bluuebunny/crossref_metadata_2025 huggingface dataset:
Convention and idiosyncrasy
Authors: Caplan David
Published: December 2021

“Convention and idiosyncrasy” shows how the successful use of recognizable artistic conventions can help a poet to enter a literature and a culture that seeks to exclude them. It can moderate skepticism, even hostility, and sanction an outsider’s admittance into a community. At the same time, respect for poetic convention hardly reigns uncontested in American literary culture. With several notable exceptions, American poetry and, even more so, its scholarly discussions value a different quality. American poets and readers alike often appreciate idiosyncrasy and the associated values of disruption, originality, innovation, strangeness, and surprise. Poets as different Phillis Wheatley, Emily Dickinson, Adrienne Rich, Charles Bernstein, and Maggie Smith consider the competing imperatives of convention and idiosyncrasy.
Habitat and developmental constraints drove 330 million years of horseshoe crab evolution
Authors: Bicknell Russell D C , Kimmig Julien , Budd Graham E , Legg David A , Bader Kenneth S , Haug Carolin , Kaiser Dorkas , Laibl Lukáš , Tashman Jessica N , Campione Nicolás E
Published: December 2021

Records of evolutionary stasis over time are central to uncovering large-scale evolutionary modes, whether by long-term gradual change or via enduring stability punctuated by rapid shifts. The key to this discussion is to identify and examine groups with long fossil records that, ideally, extend to the present day. One group often regarded as the quintessential example of stasis is Xiphosurida, the horseshoe crabs. However, when, how and, particularly, why stasis arose in xiphosurids remain fundamental, but complex, questions. Here, we explore the protracted history of fossil and living xiphosurids and demonstrate two levels of evolutionary stability: developmental stasis since at least the Pennsylvanian and shape stasis since the Late Jurassic. Furthermore, shape and diversity are punctuated by two high-disparity episodes during the Carboniferous and Triassic – transitions that coincide with forays into habitation of marginal environments. In an exception to these general patterns, body size increased gradually over this period and, thus, cannot be described under the same, often-touted, static models of evolution. Therefore, we demonstrate that evolutionary stasis can be modular and fixed within the same group at different periods and in different biological traits, while other traits experience altogether different evolutionary modes. This mosaic in the tempo and mode of evolution is not unique to Xiphosurida but likely reflects variable mechanisms acting on biological traits, for example transitions in life modes, niche occupation and major evolutionary radiations.
Understanding the Voices of Disability Advocates in Physician-Assisted Suicide Debates
Authors: Stahl Devan
Published: December 2021

Christians have an obligation to attend to the voices of persons who are crying out that their dignity and very lives are in jeopardy when physician-assisted suicide (PAS) becomes legalized. The following essay begins with an account of the concept of “disability moral psychology,” which elucidates the unique ways persons with disabilities perceive the world, based on their phenomenological experience. The author then explores the disability critique of PAS and the shared social conditions of persons who are chronically disabled and terminally ill. Finally, the author positions the disability critique within Christian moral deliberations on PAS to unearth its significance for Christian ethics. To bear witness to a compassionate God, theological and ethical judgments concerning PAS must seek perspectives from persons who claim that their dignity and even their lives are in jeopardy by the practice.
A taxonomy of the brain’s white matter: twenty-one major tracts for the 21st century
Authors: Bullock Daniel N , Hayday Elena A , Grier Mark D , Tang Wei , Pestilli Franco , Heilbronner Sarah R
Published: December 2021

The functional and computational properties of brain areas are determined, in large part, by their connectivity profiles. Advances in neuroimaging and network neuroscience allow us to characterize the human brain noninvasively, but a comprehensive understanding of the human brain demands an account of the anatomy of brain connections. Long-range anatomical connections are instantiated by white matter, which itself is organized into tracts. These tracts are often disrupted by central nervous system disorders, and they can be targeted by neuromodulatory interventions, such as deep brain stimulation. Here, we characterized the connections, morphology, traversal, and functions of the major white matter tracts in the brain. There are major discrepancies across different accounts of white matter tract anatomy, hindering our attempts to accurately map the connectivity of the human brain. However, we are often able to clarify the source(s) of these discrepancies through careful consideration of both histological tract-tracing and diffusion-weighted tractography studies. In combination, the advantages and disadvantages of each method permit novel insights into brain connectivity. Ultimately, our synthesis provides an essential reference for neuroscientists and clinicians interested in brain connectivity and anatomy, allowing for the study of the association of white matter’s properties with behavior, development, and disorders.
Error Characterization and Statistical Modeling Improves Circulating Tumor DNA Detection by Droplet Digital PCR
Authors: Henriksen Tenna V , Drue Simon O , Frydendahl Amanda , Demuth Christina , Rasmussen Mads H , Reinert Thomas , Pedersen Jakob S , Andersen Claus L
Published: December 2021

