bluuebunny/crossref_metadata_2025 huggingface dataset:
The Standardized Inclusive Numeric Academic Index
Authors: Margulies Ilana G. , Sayegh Farah , Li Hanzhou , Paine Kaitlyn M. , Zoghbi Yasmina , Warburton Andrew , Ibelli Taylor J. , Taub Peter J.
Published: June 2022

Purpose

Academic productivity is a poorly defined metric that is commonly used to determine faculty career advancement. While various indices incorporate scholarly activity, no specific index assimilates the perceived importance of a variety of academic accomplishments a physician may make. Herein, the development and validation of an algorithm to generate an academic productivity score based on surveying physicians nationwide are described.

Methods

From 2016 to 2018, an online cross-sectional survey was distributed to faculty members at an academic institution and plastic surgeons from different academic levels nationwide. Respondents were presented with randomized, binary comparisons of 42 different achievements of an academic physician and asked to choose the more important achievement. Descriptive statistics of demographics and “win rates” of each achievement were reported and an algorithm for academic productivity scoring was designed. To validate the proposed index, 30 curricula vitae of academic surgeons were anonymized and ranked in order of increasing academic achievement by 6 volunteers. Interrater reliability was assessed by Krippendorff α (α ≥ 0.800).

Results

Survey respondents completed an average of 116 (SD, 97.6) comparisons each, generating a total of 14,736 ranked comparisons. Of the 42 variables, the highest win rates were attained by being the dean of a medical school (0.90) and editor of a medical journal (0.88). The lowest win rates were attained by industry spokesperson (0.1) and members of the local medical society (0.1). Initial validity evidence found the interrater reliability for the 6 rankers to have a Krippendorff α value of 0.843. The interrater reliability between the average rater ranking and the algorithm-generated ranking had a Krippendorff α value of 0.925.

Conclusions

The present study demonstrates that the standardized inclusive numeric academic index may be used as a valid, comprehensive measure of academic productivity. Future studies should assess its application across different medical specialties.
The Social Vulnerability Index and Long-term Outcomes After Traumatic Injury
Authors: Herrera-Escobar Juan P. , Uribe-Leitz Tarsicio , Wang Joyce , Orlas Claudia P. , Moheb Mohamad El , Lamarre Taylor E. , Ahmad Niha , Hau Ka Man , Jarman Molly , Levy-Carrick Nomi C. , Sanchez Sabrina E. , Kaafarani Haytham M. A. , Salim Ali , Nehra Deepika
Published: June 2022

Objective:

The aim of this study was to evaluate the Social Vulnerability Index (SVI) as a predictor of long-term outcomes after injury.

Background:

The SVI is a measure used in emergency preparedness to identify need for resources in the event of a disaster or hazardous event, ranking each census tract on 15 demographic/social factors.

Methods:

Moderate-severely injured adult patients treated at 1 of 3 level–1 trauma centers were prospectively followed 6 to 14 months post-injury. These data were matched at the census tract level with overall SVI percentile rankings. Patients were stratified based on SVI quartiles, with the lowest quartile designated as low SVI, the middle 2 quartiles as average SVI, and the highest quartile as high SVI. Multivariable adjusted regression models were used to assess whether SVI was associated with long-term outcomes after injury.

Results:

A total of 3153 patients were included [54% male, mean age 61.6 (SD = 21.6)]. The median overall SVI percentile rank was 35th (IQR: 16th–65th). compared to low SVI patients, high SVI patients were more likely to have new functional limitations [odds ratio (OR), 1.51; 95% confidence interval (CI), 1.19–1.92), to not have returned to work (OR, 2.01; 95% CI, 1.40–2.89), and to screen positive for post-traumatic stress disorder (OR, 1.56; 95% CI, 1.12–2.17). Similar results were obtained when comparing average with low SVI patients, with average SVI patients having significantly worse outcomes.

Conclusions:

The SVI has potential utility in predicting individuals at higher risk for adverse long-term outcomes after injury. This measure may be a useful needs assessment tool for clinicians and researchers in identifying communities that may benefit most from targeted prevention and intervention efforts.
Visual Field Defect Patterns Associated With Lesions of the Retrochiasmal Visual Pathway
Authors: Cho Juno , Liao Eric , Trobe Jonathan D.
Published: June 2022

Background:

Perimetry is widely used in the localization of retrochiasmal visual pathway lesions. Although macular sparing, homonymous paracentral scotomas, and quadrantanopias are regarded as features of posterior retrochiasmal visual pathway lesions, incongruous hemianopia is regarded as a hallmark of anterior lesions. Recent studies have questioned the specificity of these defect patterns.

Methods:

Retrospective record review conducted in a single, academic, medical center using an electronic search engine with the terms ““homonymous hemianopia,” “optic tract,” “temporal lobectomy,” “visual field defect,” and “MRI.” Patients were included if they had reliable, automated, static visual fields, high-quality reviewable MRI scans, and pertinent lesions. MRI lesions were assigned to 1 of 6 retrochiasmal visual pathway segments by the study neuroradiologist. Two study authors independently reviewed the visual fields and designated 10 different defect patterns.

Results:

From an original cohort of 256 cases, only 83 had MRI-defined lesions that were limited to particular retrochiasmal segments and had visual field defect patterns that allegedly permitted localization to those particular segments. The 5 contralateral nerve fiber bundle defects were exclusive to optic tract tumors with rostral extension. Pie-in-the-sky defects were exclusive to Meyer loop lesions. Among 22 fields with macular sparing, 86% arose from the visual cortex or posterior optic radiations. Among 31 fields with homonymous quadrantanopias, 77% arose from Meyer loop, visual cortex, or posterior optic radiations. Among 13 fields with homonymous paracentral scotomas, 69% arose from visual cortex or posterior optic radiations. Optic tract lesions accounted for 70% of incongruous hemianopias but that pattern occurred uncommonly.

Conclusion:

In correlating discrete MRI-defined retrochiasmal lesions with visual field defect patterns identified on static perimetry, this study showed that macular sparing, homonymous paracentral scotomas, and quadrantanopias localized to the visual cortex and posterior optic radiations segments but not exclusively. It has differed from an earlier study in showing that incongruous hemianopias occur predominantly from optic tract lesions.
Accuracy of Visual Fields in Localizing MRI Lesions in Posterior Cerebral Artery Infarction
Authors: Cho Juno , Liao Eric , Trobe Jonathan D.
Published: June 2022

Background:

The representation of the visual field in visual cortex was established over a century ago by correlating perimetric defects with the estimated location of war wounds. The availability of high-definition MRI offers the possibility of more precise correlation.

Methods:

Homonymous hemianopias disclosed on automated visual fields (HVFs) were drawn from an electronic medical record search from 2009 to 2020 at the Michigan Medicine, a tertiary care academic medical center. The patterns of the visual field defects (VFDs) were interpreted by a consensus of 2 authors. The VFDs were correlated with the location of MRI lesions in 92 patients with posterior cerebral artery (PCA) domain ischemic strokes, as determined by the neuroradiologist author, who was masked as to the VFDs.

Results:

Among the 77 VFDs confined to 1 hemifield, 74 (96%) correctly predicted the side of the visual cortex lesion. In 3 cases, the MRI lesion in the opposite cerebral hemisphere was not foretold. Among the 15 VFDs present in both hemifields, 5 (33.3%) overestimated the MRI lesions, which were evident in only 1 hemisphere. Among the 30 VFDs confined to 1 quadrant, 29 (97%) correctly predicted the lesioned visual cortex quadrant. However, 14 VFDs failed to predict MRI lesions present in both superior and inferior visual cortex quadrants on the same side. Those unpredicted lesions mostly had subtle or indistinct signal abnormalities or were confined to anterior visual cortex, an area that is inaccessible with the HVF test protocol used in this study.

Conclusion:

In this study of PCA ischemic stroke, VFDs limited to 1 hemifield were accurate in locating the side and quadrant of the MRI visual cortex lesions. However, the quadrantic VFDs sometimes failed to predict that the lesions involved both the superior and inferior quadrants on the same side, largely because those lesions had subtle imaging features that defied accurate radiologic assessment or were out of the reach of the visual field test protocol.
Minimum Technical Requirements for Performing Ambulatory EEG
Authors: Tatum William O. , Halford Jonathan J. , Olejniczak Piotr , Selioutski Olga , Grigg-Damberger Madeleine M. , Gloss David , Acharya Jayant , Schuele Stephan , Sinha Saurabh R. , Tsuchida Tammy , Drislane Frank W.
Published: June 2022

Ambulatory EEG (AEEG) devices offer portable, multichannel, digital EEG recording with or without video in the patient's natural environment. The technology applied for AEEG recording is like the technology for routine EEG and inpatient long-term video-EEG monitoring but designed to be compact and wearable. Computer-based AEEG technology is well-suited to digital recording, signal processing, and visual display. However, acquiring interpretable EEG outside of the hospital setting presents its own technical challenges. Published guidelines have established technical standards for performing routine EEG and inpatient video-EEG monitoring, but technical standards for AEEG are lacking. Therefore, this guideline provides minimal technical standards for the performance of AEEG which are essential to ensure the quality of studies for clinical and research practice. We expect these minimum standards to evolve over time with improved performance and advances in the technology.
Democratizing Flexible Endoscopy Training: Noninferiority Randomized Trial Comparing a Box-Trainer vs a Virtual Reality Simulator to Prepare for the Fundamental of Endoscopic Surgery Exam
Authors: Mascagni Pietro , Spota Andrea , Pizzicannella Margherita , Laracca Giovanni Guglielmo , Svendrovski Anton , Fiorillo Claudio , Lim Sun Gyo , Oudkerk Pool Marinka , Dallemagne Bernard , Marescaux Jacques , Swanstrom Lee , Shlomovitz Eran , Perretta Silvana
Published: June 2022

BACKGROUND:

A considerable number of surgical residents fail the mandated endoscopy exam despite having completed the required clinical cases. Low-cost endoscopy box trainers (BTs) could democratize training; however, their effectiveness has never been compared with higher-cost virtual reality simulators (VRSs).

STUDY DESIGN:

In this randomized noninferiority trial, endoscopy novices trained either on the VRS used in the Fundamental of Endoscopic Surgery manual skills (FESms) exam or a validated BT—the Basic Endoscopic Skills Training (BEST) box. Trainees were tested at fixed timepoints on the FESms and on standardized ex vivo models. The primary endpoint was FESms improvement at 1 week. Secondary endpoints were FESms improvement at 2 weeks, FESms pass rates, ex vivo tests performance, and trainees’ feedback.

RESULTS:

Seventy-seven trainees completed the study. VRS and BT trainees showed comparable FESms improvements (25.16 ± 14.29 vs 25.58 ± 11.75 FESms points, respectively; p = 0.89), FESms pass rates (76.32% vs 61.54%, respectively; p = 0.16) and total ex vivo tasks completion times (365.76 ± 237.56 vs 322.68 ± 186.04 seconds, respectively; p = 0.55) after 1 week. Performances were comparable also after 2 weeks of training, but FESms pass rates increased significantly only in the first week. Trainees were significantly more satisfied with the BT platform (3.97 ± 1.20 vs 4.81 ± 0.40 points on a 5-point Likert scale for the VRS and the BT, respectively; p < 0.001).

CONCLUSIONS:

Simulation-based training is an effective means to develop competency in endoscopy, especially at the beginning of the learning curve. Low-cost BTs like the BEST box compare well with high-tech VRSs and could help democratize endoscopy training.
Number of Worrisome Features and Risk of Malignancy in Intraductal Papillary Mucinous Neoplasm
Authors: Zelga Piotr , Hernandez-Barco Yasmin G , Qadan Motaz , Ferrone Cristina R , Kambadakone Avinash , Horick Nora , Jah Asif , Warshaw Andrew L , Lillemoe Keith D , Balakrishnan Anita , Fernández-del Castillo Carlos
Published: June 2022

BACKGROUND:

The 2017 revised International Association of Pancreatology guidelines for management of intraductal papillary mucinous neoplasm (IPMN) describe worrisome features (WF) and high-risk stigmata (HRS), recommending resection in the latter and further work-up and close surveillance for patients with WF. The effect of multiple WF on the likelihood of malignancy has not been evaluated.

STUDY DESIGN:

Eight hundred ten patients who underwent pancreatic resection for IPMN in 2 tertiary referral centers were identified from prospective institutional databases. Patients were retrospectively categorized into subgroups according to the number of WF or HRS and presence of malignancy, defined as high-grade dysplasia (HGD) or invasive cancer on final pathology

RESULTS:

Three hundred seventy-nine (47%) patients had HRS, 370 (46%) had 1 or more WF, and 61 patients (7%) had neither. Malignancy was present in 70% (n = 267) of patients with HRS and in 30% (n = 127) of those with WF. Only 3 of 61 patients without WF/HRS had malignancy, and all only in the form of HGD. The risk of malignancy increased in a stepwise fashion with the number of WF, to 22%, 34%, and 59% with 1, 2, and 3 WF, respectively (p = 0.001), and reached 100% in patients with 4 or more WF. Although the relative risks differed for particular WF, the areas under the curve were not statistically different.

CONCLUSION:

We confirm that presence of HRS in IPMN is associated with a very high likelihood of malignancy. The presence of a single WF has a malignancy risk of 22%, and additional WF increase this risk significantly. When 3 or more WF are present, the risk is similar to that of HRS.
Five-Year Analysis of the MBSAQIP Database: Are We Getting Better?
Authors: Clapp Benjamin , Janik Michal R , El Badaoui Joseph , Dodoo Christopher , Portela Ray , Kellogg Todd , Ghanem Omar M
Published: June 2022

BACKGROUND:

The MBSAQIP has been used to evaluate risk and create risk models. Previous studies have determined what complications matter most.

STUDY DESIGN:

This study was a registry-based analysis of patients who underwent laparoscopic Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) between January 1, 2015, and December 31, 2019, at centers participating in MBSAQIP. Cases were identified using Current Procedural Terminology. Patients less than 18 years old were excluded. A chi-square test was used to assess differences in the prevalence of complications and effects across years. Using a multivariable Poisson regression model with a link log and robust estimation, prevalence ratio estimates and 95% CI were obtained.

RESULTS:

A total of 690,770 observations met the inclusion criteria. Mean (SD) age was 44.5 (±12.0) years, and mean (SD) BMI was 45.2 kg/m2 (±7.9). SG cases accounted for 73.45% of all observations. There was a significant relative reduction in readmissions, end-organ dysfunction, and all-cause mortality from 2015 to 2019 in the SG subgroup. There were also noticeable reductions in 30-day readmission, ICU admission, and end-organ dysfunction in the RYGB subgroup. For complications, bleeding, postoperative pneumonia, and stroke were significantly decreased in the RYGB subgroup, but only bleeding was significantly decreased in the SG subgroup during the 5-year study period.

CONCLUSIONS:

There has been a continuous improvement in several (but not all) outcomes through the years that the MBSAQIP has been collecting data. Different outcomes were reduced between the SG and RYGB subgroups, and the decrease in all-cause mortality was only noted in the SG subgroup.
Artificial Intelligence Methods and Artificial Intelligence-Enabled Metrics for Surgical Education: A Multidisciplinary Consensus
Authors: Vedula S Swaroop , Ghazi Ahmed , Collins Justin W , Pugh Carla , Stefanidis Dimitrios , Meireles Ozanan , Hung Andrew J , Schwaitzberg Steven , Levy Jeffrey S , Sachdeva Ajit K ,   and the Collaborative for Advanced Assessment of Robotic Surgical Skills
Published: June 2022

BACKGROUND:

Artificial intelligence (AI) methods and AI-enabled metrics hold tremendous potential to advance surgical education. Our objective was to generate consensus guidance on specific needs for AI methods and AI-enabled metrics for surgical education.

STUDY DESIGN:

The study included a systematic literature search, a virtual conference, and a 3-round Delphi survey of 40 representative multidisciplinary stakeholders with domain expertise selected through purposeful sampling. The accelerated Delphi process was completed within 10 days. The survey covered overall utility, anticipated future (10-year time horizon), and applications for surgical training, assessment, and feedback. Consensus was agreement among 80% or more respondents. We coded survey questions into 11 themes and descriptively analyzed the responses.

RESULTS:

The respondents included surgeons (40%), engineers (15%), affiliates of industry (27.5%), professional societies (7.5%), regulatory agencies (7.5%), and a lawyer (2.5%). The survey included 155 questions; consensus was achieved on 136 (87.7%). The panel listed 6 deliverables each for AI-enhanced learning curve analytics and surgical skill assessment. For feedback, the panel identified 10 priority deliverables spanning 2-year (n = 2), 5-year (n = 4), and 10-year (n = 4) timeframes. Within 2 years, the panel expects development of methods to recognize anatomy in images of the surgical field and to provide surgeons with performance feedback immediately after an operation. The panel also identified 5 essential that should be included in operative performance reports for surgeons.

CONCLUSIONS:

The Delphi panel consensus provides a specific, bold, and forward-looking roadmap for AI methods and AI-enabled metrics for surgical education.
Effect of Metformin on HIF-1α Signaling and Postoperative Adhesion Formation
Authors: Biller Marvin L , Tuffs Christopher , Bleul Marc , Tran Dinh Thien-An , Dupovac Mareen , Keppler Ulrich , Harnoss Jonathan M , Probst Pascal , Schneider Martin , Strowitzki Moritz J
Published: June 2022

BACKGROUND:

Peritoneal adhesion formation is common after abdominal surgery and results in severe complications. Tissue hypoxia is one of the main drivers of peritoneal adhesions. Thus, we determined the clinical role of hypoxia-inducible factor (HIF)-1 signaling in peritoneal adhesions and investigated whether the biguanide antidiabetic drug metformin shows HIF-inhibitory effects and could be repurposed to prevent adhesion formation.

STUDY DESIGN:

As part of the ReLap study (DRKS00013001), adhesive tissue from patients undergoing relaparotomy was harvested and graded using the adhesion grade score. HIF-1 signaling activity within tissue biopsies was determined and correlated with adhesion severity. The effect of metformin on HIF-1 activity was analyzed by quantification of HIF target gene expression and HIF-1 protein stabilization in human mesothelial cells and murine fibroblast under normoxia and hypoxia. Mice were treated with vehicle or metformin 3 days before and until 7 days after induction of peritoneal adhesions; alternatively, metformin treatment was discontinued 48 hours before induction of peritoneal adhesions.

RESULTS:

HIF-1 signaling activity correlated with adhesion severity in patient biopsies. Metformin significantly mitigated HIF-1 activity in vitro and in vivo. Oral treatment with metformin markedly prevented adhesion formation in mice even when the treatment was discontinued 48 hours before surgery. Although metformin treatment did not alter macrophage polarization, metformin reduced proinflammatory leucocyte infiltration and attenuated hypoxia-induced profibrogenic expression patterns and myofibroblast activation.

CONCLUSIONS:

Metformin mitigates adhesion formation by inhibiting HIF-1-dependent (myo)fibroblast activation, conferring an antiadhesive microenvironment after abdominal surgery. Repurposing the clinically approved drug metformin might be useful to prevent or treat postoperative adhesions.
Impact of Clinician Linkage on Unequal Access to High-Volume Hospitals for Colorectal Cancer Surgery
Authors: McDermott James , Wang Haijun , DeLia Derek , Sweeney Matthew , Bayasi Mohammed , Unger Keith , Stein David E , Al-Refaie Waddah B
Published: June 2022

BACKGROUND:

Understanding drivers of persistent surgical disparities remains an important area of cancer care delivery and policy. The degree to which clinician linkages contribute to disparities in access to quality colorectal cancer surgery is unknown. Using hospital surgical volume as a proxy for quality, the study team evaluated how clinician linkages impact access to colorectal cancer surgery at high-volume hospitals (HVHs).

STUDY DESIGN:

Maryland’s Health Services Cost Review Commission was used to evaluate 6,909 patients who underwent colon or rectal cancer operations from 2013 to 2018. Two linkages based on patient sharing were examined separately for colon and rectal cancer surgery: (1) from primary care clinicians to specialists (gastroenterologist or medical oncologist) and (2) from specialists to surgeons (general or colorectal). A referral link was defined as 9 or more shared patients between 2 clinicians. Adjusted regression models examined associations between referral links and odds of receiving colon or rectal cancer operations at HVHs.

RESULTS:

The cohort included 5,645 colon and 1,264 rectal cancer patients across 52 hospitals. Every additional referral link between a primary care clinician and a specialist connected to a HVH was associated with a 12% and 14% increased likelihood of receiving colon (odds ratio [OR] 1.12, CI 1.07 to 1.17) and rectal (OR 1.14, CI 1.08 to 1.20]) cancer operations at a HVH, respectively. Every additional referral link between a specialist and a surgeon at a HVH was associated with at least a 25% increased likelihood of receiving colon (OR 1.28, CI 1.20 to 1.36) and rectal (OR 1.25, CI 1.15 to 1.36) cancer operation at a HVH.

CONCLUSIONS:

Patients of clinicians with linkages to HVHs are more likely to have their colorectal cancer operations at these hospitals. These findings suggest that policy interventions targeting clinician relationships are an important step in providing equitable surgical care.
Disparity in Transport of Critically Injured Patients to Trauma Centers: Analysis of the National Emergency Medical Services Information System (NEMSIS)
Authors: Escobar Natalie , DiMaggio Charles , Frangos Spiros G , Winchell Robert J , Bukur Marko , Klein Michael J , Krowsoski Leandra , Tandon Manish , Berry Cherisse
Published: June 2022

BACKGROUND:

Patient morbidity and mortality decrease when injured patients meeting CDC Field Triage Criteria (FTC) are transported by emergency medical services (EMS) directly to designated trauma centers (TCs). This study aimed to identify potential disparities in the transport of critically injured patients to TCs by EMS.

STUDY DESIGN:

We identified all patients in the National EMS Information System (NEMSIS) database in the National Association of EMS State Officials East region from January 1, 2018, to December 31, 2019, with a final prehospital acuity of critical or emergent by EMS. The cohort was stratified into patients transported to TCs or non-TCs. Analyses consisted of descriptive epidemiology, comparisons, and multivariable logistic regression analysis to measure the association of demographic features, vital signs, and CDC FTC designation by EMS with transport to a TC.

RESULTS:

A total of 670,264 patients were identified as sustaining an injury, of which 94,250 (14%) were critically injured. Of those 94,250 critically injured, 56.0% (52,747) were transported to TCs. Among all critically injured women (n = 41,522), 50.4% were transported to TCs compared with 60.4% of critically injured men (n = 52,728, p < 0.001). In a multivariable logistic regression model, critically injured women were 19% less likely to be taken to a TC compared with critically injured men (OR 0.81, 95% CI 0.71–0.93, p = 0.003).

CONCLUSIONS:

Critically injured female patients are less likely to be transported to TCs when compared with their male counterparts. Performance improvement processes that assess EMS compliance with field triage guidelines should explicitly evaluate for sex-based disparities. Further studies are warranted.
Invasive grass indirectly alters seasonal patterns in seed predation
Authors: Borden Jesse B. , San Antonio Kelly M. , Tomat-Kelly Giovanna , Clark Taylor , Flory S. Luke
Published: June 2022

Invasive species threaten ecosystems globally, but their impacts can be cryptic when they occur indirectly. Invader phenology can also differ from that of native species, potentially causing seasonality in invader impacts. Yet, it is unclear if invader phenology can drive seasonal patterns in indirect effects. We used a field experiment to test if an invasive grass (
Imperata cylindrica
) caused seasonal indirect effects by altering rodent foraging and seed predation patterns through time. Using seeds from native longleaf pine (
Pinus palustris
), we found seed predation was 25% greater, on average, in invaded than control plots, but this effect varied by season. Seed predation was 24–157% greater in invaded plots during spring and autumn months, but invasion had no effect on seed predation in other months. One of the largest effects occurred in October when longleaf pine seeds are dispersed, suggesting potential effects on tree regeneration. Thus, seasonal patterns in indirect effects from invaders may cause underappreciated impacts on ecological communities.
Systemic application of the transient receptor potential vanilloid-type 4 antagonist GSK2193874 induces tail vasodilation in a mouse model of thermoregulation
Authors: O'Brien Fiona , Staunton Caroline A. , Barrett-Jolley Richard
Published: June 2022

In humans, skin is a primary thermoregulatory organ, with vasodilation leading to rapid body cooling, whereas in Rodentia the tail performs an analogous function. Many thermodetection mechanisms are likely to be involved including transient receptor potential vanilloid-type 4 (TRPV4), an ion channel with thermosensitive properties. Previous studies have shown that TRPV4 is a vasodilator by local action in blood vessels, so here, we investigated whether constitutive TRPV4 activity affects
Mus muscularis
tail vascular tone and thermoregulation. We measured tail blood flow by pressure plethysmography in lightly sedated
M. muscularis
(CD1 strain) at a range of ambient temperatures, with and without intraperitoneal administration of the blood–brain barrier crossing TRPV4 antagonist GSK2193874. We also measured heart rate (HR) and blood pressure. As expected for a thermoregulatory organ, we found that tail blood flow increased with temperature. However, unexpectedly, we found that GSK2193874 increased tail blood flow at all temperatures, and we observed changes in HR variability. Since local TRPV4 activation causes vasodilation that would increase tail blood flow, these data suggest that increases in tail blood flow resulting from the TRPV4 antagonist may arise from a site other than the blood vessels themselves, perhaps in central cardiovascular control centres.
Fast free-energy-based neutral set size estimates for the RNA genotype–phenotype map
Authors: Martin Nora S. , Ahnert Sebastian E.
Published: June 2022

The genotype–phenotype (GP) map of RNA secondary structure links each RNA sequence to its corresponding secondary structure. Previous research has shown that the large-scale structural properties of GP maps, such as the size of neutral sets in genotype space, can influence evolutionary outcomes. In order to use neutral set sizes, efficient and accurate computational methods are needed to compute them. Here, we propose a new method, which is based on free energy estimates and is much faster than existing sample-based methods. Moreover, this approach can give insight into the reasons behind neutral set size variations, for example, why structures with fewer stacks tend to have larger neutral set sizes. In addition, we generalize neutral set size calculations from the previously studied many-to-one framework, where each sequence folds into a single energetically preferred structure, to a fuller many-to-many framework, where several low-energy structures are included. We find that structures with high neutral sets in one framework also tend to have large neutral sets in the other framework for a range of parameters and thus the choice of GP map does not fundamentally affect which structures have the largest neutral set sizes.
Rigorous mathematical optimization of synthetic hepatic vascular trees
Authors: Jessen Etienne , Steinbach Marc C. , Debbaut Charlotte , Schillinger Dominik
Published: June 2022

In this paper, we introduce a new framework for generating synthetic vascular trees, based on rigorous model-based mathematical optimization. Our main contribution is the reformulation of finding the optimal global tree geometry into a nonlinear optimization problem (NLP). This rigorous mathematical formulation accommodates efficient solution algorithms such as the interior point method and allows us to easily change boundary conditions and constraints applied to the tree. Moreover, it creates trifurcations in addition to bifurcations. A second contribution is the addition of an optimization stage for the tree topology. Here, we combine constrained constructive optimization (CCO) with a heuristic approach to search among possible tree topologies. We combine the NLP formulation and the topology optimization into a single algorithmic approach. Finally, we attempt the validation of our new model-based optimization framework using a detailed corrosion cast of a human liver, which allows a quantitative comparison of the synthetic tree structure with the tree structure determined experimentally down to the fifth generation. The results show that our new framework is capable of generating asymmetric synthetic trees that match the available physiological corrosion cast data better than trees generated by the standard CCO approach.
Modelling preventive measures and their effect on generation times in emerging epidemics
Authors: Favero Martina , Scalia Tomba Gianpaolo , Britton Tom
Published: June 2022

We present a stochastic epidemic model to study the effect of various preventive measures, such as uniform reduction of contacts and transmission, vaccination, isolation, screening and contact tracing, on a disease outbreak in a homogeneously mixing community. The model is based on an infectivity process, which we define through stochastic contact and infectiousness processes, so that each individual has an independent infectivity profile. In particular, we monitor variations of the reproduction number and of the distribution of generation times. We show that some interventions, i.e. uniform reduction and vaccination, affect the former while leaving the latter unchanged, whereas other interventions, i.e. isolation, screening and contact tracing, affect both quantities. We provide a theoretical analysis of the variation of these quantities, and we show that, in practice, the variation of the generation time distribution can be significant and that it can cause biases in the estimation of reproduction numbers. The framework, because of its general nature, captures the properties of many infectious diseases, but particular emphasis is on COVID-19, for which numerical results are provided.
Feminist networks beyond the science wars: the ‘female brain’ in the 1790s and the 1990s
Authors: Govoni Paola
Published: June 2022

This paper explores female networking practices by comparing cases two centuries apart, an experiment made possible by a history of science renewed by a mutually enriching dialogue with science, technology and society studies (STS). The first part analyses the networking strategies of Clotilde Tambroni (1758–1817), a scholar who managed a university career in Bologna under the shadow of the Napoleonic wars. The second part presents some results of ongoing research on the networking strategies of a group of female feminist evolutionary biologists who, by building a ‘Darwinian feminism’ tradition, offered an alternative response to the 1990s nature-versus-nurture clashes leading to the so-called science wars. Grappling with the myth of a ‘female brain’ and building diachronic as well as synchronic networks among women scholars in both the Napoleonic wars context and the end of the Cold War, the female scholars examined here transcended dualistic simplifications about the nature of knowledge typical of their times. The two cases suggest a long-term, integrated, gendered approach that finds concrete expression in the outcomes of some recent neuroscience research as well as in the ‘gendered innovations in science’ project mentioned in my conclusions.
SWIP—a stabilized window for intravital imaging of the murine pancreas
Authors: Du Wei , Adkisson Christian , Ye Xianjun , Duran Camille L. , Chellakkan Selvanesan Benson , Gravekamp Claudia , Oktay Maja H. , McAuliffe John C. , Condeelis John S. , Panarelli Nicole C. , Norgard Robert J. , Sela Yogev , Stanger Ben Z. , Entenberg David
Published: June 2022

Pancreatitis and pancreatic ductal adenocarcinoma (PDAC) are grave illnesses with high levels of morbidity and mortality. Intravital imaging (IVI) is a powerful technique for visualizing physiological processes in both health and disease. However, the application of IVI to the murine pancreas presents significant challenges, as it is a deep, compliant, visceral organ that is difficult to access, easily damaged and susceptible to motion artefacts. Existing imaging windows for stabilizing the pancreas during IVI have unfortunately shown poor stability for time-lapsed imaging on the minutes to hours scale, or are unable to accommodate both the healthy and tumour-bearing pancreata. To address these issues, we developed an improved stabilized window for intravital imaging of the pancreas (SWIP), which can be applied to not only the healthy pancreas but also to solid tumours like PDAC. Here, we validate the SWIP and use it to visualize a variety of processes for the first time, including (1) single-cell dynamics within the healthy pancreas, (2) transformation from healthy pancreas to acute pancreatitis induced by cerulein, and (3) the physiology of PDAC in both autochthonous and orthotopically injected models. SWIP can not only improve the imaging stability but also expand the application of IVI in both benign and malignant pancreas diseases.
Comparing the age and sex trajectories of SARS-CoV-2 morbidity and mortality with other respiratory pathogens
Authors: Metcalf C. Jessica E. , Paireau Juliette , O'Driscoll Megan , Pivette Mathilde , Hubert Bruno , Pontais Isabelle , Nickbakhsh Sema , Cummings Derek A. T. , Cauchemez Simon , Salje Henrik
Published: June 2022

Comparing age and sex differences in SARS-CoV-2 hospitalization and mortality with MERS-CoV, seasonal coronaviruses, influenza and other health outcomes opens the way to generating hypotheses as to underlying mechanisms driving disease risk. Using 60-year-olds as a reference age group, we find that relative rates of hospitalization and mortality associated with the emergent coronaviruses are lower during childhood and start to increase earlier (around puberty) as compared with influenza and seasonal coronaviruses. The changing distribution of disease risk by age for emerging pathogens appears to broadly track the gradual deterioration of the immune system (immunosenescence), which starts around puberty. By contrast, differences in severe disease risk by age from endemic pathogens are more decoupled from the immune ageing process. Intriguingly, age-specific sex differences in hospitalizations are largely similar across endemic and emerging infections. We discuss potential mechanisms that may be associated with these patterns.
Vaccination-hesitancy and global warming: distinct social challenges with similar behavioural solutions
Authors: Fischer Ilan , Rubenstein Daniel I. , Levin Simon A.
Published: June 2022

Although the COVID-19 vaccine has dramatically changed the fight against the pandemic, many exhibit vaccination-hesitancy. At the same time, continued human-induced emissions of greenhouse gases pose an alarming threat to humanity. Based on the theory of Subjective Expected Relative Similarity (SERS) and a recent international study that drastically modified COVID-19 health-related attitudes, we explain why a similar approach and a corresponding public policy are expected to help resolve both behavioural issues: reduce vaccination hesitancy and motivate climate actions.
Effect of harvest time on the compositional changes in essential oils, cannabinoids, and waxes of hemp (
Cannabis sativa
L.)
Authors: Noppawan Pakin , Bainier Camille , Lanot Alexandra , McQueen-Mason Simon , Supanchaiyamat Nontipa , Attard Thomas M. , Hunt Andrew J.
Published: June 2022

Demand for cannabinoid is growing, with the global market expected to reach $9.69 billion by 2025. Understanding how chemical composition changes in hemp at different harvest times is crucial to maximizing this industrial crop value. Important compositional changes in three different compound classes (essential oils, cannabinoids, and lipids) from inflorescences (tops), leaves, and stems of hemp (
Cannabis sativa
L., Finola variety) at different harvesting stages have been investigated. Over 85% of the total extracts from the tops were cannabinoids, while leaves demonstrated the greatest quantities of wax ester and sterols. Essential oil and cannabinoid increased in tops until full flowering (third harvest), reaching 2030 µg g
−1
and 39 475 µg g
−1
, respectively. Cannabinoids decreased at seed maturity (final harvest) to 26 969 µg g
−1
. This demonstrates the importance of early harvesting to maximize cannabidiol (CBD), which is highly sought after for its therapeutic and pharmacological properties. A total of 21 161 µg g
−1
of CBD was extracted from the tops at full flowering (third harvest); however, a significant increase (63%) in the banned psychoactive tetrahydrocannabinol (THC) was observed from budding (157 µg g
−1
of biomass) to the full flowering (9873 µg g
−1
of biomass). Harvesting the tops after budding is preferable due to the high CBD content and low amounts of THC.
Prediction as a basis for skilled reading: insights from modern language models
Authors: Cevoli Benedetta , Watkins Chris , Rastle Kathleen
Published: June 2022

Reading is not an inborn human capability, and yet, English-speaking adults read with impressive speed. This study considered how predictions of upcoming words impact on this skilled behaviour. We used a powerful language model (GPT-2) to derive predictions of upcoming words in text passages. These predictions were highly accurate and showed a tight relationship to fine-grained aspects of eye-movement behaviour when adults read those same passages, including whether to skip the next word and how long to spend on it. Strong predictions that were incorrect resulted in a prediction error cost on fixation durations. Our findings suggest that predictions for upcoming words can be made based on the analysis of text statistics and that these predictions guide how our eyes interrogate text at very short timescales. These findings open new perspectives on reading and language comprehension and illustrate the capability of modern language models to inform understanding of human language processing.
Translocation of mitochondrial DNA into the nuclear genome blurs phylogeographic and conservation genetic studies in seabirds
Authors: Lucas Torres , Vincent Bretagnolle , Eric Pante
Published: June 2022

Mitochondrial DNA (mtDNA) translocated into the nuclear genome (numt), when co-analysed with genuine mtDNA, could plague phylogeographic studies. To evaluate numt-related biases in population genetics parameters in birds, which are prone to accumulating numts, we targeted the mitochondrial
mt-cytb
gene. We looked at 13 populations of Audubon's shearwater (
Puffinus lherminieri
), including five mitochondrial lineages.
mt-cytb
homologue and paralogue (numt) sequences were determined by Sanger sequencing with and without prior exonuclease digestion of nuclear DNA. Numts formed monophyletic clades corresponding to three of the five mitochondrial lineages tested (the remaining two forming a paraphyletic group). Nineteen percent of numt alleles fell outside of their expected mitochondrial clade, a pattern consistent with multiple translocation events, incomplete lineage sorting (ILS), and/or introgression. When co-analysing
mt-cytb
paralogues and homologues, excluding individuals with ambiguities underestimates genetic diversity (4%) and differentiation (11%) among least-sampled populations. Removing ambiguous sites drops the proportion of inter-lineage genetic variance by 63%. While co-analysing numts with mitochondrial sequences can lead to severe bias and information loss in bird phylogeographic studies, the separate analysis of genuine mitochondrial loci and their nuclear paralogues can shed light on numt molecular evolution, as well as evolutionary processes such as ILS and introgression.
Nanomedicine-based strategies to improve treatment of cutaneous leishmaniasis
Authors: Goonoo Nowsheen , Laetitia Huët Marie Andrea , Chummun Itisha , Karuri Nancy , Badu Kingsley , Gimié Fanny , Bergrath Jonas , Schulze Margit , Müller Mareike , Bhaw-Luximon Archana
Published: June 2022

Nanomedicine strategies were first adapted and successfully translated to clinical application for diseases, such as cancer and diabetes. These strategies would no doubt benefit unmet diseases needs as in the case of leishmaniasis. The latter causes skin sores in the cutaneous form and affects internal organs in the visceral form. Treatment of cutaneous leishmaniasis (CL) aims at accelerating wound healing, reducing scarring and cosmetic morbidity, preventing parasite transmission and relapse. Unfortunately, available treatments show only suboptimal effectiveness and none of them were designed specifically for this disease condition. Tissue regeneration using nano-based devices coupled with drug delivery are currently being used in clinic to address diabetic wounds. Thus, in this review, we analyse the current treatment options and attempt to critically analyse the use of nanomedicine-based strategies to address CL wounds in view of achieving scarless wound healing, targeting secondary bacterial infection and lowering drug toxicity.
Photoluminescence processes in
τ
-phase Ba
1.3
Ca

0.7-
x
-
y

SiO
4
:
x
D
y
3+
/
y
Tb
3+
phosphors for solid-state lighting
Authors: Golja Desta R. , Woldemariam Menberu M. , Dejene Francis B. , Kim Jung Yong
Published: June 2022

The
τ
-phase Ba
1.3
Ca

0.7-
x
-
y

SiO
4
:
x
D
y
3+
/
y
Tb
3+
phosphors co-doped with D
y
3+
(
x
= 0.03) and Tb
3+
(
y
= 0.01–0.05) trivalent rare-earth ions were prepared by the gel-combustion method. The structure–property relation of the samples was examined by X-ray diffraction, scanning electron microscopy and spectrophotometer. Here, the effect of Tb
3+
's concentration on the spectroscopic properties of Ba
1.3
Ca

0.7-
x
-
y

SiO
4
:
x
D
y
3+
/
y
Tb
3+
phosphors was explored by using the photoluminescence excitation, emission and decay curves. Importantly, the photonic energy transfer from (D
y
3+
:
4
F
9/2
+ Tb
3+
:
7
F
6
) to (D
y
3+
:
6
H
15/2
+ Tb
3+
:
5
D
4
) was observed, in which the D
y
3+
ions act as a light-emitting donor whereas the Tb
3+
ions as a light-absorbing acceptor, resulting in an enhanced emission from the co-doped Ba
1.3
Ca

0.7-
x
-
y

SiO
4
:
x
D
y
3+
/
y
Tb
3+
(
x
= 0.03 and
y
= 0.01–0.05) phosphors. Finally, the chromaticity coordinates were determined from the measured emission spectra, locating at the green and white light regions. This observation indicates that the characteristic emission colour could be tuned from white to green by varying Tb
3+
concentrations under ultraviolet light.
Conceptual preferences can be transmitted via selective social information use between competing wild bird species
Authors: Forsman Jukka T. , Kivelä Sami M. , Tolvanen Jere , Loukola Olli J.
Published: June 2022

Concept learning is considered a high-level adaptive ability. Thus far, it has been studied in laboratory via asocial trial and error learning. Yet, social information use is common among animals but it remains unknown whether concept learning by observing others occurs. We tested whether pied flycatchers (Ficedula hypoleuca) form conceptual relationships from the apparent choices of nest-site characteristics (geometric symbol attached to the nest-box) of great tits (Parus major). Each wild flycatcher female (n= 124) observed one tit pair that exhibited an apparent preference for either a large or a small symbol and was then allowed to choose between two nest-boxes with a large and a small symbol, but the symbol shape was different to that on the tit nest. Older flycatcher females were more likely to copy the symbol size preference of tits than yearling flycatcher females when there was a high number of visible eggs or a few partially visible eggs in the tit nest. However, this depended on the phenotype, copying switched to rejection as a function of increasing body size. Possibly the quality of and overlap in resource use with the tits affected flycatchers' decisions. Hence, our results suggest that conceptual preferences can be horizontally transmitted across coexisting animals, which may increase the performance of individuals that use concept learning abilities in their decision-making.
Resizing the largest known extinct rodents (Caviomorpha: Dinomyidae, Neoepiblemidae) using occipital condyle width
Authors: Engelman Russell K.
Published: June 2022

Several extinct chinchilloid rodents in the clades Dinomyidae and Neoepiblemidae grew to sizes much larger than any living rodent species. However, the exact size of these rodents is a matter of controversy, with authors disagreeing due to issues over extrapolation and model selection. Prior estimates for the two largest extinct rodents,
Phoberomys pattersoni
and
Josephoartigasia monesi
, range from 230 to 700 kg for
P. pattersoni
and 350 to 2600 kg for
J. monesi
. Here, I estimate body mass in large, extinct rodents using occipital condyle width (OCW), a strong predictor of body size in mammals, using a dataset that circumvents many of the issues faced by previous studies of species. Body masses under shape-corrected OCW are much lower than previous studies: 108–200 kg for
P. pattersoni
and 480 kg for
J. monesi
. Mass estimates for other rodent taxa (
Neoepiblema
,
Telicomys
,
Dinomys
) agree with previous studies. Estimates using skull length, corrected condyle width and head-body length are similar, suggesting estimates of 150 kg for
Phoberomys
and 480 kg for
Josephoartigasia
, and that larger estimates of 700 and 1200 kg are unlikely. High estimates in previous studies appear to be due to the unrecognized, nonlinear relationship between certain skeletal measurements (skull size) and body mass.