bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neighborhood Deprivation, Hospital Quality, and Mortality After Cancer Surgery
Authors: Bonner Sidra N. , Ibrahim Andrew M. , Kunnath Nick , Dimick Justin B. , Nathan Hari 
Published: September 2022

Objective:
To evaluate if receipt of complex cancer surgery at high-quality hospitals is associated with a reduction in disparities between individuals living in the most and least deprived neighborhoods.

Background:
The association between social risk factors and worse surgical outcomes for patients undergoing high-risk cancer operations is well documented. To what extent neighborhood socioeconomic deprivation as an isolated social risk factor known to be associated with worse outcomes can be mitigated by hospital quality is less known.

Methods:
Using 100% Medicare fee-for-service claims, we analyzed data on 212,962 Medicare beneficiaries more than age 65 undergoing liver resection, rectal resection, lung resection, esophagectomy, and pancreaticoduodenectomy for cancer between 2014 and 2018. Clinical risk-adjusted 30-day postoperative mortality rates were used to stratify hospitals into quintiles of quality. Beneficiaries were stratified into quintiles based on census tract Area Deprivation Index. The association of hospital quality and neighborhood deprivation with 30-day mortality was assessed using logistic regression.

Results:
There were 212,962 patients in the cohort including 109,419 (51.4%) men with a mean (SD) age of 73.8 (5.9) years old. At low-quality hospitals, patients living in the most deprived areas had significantly higher risk-adjusted mortality than those from the least deprived areas for all procedures; esophagectomy: 22.3% versus 20.7%; P<0.003, liver resection 19.3% versus 16.4%; P<0.001, pancreatic resection 15.9% versus 12.9%; P<0.001, lung resection 8.3% versus 7.8%; P<0.001, rectal resection 8.8% versus 8.1%; P<0.001. Surgery at a high-quality hospitals was associated with no significant differences in mortality between individuals living in the most compared with least deprived neighborhoods for esophagectomy, rectal resection, liver resection, and pancreatectomy. For example, the adjusted odds of mortality between individuals living in the most deprived compared with least deprived neighborhoods following esophagectomy at low-quality hospitals (odds ratio=1.22, 95% CI: 1.14–1.31, P<0.001) was higher than at high-quality hospitals (odds ratio=0.98, 95% CI: 0.94–1.02, P=0.03).

Conclusion and Relevance:
Receipt of complex cancer surgery at a high-quality hospital was associated with no significant differences in mortality between individuals living in the most deprived neighborhoods compared with least deprived. Initiatives to increase access referrals to high-quality hospitals for patients from high deprivation levels may improve outcomes and contribute to mitigating disparities.
Three-Dimensional Mapping of Sternum Fractures from High-Energy Trauma
Authors: LaRoque Michael C. , Obermeier Michael C. , Cole Peter A. 
Published: September 2022

ABSTRACT

Background
Sternum fractures are relatively uncommon injuries which generally occur as a result of a high-energy mechanism, and are often associated with significant concomitant injuries. These injuries may result in decreased quality of life if not properly addressed, and yet are rarely operated on. The purpose of this project is to evaluate high energy sternum fracture patterns using a previously published three-dimensional (3D) computed tomography (CT) reconstruction process to produce fracture frequency maps.

Methods
Patients aged 18 years and older presenting to a level 1 trauma center with sternum fractures due to high-energy trauma between October 2013 and January 2022 were included. A 3D reconstruction and reduction was performed for each sternum using medical image processing software (Materialise NV, Leuven, Belgium). The reconstructions were subsequently overlaid onto a template sternum and normalized using bony landmarks. Fracture lines for each injured sternum were transferred onto the template, creating 3D frequency maps.

Results
A total of 120 patients met inclusion criteria. The study population had a uniform age distribution and was 57.5% male. The most common mechanism of injury was motor vehicle collision (64.2%). The breakdown of sternum fractures were isolated sternal body (55.8%), isolated manubrium (31.7%), and combined sternal body and manubrium fractures (12.5%). No xiphoid fractures were observed. Sternal body fractures were a near even mix of transverse (31.7%), oblique (32.9%), and comminuted (35.4%), while 75.5% of manubrium fractures were oblique. The most common associated injuries included rib fractures (80.8%) and traumatic brain injury (61.7%).