Background

Droplet digital PCR (ddPCR) is a widely used and sensitive application for circulating tumor DNA (ctDNA) detection. As ctDNA is often found in low abundance, methods to separate low-signal readouts from noise are necessary. We aimed to characterize the ddPCR-generated noise and, informed by this, create a sensitive and specific ctDNA caller.

Methods

We built 2 novel complimentary ctDNA calling methods: dynamic limit of blank and concentration and assay-specific tumor load estimator (CASTLE). Both methods are informed by empirically established assay-specific noise profiles. Here, we characterized noise for 70 mutation-detecting ddPCR assays by applying each assay to 95 nonmutated samples. Using these profiles, the performance of the 2 new methods was assessed in a total of 9447 negative/positive reference samples and in 1311 real-life plasma samples from colorectal cancer patients. Lastly, performances were compared to 7 literature-established calling methods.

Results

For many assays, noise increased proportionally with the DNA input amount. Assays targeting transition base changes were more error-prone than transversion-targeting assays. Both our calling methods successfully accounted for the additional noise in transition assays and showed consistently high performance regardless of DNA input amount. Calling methods that were not noise-informed performed less well than noise-informed methods. CASTLE was the only calling method providing a statistical estimate of the noise-corrected mutation level and call certainty.

Conclusions

Accurate error modeling is necessary for sensitive and specific ctDNA detection by ddPCR. Accounting for DNA input amounts ensures specific detection regardless of the sample-specific DNA concentration. Our results demonstrate CASTLE as a powerful tool for ctDNA calling using ddPCR.
Insights on fault reactivation during the 2019 November 11, Mw 4.9 Le Teil earthquake in southeastern France, from a joint 3-D geological model and InSAR time-series analysis
Authors: Marconato L , Leloup P H , Lasserre C , Jolivet R , Caritg S , Grandin R , Métois M , Cavalié O , Audin L
Published: December 2021

The 2019, Mw 4.9 Le Teil earthquake occurred in southeastern France, causing substantial damage in this slow deforming region. Field observations, remote sensing and seismological studies following the event revealed that coseismic slip concentrates at shallow depth along a ∼5 km long rupture associated with surface breaks and a thrusting mechanism. We further investigate this earthquake by combining geological field mapping, 3-D geology, InSAR time-series analysis and a coseismic slip inversion. From structural, stratigraphic and geological data collected around the epicentre, we first produce a 3-D geological model of the region surrounding the rupture using the GeoModeller software. Our model includes the geometry of the geological layers and the main faults, including the La Rouvière Fault, (LRF) the Oligocene normal fault that ruptured during the earthquake. We generate a time-series of surface displacement from Sentinel-1 SAR data ranging from early 2019 January to late 2020 January using the NSBAS processing chain. The spatio-temporal patterns of surface displacement for this time span show neither a clear pre-seismic signal nor significant post-seismic transient deformation. We extract the coseismic displacement pattern from the InSAR time-series, highlighting along-strike variations of coseismic surface slip. The maximum relative displacement along the line of sight is up to ∼16 cm and is located in the southwestern part of the rupture. We invert for the slip distribution on the fault from the InSAR coseismic surface displacement field. Constraining our fault geometry from the geological model, acceptable fault dip ranges between 55° and 60°. Our model confirms the reactivation of LRF, with reverse slip at very shallow depth and two main slip patches reaching, respectively, 30 and 24 cm of slip, both around 500 m depth. We finally discuss how the 3-D fault geometry and geological structure may have impacted the slip distribution and propagation during the earthquake. This study is a step to reassess the seismic hazard of the many faults similar to the La Rouvière one along the Cévennes fault system, in a densely populated area hosting several sensitive nuclear sites.
A review on the ethnopharmacology, phytochemistry and pharmacology of Polygonum hydropiper Linn.
Authors: Bairagi Juli , Saikia Purba J , Boro Freeman , Hazarika Ajit
Published: December 2021

Objectives

Polygonum hydropiper is a herb with worldwide distribution, having tremendous value as traditional medicine among different communities. It is used to cure many kinds of ailments such as gynaecological disorders, ulcer, anxiety, pain, cancer, etc. The present review gives emphasis on a thorough and updated study of the botanical description and taxonomy, distribution, habitat, ethnopharmacology, phytochemical constituents, pharmacological activities and toxicological aspects of P. hydropiper.

