bluuebunny/crossref_metadata_2025 huggingface dataset:
Patterns in Academic Cosmetic Surgery Practice
Authors: Moore Reece , Zilinskas Kasparas , Tarabishy Sami , Herrera Fernando Antonio
Published: June 2022

Purpose

Although growth in cosmetic surgery remains constant in the private setting, academic cosmetic surgery practices are often underdeveloped. Our study aims to determine which patient populations access academic cosmetic surgery services.

Methods

The 2018 Health Care Utilization Project Nationwide Ambulatory Surgery Sample database was used for data analysis. Encounters for the following American Society of Plastic Surgery top 5 procedures for 2020 were selected: blepharoplasty, breast augmentation, liposuction, rhinoplasty, and rhytidectomy. Patient encounter data were collected because it relates to median income, geographic location, and primary payer status.

Results

The 2018 Nationwide Ambulatory Surgery Sample data set contained 44,078 encounters at academic surgical centers for the procedures listed previously. Low-income patients account for 13.7% of academic cosmetic surgery encounters compared with 37.9% for high-income patients. Breast augmentation rates are higher among low-income patients (20.5% vs 17.2%, P < 0.001), and high-income patients undergo rhytidectomy more frequently (5.7% vs 3.0%, P < 0.001). In the academic setting, patients from large metropolitan areas encompass the majority of cosmetic encounters (71.0%), and these patients are more likely to proceed with rhinoplasty, rhytidectomy, and liposuction procedures (P < 0.001). Patients from smaller metropolitan areas undergo blepharoplasty more frequently compared with those from larger metropolitan areas (56.4% vs 41.8%, P < 0.001). Self-pay and privately insured patients comprise the majority of academic cosmetic surgery encounters (40.8% and 29.9%, respectively). Eighty-eight percent of Medicare patients within this cohort underwent blepharoplasty, whereas self-pay patients accessed breast augmentation, liposuction, and rhytidectomy more often than other insured patients.

Conclusions

Income status, patient location, and primary payer status play an important role in academic cosmetic surgery access rates and procedure preferences. Academic cosmetic practices can use these insights to tailor their services to the populations they serve.
Surgical Delay-Induced Hemodynamic Alterations of the Superficial Inferior Epigastric Artery Flap for Autologous Breast Reconstruction
Authors: Hoffman Ryan D. , Maddox Suma S. , Meade Anna E. , St. Hilaire Hugo , Zampell Jamie C. , Allen Robert J.
Published: June 2022

Background

The superficial inferior epigastric artery (SIEA) flap allows transfer of tissue without violating the rectus fascia. Traditionally it is best used in single stage reconstruction when vessel caliber is 1.5 mm; 56% to 70% of SIEAs are less than 1.5 mm and, therefore, not reliable. We aim to demonstrate the increased reliability of SIEA through surgical delay by quantifying reconstructive outcomes and delay-induced hemodynamic alterations.

Methods

Patients presenting for autologous breast reconstruction between May 2019 and October 2020 were evaluated with preoperative imaging and received either delayed SIEA or delayed deep inferior epigastric (DIEP) reconstruction based on clinical considerations, such as prior surgery and perforator size/location. Prospective data were collected on operative time, length of stay, and complications. Arterial diameter and peak flow were quantified with Doppler ultrasound predelay and postdelay.

Results

Seventeen delayed SIEA flaps were included. The mean age (± SD) was 46.2 ± 10.55 years, and body mass index was 26.7 ± 4.26 kg/m2. Average hospital stay after delay was 0.85 ± 0.90 days, and duration before reconstruction was 6 days to 14.5 months. Delay complications included 1 abdominal seroma (n = 1, 7.7%). Superficial inferior epigastric artery diameter predelay (mean ± 95% confidence interval) was 1.37 ± 0.20 mm and increased to 2.26 ± 0.24 mm postdelay. A significant increase in diameter was noted 0.9 ± 0.22 mm (P < 0.0001). Mean peak flow predelay was 14.43 ± 13.38 cm/s and 44.61 ± 60.35 cm/s (n = 4, P = 0.1822) postdelay.

Conclusions

Surgical delay of the SIEA flap augments SIEA diameter, increasing the reliability of this flap for breast reconstruction. Superficial inferior epigastric artery delay results in low rates of complications and no failures in our series. Although more patients are needed to assess increase in arterial flow, use of surgical delay can expand the use of SIEA flap reconstruction and reduce abdominal morbidity associated with abdominal flap breast reconstruction.
The Impact of Tissue Expander Nipple Asymmetry on Final Implant Symmetry After Bilateral Nipple Sparing Mastectomy
Authors: Nores Gabriella Garcia , Carlson Grant W.
Published: June 2022

Background

Asymmetry of nipple position is common in the female population and very difficult to correct after nipple sparing mastectomy (NSM). There are scant data on the impact of tissue expander (TE) nipple asymmetry on final implant nipple symmetry after bilateral NSM.

Methods

A retrospective review of an institutional review board–approved prospective database of NSM and immediate 2-stage implant reconstruction between June 2014 and December 2019 was performed. BCCT.core software was used to examine TE and final implant nipple asymmetry as well as relative breast implant position. Horizontal and/or vertical asymmetry and breast retraction assessment (BRA) were evaluated. Moderate asymmetry was defined as ≥1 cm and severe asymmetry as ≥2 cm. Lower breast contour ≥1 cm defined implant malposition.