Conclusions
This study presents the fractures from sternum injuries in 3D, and provides insight into reproducible sternum injury patterns that have not previously been analyzed in this format. This fracture mapping technique presents numerous injury patterns simultaneously such that more frequent morphologies can be appreciated for different patient groups.

Level of Evidence
Level IV, Diagnostic Test
A Method for Identifying the Learning Curve for the Surgical Stabilization of Rib Fractures
Authors: Delman Aaron M. , Turner Kevin M. , Ammann Allison M. , Millar D A. , Goodman Michael D. , Janowak Christopher F. 
Published: September 2022

Abstract

Introduction
Surgical stabilization of rib fractures (SSRF) is an accepted efficacious treatment modality for patients with severe chest wall injuries. Despite increased adoption of SSRF, surgical learning curves are unknown. We hypothesized intraoperative duration could define individual SSRF learning curves.

Methods
Consecutive SSRF operations between January 2017 to December 2021 at a single institution were reviewed. Operative time, as measured from incision until skin closure, was evaluated by Cumulative Sum (CUSUM) methodology using a range of acceptable “missteps” to determine the learning curves. Misstep was defined by extrapolation of accumulated operative time data.

Results
83 patients underwent SSRF by 3 surgeons during this retrospective review. Average operative times ranged from 135 minutes for 2 plates to 247 minutes for 7 plates. Using polynomial regression of average operative times, 75 minutes for general procedural requirements plus 35 minutes per plate were derived as the anticipated operative times per procedure. Cumulative sum analyses using 5%, 10%, 15% and 20% incident rates for not meeting expected operative times, or “missteps” were used. An institutional learning curve between 15-55 SSRF operations was identified assuming a 90% performance rate. An individual learning curve of 15-20 operations assuming a 90% performance rate was observed. After this period operative times stabilized or decreased for surgeons A, B, and C.

Conclusion
The institutional and individual surgeon learning curves for SSRF appears to steadily improve after 15-20 operations using operative time as a surrogate for performance. The implementation of SSRF programs by trauma/acute care surgeons is feasible with an attainable learning curve.

Level of Evidence
IV
Redefining the Costal Margin: A Pilot Study
Authors: Laswi Mujahed , Lesperance Rich , Kaye Adam , Bauman Zachary , Hansen Adam , Achay Jennifer , Kubalak Steven , Eriksson Evert 
Published: September 2022

Abstract

Background
Classical teaching of rib anatomy contends that the false ribs (7-10th) fuse anteriorly to form the costal margin of the chest. Slipped rib syndrome consists of false rib subluxation into the thorax with symptomatic impingement of the intercostal nerve. We sought to determine the incidence of this anatomic finding through anatomical study of the costal margin.

Methods
Cadavers were evaluated for mobility and attachment of the 9th and 10th ribs. Experienced anatomists and chest wall surgeons conducted a standardized dissection and assessed rib tip mobility using predefined criteria. Videos of dissections were submitted to a single investigator who reviewed the findings.

Results
Costal margins of 40 cadavers (45% male) were evaluated bilaterally. The average age was 83+/-11 years. The 9th rib was found to be attached to the 8th rib 100% of the time by an interchondral cartilaginous attachment along the body of the 8th and 9th ribs. Internal subluxation was noted in 19%(15/80) and the tip of the rib was mobile in 86%(69/80) evaluations. The 10th rib was attached to the 9th rib in 18%(14/80). A “floating” 10th rib was noted in 59%(47/80) of specimens. Subluxation was noted in 33% (26/60). Half of the ribs that subluxed moved medially to the 9th rib and half moved externally. An upwardly hooked tip was noted in 10%(8/80). Ribs with a hooked tip subluxed in 63% (5/8) and all of these ribs (5/5) moved to the interior of the chest (p = 0.020).

Conclusion
The 9th rib is commonly attached to the 8th rib, but the 10th rib is often not attached to the 9th rib. Most commonly, the 10th rib is a “floating” rib. Internal subluxation of the 10th rib as well as the presence of a hooked tip may predispose individuals to the development of “Slipped Rib Syndrome”.