Methods

The information included in this review was collected from different scientific databases like PubMed, ScienceDirect, Google Scholar, etc. In addition to the botanical description and taxonomy, lots of ethnomedicinal use of the water-pepper plant could be found.

Result

A good number of compounds belonging to the categories like alkaloids, carbohydrates, flavonoids, etc. were confirmed to be present in the plant. Moreover, in different studies, this plant was found to possess activities like anti-Alzheimer, antibacterial, antidementia, antifertility, neuropharmacological, sedative, anxiolytic, thrombolytic and membrane-stabilizing activity, etc. with minimal toxicity.

Conclusion

These properties may be directly related to its possession of a large number of bioactive molecules of different categories. Based on these properties, isolation of responsible compound(s), evaluation of molecular mechanisms of their action and clinical trials are recommended.
The impact of r-process heating on the dynamics of neutron star merger accretion disc winds and their electromagnetic radiation
Authors: Klion Hannah , Tchekhovskoy Alexander , Kasen Daniel , Kathirgamaraju Adithan , Quataert Eliot , Fernández Rodrigo
Published: December 2021

Neutron star merger accretion discs can launch neutron-rich winds of >10−2M⊙. This ejecta is a prime site for r-process nucleosynthesis, which will produce a range of radioactive heavy nuclei. The decay of these nuclei releases enough energy to accelerate portions of the wind by ∼0.1c. Here, we investigate the effect of r-process heating on the dynamical evolution of disc winds. We extract the wind from a 3D general relativistic magnetohydrodynamic simulation of a disc from a post-merger system. This is used to create inner boundary conditions for 2D hydrodynamic simulations that continue the original 3D simulation. We perform two such simulations: one that includes the r-process heating, and another one that does not. We follow the hydrodynamic simulations until the winds reach homology (60 s). Using time-dependent multifrequency multidimensional Monte Carlo radiation transport simulations, we then calculate the kilonova light curves from the winds with and without dynamical r-process heating. We find that the r-process heating can substantially alter the velocity distribution of the wind, shifting the mass-weighted median velocity from 0.06c to 0.12c. The inclusion of the dynamical r-process heating makes the light curve brighter and bluer at $\sim 1\, \mathrm{d}$ post-merger. However, the high-velocity tail of the ejecta distribution and the early ($\lesssim 1\, \mathrm{d}$) light curves are largely unaffected.
Atmospheric mass-loss and stellar wind effects in young and old systems – I. Comparative 3D study of TOI-942 and TOI-421 systems
Authors: Kubyshkina Daria , Vidotto Aline A , Villarreal D’Angelo Carolina , Carolan Stephen , Hazra Gopal , Carleo Ilaria
Published: December 2021

At young ages, when radiation from the host star is high, and the planet is hot and inflated after formation, planetary atmospheric mass-loss can be extremely strong compared to older planets. In turn, stellar winds are faster and denser for young stars compared to evolved main-sequence stars. Their interaction with escaping planetary atmospheres can substantially affect atmospheric mass-loss rates, as well as the observable signatures of escaping atmospheres, with both effects expected to occur differently for young and evolved planets. We perform a comparative study of two systems around stars of similar masses but very different ages (50 Myr and 9 Gyr): TOI-942 and TOI-421. Both stars host two sub-Neptune-like planets at similar orbits and in similar mass ranges, which allows a direct comparison of the atmospheric escape and interactions with the stellar winds in the young and old systems. We perform the 3D atmospheric modelling of the four planets in TOI-942 and TOI-421 systems and make the theoretical predictions of possible observational signatures in Ly α absorption. We find that accounting for the stellar wind interacting with planetary atmospheres is crucial for the interpretation of the observations for young planets. Additionally, we show that a particular energy distribution along the XUV spectra has a minor effect on the atmospheric mass-loss rates, but it is of crucial importance for modelling the Ly α absorption and therefore for interpretation of observations.
Probing the non-thermal emission geometry of AR Sco via optical phase-resolved polarimetry
Authors: du Plessis Louis , Venter Christo , Wadiasingh Zorawar , Harding Alice K , Buckley David A H , Potter Stephen B , Meintjes P J
Published: December 2021