Results

Twenty-three patients met the inclusion criteria. Linear regression analysis showed a significant relationship between TE BRA and final BRA (R
2 = 0.2321, P = 0.02) with a mean TE BRA of 2.04 and a mean final BRA of 1.53 (P = 0.05). Tissue expander nipple asymmetry was predictive of final BRA score: no TE asymmetry, 0.87, versus TE nipple asymmetry, 1.67 (P = 0.02). Tissue expander lower breast contour ≥1 cm occurred in 8 patients (36.4%) and was associated with implant nipple asymmetry in 7 (87.5%). The second stage of reconstruction significantly improved the nipple asymmetry in those with TE malposition (TE BRA, 2.34, vs final BRA, 1.67; P = 0.05). Two patients who received radiation had increased BRA scores (radiation, 2.14, vs no radiation, 1.47; P = 0.004).

Conclusions

Tissue expander nipple asymmetry as measured by BRA score or nipple asymmetry was predictive of final nipple symmetry. The second stage of TE reconstruction improves the nipple asymmetry. Final implant exchange can allow for pocket and implant manipulation, improving nipple symmetry. Radiation therapy to TE reconstruction has a negative impact on nipple symmetry after the final stage.
Sophocles and the Wound of Philoctetes
Authors: Lineaweaver William
Published: June 2022

The dramatic story of the Greek hero Philoctetes encompasses a psychological concept of healing and a chronic wound that can be understood as a chronically infected traumatic pseudoaneurysm.
Relationship of Adjuvant Radiation and the Lymphedema Index
Authors: Wainwright D’Arcy , Weinstein Brielle , Tavares Tina , Panetta Nicholas J.
Published: June 2022

Background

Immediate lymphaticovenular bypass (immediate lymphatic reconstruction [ILR]) at the time of axillary lymph node dissection has emerged as a preventative paradigm to decrease the incidence of breast cancer–related lymphedema in high-risk patients. These patients are often treated with adjuvant therapies, including radiation. Bioimpedance spectroscopy is a validated tool for trending breast cancer–related lymphedema and identifying subclinical disease. Lymphedema Index (LDEX) values are commonly obtained in ILR patients; however, postoperative trends and relationships with adjuvant treatments are yet to be reported in the literature.

Methods

After International Review Board approval, 100 consecutive patients underwent axillary lymph node dissection with axillary reverse lymphatic mapping and ILR at a tertiary cancer center. These patients were then followed prospectively in a multidisciplinary lymphedema clinic at 3-month intervals with clinical examination, circumferential limb girth measurements and bioimpedance spectroscopy (LDEX).

Results

Seventy-two patients met inclusion for analysis at 3 months, 60 at 6 months, 51 at 9 months, 45 at 12 months, 41 at 15 months, and 22 at 18 months. A majority of the patients included underwent adjuvant radiation. Average LDEX score for patients who developed lymphedema was 3.02 at 3 months, at 29.1 months, 17.8 at 9 months, 15.05 at 12 months, 18.75 at 15 months, and 7.7 at 18 months. Patients who went on to develop lymphedema had a higher LDEX score at 6 months (29.1 vs 3.20, P = 0.1329), which reached a significant difference beginning at 9 months (17.8 vs 3.19, P = 0.0004). All patients who went on to develop lymphedema received adjuvant radiation.

Conclusions

These data provide valuable insight guiding follow-up after ILR. Six-month LDEX is much higher in patients who developed lymphedema, all of which underwent adjuvant radiation therapy, which correlates with the time of completion of their treatment. Average LDEX value after this remains significantly higher in this population. Patients who demonstrate this increase in LDEX and received adjuvant radiation are at highest risk to develop lymphedema despite ILR. All patients who developed lymphedema despite ILR had adjuvant radiation, and this is likely a contributing factor. Injury from adjuvant radiation and its impact after ILR is not insignificant and warrants further studies.
Patient Perspectives on Resident Involvement in Plastic Surgery
Authors: White-Dzuro Colin Garrett , Nguyen Lyly , Glassman Gabriella E. , Drolet Brian C.
Published: June 2022

Objective

The objective of this study is to understand how patients at a large academic hospital perceive the training levels of residents and attendings and their perspectives on resident involvement in surgery.

Design

This is a cross-sectional survey-based study.

Setting

Patients who received care at Vanderbilt University Medical Center were asked to respond to our anonymous electronic survey via email.

Participants

There were 3370 patients who underwent plastic surgery within the last 3 years at Vanderbilt University Medical Center were asked to participate. Eight hundred thirty-seven surveys were returned, representing a 24.8% response rate.

Results

There were 58.7% of the patients that were confident that a resident has completed medical school. There were 58.4% that report that they usually know if a resident will be assisting their surgeon in the OR, but 86.3% agree that they would like to know if a resident will be involved in their surgery. There were 76.3% that are comfortable with a resident performing parts of their surgery as long as their surgeon is ready to take over if needed.