Level of Evidence
Level II Diagnostic Test
PASC in Solid Organ Transplant Recipients With Self-reported SARS-CoV-2 Infection
Authors: Alasfar Sami , Chiang Teresa Po-Yu , Snyder Andrew J. , Ou Michael T. , Boyarsky Brian J. , Abedon Aura T. , Alejo Jennifer L. , Cook Sydney , Cochran Willa , Brigham Emily , Parker Ann M. , Garonzik-Wang Jacqueline , Massie Allan B. , Brennan Daniel C. , Vannorsdall Tracy , Segev Dorry L. , Avery Robin K. 
Published: September 2022

Background.
Postacute sequelae of SARS-CoV-2 infection (PASC) is an increasingly recognized phenomenon and manifested by long-lasting cognitive, mental, and physical symptoms beyond the acute infection period. We aimed to estimate the frequency of PASC symptoms in solid organ transplant (SOT) recipients and compared their frequency between those with SARS-CoV-2 infection requiring hospitalization and those who did not require hospitalization.

Methods.
A survey consisting of 7 standardized questionnaires was administered to 111 SOT recipients with history of SARS-CoV-2 infection diagnosed >4 wk before survey administration.

Results.
Median (interquartile range) time from SARS-CoV-2 diagnosis was 167 d (138–221). Hospitalization for SARS-CoV-2 infection was reported in 33 (30%) participants. Symptoms after the COVID episode were perceived as following: significant trauma (53%), cognitive decline (50%), fatigue (41%), depression (36%), breathing problems (35%), anxiety (23%), dysgeusia (22%), dysosmia (21%), and pain (19%). Hospitalized patients had poorer median scores in cognition (Quick Dementia Rating System survey score: 2.0 versus 0.5, P = 0.02), quality of life (Health-related Quality of Life survey: 2.0 versus 1.0, P = 0.015), physical health (Global physical health scale: 10.0 versus 11.0, P = 0.005), respiratory status (Breathlessness, Cough and Sputum Scale: 1.0 versus 0.0, P = 0.035), and pain (Pain score: 3 versus 0 out of 10, P = 0.003). Among patients with infection >6 mo prior, some symptoms were still present as following: abnormal breathing (42%), cough (40%), dysosmia (29%), and dysgeusia (34%).

Conclusions.
SOT recipients reported a high frequency of PASC symptoms. Multidisciplinary approach is needed to care for these patients beyond the acute phase.
Diverse transcriptomic response of cellular system following low-dose exposure of mesoporous nanoparticles
Authors: Mittal Deepti , Ali Syed Azmal 
Published: September 2022

AbstractMesoporous nanoparticles (NPs) are an interesting drug delivery system that has generated considerable attention in the biomedical sector. Despite recent attempts to conduct safety assessments using traditional methods based on phenotypic data, our understanding of the underlying molecular processes produced by mesoporous NPs is still in its infancy. In the present study, RNA sequencing was used to assess the biological perturbations and the pathways induced in response to early exposure of two different mesoporous NPs; mesoporous silica NPs (MSN) and mesoporous carbon NPs (MCN) in human liver hepatocellular carcinoma cells. In order to better understand the risks associated with NPs, it is required to consider the initial low-dose exposure effects that mimic the real exposure scenario. No overt toxicity was detected in the MTT assay when performed at 6 hours at low concentrations (MCN 25 g/ml and MSN 15 g/ml) of NPs; thus, we have selected this dose for RNA sequencing analysis. Our transcriptomics analysis showed significant differences in the expression of many genes after exposure to both NPs. Surprisingly, both NPs frequently deregulated 52.9 percent of upregulated and 42 percent of downregulated genes. Gene ontology categories, in particular, revealed comparable perturbations of biological reactions in the cellular system. HepG2 cells reacted to mesoporous NPs by allowing alterations in genes involved in cytoskeleton reorganisation (ATAT1, DMTN, PTK2 and PFN2). Exposure to mesoporous NPs increased transcripts expressing ubiquitin ligase (RNF187, ARIH2, VHL, and RAB40C), transferase (FBXO3 and WDSUB1), conjugating (UBE2J2), and also proteasomal subunits (PSMD2, PSMD13) enzymes, indicating that protein turnover rates are altered in response to environmental damage. In addition, DNA damage and DNA damage checkpoint genes were upregulated, indicating that NPs induced stress in the cells. These finding showed low dosage acute exposure have comparable responses between mesoporous NPs. These results may add further knowledge in conceptualization of Safer-by-Design strategy of NPs in biomedical field.
Sympetrum sanguineum Newman, 1833 (Odonata, Anisoptera) - only one species with dimorphic females or two sibling species with identical males?
Authors: Felicia Babalean Anda 
Published: September 2022