AR Sco is a binary system that contains a white and red dwarf. The rotation rate of the white dwarf (WD) has been observed to slow down, analogous to rotation-powered radio pulsars; it has thus been dubbed a ‘white dwarf pulsar’. We previously fit the traditional radio pulsar rotating vector model to the linearly polarized optical data from this source, constraining the system geometry as well as the WD mass. Using a much more extensive data set, we now explore the application of the same model to binary phase-resolved optical polarimetric data, thought to be the result of non-thermal synchrotron radiation, and derive the magnetic inclination angle α and the observer angle ζ at different orbital phases. We obtain an ∼10° variation in α and ∼30° variation in ζ over the orbital period. The variation patterns in these two parameters is robust, regardless of the binning and epoch of data used. We speculate that the observer is detecting radiation from an asymmetric emission region that is a stable structure over several orbital periods. The success of this simple model lastly implies that the pitch angles of the particles are small and the pulsed, non-thermal emission originates relatively close to the WD surface.
Exoplanets in the Galactic context: planet occurrence rates in the thin disc, thick disc, and stellar halo of Kepler stars
Authors: Bashi Dolev , Zucker Shay
Published: December 2021

In order to gain a better understanding of planet formation and evolution, it is important to examine the statistics of exoplanets in the Galactic context. By combining information on stellar elemental abundances and kinematics, we constructed separate samples of Kepler stars according to their affiliation to the Galactic components of thin disc, thick disc, and stellar halo. Using a Bayesian analysis with conjugate priors, we then investigated how planet occurrence rates differ in different regions of planet properties. We find that young, slow, and metal-rich stars, associated mainly with the thin disc, host on average more planets (especially close-in super Earths) compared to the old, fast, and metal-poor thick disc stars. We further assess the dependence between stellar properties such as spectral type and metallicity, and planet occurrence rates. The trends we find agree with those found by other authors as well. We argue that in the Galactic context, these are probably not the main properties that affect planet occurrence rates, but rather the dynamical history of stars, and especially stellar age and kinematics, impact the current distribution of planets in the Galaxy.
Destruction of AlF: a quantum study of its ground-state photodissociation
Authors: Qin Zhi , Bai Tianrui , Liu Linhua
Published: December 2021

Photodissociation by ultraviolet photons is the key destruction pathway for aluminium monofluoride (AlF) in the envelope of the carbon star IRC +10216 from the stellar photosphere up to the outer layers. However, there is no available photodissociation data for AlF, which hampers the prediction of the abundances of Al-bearing molecules in astrochemical models. Here, we present an ab initio study of AlF photodissociation. Potential energy curves of seven singlet states for AlF were computed by the internally contracted multireference single and double configuration-interaction method and aug-cc-pCV5Z-DK basis set, along with the transition dipole moments from excited singlet states to the ground state. State-resolved cross sections for the direct photodissociation from 36 349 ground rovibrational levels ( υ″≤120, J″≤360) to six singlet excited states were calculated by the quantum mechanical method. We found that the 21Π←X 1Σ+, 31Π←X 1Σ+, and 41Π←X 1Σ+ transitions have extremely strong absorption for lower wavelengths, especially between the Lyman and  Lyman α ones. Photodissociation cross sections in local thermal equilibrium were estimated for gas temperatures from 500 to 20 000 K. Finally, the cross sections were utilized to calculate the photodissociation rates in the interstellar and blackbody radiation fields. The obtained photodissociation cross sections and rates can be used to determine the abundance of AlF in astrochemical models.
Focusing of non-linear eccentric waves in astrophysical discs – II. Excitation and damping of tightly wound waves
Authors: Lynch Elliot M
Published: December 2021

In this paper, I develop a non-linear theory of tightly wound (highly twisted) eccentric waves in astrophysical discs, based on the averaged Lagrangian method of Whitham. Viscous dissipation is included in the theory by use of a pseudo-Lagrangian. This work is an extension of the theory developed by Lee & Goodman to 3D discs, with the addition of viscosity. I confirm that linear tightly wound eccentric waves are overstable and are excited by the presence of a shear viscosity and show that this persists for weakly non-linear waves. I find the waves are damped by shear viscosity when the wave become sufficiently non-linear, a result previously found in particulate discs. Additionally, I compare the results of this model to recent simulations of eccentric waves propagating in the inner regions of black hole discs and show that an ingoing eccentric wave can be strongly damped near the marginally stable orbit, resulting in a nearly circular disc, with a strong azimuthal variation in the disc density.
HyDRo: atmospheric retrieval of rocky exoplanets in thermal emission
Authors: Piette Anjali A A , Madhusudhan Nikku , Mandell Avi M
Published: December 2021