Conclusions

Patient understanding of a resident physician's education and abilities remains low. There is a discrepancy between the number of patients who would like to know if a resident will be involved in their surgery versus the number who are actually told if a resident will be involved.
Persistence of suicidal ideation within acute phase treatment of major depressive disorder: analysis of clinical predictors
Authors: Olgiati Paolo , Serretti Alessandro
Published: June 2022

Suicidal ideation (SI) is common in major depressive disorder (MDD), and it is a risk factor for suicidal behaviour. Antidepressants are effective in reducing SI, but in some subjects, SI may persist for weeks. This study aimed to disentangle the contribution of baseline clinical characteristics in SI nonremission at week 6. Research involved 198 outpatients with MDD and SI collected within the Combining Medications to Enhance Depression Outcomes trial and treated with different antidepressant combinations. Although SI decreased from baseline to week 6 (P < 0.0001), 78 patients (39%) failed to achieve SI remission. Insomnia [OR, 0.72; 95% confidence interval (CI), 0.52–0.99], reduced need for sleep (OR, 0.75; 95% CI, 0.58–0.99), self-confidence (OR, 0.52; 95% CI, 0.32–0.82), cheerfulness (OR, 0.57; 95% CI, 0.33–0.98), and comorbid panic disorder (OR, 0.93; 95% CI, 0.87–0.99) at baseline were associated with lack of SI remission after controlling for baseline depression and SI scores. The combination of baseline SI and insomnia was moderately effective in predicting the lack of SI remission, with a specificity of 80% (95% CI, 72–87%) and an NPV of 68% (95% CI, 63–72%). In individuals with MDD and SI, the presence of insomnia and bipolar features should prompt a search for more effective treatment solutions in order to favour SI remission and prevent suicidal behaviour.
Linking physiology to ecosystem function: how vulnerable are different functional groups to climate change?
Authors: da Silva Carmen R.B. , Beaman Julian E. , Youngblood Jacob P. , Kellermann Vanessa , Diamond Sarah E.
Published: June 2022

The resilience of ecosystem function under global climate change is governed by individual species vulnerabilities and the functional groups they contribute to (e.g. decomposition, primary production, pollination, primary, secondary and tertiary consumption). Yet it remains unclear whether species that contribute to different functional groups, which underpin ecosystem function, differ in their vulnerability to climate change.

It is important to examine if functional group vulnerability differs across space (e.g. tropical vs temperate latitudes) to determine if some regions will be more vulnerable to loss of ecosystem function than others, and to examine whether localized effects of particular community compositions override global patterns of functional group vulnerability.

We used existing upper thermal limit data across a range of terrestrial species (N = 1,743) to calculate species warming margins (degrees distance between a species upper thermal limit and the maximum environmental temperature they inhabit), as a metric of climate change vulnerability, to determine whether species that comprise different functional groups exhibit differential vulnerability to climate change, and if vulnerability trends change across geographic space.

We found that primary producers had the broadest warming margins across the globe (μ = 21.85 °C) and that tertiary consumers had the narrowest warming margins (μ = 4.37 °C), where vulnerability tended to increase with trophic level.

Species that contribute towards primary production were more vulnerable in low-latitude than mid-latitude regions, but warming margins across all other functional groups did not differ across regions when evolutionary history was considered. However, when evolutionary history was excluded from the analyses (as closely related species often play similar functional roles within ecosystems demonstrating true variation in functional group warming margins) we found that pollinators are more vulnerable in mid-latitude regions and that primary producers are more vulnerable in low-latitude environments.

This study provides a critical first step in linking individual species vulnerabilities with whole ecosystem responses to climate change.
Specific detection and deletion of the Sigma-1 receptor in neurons and glial cells for functional characterization in vivo
Authors: Liu Qing , Guo Qilin , Fang Li-Pao , Yao Honghong , Scheller Anja , Kirchhoff Frank , Huang Wenhui
Published: June 2022

The chaperon protein sigma-1 receptor (S1R) has been discovered over forty years ago. Recent pharmacological studies using S1R exogenous ligands demonstrated a promising therapeutical potential of targeting the S1R for several neurological disorders. Although intensive in vitro studies have revealed S1Rs are mainly residing at the membrane of the endoplasmic reticulum (ER), the cell-specific in vivo expression pattern of S1Rs is still unclear, mainly due to the lack of a reliable detection method which also prevented a comprehensive functional analysis.

Here, first, we identified a highly specific antibody using S1R knockout (KO) mice and established an immunohistochemical protocol involving a 1% SDS antigen retrieval step. Second, we characterized the S1R expression in the mouse brain and can demonstrate that the S1R is widely expressed: in principal neurons, interneurons, and all glial cell types. Finally, we generated a novel Cre-dependent S1R conditional KO mouse (S1R flox) to study cell type-specific functions of the S1R. As a proof of concept, we successfully ablated S1R expressions in neurons or microglia employing neuronal and microglial Cre-expressing mice, respectively. In summary, we provide powerful tools to cell-specifically detect, delete and functionally characterize S1R in vivo.
Quantitative analysis of rabies virus-based synaptic connectivity tracing
Authors: Tran-Van-Minh Alexandra , Ye Zhiwen , Rancz Ede
Published: June 2022

Monosynaptically restricted rabies viruses have been used for more than a decade for synaptic connectivity tracing. However, the verisimilitude of quantitative conclusions drawn from these experiments is largely unknown. The primary reason is the simple metrics commonly used, which generally disregard the effect of starter cell numbers. Here we present an experimental dataset with a broad range of starter cell numbers and explore their relationship with the number of input cells across the brain using descriptive statistics and modelling. We show that starter cell numbers strongly affect input fraction and convergence index measures, making quantitative comparisons unreliable. Furthermore, we suggest a principled way to analyse rabies derived connectivity data by taking advantage of the starter vs input cell relationship that we describe and validate across independent datasets.
Electrophysiological Markers of Memory Consolidation in the Human Brain when Memories are Reactivated during Sleep
Authors: Creery Jessica D. , Brang David J. , Arndt Jason D. , Bassard Adrianna , Towle Vernon L. , Tao James X. , Wu Shasha , Rose Sandra , Warnke Peter C. , Issa Naoum , Paller Ken A.
Published: June 2022

Human accomplishments depend on learning, and effective learning depends on consolidation. Consolidation is the process whereby new memories are gradually stored in an enduring way in the brain so that they can be available when needed. For factual or event knowledge, consolidation is thought to progress during sleep as well as during waking states, and to be mediated by interactions between hippocampal and neocortical networks. However, consolidation is difficult to observe directly, but rather is inferred through behavioral observations. Here, we investigated overnight memory change by measuring electrical activity in and near the hippocampus. Electroencephalographic (EEG) recordings were made in five patients from electrodes implanted to determine whether a surgical treatment could relieve their seizure disorders. One night, while each patient slept in a hospital monitoring room, we recorded electrophysiological responses to 10-20 specific sounds that were presented very quietly, to avoid arousal. Half of the sounds had been associated with objects and their precise spatial locations that patients learned before sleep. After sleep, we found systematic improvements in spatial recall, replicating prior results. We assume that when the sounds were presented during sleep, they reactivated and strengthened corresponding spatial memories. Notably, the sounds also elicited oscillatory intracranial EEG activity, including increases in theta, sigma, and gamma EEG bands. Gamma responses, in particular, were consistently associated with the degree of improvement in spatial memory exhibited after sleep. We thus conclude that this electrophysiological activity in the hippocampus and adjacent medial temporal cortex reflects sleep-based enhancement of memory storage.

Significance Statement

Sleep contributes to memory consolidation, we presume, because memories are replayed during sleep. Understanding this aspect of consolidation can help with optimizing normal learning in many contexts, and with treating memory disorders and other diseases. Here, we systematically manipulated sleep-based processing using targeted memory reactivation; brief sounds coupled with pre-sleep learning were quietly presented again during sleep, producing (a) recall improvements for specific spatial memories associated with those sounds, and (b) physiological responses in the sleep EEG. Neural activity in the hippocampus and adjacent medial temporal cortex was thus found in association with memory consolidation during sleep. These findings advance understanding of consolidation by linking beneficial memory changes during sleep to both memory reactivation and specific patterns of brain activity.
Macroscale Adipose Tissue from Cellular Aggregates: A Simplified Method of Mass Producing Cell-Cultured Fat for Food Applications
Authors: Yuen John SK , Saad Michael K , Xiang Ning , Barrick Brigid M , DiCindio Hailey , Li Chunmei , Zhang Sabrina W , Rittenberg Miriam , Lew Emily T , Leung Glenn , Pietropinto Jaymie A , Kaplan David L
Published: June 2022

We present a method of producing bulk cell-cultured fat tissue for food applications. Mass transport limitations (nutrients, oxygen, waste diffusion) of macroscale 3D tissue culture are circumvented by initially culturing murine or porcine adipocytes in 2D, after which bulk fat is produced by mechanically harvesting and aggregating the lipid-filled adipocytes into 3D fats using alginate or transglutaminase binders. The 3D fats were visually similar to fat tissue harvested from animals, with matching textures based on uniaxial compression tests. The mechanical properties of cultured fat tissues were based on binder choice and concentration, and changes in the fatty acid compositions of cellular triacylglyceride and phospholipids were observed after lipid supplementation (soybean oil) during in vitro culture. This approach of aggregating individual adipocytes into a bulk 3D tissue provides a scalable and versatile strategy to produce cultured fat tissue for food-related applications, thereby addressing a key obstacle in cultivated meat production.

Graphical Abstract
Quantifying chemodiversity considering biochemical and structural properties of compounds with the R packagechemodiv
Authors: Petrén Hampus , Köllner Tobias G. , Junker Robert R.
Published: June 2022

Plants produce large numbers of phytochemical compounds affecting plant physiology and interactions with their biotic and abiotic environment. Recently, chemodiversity has attracted considerable attention as an ecologically and evolutionary meaningful way to characterize the phenotype of a mixture of phytochemical compounds.

Currently used measures of phytochemical diversity, and related measures of phytochemical dissimilarity, generally do not take structural or biosynthetic properties of compounds into account. Such properties can be indicative of the compounds’ function and inform about their biosynthetic (in)dependence, and should therefore be included in calculations of these measures.

We introduce the R packagechemodiv, which retrieves biochemical and structural properties of compounds from databases and provides functions for calculating and visualizing chemical diversity and dissimilarity for phytochemicals and other types of compounds. Our package enables calculations of diversity that takes the richness, relative abundance and – most importantly – structural and/or biosynthetic dissimilarity of compounds into account. We illustrate the use of the package with examples on simulated and real datasets.