AbstractIn this paper it is described a new Sympetrum species - Sympetrum bigeminus sp. nov. from Romania. The male of this new species is similar almost to identity with Sympetrum sanguineum from which differs only in the more conspicuous lateral thoracic sutures. The females are different from Sympetrum sanguineum by the vulvar scale, which is prominent (well visible in lateral view), incurved, with a deep concavity, and shortly bilobed, thus showing morphological characters of a different and distinct species.
Protein Kinase A Activity In The Leading Edge of Migrating Cells Is Dependent On The Activity of Focal Adhesion Kinase
Authors: Svec Kathryn V. , Kang Mingu , Howe Alan K. 
Published: September 2022

ABSTRACTProtein Kinase A (PKA) is a pleiotropic serine/threonine kinase whose localized and dynamic activity is required for cellular migration. Several cell types have shown robust PKA activity in the leading edge during migration. This activity is regulated by changes in actomyosin contractility, but the mechanism of the mechanochemical regulation of PKA remains unclear. Our ongoing investigation into this mechanism led us to discover a novel relationship between PKA and the non-receptor tyrosine kinase Focal Adhesion Kinase (FAK). Here, we find that while inhibition of actomyosin contractility leads to a relatively slow decrease in total cellular levels of phosphorylated FAK over tens of minutes, it decreases the focal adhesion-associated pool of both phospho-FAK and phospho-paxillin within two minutes, similar to the timing of the effect of inhibition of contractility on leading edge PKA activity. We then show that pharmacologic inhibition of FAK rapidly decreases leading edge PKA activity. Additionally, leading edge PKA activity is significantly reduced in FAK-null mouse embryonic fibroblasts and essentially eliminated by also silencing expression of the closely-related kinase Pyk2 in these cells. Importantly, leading edge PKA activity in FAK-null cells is rescued by re-expression of wild-type but not kinase-dead FAK. Taken together, these observations show that FAK activity is required for localized regulation of PKA during cell migration and, in so doing, establish a novel and unexpected connection between an adhesion-regulated tyrosine kinase and a serine/threonine kinase canonically downstream of G-protein coupled receptor and second-messenger signaling.
The Role of Frontal Eye Field in Saccadic Mixed-strategy Decision-making
Authors: Xie Siwei , Abunafeesa Abdullahi , Gu Yong , Yang Mingpo , Wang Xiaochun , Tu Jiahao , Thevarajah Dhushan , Dorris Michael Christopher 
Published: September 2022

AbstractGame theory can predict the distribution of choices in aggregate during mixed-strategy games, yet the neural process mediating individual probabilistic choices remains poorly understood. Here, we examined the role of frontal eye field (FEF) in a decision-making task when macaques were trained to play a mixed-strategic game – Matching Pennies – against a computer opponent. Neuronal activities of FEF neurons predicted the animals’ upcoming saccadic choices and these activities became increasingly more selective as the choice deadline approached. Subthreshold electrical micro-stimulation applied in FEF also biased choices. Extended stimulation biased choices towards the preferred FEF vector whereas early termination of stimulation biased choices away from the preferred FEF vector. By contrast, micro-stimulation biased choices in the preferred direction during a non-strategic perceptual luminance discrimination task. We conclude that FEF is causally contributing to mixed-strategy decision-making process although the timing of FEF activation contributes to the decision process in a more non-linear manner during strategic compared to perceptual decision-making.
Medial accumbens shell spiny projection neurons encode relative reward preference
Authors: Pedersen Christian E. , Gowrishankar Raajaram , Piantadosi Sean C. , Castro Daniel C. , Gray Madelyn M. , Zhou Zhe C. , Kan Shane A. , Murphy Patrick J. , O’Neill Patrick R. , Bruchas Michael R. 
Published: September 2022

