bluuebunny/crossref_metadata_2025 huggingface dataset:
Exome risk score for predicting susceptibility to and severity of isolated thoracic aortic aneurysm
Authors: Li Yang , Song Li , Rong Wei , Zhang Yuanwei , Yao Xiaoming , Fang Xiaodong , Li Yulin , Du Jie
Published: May 2022

Isolated thoracic aortic aneurysms (TAAs) are asymptomatic before dissection or rupture and heterogeneous in clinical phenotype. It is urgent need but difficult to identify individuals at high risk to enable enhanced screening or preventive therapies. Because TAAs have a genetic component, one possible approach is to stratify individuals based on inherited DNA variations. Here, we constructed an integrated exome risk score (ERS) based on both common and rare variants found in whole-exome sequencing through a machine-learning framework in discovery population consisting of 551 cases and 1071 controls. We evaluated the performance of the ERS in an independent population including 151 cases and 779 controls with a raw odds ratio (OR) per 1 standard deviation (SD) = 1.95 and area under the receiver operating characteristic curve (AUC) = 0.680. When adjusted by gender and the first four principal components, OR per SD = 1.68 and AUC reached 0.783. Individuals in the top 20% of ERS distribution had an OR of 3.20 compared with others. Finally, we found that individuals with top 20% ERS developed TAA at a younger age (P = 0.002) and with a larger diameter (P = 0.016) compared with lower ERS, and were more likely to suffer from aortic root aneurysms (P = 0.009). Our analysis provides a global view of the genetic components of isolated TAA. The exome score developed and evaluated here is the first polygenic risk score for TAA and is a promising predictor of disease risk and severity, which will facilitate the implementation of the risk-reduction strategies.
Basic and applied research collaboration trends in the pharmaceutical industry
Authors: Vandaie Ramin
Published: May 2022

Firms in science-driven industries have traditionally devoted significant resources to basic scientific research. The intensity and outcomes of such investments, however, have changed over time. In this paper, we explore the trends in pharmaceutical companies’ scientific research over a two-decade period between 1990 and 2009. The results of our analyses reveal that the scientific output of large pharmaceutical companies as measured by the publications of company scientists has significantly increased over time. We also find that company scientists’ collaboration with external scientists has increased over time and across the board regardless of company size. Finally, we observe a decline in research and development alliance activities of pharmaceutical companies with the effect being weaker for large firms.
Antibody Duration After Infection From SARS-CoV-2 in the Texas Coronavirus Antibody Response Survey
Authors: Swartz Michael D , DeSantis Stacia M , Yaseen Ashraf , Brito Frances A , Valerio-Shewmaker Melissa A , Messiah Sarah E , Leon-Novelo Luis G , Kohl Harold W , Pinzon-Gomez Cesar L , Hao Tianyao , Zhang Shiming , Talebi Yashar , Yoo Joy , Ross Jessica R , Gonzalez Michael O , Wu Leqing , Kelder Steven H , Silberman Mark , Tuzo Samantha , Pont Stephen J , Shuford Jennifer A , Lakey David , Boerwinkle Eric
Published: May 2022

Understanding the duration of antibodies to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus that causes COVID-19 is important to controlling the current pandemic. Participants from the Texas Coronavirus Antibody Response Survey (Texas CARES) with at least 1 nucleocapsid protein antibody test were selected for a longitudinal analysis of antibody duration. A linear mixed model was fit to data from participants (n = 4553) with 1 to 3 antibody tests over 11 months (1 October 2020 to 16 September 2021), and models fit showed that expected antibody response after COVID-19 infection robustly increases for 100 days postinfection, and predicts individuals may remain antibody positive from natural infection beyond 500 days depending on age, body mass index, smoking or vaping use, and disease severity (hospitalized or not; symptomatic or not).
Toward Inclusive Digital Mobility Services: a Population Perspective
Authors: Goodman-Deane Joy , Kluge Jakob , Roca Bosch Elisabet , Nesterova Nina , Bradley Mike , Waller Sam , Hoeke Lisette , Clarkson P John
Published: May 2022

Digital mobility services have great potential to increase passengers’ transportation options, improve their experiences and reduce exclusion. However, these advantages are only available to those who can access and use these services effectively. To facilitate the development of inclusive services, information is needed on the range of potential users’ technology access, use, attitudes and capabilities. A population-representative survey examining these characteristics was carried out with 1010 participants in Germany in 2020. The results are examined for groups and intersections of groups identified in previous work as particularly vulnerable to either digital or mobility exclusion. Older people, people with disabilities and people with low education levels had particularly low levels of all technology variables. Caution is thus required when rolling out digital mobility services. Non-digital alternatives are needed to ensure an inclusive service and any digital interfaces need to be designed carefully to be usable by and reassuring to digital novices.
The Secret Life of Energy in Refugee Camps: Invisible Objects, Technologies, and Energy Systems in Humanitarianism
Authors: Rosenberg-Jansen Sarah
Published: May 2022

Within humanitarian systems and refugee spaces, energy technologies are often invisible and unrecognized. Beyond basic UN and emergency interventions to supply solar lanterns, lie vibrant systems of connection underpinning refugee electricity and cooking access: a world of energy needs and provision exist within refugee camps in East Africa. The article frames energy within forced migration debates on technology: contributing to the social anthropology and migration studies literature by exploring the material culture of energy in humanitarian contexts. The article argues that some forms of energy are highly visible—for example, solar lanterns and cookstoves—while others remain invisible. Certain objects are in danger of becoming fetishized by the humanitarian system while others are neglected and ignored. Analysis for this article reveals the invisibility of energy as a marginalized topic, highlights the methodological challenges of revealing the energy needs of displaced people, and explores institutional ignorance on the importance of energy.
Post malaria acute motor axonal neuropathy
Authors: Zayet Souheil , Klopfenstein Timothée , Quadrio Isabelle , Clerc Mélitine , Vossah Eklu , Gendrin Vincent , Hagenkötter Beate
Published: May 2022

We report herein the first case of acute motor axonal neuropathy syndrome after severe Plasmodium falciparum malaria in a traveller, diagnosed through neurophysiological findings and high level of neurofilaments light chain in cerebrospinal fluid analysis, with negative testing for anti-ganglioside antibodies.
On infinitary Gödel logics
Authors: Pischke Nicholas
Published: May 2022

We study propositional and first-order Gödel logics over infinitary languages, which are motivated semantically by corresponding interpretations into the unit interval $[0,1]$. We provide infinitary Hilbert-style calculi for the particular (propositional and first-order) cases with con-/disjunctions of countable length and prove corresponding completeness theorems by extending the usual Lindenbaum–Tarski construction to the infinitary case for a respective algebraic semantics via complete linear Heyting algebras. We provide infinitary hypersequent calculi and prove corresponding cut-elimination theorems in the Schütte–Tait style. Initial observations are made regarding truth-value sets other than $[0,1]$.
Improving the solar wind density model used in processing of spacecraft ranging observations
Authors: Aksim Dan , Pavlov Dmitry
Published: May 2022

Solar wind plasma as a cause of radio signal delay plays an important role in solar and planetary science. Early experiments studying the distribution of electrons near the Sun from spacecraft ranging measurements were designed so that the radio signal was passing close to the Sun. At present, processing of spacecraft tracking observations serves a different goal: precise (at metre level) determination of orbits of planets, most importantly Mars. The solar wind adds a time-varying delay to those observations, which is, in this case, unwanted and must be subtracted prior to putting the data into the planetary solution. Present planetary ephemerides calculate the delay assuming a symmetric stationary power-law model for the solar wind density. The present work, based on a custom variant of the EPM lunar–planetary ephemeris, questions the accuracy and correctness of that assumption and examines alternative models based on in situ solar wind density data provided by OMNI and on the ENLIL numerical model of the solar wind.
Mathematical encoding within multiresonant planetary systems as SETI beacons
Authors: Clement Matthew S , Raymond Sean N , Veras Dimitri , Kipping David
Published: May 2022

How might an advanced alien civilization manipulate the orbits within a planetary system to create a durable signpost that communicates its existence? While it is still debated whether such a purposeful advertisement would be prudent and wise, we propose that mean-motion resonances between neighbouring planets – with orbital periods that form integer ratios – could in principle be used to encode simple sequences that one would not expect to form in nature. In this letter, we build four multiresonant planetary systems and test their long-term orbital stability. The four systems each contain six or seven planets and consist of (i) consecutive integers from 1 to 6; (ii) prime numbers from 2 to 11; (iii) the Fibonacci sequence from 1 to 13; and (iv) the Lazy Caterer sequence from 1 to 16. We built each system using N-body simulations with artificial migration forces. We evaluated the stability of each system over the full 10 Gyr integration of the Sun’s main-sequence phase. We then tested the stability of these systems for an additional 10 Gyr, during and after post-main-sequence evolution of the central stars (assumed to be Sun-like) to their final, white dwarf phase. The only system that was destabilized was the consecutive integer sequence (system i). The other three sequences therefore represent potential Search for Extraterrestrial Intelligence (SETI) beacons.
The outer orbit of the high-mass stellar triple system Herschel 36 determined with the VLTI
Authors: Sanchez-Bermudez J , Hummel C A , Díaz-López J , Alberdi A , Schödel R , Arias J I , Barbá R H , Bastida-Escamilla E , Brandner W , Maíz Apellániz J , Pott J-U
Published: May 2022

Multiplicity is a ubiquitous characteristic of massive stars. Multiple systems offer us a unique observational constraint on the formation of high-mass systems. Herschel 36 A is a massive triple system composed of a close binary (Ab1-Ab2) and an outer component (Aa). We measured the orbital motion of the outer component of Herschel 36 A using infrared interferometry with the AMBER and PIONIER instruments of ESO’s Very Large Telescope Interferometer. Our immediate aims are to constrain the masses of all components of this system and to determine if the outer orbit is co-planar with the inner one. Reported spectroscopic data for all two components of this system and our interferometric data allow us to derive full orbital solutions for the outer orbit Aa-Ab and the inner orbit Ab1-Ab2. For the first time, we derive the absolute masses of mAa = 22.3 ± 1.7, mAb1  = 20.5 ± 1.5, and mAb2  = 12.5 ± 0.9 M⊙. Despite not being able to resolve the close binary components, we infer the inclination of their orbit by imposing the same parallax as the outer orbit. Inclinations derived from the inner and outer orbits imply a modest difference of about 22° between the orbital planes. We discuss this result and the formation of Herschel 36 A in the context of Core Accretion and Competitive Accretion models, which make different predictions regarding the statistic of the relative orbital inclinations.
Results from The COPAINS Pilot Survey: Four new brown dwarfs and a high companion detection rate for accelerating stars
Authors: Bonavita M , Fontanive C , Gratton R , Mužić K , Desidera S , Mesa D , Biller B , Scholz A , Sozzetti A , Squicciarini V
Published: May 2022