By providing the R packagechemodivfor quantifying multiple aspects of chemodiversity, we hope to facilitate investigations of how chemodiversity varies across levels of biological organization, and its importance for the ecology and evolution of plants and other organisms.
AMPK deficiency in smooth muscles causes persistent pulmonary hypertension after birth and premature death
Authors: Moral-Sanz Javier , Lewis Sophronia A. , MacMillan Sandy , Meloni Marco , McClafferty Heather , Viollet Benoit , Foretz Marc , del-Pozo Jorge , Evans A. Mark
Published: June 2022

We address a paradox, that AMPK may facilitate hypoxic pulmonary vasoconstriction and its deficiency precipitate pulmonary hypertension. Here we show that AMPK-α1/α2 deficiency in smooth muscles promotes persistent pulmonary hypertension of the newborn. Accordingly, dual AMPK-α1/α2 deletion in smooth muscles causes premature death of mice after birth, associated with increased muscularization and remodeling throughout the pulmonary arterial tree, reduced alveolar numbers and alveolar membrane thickening, but with no edema. Spectral Doppler ultrasound indicates pulmonary hypertension and attenuated hypoxic pulmonary vasoconstriction. Age-dependent right ventricular pressure elevation, dilation and reduced cardiac output was also evident. KV1.5 potassium currents of pulmonary arterial myocytes are markedly smaller under normoxia, which is known to facilitate pulmonary hypertension. Mitochondrial fragmentation and reactive oxygen species accumulation is also evident. Importantly, there is no evidence of systemic vasculopathy or hypertension in these mice. Moreover, hypoxic pulmonary vasoconstriction is attenuated by AMPK-α1 or AMPK-α2 deletion without triggering pulmonary hypertension.
Overall patterns of eye-specific retino-geniculo-cortical projections to layers III, IV and VI in primary visual cortex of the prosimian galago, and correlation with cytochrome oxidase blobs
Authors: Olavarria Jaime F. , Qi Huixin , Takahata Toru , Kaas Jon H.
Published: June 2022

Studies in galago have not provided a comprehensive description of the organization of eye specific retino-geniculate-cortical projections to the recipient layers in V1. Here we demonstrate the overall patterns of ocular dominance domains in layers III, IV and VI revealed after injecting the transneuronal tracer wheat germ agglutinin conjugated to horseradish peroxidase (WGA- HRP) into one eye. We also correlate these patterns with the array of cytochrome oxidase (CO) blobs in tangential sections through the unfolded and flattened cortex. In layer IV, we observed for the first time that eye-specific domains form an interconnected pattern of bands 200-250 um wide arranged such that they do not show orientation bias and do not meet the V1 border at right angles, as is the case in macaques. We also observed distinct patterns of ocular dominance patches in layer III and layer VI. The patches in layer III, likely corresponding to patches of K LGN input described previously, align with layer IV ocular dominance columns (ODCs) of the same eye dominance. Moreover, the layer III patches overlap partially with virtually all CO blobs in both hemispheres, implying that CO blobs receive K LGN input from both eyes. Finally, we found that CO blobs straddle the border between neighboring layer IV ODCs. These results, together with studies showing that a high percentage of cells in CO blobs are monocular, suggest that CO blobs consist of ipsilateral and contralateral subregions that are in register with underlying layer IV ocular dominance columns of the same eye dominance. In macaques and humans, CO blobs are centered on ODCs in layer IV. Our finding that CO blobs in galago straddle the border of neighboring layer IV ODCs suggests that this may represent an alternative way by which visual information is processed by eye specific modular architecture in mammalian V1.
Long wavelength light reduces the negative consequences of dim light at night in the Cntnap2 mouse model of autism
Authors: Wang Huei Bin , Zhou David , Luk Shu Hon Christopher , Cha Hye In , Mac Amanda , Chae Rim , Matynia Anna , Harrison Ben , Afshari Sina , Block Gene D. , Ghiani Cristina A. , Colwell Christopher S.
Published: June 2022

Many patients with autism spectrum disorders (ASD) show disturbances in their sleep/wake cycles, and may be particularly vulnerable to the impact of circadian disruptors. We have previously shown that exposure to dim light at night (DLaN) in contactin associated protein-like 2 knock out (Cntnap2 KO) mice disrupts diurnal rhythms, increases repetitive behaviors while reducing social interactions. These negative effects of DLaN may be mediated by intrinsically photosensitive retinal ganglion cells (ipRGCs) expressing the photopigment melanopsin, which is maximally sensitive to blue light (480nm). In this study, we used a light-emitting diode (LED) array that enabled us to shift the spectral properties of the DLaN while keeping the intensity at 10 lx. First, using wild-type (WT) mice, we confirmed that the short-wavelength enriched lighting produced strong acute suppression of locomotor activity (masking), robust light-induced phase shifts, and c-Fos expression in the suprachiasmatic nucleus, while the long-wavelength enriched lighting evoked much weaker responses. Furthermore, exposure of WT mice to the short-wavelength light at night reduced the amplitude of locomotor activity rhythms and impaired social interactions. Mice lacking the melanopsin expressing ipRGCs (Opn4DTA mice) were resistant to these negative effects of DLaN. Importantly, the shift of the DLaN stimulus to longer wavelengths ameliorated the negative impact on the activity rhythms and autistic behaviors (i.e. reciprocal social interactions, repetitive grooming) of the Cntnap2 KO model. The short-, but not the long-wavelength enriched, DLaN triggered cFos expression in the peri-habenula region as well as in the basolateral amygdala (BLA). Finally, DLaN-driven c-Fos induction in BLA glutamatergic neurons was about 3-fold higher in the Cntnap2 KO mice, suggesting that these cells may be particularly vulnerable to the effects of photic disruption. Broadly, our findings suggest that the spectral properties of light at night should be considered in the management of ASD and other neurodevelopmental disorders.
GeneToList: A web application to assist with gene identifiers for the non-bioinformatics-savvy scientist
Authors: Breidenbach Joshua D. , Begue E. Francis , Kennedy David J. , Haller Steven T.
Published: June 2022

The increasing incorporation of omics technology into clinical and translational medicine presents challenges to end users of the large and complex datasets that are generated by these methods. A particular challenge in genomics is that the nomenclature for genes is not uniform between large genomic databases or between commonly used genetic analysis tools. Furthermore, outdated genomic nomenclature can still be found amongst scientific communications including peer-reviewed manuscripts. Therefore, a web application (GeneToList) was developed to assist is gene ID conversion and alias matching, with a specific focus on achieving a user-friendly interface for the non-bioinformatics-savvy scientist.

Availability and implementation

GeneToList is available at https://www.genetolist.com/. The tool is a web application that is compatible with many standard browsers.

Contact

Joshua.Breidenbach@UToledo.edu or support@genetolist.com
Structural remodelling of the carbon-phosphorus lyase machinery by a dual ABC ATPase
Authors: Amstrup Søren K. , Sofos Nicholas , Karlsen Jesper L. , Skjerning Ragnhild B. , Boesen Thomas , Enghild Jan J. , Hove-Jensen Bjarne , Brodersen Ditlev E.
Published: June 2022

Phosphorus is an essential macronutrient for all microorganisms and can be extracted from the environment by several metabolic pathways. In Escherichia coli, the 14-cistron phn operon encoding the carbon-phosphorus (C-P) lyase enzymatic machinery allows for extraction of phosphorus from a wide range of phosphonates characterised by the highly stable C-P bond.1, 2 As part of a complex, multi-step pathway, the PhnJ subunit was proposed to cleave the C-P bond via a radical reaction, however, the details of the mechanism were not immediately compatible with the structure of the 220 kDa PhnGHIJ C-P lyase core complex, leaving a significant gap in our understanding of phosphonate breakdown in bacteria.3, 4 Here we show using single-particle cryogenic-electron microscopy that PhnJ mediates binding of a unique double dimer of ATP-binding cassette (ABC) proteins, PhnK and PhnL to the core complex. ATP hydrolysis by PhnK induces drastic structural remodelling leading to opening of the core and reconfiguration of a metal-binding site located at the interface between the PhnI and PhnJ subunits. Our results offer new insights into the mechanism underlying C-P lyase and uncover a hitherto unknown configuration of ABCs that have wide-ranging implications for our understanding of the role of this module in biological systems.
Dual IgA/IgG family autoantibodies from individuals at-risk for rheumatoid arthritis identify an arthritogenic strain ofSubdoligranulum
Authors: Chriswell Meagan , Lefferts Adam R. , Clay Michael , Hsu Alex , Seifert Jennifer , Feser Marie L. , Rims Cliff , Bloom Michelle , Bemis Elizabeth A. , Demoruelle M. Kristen , Deane Kevin D. , James Eddie A. , Buckner Jane H. , Robinson William H. , Holers V. Michael , Kuhn Kristine A.
Published: June 2022

The mucosal origins hypothesis of rheumatoid arthritis (RA) proposes a central role for mucosal immune responses in the initiation and/or perpetuation of the systemic autoimmunity that occurs with disease. However, the connection between the mucosa and systemic autoimmunity in RA remains unclear. Using dual IgA/IgG family plasmablast-derived monoclonal autoantibodies obtained from peripheral blood of individuals at-risk for RA, we identified cross-reactivity between RA-relevant autoantigens and bacterial taxa in the closely related familiesLachnospiraceaeandRuminococcaceae. After generating bacterial isolates withinLachnospiraceae/RuminococcaceaegenusSubdoligranulumfrom the feces of an individual, we confirmed monoclonal antibody binding as well as MHC class II dependent CD4+ T cell activation in RA cases compared to controls. Additionally, whenSubdoligranulumisolate 7 but not isolate 1 colonized germ-free mice, it stimulated Th17 cell expansion, serum RA-relevant IgG autoantibodies, and joint swelling reminiscent of early RA with histopathology characterized by antibody deposition and complement activation. Systemic immune responses were likely due to the generation of colon isolated lymphoid follicles (ILFs) driving increased fecal and serum IgA by isolate 7, as B and T cell depletion not only halted intestinal immune responses but also eliminated detectable clinical disease. In aggregate, these findings demonstrate one mucosal mechanism in RA through which an intestinal strain of bacteria can drive systemic autoantibody generation and joint-centered antibody deposition and immune activation.

One-sentence summary

Subdoligranulum spp.targeted by rheumatoid arthritis (RA)-relevant autoantibodies activate T cells in individuals with RA, and in mice stimulate autoantibodies and joint swelling associated with antibody deposition and complement activation.
Beyond winglets: evolutionary scaling of flight-related morphology in stick insects (Phasmatodea)
Authors: Zeng Yu , Park Sehoon , Gonzales Camille , Yom Stephanie , Rahim Faszly , Dudley Robert
Published: June 2022

The first winged insects evolved from a wingless ancestor, but details of the transition to a fully-winged morphology remain unclear. Studying extant pterygotes with partial wings, such as the stick insects (Order Phasmatodea), may help us to understand such a transition. Here, we address how a series of flight-related morphological parameters may correlate with flight evolution by studying different phasmids representing a volancy continuum ranging from miniaturized to full-sized wings. Variation in phasmid wing shape, venation, wing mass and the mass of flight muscle can be described by specific scaling laws referenced to wing length and wing loading. Also, the mass distribution of the body-leg system is conserved in spite of a wide range of variation in body shape. With reduced wing size and increased wing loading, the longitudinal position of the wing-bearing thoracic segments is shifted closer to the insects’ center of body mass. These results demonstrate complex reconfiguration of the flight system during wing morphological transitions in phasmids, with various anatomical features potentially correlated with reduced flight performance attained with partial wings. Although these data represent phasmid-specific features of the flight apparatus and body plan, the associated scaling relationships can provide insight into functionality of intermediate conditions between wingless and fully-winged insects more generally.
Using Interpretable Machine Learning to Massively Increase the Number of Antibody-Virus Interactions Across Studies
Authors: Einav Tal , Ma Rong
Published: June 2022

A central challenge in every field of biology is to use existing measurements to predict the outcomes of future experiments. In this work, we consider the wealth of antibody inhibition data against variants of the influenza virus. Due to this virus’s genetic diversity and evolvability, the variants examined in one study will often have little-to-no overlap with other studies, making it difficult to discern common patterns or unify datasets for further analysis. To that end, we develop a computational framework that predicts how an antibody or serum would inhibit any variant fromany other study. We use this framework to greatly expand seven influenza datasets utilizing hemagglutination inhibition, validating our method upon 200,000 existing measurements and predicting 2,000,000 new values ± uncertainties. With these new values, we quantify the transferability between seven vaccination and infection studies in humans and ferrets, show that the serum potency is negatively correlated with breadth, and present a tool for pandemic preparedness. This data-driven approach does not require any information beyond each virus’s name and measurements, and even datasets with as few as 5 viruses can be expanded, making this approach widely applicable. Future influenza studies using hemagglutination inhibition can directly utilize our curated datasets to predict newly measured antibody responses against ≈80 H3N2 influenza viruses from 1968-2011, whereas immunological studies utilizing other viruses or a different assay only need a single partially-overlapping dataset to extend their work. In essence, this approach enables a shift in perspective when analyzing data from “what you see is what you get” into “what anyone sees is what everyone gets.”
From pseudotime to true dynamics: reconstructing a real-time axis for T cells differentiation
Authors: Gavish Avishai , Chain Benny , Salame Tomer M , Antebi Yaron E , Katz Shir , Reich-Zeliger Shlomit , Friedman Nir
Published: June 2022

Numerous methods have recently emerged for ordering single cells along developmental trajectories. However, accurate depiction of developmental dynamics can only be achieved after rescaling the trajectory according to the relative time spent at each developmental point. We formulate a model which estimates local cell densities and fluxes, and incorporates cell division and apoptosis rates, to infer the real time dimension of the developmental trajectory. We validate the model using mathematical simulations, and apply it on experimental high dimensional cytometry data obtained from the mouse thymus to construct the true time-profile of the thymocyte developmental process. Our method can easily be implemented in any of the existing tools for trajectory inference.
DNA barcoding echinoderms from the East Coast of South Africa. The challenge to maintain DNA data connected with taxonomy
Authors: Sonet Gontran , Smitz Nathalie , Vangestel Carl , Samyn Yves
Published: June 2022

Echinoderms are marine water invertebrates that are represented by more than 7000 extant species, grouped in five classes and showing diverse morphologies (starfish, sea lilies, feather stars, sea urchins, sea cucumbers, brittle and basket stars). In an effort to further study their diversity, DNA barcodes (DNA fragments of the 5’ end of the cytochrome c oxidase subunit I gene, COI) have been used to complement morphological examination in identifying evolutionary lineages. Although divergent clusters of COI sequences were reported to generally match morphological species delineations, they also revealed some discrepancies, suggesting overlooked species, ecophenotypic variation or multiple COI lineages within one species. Here, we sequenced COI fragments of 312 shallow-water echinoderms of the East Coast of South Africa (KwaZulu-Natal Province) and compared morphological identifications with species delimitations obtained with four methods that are exclusively based on COI sequences. We identified a total of 103 morphospecies including 18 that did not exactly match described species. We also report 46 COI sequences that showed large divergences (>5% p-distances) with those available to date and publish the first COI sequences for 30 species. Our analyses also identified discordances between morphological identifications and COI-based species delimitations for a considerable proportion of the morphospecies studied here (49/103). For most of them, further investigation is necessary to keep a sound connection between taxonomy and the growing importance of DNA-based research.
Cognitive exertion affects the appraisal of one’s own and other people’s pain
Authors: Riontino Laura , Fournier Raphael , Lapteva Alexandra , Silvestrini Nicolas , Schwartz Sophie , Corradi-Dell’Acqua Corrado
Published: June 2022

Correctly evaluating others’ pain is a crucial prosocial ability, especially relevant for the healthcare system. In clinical settings, caregivers assess their patients’ pain under high workload and fatigue, often while dealing with competing information/tasks. However, the effect played by such cognitive strain in the appraisal of others’ pain remains unclear. Following embodied accounts that posit a shared representational code between self and others’ states, it could be hypothesized that the representation of people’s pain might be influenced by cognitive exertion similarly to first-hand experiences.