AbstractMedial nucleus accumbens shell (mNAcSh) is a critical brain region for driving motivated behaviors. Despite this well-established role, the underlying reward processing of individual neurons, circuits and cell-types within mNAcSh remains largely unknown. Here, we leverage deep brain 2-photon calcium imaging through endoscopic lenses to record mNAcSh spiny projection neuron (SPN) ensemble responses to rewards of different concentrations and to reward-predictive cues across cue-reward learning. Reward responses were found to be heterogeneous and particularly differentiated based on reward concentration and cell type. A large subpopulation of reward-excited enkephalinergic SPNs were found to be specifically recruited during consumption of high concentration, unpreferred reward. A major enkephalinergic efferent projection from mNAcSh to ventral pallidum (VP) was also found to be recruited to high concentration but unpreferred reward and to causally drive low positive reward preference. Enkephalin and dynorphinergic SPNs in mNAcSh distinctly represent rewards of different preference and propagate distinct signals through efferent projections to drive consummatory behavior.
Vestigial-dependent recruitment contributes to robust patterning but is not required for wing-fate induction in Drosophila
Authors: Flores-Flores Marycruz , Muñoz-Nava Luis Manuel , Zartman Jeremiah , Nahmad Marcos 
Published: September 2022

AbstractCell recruitment is a process by which a differentiated cell induces neighboring cells to adopt its same cell fate. In Drosophila, cells expressing the wing selector gene, vestigial (vg), drive a feed-forward recruitment signal that propagates Vg expression suggesting that the Vg pattern is established as a wavefront throughout the wing pouch. However, the dynamics of Vg pattern formation does not meet this expectation. Here we show that an induction signal may drive Vg expression without Vg feedforward recruitment several cells away from the dorsal-ventral (DV) boundary. Particularly, when Vg expression is strongly inhibited either at the DV boundary or away from it, the activation of the vg Quadrant Enhancer still occurs at a distance, although the levels and precision of the pattern are compromised. Using live imaging of a dual-fluorescent reporter system, we show that contact-dependent cell recruitment does occur in wild-type conditions suggesting that a combination of a long-range induction signal and a signal-relay recruitment establishes Vg patterning in a robust manner. Overall, our findings reveal a previously unidentified role of cell recruitment as a robustness-conferring patterning mechanism.Summary StatementRobust formation of the Vg pattern is established by two mechanisms: a fast, long-range, but noisy induction signal; and a more precise signal relay, contact-dependent, cell recruitment process.
Target-template relationships in protein structure prediction and their effect on the accuracy of thermostability calculations
Authors: Lihan Muyun , Lupyan Dmitry , Oehme Daniel 
Published: September 2022

AbstractImproving protein thermostability has been a labor- and time-consuming process in industrial applications of protein engineering. Advances in computational approaches have facilitated the development of more efficient strategies to allow the prioritization of stabilizing mutants. Among these is FEP+, a free energy perturbation implementation that uses a thoroughly tested physics-based method to achieve unparalleled accuracy in predicting changes in protein thermostability. To gauge the applicability of FEP+ to situations where crystal structures are unavailable, here we have applied the FEP+ approach to homology models of 12 different proteins covering 316 mutations. By comparing predictions obtained with homology models to those obtained using crystal structures, we have identified that local rather than global sequence conservation between target and template sequence is a determining factor in the accuracy of predictions. By excluding mutation sites with low local sequence identity (<40%) to a template structure, we have obtained predictions with comparable performance to crystal structures (R2 of 0.67 and 0.63 and an RMSE of 1.20 and 1.16 kcal/mol for crystal structure and homology model predictions, respectively) for identifying stabilizing mutations when incorporating residue scanning into a cascade screening strategy. Additionally, we identify and discuss inherent limitations in sequence alignments and homology modeling protocols that translate into the poor FEP+ performance of a few select examples. Overall, our retrospective study provides detailed guidelines for the application of the FEP+ approach using homology models for protein thermostability predictions, which will greatly extend this approach to studies that were previously limited by structure availability.