 and 2022. Information was collected on demographic variables, comorbidities, medication use, history of radiation, and DRT outcomes. The primary outcome was DRT loss, defined as exposed calvarium or DRT detachment based on postoperative follow-up documentation. Kaplan-Meier survival analysis and multivariable Cox proportional-hazard regressions were used to compare DRT loss in irradiated and nonirradiated defects. Multivariable logistic regressions were used to compare 30-day postoperative complications (infection, hematoma, or seroma) in irradiated and nonirradiated defects.

Results:
In total, 158 cases were included. Twenty-eight (18%) patients had a preoperative history of radiation to the scalp. The mean follow-up time after DRT placement was 2.6 months (SD: 4.5 mo). The estimated probability of DRT survival at 2 months was 91% (95% CI: 83%–100%) in nonirradiated patients and 65% (95% CI: 48%–88%) in irradiated patients. In the 55 patients with a bony wound base, preoperative head radiation was associated with a higher likelihood of DRT loss (hazard ratio: 11). Half the irradiated defects experienced uncomplicated total wound closure using Integra Wound Matrix Dressing with or without second-stage reconstruction.

Conclusions:
Dermal regeneration template can offer durable coverage in nonirradiated scalp defects. Although DRT loss is more likely in irradiated scalp defects, successful DRT-based reconstruction is possible in select cases.
Synthetic coevolution reveals adaptive mutational trajectories of neutralizing antibodies and SARS-CoV-2
Authors: Ehling Roy A. , Minot Mason , Overath Max D. , Sheward Daniel J. , Han Jiami , Gao Beichen , Taft Joseph M. , Pertseva Margarita , Weber Cédric R. , Frei Lester , Bikias Thomas , Murrell Ben , Reddy Sai T. 
Published: April 2024

ABSTRACTThe Covid-19 pandemic showcases a coevolutionary race between the human immune system and SARS-CoV-2, mirroring the Red Queen hypothesis of evolutionary biology. The immune system generates neutralizing antibodies targeting the SARS-CoV-2 spike protein’s receptor binding domain (RBD), crucial for host cell invasion, while the virus evolves to evade antibody recognition. Here, we establish a synthetic coevolution system combining high-throughput screening of antibody and RBD variant libraries with protein mutagenesis, surface display, and deep sequencing. Additionally, we train a protein language machine learning model that predicts antibody escape to RBD variants. Synthetic coevolution reveals antagonistic and compensatory mutational trajectories of neutralizing antibodies and SARS-CoV-2 variants, enhancing the understanding of this evolutionary conflict.
Isolation and Characterization of aHalomonasSpecies for Non-Axenic Growth-Associated Production of Bio-Polyesters from Sustainable Feedstocks
Authors: Woo Sung-Geun , Averesch Nils J. H. , Berliner Aaron J. , Deutzmann Joerg S. , Pane Vince E. , Chatterjee Sulogna , Criddle Craig S. 
Published: April 2024

ABSTRACTBiodegradable plastics are urgently needed to replace petroleum-derived polymeric materials and prevent their accumulation in the environment. To this end, we isolated and characterized a halophilic and alkaliphilic bacterium from the Great Salt Lake in Utah. The isolate was identified as aHalomonasspecies and designated “CUBES01”. Full-genome sequencing and genomic reconstruction revealed the unique genetic traits and metabolic capabilities of the strain, including the common polyhydroxyalkanoate (PHA) biosynthesis pathway. Fluorescence staining identified intracellular polyester granules that accumulated predominantly during the strain’s exponential growth, a feature rarely found among natural PHA producers. CUBES01 was found to metabolize a range of renewable carbon-feedstocks, including glucosamine and acetyl-glucosamine, as well as sucrose, glucose, fructose, and further also glycerol, propionate, and acetate. Depending on the substrate, the strain accumulated up to ∼60% of its biomass [dry w/w] in poly(3-hydroxbutyrate), while reaching a doubling time of 1.7 h at 30◦C and an optimum osmolarity of 1 M sodium chloride and a pH of 8.8. The physiological preferences of the strain may not only enable long-term aseptic cultivation but can also facilitate the release of intracellular products through osmolysis. Development of a minimal medium also allowed the estimation of maximum PHB production rates, which were projected to exceed 5 gPHB/h. Finally, also the genetic tractability of the strain was assessed in conjugation experiments: two orthogonal plasmid-vectors were stable in the heterologous host, thereby opening the possibility of genetic engineering through the introduction of foreign genes.IMPORTANCEThe urgent need for renewable replacements for synthetic materials may be addressed through microbial biotechnology. To simplify the large-scale implementation of such bio-processes, robust cell factories that can utilize sustainable and widely available feedstocks are pivotal. To this end, non-axenic growth-associated production could reduce operational costs and enhance biomass productivity, thereby improving commercial competitiveness. Another major cost factor is downstream processing. Especially in the case of intracellular products, such as bio-polyesters. Simplified cell-lysis strategies could also further improve economic viability.
Seq-Scope Protocol: Repurposing Illumina Sequencing Flow Cells for High-Resolution Spatial Transcriptomics
Authors: Kim Yongsung , Cheng Weiqiu , Cho Chun-Seok , Hwang Yongha , Si Yichen , Park Anna , Schrank Mitchell , Hsu Jer-En , Xi Jingyue , Kim Myungjin , Pedersen Ellen , Koues Olivia I. , Wilson Thomas , Jun Goo , Kang Hyun Min , Lee Jun Hee 
Published: April 2024

ABSTRACTSpatial transcriptomics (ST) technologies represent a significant advance in gene expression studies, aiming to profile the entire transcriptome from a single histological slide. These techniques are designed to overcome the constraints faced by traditional methods such as immunostaining and RNAin situhybridization, which are capable of analyzing only a few target genes simultaneously. However, the application of ST in histopathological analysis is also limited by several factors, including low resolution, a limited range of genes, scalability issues, high cost, and the need for sophisticated equipment and complex methodologies. Seq-Scope—a recently developed novel technology—repurposes the Illumina sequencing platform for high-resolution, high-content spatial transcriptome analysis, thereby overcoming these limitations. Here we provide a detailed step-by-step protocol to implement Seq-Scope with an Illumina NovaSeq 6000 sequencing flow cell that allows for the profiling of multiple tissue sections in an area of 7 mm × 7 mm or larger. In addition to detailing how to prepare a frozen tissue section for both histological imaging and sequencing library preparation, we provide comprehensive instructions and a streamlined computational pipeline to integrate histological and transcriptomic data for high-resolution spatial analysis. This includes the use of conventional software tools for single cell and spatial analysis, as well as our recently developed segmentation-free method for analyzing spatial data at submicrometer resolution. Given its adaptability across various biological tissues, Seq-Scope establishes itself as an invaluable tool for researchers in molecular biology and histology.KEY POINTSThe protocol outlines a method for repurposing an Illumina NovaSeq 6000 flow cell as a spatial transcriptomics array, enabling the generation of high-resolution spatial datasets.The protocol introduces a streamlined data analysis pipeline that produces a spatial digital gene expression matrix suitable for various single-cell and spatial transcriptome analysis methods.The protocol allows for the capture of histology images from the same tissue section subjected to spatial transcriptomics analysis and allows users to precisely align the transcriptome dataset with the histological image using fiducial marks engraved on the flow cell surface.Leveraging commonly available Illumina equipment, the protocol offers researchers ultra-high submicrometer resolution in spatial transcriptomics analysis with a comprehensive pipeline, rapid turnaround, cost efficiency, and versatility.
Field evidence for the role of plant volatiles induced by caterpillar-derived elicitors in the prey location behavior of predatory social wasps
Authors: Grof-Tisza Patrick , Turlings Ted C.J. , Bustos-Segura Carlos , Benrey Betty 
Published: April 2024

ABSTRACTOne assumed function of herbivore-induced plant volatiles (HIPVs) is to attract natural enemies of the inducing herbivores. Field evidence for this is scarce and often indirect. Also, the assumption that elicitors in insect oral secretions that trigger the volatile emissions are essential for attraction of natural enemies has not yet been demonstrated under field conditions.After observing social wasps removing caterpillars from maize plants in an agricultural field, we hypothesized that these wasps use HIPVs to locate their prey. To test this, we conducted an experiment that simultaneously explored the importance of caterpillar oral secretions in the interaction.We found thatSpodopteracaterpillars placed on mechanically damaged plants treated with oral secretion were more likely to be attacked by wasps compared to caterpillars on plants that were only mechanically wounded. Both of the the latter treatments were considerably more attractive than plants that were only treated with oral secretion or left untreated. Subsequent analyses of headspace volatiles confirmed differences in emitted volatiles that likely account for the differential predation events across the treatments.These findings highlight the importance of HIPVs in prey location by social wasps and provide evidence for the role that elicitors play in inducing attractive odor blends.