Fifty participants underwent one of two demanding tasks, involving either working memory (Experiment 1: N-Back task) or cognitive interference (Experiment 2: Stroop task). After each task, participants were exposed to painful laser stimulations at three intensity levels (low, medium, high), or video-clips of patients experiencing three intensity levels of pain (low, medium, high). Participants rated the intensity of each pain event on a visual analogue scale.

We found that the two tasks influenced rating of both one’s own and others’ pain, by decreasing the sensitivity to medium and high events. This was observed either when comparing the demanding condition to a control (Stroop), or when modelling linearly the difficulty/performance of each depleting task (N-Back).

We provide converging evidence that cognitive exertion affects the subsequent appraisal of one’s own and likewise others’ pain. Healthcare personnel should be aware that high workload might alter their cognitive abilities.

Perspective

this research shows that cognitive effort aftereffects impact negatively the assessment of of medium/high pain in others, reminiscently to what was observed in first-hand experiences. Healthcare professionals should be aware that high workload and severe cognitive fatigue could affect their diagnostic skills.
Effects of Oxygen Plasma Treatment on Parylene C and Parylene N Membrane Biocompatibility for Tissue Barrier Models
Authors: Gholizadeh Shayan , Lincoln Daniela M. , Allahyari Zahra , Widom Louis P. , Carter Robert N. , Gaborski Thomas R.
Published: June 2022

Porous membranes are integral components of in vitro tissue barrier and co-culture models and their interaction with cells and tissues directly affects the performance and credibility of these models. Plasma-treated Parylene C and Parylene N are two biocompatible Parylene variants with perceived potential for use in these models but their biocompatibility and biological interactions at their interface with cells are not well understood. Here, we use a simple approach for benchtop oxygen plasma treatment and investigate the changes in cell spreading and extracellular matrix deposition as well as the changes in material surface properties. Our results support the previous findings on the persistent effects of plasma treatment on Parylene biocompatibility while showing a more pronounced improvement for Parylene C over Parylene N. It is observed that although both increased surface roughness and persistent increases in oxygen species govern the plasma-driven improvement, the changes in oxygen concentration at the interface are the dominant factor. Overall, the results of this study provide a clear picture of potential mechanisms of plasma-induced changes in synthetic polymers which have implications for their use in in vitro model systems and other BioMEMS applications.
Metamorphosis of memory circuits in Drosophila reveal a strategy for evolving a larval brain
Authors: Truman James W. , Price Jacquelyn , Miyares Rosa L. , Lee Tzumin
Published: June 2022

Insects like Drosophila produce a second brain adapted to the form and behavior of a larva. Neurons for both larval and adult brains are produced by the same stem cells (neuroblasts) but the larva possesses only the earliest born neurons produced from each. To understand how a functional larval brain is made from this reduced set of neurons, we examined the origins and metamorphic fates of the neurons of the larval and adult mushroom body circuits. The adult mushroom body core is built sequentially of γ Kenyon cells, that form a medial lobe, followed by α’β’, and αβ Kenyon cells that form additional medial lobes and two vertical lobes. Extrinsic input (MBINs) and output (MBONs) neurons divide this core into computational compartments. The larval mushroom body contains only γ neurons. Its medial lobe compartments are roughly homologous to those of the adult and same MBONs are used for both. The larval vertical lobe, however, is an analogous “facsimile” that uses a larval-specific branch on the γ neurons to make up for the missing α’β’, and αβ neurons. The extrinsic cells for the facsimile are early-born neurons that trans-differentiate to serve a mushroom body function in the larva and then shift to other brain circuits in the adult. These findings are discussed in the context of the evolution of a larval brain in insects with complete metamorphosis.
Molecular insights into human Shieldin complex assembly and recruitment to DSBs
Authors: Susvirkar Vivek , Faesen Alex C.
Published: June 2022

The Shieldin complex represses end resection at DNA double-strand breaks (DSBs) and thereby serves as a pro-non homologous end joining (NHEJ) factor in the G1 phase of the cell cycle. Its components SHLD1, SHLD2, SHLD3 and REV7 are recruited in a hierarchical fashion. SHLD3 and REV7 localize first to DSBs, while the subsequently recruited SHLD2 is the only known DNA binding protein in the complex. The molecular details of the initial recruitment of SHLD3 and REV7, and the subsequent assembly of Shieldin on DSBs are unclear. Here, we report the identification of a promiscuous DNA binding domain in the C-terminal half of SHLD3. At the N-terminus, SHLD3 interacts with a dimer of REV7 molecules. We show that the interaction between SHLD3 and the first REV7 is remarkably slow, which is likely due to the substantial activation energy required to remodel mobile structural elements within the REV7 molecule to allow for binding to SHLD3. In contrast, the interaction between SHLD3 and SHLD2 with a second REV7 molecule is fast and does not require structural remodelling. Overall, these results provide insights into the rate-limiting step of the molecular assembly and recruitment of Shieldin complex at DNA DSBs.