The last decade of direct imaging (DI) searches for sub-stellar companions has uncovered a widely diverse sample that challenges the current formation models, while highlighting the intrinsically low occurrence rate of wide companions, especially at the lower end of the mass distribution. These results clearly show how blind surveys, crucial to constrain the underlying planet and sub-stellar companion population, are not an efficient way to increase the sample of DI companions. It is therefore becoming clear that efficient target selection methods are essential to ensure a larger number of detections. We present the results of the COPAINS Survey conducted with SPHERE/VLT, searching for sub-stellar companions to stars showing significant proper motion differences (Δμ) between different astrometric catalogues. We observed twenty-five stars and detected ten companions, including four new brown dwarfs: HIP 21152 B, HIP 29724 B, HD 60584 B and HIP 63734 B. Our results clearly demonstrates how astrometric signatures, in the past only giving access to stellar companions, can now thanks to Gaia reveal companions well in the sub-stellar regime. We also introduce FORECAST (Finley Optimised REtrieval of Companions of Accelerating STars), a tool which allows to check the agreement between position and mass of the detected companions with the measured Δμ. Given the agreement between the values of the masses of the new sub-stellar companions from the photometry with the model-independent ones obtained with FORECAST, the results of COPAINS represent a significant increase of the number of potential benchmarks for brown dwarf and planet formation and evolution theories.
The MaNGA firefly Value-Added-Catalogue: resolved stellar populations of 10,010 nearby galaxies
Authors: Neumann Justus , Thomas Daniel , Maraston Claudia , Hill Lewis , Nanni Lorenza , Wenman Oliver , Lian Jianhui , Comparat Johan , Gonzalez-Perez Violeta , Westfall Kyle B , Yan Renbin , Chen Yanping , Stringfellow Guy S , Bershady Matthew A , Brownstein Joel R , Drory Niv , Schneider Donald P
Published: May 2022

We present the MaNGAfireflyValue-Added-Catalogue (VAC) – a catalogue of ∼3.7 million spatially resolved stellar population properties across 10,010 nearby galaxies from the final data release of the MaNGA survey. The full spectral fitting code firefly is employed to derive parameters such as stellar ages, metallicities, stellar and remnant masses, star formation histories, star formation rates and dust attenuation. In addition to Voronoi-binned measurements, our VAC also provides global properties, such as central values and radial gradients. Two variants of the VAC are available: presenting the results from fits using the M11-MILES and the novel MaStar stellar population models. MaStar allows to constrain the fit over the whole MaNGA wavelength range, extends the age-metallicity parameter space, and uses empirical spectra from the same instrument as MaNGA. The fits employing MaStar models find on average slightly younger ages, higher mass-weighted metallicities and smaller colour excesses. These differences are reduced when matching wavelength range and converging template grids. We further report that firefly stellar masses are systematically lower by ∼0.3 dex than masses from the MaNGA PCA and Pipe3D VACs, but match masses from the NSA best with only ∼0.1 dex difference. Finally, we show that firefly stellar ages correlate with spectral index age indicators HδA and Dn(4000), though with a clear additional metallicity dependence.
First measurement of the characteristic depletion radius of dark matter haloes from weak lensing
Authors: Fong Matthew , Han Jiaxin , Zhang Jun , Yang Xiaohu , Gao Hongyu , Wang Jiaqi , Li Hekun , Katsianis Antonios , Alonso Pedro
Published: May 2022

We use weak lensing observations to make the first measurement of the characteristic depletion radius, one of the three radii that characterize the region where matter is being depleted by growing haloes. The lenses are taken from the halo catalogue produced by the extended halo-based group/cluster finder applied to DESI Legacy Imaging Surveys DR9, while the sources are extracted from the DECaLS DR8 imaging data with the fourier_quad pipeline. We study halo masses $12 \lt \log (M_{\rm grp} \,[{\rm M_{\odot }}\, h^{-1}]) \le 15.3$ within redshifts 0.2 ≤ z ≤ 0.3. The virial and splashback radii are also measured and used to test the original findings on the depletion region. When binning haloes by mass, we find consistency between most of our measurements and predictions from the cosmicgrowth simulation, with exceptions to the lowest mass bins. The characteristic depletion radius is found to be roughly 2.5 times the virial radius and 1.7–3 times the splashback radius, in line with an approximately universal outer density profile, and the average enclosed density within the characteristic depletion radius is found to be roughly 29 times the mean matter density of the Universe in our sample. When binning haloes by both mass and a proxy for halo concentration, we do not detect a significant variation of the depletion radius with concentration, on which the simulation prediction is also sensitive to the choice of concentration proxy. We also confirm that the measured splashback radius varies with concentration differently from simulation predictions.
Progressive chromatin silencing of ABA biosynthesis genes permits seed germination in Arabidopsis
Authors: Yang Deyue , Zhao Fengli , Zhu Danling , Chen Xi , Kong Xiangxiong , Wu Yufeng , Chen Min , Du Jiamu , Qu Li-Jia , Wu Zhe
Published: May 2022

Seed germination represents a major developmental switch in plants that is vital to agriculture, but how this process is controlled at the chromatin level remains obscure. Here we demonstrate that successful germination in Arabidopsis thaliana requires a chromatin mechanism that progressively silences 9-CIS-EPOXYCAROTENOID DIOXYGENASE 6 (NCED6), which encodes a rate-limiting enzyme in abscisic acid (ABA) biosynthesis, through the cooperative action of the RNA-binding protein RZ-1 and the polycomb repressive complex 2 (PRC2). Simultaneous inactivation of RZ-1 and PRC2 blocked germination and synergistically derepressed NCEDs and hundreds of genes. At NCED6, in part by promoting H3 deacetylation and suppressing H3K4me3, RZ-1 facilitates transcriptional silencing and also an H3K27me3 accumulation process that occurs during seed germination and early seedling growth. Genome-wide analysis revealed that RZ-1 is preferentially required for transcriptional silencing of many PRC2 targets early during seed germination, when H3K27me3 is not yet established. We propose RZ-1 confers a novel silencing mechanism to compensate for and synergize with PRC2. Our work highlights the progressive chromatin silencing of ABA biosynthesis genes via the RNA-binding protein RZ-1 and PRC2 acting in synergy, a process that is vital for seed germination.
CRISPR/Cas9 disruption of UGT71L1 in poplar connects salicinoid and salicylic acid metabolism and alters growth and morphology
Authors: Gordon Harley , Fellenberg Christin , Lackus Nathalie D , Archinuk Finn , Sproule Amanda , Nakamura Yoko , K�llner Tobias G , Gershenzon Jonathan , Overy David P , Constabel C Peter
Published: May 2022

Salicinoids are salicyl alcohol-containing phenolic glycosides with strong antiherbivore effects found only in poplars and willows. Their biosynthesis is poorly understood, but recently a UDP-dependent glycosyltransferase, UGT71L1, was shown to be required for salicinoid biosynthesis in poplar tissue cultures. UGT71L1 specifically glycosylates salicyl benzoate, a proposed salicinoid intermediate. Here, we analyzed transgenic CRISPR/Cas9-generated UGT71L1 knockout plants. Metabolomic analyses revealed substantial reductions in the major salicinoids, confirming the central role of the enzyme in salicinoid biosynthesis. Correspondingly, UGT71L1 knockouts were preferred to wild-type by white-marked tussock moth (Orgyia leucostigma) larvae in bioassays. Greenhouse-grown knockout plants showed substantial growth alterations, with decreased internode length and smaller serrated leaves. Reinserting a functional UGT71L1 gene in a transgenic rescue experiment demonstrated that these effects were due only to the loss of UGT71L1. The knockouts contained elevated salicylate (SA) and jasmonate (JA) concentrations, and also had enhanced expression of SA- and JA-related genes. SA is predicted to be released by UGT71L1 disruption, if salicyl salicylate is a pathway intermediate and UGT71L1 substrate. This idea was supported by showing that salicyl salicylate can be glucosylated by recombinant UGT71L1, providing a potential link of salicinoid metabolism to SA and growth impacts. Connecting this pathway with growth could imply that salicinoids are under additional evolutionary constraints beyond selective pressure by herbivores.
Directing cyanobacterial photosynthesis in a cytochrome c oxidase mutant using a heterologous electron sink
Authors: Torrado Alejandro , Connabeer Hannah M , Röttig Annika , Pratt Nicola , Baylay Alison J , Terry Matthew J , Moore C Mark , Bibby Thomas S
Published: May 2022

Photosynthesis holds the promise of sustainable generation of useful products using light energy. Key to realizing this potential is the ability to rationally design photosynthesis to redirect energy and reductant derived from photons to desired products. Cytochrome P450s (P450s), which catalyze a broad array of reactions, have been engineered into a variety of photosynthetic organisms, where their activity has been shown to be photosynthesis-dependent, thus acting as heterologous sinks of electrons derived from photosynthesis. Furthermore, the addition of P450s can increase the photosynthetic capacity of the host organism. In this study, we developed this technology further using a P450 (CYP1A1) expressed in the cyanobacterium Synechococcus sp. PCC 7002. We show that rationally engineering photosynthesis by the removal of a competing electron sink, the respiratory terminal oxidase cytochrome c oxidase, increased the activity of CYP1A1. We provide evidence that this enhanced CYP1A1 activity was facilitated via an increase in the flux of electrons through Photosystem I. We also conducted a transcriptomic analysis on the designed strains to gain a more holistic understanding of how the cell responds to rational engineering. We describe a complex response including changes in expression of genes involved in photosynthesis and electron transfer linked to respiration. Specifically, the expression of CYP1A1 resulted in the reduction in expression of other natural electron dissipation pathways. This study emphasizes the potential for engineering photosynthetic organisms in biotechnology but also highlights the need to consider the broader impacts on cellular metabolism of any rationally induced changes.
The transcription factor MdMYB2 influences cold tolerance and anthocyanin accumulation by activating SUMO E3 ligase MdSIZ1 in apple
Authors: Jiang Han , Zhou Li-Jie , Gao Huai-Na , Wang Xiao-Fei , Li Zhi-Wen , Li Yuan-Yuan
Published: May 2022

Conjugation of the small ubiquitin-like modifier (SUMO) peptide to target proteins is an important post-translational modification. SAP AND MIZ1 DOMAIN-CONTAINING LIGASE1 (MdSIZ1) is an apple (Malus domestica Borkh). SUMO E3 ligase that mediates sumoylation of its targets during plant growth and development under adverse environmental conditions. However, it is unclear how MdSIZ1 senses the various environmental signals and whether sumoylation is regulated at the transcriptional level. In this study, we analyzed the MdSIZ1 promoter and found that it contained an MYB binding site (MBS) motif that was essential for the response of MdSIZ1 to low temperature (LT) and drought. Subsequently, we used yeast one-hybridization screening to demonstrate that a MYB transcription factor, MdMYB2, directly bound to the MBS motif in the MdSIZ1 promoter. Phenotypic characterization of MdMYB2 and MdSIZ1 suggested that the expression of both MdMYB2 and MdSIZ1 substantially improved cold tolerance in plants. MdMYB2 was induced by LT and further activated the expression of MdSIZ1, thereby promoting the sumoylation of MdMYB1, a key regulator of anthocyanin biosynthesis in apple. MdMYB2 promoted anthocyanin accumulation in apple fruits, apple calli, and Arabidopsis (Arabidopsis thaliana) in an MdSIZ1-dependent manner. In addition, the interaction of MdMYB2 and the MdSIZ1 promoter substantially improved plant tolerance to cold stress. Taken together, our findings reveal an important role for transcriptional regulation of sumoylation and provide insights into plant anthocyanin biosynthesis regulation mechanisms and stress response.
Panel sequencing links rare, likely damaging gene variants with distinct clinical phenotypes and outcomes in juvenile-onset SLE
Authors: Charras Amandine , Haldenby Sam , Smith Eve M D , Egbivwie Naomi , Olohan Lisa , Kenny John G , Schwarz Klaus , Roberts Carla , Al-Abadi Eslam , Armon Kate , Bailey Kathryn , Ciurtin Coziana , Gardner-Medwin Janet , Haslam Kirsty , Hawley Daniel P , Leahy Alice , Leone Valentina , McErlane Flora , Modgil Gita , Pilkington Clarissa , Ramanan Athimalaipet V , Rangaraj Satyapal , Riley Phil , Sridhar Arani , Beresford Michael W , Hedrich Christian M
Published: May 2022

Objectives

Juvenile-onset systemic lupus erythematosus (jSLE) affects 15–20% of lupus patients. Clinical heterogeneity between racial groups, age groups and individual patients suggests variable pathophysiology. This study aimed to identify highly penetrant damaging mutations in genes associated with SLE/SLE-like disease in a large national cohort (UK JSLE Cohort Study) and compare demographic, clinical and laboratory features in patient sub-cohorts with ‘genetic’ SLE vs remaining SLE patients.

Methods

Based on a sequencing panel designed in 2018, target enrichment and next-generation sequencing were performed in 348 patients to identify damaging gene variants. Findings were integrated with demographic, clinical and treatment related datasets.

Results

Damaging gene variants were identified in ∼3.5% of jSLE patients. When compared with the remaining cohort, ‘genetic’ SLE affected younger children and more Black African/Caribbean patients. ‘Genetic’ SLE patients exhibited less organ involvement and damage, and neuropsychiatric involvement developed over time. Less aggressive first line treatment was chosen in ‘genetic’ SLE patients, but more second and third line agents were used. ‘Genetic’ SLE associated with anti-dsDNA antibody positivity at diagnosis and reduced ANA, anti-LA and anti-Sm antibody positivity at last visit.

Conclusion

Approximately 3.5% of jSLE patients present damaging gene variants associated with younger age at onset, and distinct clinical features. As less commonly observed after treatment induction, in ‘genetic’ SLE, autoantibody positivity may be the result of tissue damage and explain reduced immune complex-mediated renal and haematological involvement. Routine sequencing could allow for patient stratification, risk assessment and target-directed treatment, thereby increasing efficacy and reducing toxicity.
Does Money Talk? Divestitures and Corporate Environmental and Social Policies
Authors: Gantchev Nickolay , Giannetti Mariassunta , Li Rachel
Published: May 2022

Can shareholders’ divestitures and threats of exit trigger improvements in firms’ environmental and social (E&S) policies? We show that E&S incidents are followed by some, but relatively small, divestitures. Nevertheless, following E&S incidents, firms with a one-standard-deviation higher E&S-conscious institutional ownership decrease their greenhouse gas emissions by 36.5% and improve their E&S scores by 7.2% more than other firms if their managers receive equity compensation. We do not observe any improvements associated with sales in E&S-conscious countries. Our results suggest that the threats of future exits and divestitures can improve E&S policies if shareholders are E&S-conscious and managers’ compensation is linked to the stock price.
Measuring “pain load” during general anesthesia
Authors: Green Stephen , Karunakaran Keerthana Deepti , Peng Ke , Berry Delany , Kussman Barry David , Micheli Lyle , Borsook David
Published: May 2022

Introduction

Functional near-infrared spectroscopy (fNIRS) allows for ongoing measures of brain functions during surgery. The ability to evaluate cumulative effects of painful/nociceptive events under general anesthesia remains a challenge. Through observing signal differences and setting boundaries for when observed events are known to produce pain/nociception, a program can trigger when the concentration of oxygenated hemoglobin goes beyond ±0.3 mM from 25 s after standardization.

Method

fNIRS signals were retrieved from patients undergoing knee surgery for anterior cruciate ligament repair under general anesthesia. Continuous fNIRS measures were measured from the primary somatosensory cortex (S1), which is known to be involved in evaluation of nociception, and the medial polar frontal cortex (mPFC), which are both involved in higher cortical functions (viz. cognition and emotion).

Results

A ±0.3 mM threshold for painful/nociceptive events was observed during surgical incisions at least twice, forming a basis for a potential near-real-time recording of pain/nociceptive events. Evidence through observed true positives in S1 and true negatives in mPFC are linked through statistically significant correlations and this threshold.

Conclusion

Our results show that standardizing and observing concentrations over 25 s using the ±0.3 mM threshold can be an arbiter of the continuous number of incisions performed on a patient, contributing to a potential intraoperative pain load index that correlates with post-operative levels of pain and potential pain chronification.
Dietary Folate Intake and Fecundability in Two Preconception Cohorts
Authors: Cueto Heidi T. , Jacobsen Bjarke H. , Laursen Anne Sofie Dam , Riis Anders H. , Hatch Elizabeth E. , Wise Lauren A. , Trolle Ellen , Sørensen Henrik Toft , Rothman Kenneth J. , Wesselink Amelia K. , Willis Sydney , Johannesen Benjamin R. , Mikkelsen Ellen M.
Published: May 2022

(Abstracted from Hum Reprod 2022;37(4):828–837)

Folate is an antioxidant micronutrient present in many vegetables, fruits, whole grains, beans, and the liver. Its synthetic counterpart, folic acid, is used as a dietary supplement for fortification of wheat and other foods.
Impact of Homologous Recombination Status and Responses With Veliparib Combined With First-Line Chemotherapy in Ovarian Cancer in the Phase 3 VELIA/GOG-3005 Study
Authors: Swisher Elizabeth M. , Aghajanian Carol , O'Malley David M. , Fleming Gini F. , Kaufmann Scott H. , Levine Douglas A. , Birrer Michael J. , Moore Kathleen N. , Spirtos Nick M. , Shahin Mark S. , Reid Thomas J. , Friedlander Michael , Steffensen Karina Dahl , Okamoto Aikou , Sehgal Vasudha , Ansell Peter J. , Dinh Minh H. , Bookman Michael A. , Coleman Robert L.
Published: May 2022

(Abstracted from Gynecol Oncol 2022;164:245–253)

Cancers with genetic homologous repair defects such as the breast cancer susceptibility genes BRCA1 and BRCA2 are particularly sensitive to poly (ADP-ribose) polymerase (PARP) inhibition. Identification of other homologous recombination deficiencies (HRD) beyond BRCA loss could expand utilization of PARP inhibitors (PARPi).
Expanding Homogeneous Culture of Human Primordial Germ Cell–Like Cells Maintaining Germline Features Without Serum or Feeder Layers
Authors: Kobayashi Mutsumi , Kobayashi Misato , Odajima Junko , Shioda Keiko , Hwang Young Sun , Sasaki Kotaro , Chatterjee Pranam , Kramme Christian , Kohman Richie E. , Church George M. , Loehr Amanda R. , Weiss Robert S. , Jüppner Harald , Gell Joanna J. , Lau Ching C. , Shioda Toshi
Published: May 2022

(Abstracted from Stem Cell Rep 2022;17(3):507–521)

Primordial germ cells (PGCs) are embryonic precursors of gametes that are extensively studied in research settings. Human primordial PGC–like cells (hPGCLCs) are a surrogate model for embryonic PGCs that present difficulties in in vitro cell culture and expansion due to rapid loss of PGC-like identity and limited cell survival.
Perinatal Death by Bile Acid Levels in Intrahepatic Cholestasis of Pregnancy: A Systematic Review
Authors: Di Mascio Daniele , Quist-Nelson Johanna , Riegel Melissa , George Brandon , Saccone Gabriele , Brun Romana , Haslinger Christian , Herrera Christina , Kawakita Tetsuya , Lee Richard H. , Panici Pierluigi Benedetti , Berghella Vincenzo
Published: May 2022

(Abstracted from J Matern Fetal Neonatal Med 2021;34(21):3614–3622)

Intrahepatic cholestasis of pregnancy (ICP) is characterized by elevated total bile acids (TBAs) and is the most common liver disease during pregnancy. The etiology and pathophysiology of ICP are not well understood, but genetics, ethnicity, hormones, nutrition, and the environment have been cited as risk factors.
Trends, Characteristics, and Outcomes of Placenta Accreta Spectrum: A National Study in the United States
Authors: Matsuzaki Shinya , Mandelbaum Rachel S. , Sangara Rauvynne N. , McCarthy Lauren E. , Vestal Nicole L. , Klar Maximilian , Matsushima Kazuhide , Amaya Rodolfo , Ouzounian Joseph G. , Matsuo Koji
Published: May 2022

(Abstracted from Am J Obstet Gynecol 2021;225:534.e1–534.e38)

Placenta accreta spectrum (PAS) describes the phenomenon wherein the trophoblastic placental tissue morbidly attaches to the myometrium of the gravid uterus, preventing normal detachment and causing morbidity. Depending on the degree of invasion, PAS is categorized as accreta if attached to the myometrium without decidua, increta if invasion occurs into the myometrium, and percreta if invasion through the myometrium into surrounding organs occurs.
A Novel Innovation and Entrepreneurship (I&E) Training Program for Biomedical Research Trainees
Authors: Grailer Joseph G. , Alhallak Kinan , Antes Alison L. , Kinch Michael S. , Woods Letha , Toker Emre , Garbutt Jane M.
Published: May 2022

Problem

Contemporary science emphasizes efficient translation of scientific discoveries into tangible, innovative products and services to improve human health. Therefore, researchers need skills in innovation and entrepreneurship (I&E) to select which problems to address and bring to market the most promising solutions. Training in this skillset is not currently available to most biomedical research trainees.

Approach

The Entrepreneurship for Biomedicine (E4B) training program was created to develop biomedical researchers’ I&E skills. The program comprises 2 semester-length courses: E4B1 teaches core skills; E4B2 focuses on advanced skills for those interested in pursuing funding for a new venture. In addition to traditional entrepreneurship training, E4B teaches ethics and personal skills such as resilience, communication, and team-building. Each course is delivered online and requires about 4 hours weekly. Program elements include short videos for didactic content; a team-based capstone project; mentorship from experienced entrepreneurs; and a live, virtual pitch presentation. The program is housed at Washington University School of Medicine in St. Louis and is open to pre- and postdoctoral biomedical research trainees and faculty nationwide.

Outcomes

In 2020, 77 trainees completed E4B1 and 13 went on to complete E4B2. Trainees in both courses were satisfied with learning content and mentorship and would recommend the program to a friend. Pre- and postanalyses demonstrated that trainees’ confidence in their knowledge about and ability to perform I&E tasks taught throughout the program increased. Since completion, 4 graduates have received external funding for an innovation and 3 have started a company.

Next Steps

E4B is well accepted, and this preliminary evaluation suggests the program is effective. It could serve to support medical school curricula, business competitions, and technology transfer efforts, which are opportunities for future exploration. A more robust evaluation is planned and recruitment will be expanded to increase participation from women and underrepresented populations.
Expanding Underrepresented in Medicine to Include Lesbian, Gay, Bisexual, Transgender, and Queer Individuals
Authors: Kelly Tim , Rodriguez Sarah B.
Published: May 2022

In 2003, the Association of American Medical Colleges (AAMC) stopped using the term “underrepresented minority” and instead adopted “underrepresented in medicine.” This was not the first time the AAMC revised this definition. In this article, the authors call on the AAMC to revise and expand this definition to include another group that is underrepresented in medicine: lesbian, gay, bisexual, transgender, and queer (LGBTQ) individuals. It is difficult to know whether LGBTQ populations are underrepresented in medicine; however, the data that do exist suggest a significant lack of LGBTQ representation in medicine. It is unclear if this underrepresentation is due to a true numerical lack of LGBTQ physicians, to LGBTQ physicians not publicly self-identifying due to anti-LGBTQ sentiments and reactions, or to both.

The authors urge the AAMC to take 3 actions: to anonymously and sensitively poll physicians nationwide to obtain a better estimate of the current number of LGBTQ physicians, to formulate improved standards for an LGBTQ health curriculum for all medical trainees to consistently produce LGBTQ-competent physicians, and to once again expand its definition of underrepresented in medicine to include LGBTQ populations. Such a change to this definition would likely lead to concerted efforts to increase the number of LGBTQ physicians, which could then lead to increased visibility, inclusivity, and mentorship programs where LGBTQ trainees could thrive. With these 3 actions, the authors believe that the AAMC has the opportunity to forge a path forward that is not only beneficial to LGBTQ trainees but also to LGBTQ patients who currently face a myriad of health disparities due to the lack of LGBTQ-identifying and LGBTQ-competent physicians.
Learning the Language of Medical Device Innovation: A Longitudinal Interdisciplinary Elective for Medical Students
Authors: Maloney Lauren M. , Hakimi Mathew , Hays Thomas , Adachi Joseph , Chau Annie , Esper Brecken S. , Koulouris Vasilios , Kung Preston , Meier Karl R. , Schum Ryan S. , Sha Sha , Wong Ada , Wu Ariel , Yin Wei , Page Christopher R.
Published: May 2022

Problem

Physicians are playing a growing role as clinician–innovators. Academic physicians are well positioned to contribute to the medical device innovation process, yet few medical school curricula provide students opportunities to learn the conceptual framework for clinical needs finding, needs screening, concept generation and iterative prototyping, and intellectual property management. This framework supports innovation and encourages the development of valuable interdisciplinary communication skills and collaborative learning strategies.

Approach

Our university offers a novel 3-year-long medical student Longitudinal Interdisciplinary Elective in Biodesign (MSLIEB) that teaches medical device innovation in 4 stages: (1) seminars and small-group work, (2) shared clinical experiences for needs finding, (3) concept generation and product development by serving as consultants for biomedical engineering capstone projects, and (4) reflection and mentorship. The MSLIEB objectives are to: create a longitudinal interdisciplinary peer mentorship relationship between undergraduate biomedical engineering students and medical students, and encourage codevelopment of professional identities in relation to medical device innovation.

Outcomes

The MSLIEB enrolled 5 entering cohorts from 2017 to 2021 with a total of 37 medical student participants. The first full entering cohort of 12 medical students produced 8 mentored biomedical engineering capstone projects, 7 of which were based on clinical needs statements derived from earlier in the elective. Medical student participants have coauthored poster and oral presentations; contributed to projects that won WolfieTank, a university-wide competition modeled after the television show Shark Tank; and participated in the filing of provisional patents. Students reflecting on the course reported a change in their attitude towards existing medical problems, felt better-equipped to collaboratively design solutions for clinical needs, and considered a potential career path in device design.

Next Steps

The MSLIEB will be scaled up by recruiting additional faculty, broadening clinical opportunities to include the outpatient setting, and increasing medical student access to rapid prototyping equipment.
Academic Medical Centers and the U.S. Department of Veterans Affairs: A 75-Year Partnership Influences Medical Education, Scientific Discovery, and Clinical Care
Authors: Petrakis Ismene L. , Kozal Michael
Published: May 2022

The historic academic affiliation program between the U.S. Department of Veterans Affairs and academic medical centers recently marked its 75th anniversary. The partnership has dramatically influenced medical education, research, and clinical care in the United States. In commemorating the anniversary, this article highlights areas in medicine that the partnership has influenced. The authors provide examples from their own experiences of particularly effective collaborations and describe some of the limitations they have encountered. Looking toward the future, they highlight other areas in which collaboration may be particularly effective.
Cervical Disc Replacement for Radiculopathy Versus Myeloradiculopathy
Authors: Alluri Ram K. , Vaishnav Avani S. , Sivaganesan Ahilan , Albert Todd J. , Huang Russel C. , Qureshi Sheeraz A.
Published: May 2022

Study Design:

Retrospective cohort study.

Objectives:

The aim was to compare the minimally clinically important difference (MCID) across multiple patient-reported outcomes (PROs) in patients undergoing cervical disc replacement (CDR) for cervical spondylotic radiculopathy versus myeloradiculopathy.

Summary of Background Data:

To date, a limited number of studies have demonstrated mostly similar results in patients with cervical spondylotic radiculopathy or myeloradiculopathy undergoing CDR. However, each of these previous studies have focused on statistically significant differences, which may not correlate with patient perceived improvements in outcomes or success.

Methods:

Patients who underwent 1 or 2-level CDR with radiculopathy versus myeloradiculopathy were identified, and prospectively collected data was retrospectively reviewed. Demographic variables, preoperative diagnosis, and operative variables were collected for each patient. The following PROs were prospectively collected: Neck Disability Index (NDI), visual analog scale (VAS)-Neck, VAS-Arm, Short Form-12 Health Survey (SF-12) Physical Component Score (PCS), SF-12 Mental Component Score (MCS), PROMIS Physical Function (PF). An MCID analysis of PROs for each diagnosis group was performed and the percentage of patients achieving the MCID was compared between the two diagnosis groups.

Results:

Eight-five patients, of which 56% had radiculopathy and 44% had myeloradiculopathy. MCID analysis demonstrated that at 6-week, 12-week, and final postoperative follow-up there was no significant difference in the percentage of patients with radiculopathy or myeloradiculopathy achieving the MCID for each PRO assessed. In both diagnosis groups the percentage of patients achieving the MCID for each PRO continued to increase from the 6-week to final postoperative follow-up except for the SF-12 MCS in patients with myeloradiculopathy.

Conclusions:

The percentage of patients achieving the MCID was not significantly different at each postoperative period assessed in the radiculopathy and myeloradiculopathy groups treated with CDR. In addition, the percentage of patients achieving the MCID continued to increase from 6 weeks to final follow-up in both groups for almost all PROs assessed.
Radiobiology of Select Radionuclides in Hanford Site Tank Waste
Authors: Brooks Antone L. , Hoel David , Glines Wayne M.
Published: May 2022

There are several important radionuclides involved in the “clean-up” or environmental isolation of nuclear waste contained in US Department of Energy Hanford Site underground waste tanks that drive many of the decisions associated with this activity. To make proper human health risk analyses and ensure that the most appropriate decisions are made, it is important to understand the radiation biology and the human health risk associated with these radionuclides. This manuscript provides some basic radiological science, in particular radiation biology, for some of these radionuclides, i.e., 3H, 90Sr, 137Cs, 99Tc, 129I, and the alpha emitters 239, 240Pu, 233,234,235,238 U, and 241Am. These radionuclides were selected based on their designation as “constituents of potential concern,” historical significance, or potential impact on human health risk. In addition to the radiobiology of these select radionuclides, this manuscript provides brief discussions of the estimated cost of planned management of Hanford tank waste and a comparison with releases into the Techa River from activities associated with the Mayak Production Association. A set of summary conclusions of the potential human health risks associated with these radionuclides is given.
CHANDELIER-ASSISTED VERSUS STANDARD SCLERAL BUCKLING FOR PRIMARY RHEGMATOGENOUS RETINAL DETACHMENT
Authors: Albalkini Ahmed Saad , Abdullatif Abdussalam M. , Albalkini Mohamed Saad , Macky Tamer A. , Khattab Ayman , Attya Mohamed
Published: May 2022

Purpose:

To compare anatomical outcomes, functional outcomes, and rate of complications of standard scleral buckling (SSB) versus chandelier-assisted scleral buckling (CSB) in phakic eyes with rhegmatogenous retinal detachment.

Methods:

Patients were randomly assigned to either SSB or CSB. Surgical success/failure rate, corrected distance visual acuity, surgical operating time, and rate of intraoperative and postoperative complications including epiretinal membranes by spectral domain optical coherence tomography were compared between groups.

Results:

A total of 50 eyes of 49 patients were included. At 6 months, there was no statistically significant difference between groups in primary success, or final anatomical success (P > 0.9); mean corrected distance visual acuity at any visit (P values >0.05); or mean surgical time: 120.3 ± 39.05 and 102.48 ± 43.76 minutes for the SSB and CSB, respectively (P = 0.1). The CSB had a higher rate of postoperative complications (34.8%) compared with the SSB (3.8%) (P < 0.05). On spectral domain optical coherence tomography, CSB had a statistically significant higher rate of epiretinal membranes compared with SSB (44% vs. 19% [P < 0.05]) and showed vitreous entrapment in the chandelier sclerotomy site on the ultrasonic biomicroscopy.

Conclusion:

Chandelier-assisted scleral buckling surgery does not offer encouraging advantages over SSB. On the contrary, we detected a higher rate of complications with CSB especially epiretinal membranes development.