Emission spectroscopy is a promising technique to observe atmospheres of rocky exoplanets, probing both their chemistry and thermal profiles. We present hydro, an atmospheric retrieval framework for thermal emission spectra of rocky exoplanets. hydro does not make prior assumptions about the background atmospheric composition, and can therefore be used to interpret spectra of secondary atmospheres with unknown compositions. We use hydro to assess the chemical constraints which can be placed on rocky exoplanet atmospheres using JWST. First, we identify the best currently known rocky exoplanet candidates for spectroscopic observations in thermal emission with JWST, finding >30 known rocky exoplanets whose thermal emission will be detectable by JWST/MIRI in fewer than 10 eclipses at R ∼ 10. We then consider the observations required to characterize the atmospheres of three promising rocky exoplanets across the ∼400–800 K equilibrium temperature range: Trappist-1 b, GJ 1132 b, and LHS 3844 b. Considering a range of CO2- to H2O-rich atmospheric compositions, we find that as few as eight eclipses of LHS 3844 b or GJ 1132 b with MIRI LRS will be able to place important constraints on the chemical compositions of their atmospheres. This includes confident detections of CO2 and H2O in the case of a cloud-free CO2-rich composition, besides ruling out a bare rock scenario. Similarly, 30 eclipses of Trappist-1 b with MIRI LRS can allow detections of a cloud-free CO2-rich or CO2-H2O atmosphere. hydro will allow important atmospheric constraints for rocky exoplanets using JWST observations, providing clues about their geochemical environments.
Simultaneous borrowing and saving in microfinance
Authors: Dasgupta Dyotona , Roy Chowdhury Prabal
Published: December 2021

This paper provides a rationale for one of the most widely practised mechanisms by microfinance institutions (MFIs)—simultaneous borrowing and saving. Unlike the existing literature, our explanation does not involve any behavioral aspect. We study a dynamic relationship between a benevolent MFI and a borrower who is subject to an ex post moral hazard problem. The optimum contract involves simultaneous borrowing and saving—at each date, the MFI provides a small loan, the borrower invests that in a production technology, and saves the net return with the MFI. These help her to accumulate a lumpsum amount and ‘graduate’ to an improved lifetime utility which is not achievable when only credit is provided. Over time, as her savings increase, her incentive to repay increases. The optimal loan scheme is weakly progressive, i.e. weakly increasing over time. We also provide a sufficient condition for the non-existence of any incentive compatible contract.
Molecular Dosimetry of DNA Adducts in Rats Exposed to Vinyl Acetate Monomer
Authors: Hsiao Yun-Chung , Liu Chih-Wei , Hoffman Gary , Fang Caroline , Lu Kun
Published: December 2021

Vinyl acetate monomer (VAM) is heavily used to synthesize polymers. Previous studies have shown that inhaled VAM, being metabolized to acetaldehyde, may form DNA adducts including N2-ethylidene-deoxyguanosine (N2-EtD-dG), which may subsequently cause mutations and contribute to its carcinogenesis. Currently, there is little knowledge on the molecular dosimetry between VAM exposure and DNA adducts under dosages relevant to human exposure. In this study, 0.02, 0.1, 1, 10, 50, 200, and 600 ppm VAM were exposed to rats by inhalation for 14 days (6 h/day). The use of [13C2]-VAM allows unambiguous differentiation and quantification of the exogenous and endogenous N2-EtD-dG by highly sensitive LC-MS/MS. Our data indicate that VAM-induced exogenous DNA adducts were formed in a non-linear manner. Exogenous DNA adducts were only detected in the nasal epithelium of rats exposed to 10, 50, 200, and 600 ppm VAM, whereas endogenous adducts were found in all nasal and other tissues analyzed. In addition, ratios of exogenous/endogenous DNA adducts were less than 1 with the dose up to 50 ppm, indicating that endogenous DNA adducts are predominant at low VAM concentrations. Moreover, differential dose-response in terms of exogenous DNA adduct formation were observed between nasal respiratory and olfactory epithelium. Furthermore, the lack of exogenous DNA adducts in distant tissues, including peripheral blood mononuclear cells, liver, brain, and bone marrow, indicates that VAM and/or its metabolite do not distribute systemically to cause DNA damage in distant tissues. Together, these results provided new molecular dosimetry to improve science-based cancer risk assessments of VAM.
Comparative Transcriptome Analyses Reveal Conserved and Distinct Mechanisms of the SDHI Fungicide Benzovindiflupyr Inhibiting Colletotrichum
Authors: Liang Xiaoyu , Zou Lijun , Lian Wenxu , Wang Meng , Yang Ye , Zhang Yu
Published: December 2021

Colletotrichum leaf disease (CLD) is an annual production concern for commercial growers worldwide. The succinate dehydrogenase inhibitor (SDHI) fungicide benzovindiflupyr shows higher bioactivity against CLD than other SDHIs. However, the mechanism underlying such difference remains unclear. In this study, benzovindiflupyr exhibits good inhibitory activity against Colletotrichum siamense and C. nymphaeae in vitro and in vivo. To reveal its mechanism for inhibiting Colletotrichum, we compared transcriptomes of C. siamense and C. nymphaeae under treatment with benzovindiflupyr and boscalid. Benzovindiflupyr exhibited higher inhibitory activity against SDH enzyme than boscalid, resulting in a greater reduction in the ATP content of Colletotrichum isolates. Most of the metabolic pathways induced in these fungicide-treated isolates were similar, indicating that benzovindiflupyr exhibited a conserved mechanism of SDHIs inhibiting Colletotrichum. At the same level of suppressive SDH activity, benzovindiflupyr activated more than three times greater gene numbers of Colletotrichum than boscalid, suggesting that benzovindiflupyr could activate distinct mechanisms against Colletotrichum. Membrane-related gene ontology terms, mainly including intrinsic components of membrane, were highly abundant for the benzovindiflupyr-treated isolates rather than boscalid-treated isolates. Only benzovindiflupyr increased the relative conductivities of hyphae, indicating that it could damage the cell membrane and increase mycelial electrolyte leakage. Thus, we proposed that the high bioactivity of benzovindiflupyr against Colletotrichum occurred by inhibiting SDH activity and damaging the cell membrane at the same time. The research improves our understanding the mode of action of SDHI fungicides against Colletotrichum.
Effect of Electroencephalography Spectral Edge Frequency (SEF) and Patient State Index (PSI)-Guided Propofol-Remifentanil Anesthesia on Delirium After Laparoscopic Surgery: The eMODIPOD Randomized Controlled Trial
Authors: Wang E. , Wang Lu , Ye Chunyan , Luo Ning , Zhang Yanrong , Zhong Yugui , Zhu Maoen , Zou Yu , Li Qian , Li Longyan , Song Zongbin , Luo Hui , Dai Feng , Liu Hong , Gelb Adrian W. , Guo Qulian , Meng Lingzhong ,   for the eMODIPOD Research Group
Published: December 2021

Background:

The effect of SedLine electroencephalography (EEG)-guided anesthetic care on postoperative delirium (POD) has not been studied.

Methods:

This single-center randomized EEG Monitoring tO Decrease the Incidence of Post-Operative Delirium (eMODIPOD) trial involved 1560 patients aged 50 years or above undergoing laparoscopic surgery. Propofol-remifentanil anesthesia was guided either by SedLine (EEG-guided care, n=779) or not (usual care, n=781). The goal of EEG-guided care was to maintain spectral edge frequency between 10 and 15 and patient state index (PSI) between 25 and 50. The primary outcome was the incidence of POD on postoperative days 1 to 5. The secondary outcomes included emergence delirium, composite moderate-to-severe complications, length of hospital stay, intensive care unit admission, 30-day hospital readmission and all-cause mortality, and intraoperative awareness.

Results:

Of the 1560 randomized patients, 1545 were included in the modified intention-to-treat analysis. The median propofol administered for anesthesia maintenance was 900 mg and 1000 mg in the EEG-guided and usual care groups, respectively (P=0.21). POD occurred in 1.0% (8/771) and 1.2% (9/774) of patients in the EEG-guided and usual care groups, respectively (risk ratio: 0.89; 95% confidence interval: 0.35-2.30). There were no between-group differences in all secondary outcome measures. