bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Novel Risk Model for Predicting Dysphagia after Tongue Reconstruction: A Retrospective Multicenter Study in Japan
Authors: Araki Jun , Mori Keita , Yasunaga Yoshichika , Onitsuka Tetsuro , Yurikusa Takashi , Sakuraba Minoru , Higashino Takuya , Hashikawa Kazunobu , Ishida Katsuhiro , Sarukawa Shunji , Hamahata Atsumori , Kimata Yoshihiro , Matsumoto Hiroshi , Terao Yasunobu , Yokogawa Hideki , Sekido Mitsuru , Asato Hirotaka , Miyamoto Shimpei , Hyodo Ikuo , Nakagawa Masahiro ,   on behalf of the OPERA study group
Published: March 2023

Background:
There is no consensus on the postoperative outcomes of tongue reconstruction. Therefore, we developed a novel risk model for predicting dysphagia after tongue reconstruction.

Methods:
This retrospective study was conducted by the Oral Pharyngeal Esophageal Operation and Reconstruction Analytical group across 31 cancer centers and university hospitals in Japan. A total of 532 patients (390 [73.3%] men and 142 [26.7%] women; median age at surgery: 60 years [range, 15–88 years]) who were diagnosed with oral tongue squamous cell carcinoma and underwent tongue reconstruction following glossectomy between 2009 and 2013 were included. Independent risk factors were identified using univariate regression analysis and converted to a binary format for multivariate analysis. An integer value was assigned to each risk factor to calculate a total score capable of quantifying the risk of feeding tube dependence.

Results:
Overall, 54 patients (10.2%) required a feeding tube at the time of evaluation. Predictive factors for feeding tube dependence were advanced age, lower American Society of Anesthesiologists physical status, low body mass index, lower serum albumin, comorbid hypertension and diabetes, extended tongue defect, resection beyond the tongue, laryngeal suspension, postoperative radiation, and no functional teeth. In multivariate logistic regression analysis, age ≥58.5 years, postoperative radiation, wider tongue defect, and body mass index <21.27 kg/m 2 earned 6, 4, 3, and 2 points, respectively, for a maximum total score of 15.

Conclusions:
Our risk model provides a mathematical tool for estimating the individual risk of postoperative feeding tube dependence before tongue reconstruction.
“Clinical Outcomes of Bilateral Cleft Lip and Palate Repair with Nasoalveolar Molding and Gingivoperiosteoplasty from Birth to Facial Maturity”
Authors: Rochlin Danielle H. , Park Jenn , Parsaei Yassmin , Kalra Aneesh , Staffenberg David A. , Cutting Court B. , Grayson Barry H. , Shetye Pradip R. , Flores Roberto L. 
Published: March 2023

Background:
The long-term effect of nasoalveolar molding (NAM) on patients with bilateral cleft lip and palate (BCLP) are unknown. We report clinical outcomes of facially-mature patients with complete BCLP who underwent NAM and gingivoperiosteoplasty (GPP).

Methods”
A single-institution retrospective study of non-syndromic patients with complete BCLP who underwent NAM between 1991-2000 was performed. All study patients were followed to skeletal maturity, at which time a lateral cephalogram was obtained. Total number of cleft operations and cephalometric parameters were compared to a previously published external cohort of patients with complete and incomplete BCLP in which a minority (16.7%) underwent presurgical orthopedics prior to cleft lip repair without GPP.

Results:
Twenty-four patients with BCLP comprised the study cohort. All patients underwent GPP, 13 (54.2%) underwent alveolar bone graft, and 9 (37.5%) required speech surgery. The median number of operations per patient was 5 [interquartile range (IQR) 2], compared to 8 (IQR 3) in the external cohort (p<0.001). Average age at the time of lateral cephalogram was 18.64 (1.92) years. There was no significant difference between our cohort and the external cohort with respect to SNA [73 °(6°) vs. 75°(11°), p=0.186] or SNB [78°(6°) vs. 74°(9°), p=0.574]. Median ANB was -3°(5°) compared to -1°(7°; p=0.024). Twenty patients (83.3%) underwent orthognathic surgery.

Conclusions:
Patients with BCLP who underwent NAM and GPP were associated with significantly fewer total cleft operations and mixed midface growth outcomes at facial maturity compared to patients who did not undergo this treatment protocol.
Predictors of care discontinuity in geriatric trauma patients
Authors: Castillo-Angeles Manuel , Zogg Cheryl K. , Jarman Molly P. , Nitzschke Stephanie L. , Askari Reza , Cooper Zara , Salim Ali , Havens Joaquim M. 
Published: March 2023

BACKGROUND
Readmission to a non–index hospital, or care discontinuity, has been shown to have worse outcomes among surgical patients. Little is known about its effect on geriatric trauma patients. Our goal was to determine predictors of care discontinuity and to evaluate its effect on mortality in this geriatric population.

METHODS
This was a retrospective analysis of Medicare inpatient claims (2014–2015) of geriatric trauma patients. Care discontinuity was defined as readmission within 30 days to a non–index hospital. Demographic and clinical characteristics (including readmission diagnosis category) were collected. Multivariate logistic regression analysis was performed to identify predictors of care discontinuity and to assess its association with mortality.

RESULTS
We included 754,313 geriatric trauma patients. Mean age was 82.13 years (SD, 0.50 years), 68% were male and 91% were White. There were 21,615 (2.87%) readmitted within 30 days of discharge. Of these, 34% were readmitted to a non–index hospital. Overall 30-day mortality after readmission was 25%. In unadjusted analysis, readmission to index hospitals was more likely to be due to surgical infection, GI complaints, or cardiac/vascular complaints. After adjusted analysis, predictors of care discontinuity included readmission diagnoses, patient- and hospital-level factors. Care discontinuity was not associated with mortality (OR, 0.93; 95% confidence interval, 0.86–1.01).

CONCLUSION
More than a third of geriatric trauma patients are readmitted to a non–index hospital, which is driven by readmission diagnosis, travel time and hospital characteristics. However, unlike other surgical settings, this care discontinuity is not associated with increased mortality. Further work is needed to understand the reasons for this and to determine which standardized processes of care can benefit this population.

LEVEL OF EVIDENCE
Prognostic and Epidemiological; Level IV.
A Virtual Photovoice Study of Older African Americans Perceptions of Neurovascular Clinical Trials
Authors: Shaw Ashley R. , Lofton Saria , Vidoni Eric D. 
Published: March 2023

Background:
Alzheimer disease (AD) poses a major public health crisis, especially among African Americans (AAs) who are up to 3 times more likely to develop AD compared with non-Hispanic Whites. Moreover, cardiovascular risk factors represent a precursor to cognitive decline, which contributes to racial/ethnic disparities seen within AD. Despite these disparities, AAs are underrepresented in neurovascular research. The purpose of this qualitative virtual photovoice project is to explore how older Midwestern AAs perceive neurovascular clinical trials.

Methods:
Five photovoice sessions were held virtually over a 3-month period. Participants took photos each week that captured the salient features of their environment that described their perceptions and experiences related to neurovascular clinical trials. Structured discussion using the SHOWED method was used to generate new understandings about the perspectives and experiences in neurovascular clinical trials. Data was analyzed using strategies in participatory visual research.

Results:
A total of 10 AAs aged 55 years and older participated and a total of 6 themes emerged from the photovoice group discussions.

Conclusion:
Findings from this study inform the development of culturally appropriate research protocols and effective recruitment strategies to enhance participation among older AAs in neurovascular clinical trials.
Creatinine Clearance May Predict Goal Enoxaparin Dose in Trauma
Authors: Park Greigory , Dhillon Navpreet K , Fierro Nicole M , Drevets Peter , Stupinski John , Ley Eric J 
Published: March 2023

Background:
Guidelines for enoxaparin dosing after trauma recommend an initial dose of 40mg twice daily for most patients and then adjusting by anti-Xa levels. Previous studies indicated higher enoxaparin doses are necessary with higher creatinine clearance levels (CrCl). We sought to determine if the goal enoxaparin dose correlates with the admission CrCl to reduce the reliance on measuring anti-Xa levels.

Study Design:
A retrospective review was conducted of patients admitted to an urban, academic Level 1 trauma center from April 2017 to February 2020. Patients started on enoxaparin who reached goal anti-Xa trough levels were included, and patients were excluded if they did not reach goal anti-Xa levels. Data collection included patient demographics, injury characteristics, admission CrCl, and the final enoxaparin dose. CrCl was then correlated with the final enoxaparin dose.

Results:
Of the 421 patients included, mean age was 46.6 years and 73% were male. The median goal enoxaparin dose was 40mg twice daily. Mean CrCl significantly increased with increasing doses of enoxaparin (20 mg twice daily: 69.2 mL/min, 30 mg twice daily: 89mL/min, 40 mg twice daily:112.8 mL/min, 50 mg twice daily:140.5mL/min, 60 mg twice daily: 147.4 mL/min, and 70mg twice daily: 140 mL/min 69.2.0 mL/min; p<0.01).

Conclusions:
Admission CrCl may predict the enoxaparin dose required to achieve adequate anti-Xa levels. Our data indicate that CrCl of approximately 70mL/min, 90mL/min, 110mL/min, 140ml/min and 150ml/min may predict the twice daily enoxaparin doses of 20mg, 30mg, 40mg, 50mg, and 60mg respectively. CrCl dosing guidance may reduce the time to goal anti-Xa levels and reduce the frequency of anti-Xa measurements. Further research is necessary, and enoxaparin dosing should continue to be monitored by anti-Xa levels.
Universal recording of cell-cell contactsin vivofor interaction-based transcriptomics
Authors: Nakandakari-Higa Sandra , Canesso Maria C. C. , Walker Sarah , Chudnovskiy Aleksey , Jacobsen Johanne T. , Bilanovic Jana , Parigi S. Martina , Fiedorczuk Karol , Fuchs Elaine , Bilate Angelina M. , Pasqual Giulia , Mucida Daniel , Pritykin Yuri , Victora Gabriel D. 
Published: March 2023

AbstractCellular interactions are essential for tissue organization and functionality. In particular, immune cells rely on direct and usually transient interactions with other immune and non-immune populations to specify and regulate their function. To study these “kiss-and-run” interactions directlyin vivo, we previously developed LIPSTIC (Labeling Immune Partnerships by SorTagging Intercellular Contacts), an approach that uses enzymatic transfer of a labeled substrate between the molecular partners CD40L and CD40 to label interacting cells. Reliance on this pathway limited the use of LIPSTIC to measuring interactions between CD4+helper T cells and antigen presenting cells, however. Here, we report the development of a universal version of LIPSTIC (uLIPSTIC), which can record physical interactions both among immune cells and between immune and non-immune populations irrespective of the receptors and ligands involved. We show that uLIPSTIC can be used, among other things, to monitor the priming of CD8+T cells by dendritic cells, reveal the cellular partners of regulatory T cells in steady state, and identify germinal center (GC)-resident T follicular helper (Tfh) cells based on their ability to interact cognately with GC B cells. By coupling uLIPSTIC with single-cell transcriptomics, we build a catalog of the immune populations that physically interact with intestinal epithelial cells (IECs) and find evidence of stepwise acquisition of the ability to interact with IECs as CD4+T cells adapt to residence in the intestinal tissue. Thus, uLIPSTIC provides a broadly useful technology for measuring and understanding cell–cell interactions across multiple biological systems.
Direct Comparison of Lysine vs. Site-specific Protein Surface Immobilization in Single-molecule Mechanical Assays
Authors: Liu Haipei , Liu Zhaowei , Santos Mariana Sá , Nash Michael A. 
Published: March 2023

AbstractSingle-molecule force spectroscopy (SMFS) is a powerful method for studying folding states and mechanical properties of proteins, however, it requires surface immobilization of proteins onto force-transducing probes such as cantilevers or microscale beads. A common immobilization method relies on coupling surface-exposed lysine residues to carboxylated surfaces using 1-ethyl-3-(3-dimethyl-aminopropyl) carbodiimide and N-hydroxysuccinimide (EDC/NHS). Because proteins typically contain many lysine groups, this strategy results in a heterogeneous distribution of tether positions in the molecule. Genetically encoded peptide tags (e.g., ybbR) provide alternative chemistries for achieving site-specific immobilization, but thus far a direct comparison of site-specific vs. lysine-based immobilization strategies to assess effects on the observed mechanical properties was lacking. Here, we directly compared lysine- vs. ybbR-based protein immobilization in SMFS assays using several model polyprotein systems. Our results show that lysine-based immobilization results in significant signal deterioration for monomeric streptavidin-biotin interactions, and loss of the ability to correctly classify unfolding pathways in a multipathway Cohesin-Dockerin system. We developed a mixed immobilization approach where a site-specifically tethered ligand was used to probe surface-bound proteins immobilized through lysine groups, and found partial recovery of specific signals. The mixed immobilization approach represents a viable alternative for mechanical assays onin vivo-derived samples or other proteins of interest where genetically encoded tags are not feasible.
Leptomeningeal anti-tumor immunity follows unique signaling principles
Authors: Remsik Jan , Tong Xinran , Kunes Russell Z. , Li Min Jun , Osman Ahmed , Chabot Kiana , Sener Ugur T. , Wilcox Jessica A. , Isakov Danielle , Snyder Jenna , Bale Tejus A. , Chaligné Ronan , Pe’er Dana , Boire Adrienne 
Published: March 2023

AbstractMetastasis to the cerebrospinal fluid (CSF)-filled leptomeninges, or leptomeningeal metastasis (LM), represents a fatal complication of cancer. Proteomic and transcriptomic analyses of human CSF reveal a substantial inflammatory infiltrate in LM. We find the solute and immune composition of CSF in the setting of LM changes dramatically, with notable enrichment in IFN-γ signaling. To investigate the mechanistic relationships between immune cell signaling and cancer cells within the leptomeninges, we developed syngeneic lung, breast, and melanoma LM mouse models. Here we show that transgenic host mice, lacking IFN-γ or its receptor, fail to control LM growth. Overexpression ofIfngthrough a targeted AAV system controls cancer cell growth independent of adaptive immunity. Instead, leptomeningeal IFN-γ actively recruits and activates peripheral myeloid cells, generating a diverse spectrum of dendritic cell subsets. These migratory, CCR7+ dendritic cells orchestrate the influx, proliferation, and cytotoxic action of natural killer cells to control cancer cell growth in the leptomeninges. This work uncovers leptomeningeal-specific IFN-γ signaling and suggests a novel immune-therapeutic approach against tumors within this space.
Drosophilamodel to clarify the pathological significance of OPA1 in autosomal dominant optic atrophy
Authors: Nitta Yohei , Osaka Jiro , Maki Ryuto , Hakeda-Suzuki Satoko , Suzuki Emiko , Ueki Satoshi , Suzuki Takashi , Sugie Atsushi 
Published: March 2023

AbstractAutosomal dominant optic atrophy (DOA) is a progressive form of blindness caused by degeneration of retinal ganglion cells and their axons, mainly caused by mutations in the OPA1 mitochondrial dynaminlikeGTPase (OPA1) gene.OPA1encodes a dynamin-like GTPase present in the mitochondrial inner membrane. When associated with OPA1 mutations, DOA can present not only ocular symptoms but also multi-organ symptoms (DOA plus). DOA plus often results from point mutations in the GTPase domain, which are assumed to have dominant negative effects. However, the presence of mutations in the GTPase domain does not always result in DOA plus. Therefore, an experimental system to distinguish between DOA and DOA plus is needed. In this study, we found that loss-of-function mutations of thedOPA1gene inDrosophilacan imitate the pathology of optic nerve degeneration observed in DOA. We successfully rescued this degeneration by expressing the humanOPA1(hOPA1) gene, indicating thathOPA1is functionally interchangeable withdOPA1in the fly system. However, mutations previously identified did not ameliorate thedOPA1deficiency phenotype. By expressing both WT and DOA plus mutanthOPA1forms in the optic nerve ofdOPA1mutants, we observed that DOA plus mutations suppressed the rescue, facilitating the distinction between loss-of-function and dominant negative mutations inhOPA1. This fly model aids in distinguishing DOA from DOA plus and guides initialhOPA1mutation treatment strategies.
The ATP-bound State of the Uncoupling Protein 1 (UCP1) from Molecular Simulations
Authors: Jacobsen Luise , Lydersen Laura , Khandelia Himanshu 
Published: March 2023

AbstractThe uncoupling protein 1 (UCP1) dissipates the transmembrane (TM) proton gradient in the inner mitochondrial membrane (IMM) by leaking protons across the membrane, producing heat in the process. Such non-shivering production of heat in brown adipose tissue can combat obesity-related diseases. UCP1 associated proton leak is activated by free fatty acids and inhibited by purine nucleotides. The mechanism of proton leak remains unknown, in part due to the unavailability of high-resolution structures of the protein. As a result, the binding site of the activators (fatty acids) and inhibitors (nucleotides) is unknown. Using molecular dynamics simulations, we generate a conformational ensemble of UCP1. Using Metadynamics-based free energy calculations, we converge on the most likely ATP-bound conformation of UCP1. Our conformational ensemble provides a molecular basis of a breadth of prior biochemical data available for UCP1. Based on the simulations, we make the following testable predictions about the mechanisms of activation of proton leak and proton leak inhibition by ATP: (1) R277 plays the dual role of stabilising ATP at the binding site for inhibition, and acting as a proton surrogate for D28 in the absence of a proton during proton transport (2) the binding of ATP to UCP1 is mediated by residues R84, R92, R183, and S88 (3) R92 shuttles ATP from the E191-R92 gate in the inter-membrane space to the nucleotide binding site, and serves to increase ATP affinity (4) ATP can inhibit proton leak by controlling the ionisation states of matrix facing lysine residues such as K269 and K56 and (5) fatty acids can bind to UCP1 from the IMM either via the cavity between TM1 and TM2 or between TM5 and TM6. Our simulations set the platform for future investigations into the proton transport and inhibition mechanisms of UCP1.
Novel Endogenous Engineering Platform for Robust Loading and Delivery of Functional mRNA by Extracellular Vesicles
Authors: Zickler Antje M. , Liang Xiuming , Gupta Dhanu , Mamand Doste , Luca Mariacristina De , Corso Giulia , Errichelli Lorenzo , Hean Justin , Sen Titash , Elsharkasy Omnia M. , Kamei Noriyasu , Niu Zheyu , Zhou Guannan , Zhou Houze , Roudi Samantha , Wiklander Oscar P. B. , Görgens André , Nordin Joel Z. , Castilla-Llorente Virginia , Andaloussi Samir EL 
Published: March 2023

ABSTRACTMessenger RNA (mRNA) has emerged as an attractive therapeutic molecule for a plethora of clinical applications. Forin vivofunctionality, mRNA therapeutics require encapsulation into effective, stable, and safe delivery systems to protect the cargo from degradation and reduce immunogenicity. Here, a bioengineering platform for efficient mRNA loading and functional delivery using bionormal nanoparticles, Extracellular Vesicles (EVs), is established by expressing a highly specific RNA-binding domain fused to CD63 in EV producer cells stably expressing the target mRNA. The additional combination with a fusogenic endosomal escape moiety, VSVg, enables functional mRNA deliveryin vivoat doses substantially lower than currently used clinically with synthetic lipid-based nanoparticles. Importantly, the application of EVs loaded with effective cancer immunotherapy proves highly effective in an aggressive melanoma mouse model. This technology addresses substantial drawbacks currently associated with EV-based nucleic acid delivery systems and is a leap forward to clinical EV applications.Graphical Abstract(Figure created using BioRender)
Genetic and Environmental interactions contribute to immune variation in rewilded mice
Authors: Oyesola Oyebola , Downie Alexander E. , Howard Nina , Barre Ramya S. , Kiwanuka Kasalina , Zaldana Kimberly , Chen Ying-Han , Menezes Arthur , Lee Soo Ching , Devlin Joseph , Mondragón-Palomino Octavio , Silva Souza Camila Oliveira , Herrmann Christin , Koralov Sergei , Cadwell Ken , Graham Andrea L. , Loke P’ng 
Published: March 2023

AbstractThe relative and synergistic contributions of genetics and environment to inter-individual immune response variation remain unclear, despite its implications for understanding both evolutionary biology and medicine. Here, we quantify interactive effects of genotype and environment on immune traits by investigating three inbred mouse strains rewilded in an outdoor enclosure and infected with the parasite,Trichuris muris. Whereas cytokine response heterogeneity was primarily driven by genotype, cellular composition heterogeneity was shaped by interactions between genotype and environment. Notably, genetic differences under laboratory conditions can be decreased following rewilding, and variation in T cell markers are more driven by genetics, whereas B cell markers are driven more by environment. Importantly, variation in worm burden is associated with measures of immune variation, as well as genetics and environment. These results indicate that nonheritable influences interact with genetic factors to shape immune variation, with synergistic impacts on the deployment and evolution of defense mechanisms.
Emergence of power-law distributions in protein-protein interaction networks through study bias
Authors: Blumenthal David B. , Lucchetta Marta , Kleist Linda , Fekete Sándor P. , List Markus , Schaefer Martin H. 
Published: March 2023

AbstractProtein-protein interaction (PPI) networks are power-law-distributed. However, the experimental procedures for detecting PPIs are affected by technical and study bias. For instance, cancer-associated proteins have received disproportional attention. Moreover, bait proteins in large-scale experiments tend to have many false-positive interaction partners. This raises the question of whether PL distributions in observed PPI networks could be explained by these biases alone. To assess this question, we studied the degree distribution of thousands of PPI networks of controlled provenance. Our findings are supported by mathematical models and extensive simulations and indicate that study bias and technical bias suffice to produce the observed PL distribution. It is, hence, problematic to derive hypotheses about the degree distribution and the true biological interactome from the PL distributions in observed PPI networks. Our study casts doubt on the use of the PL property of biological networks as a modeling assumption or quality criterion in network biology.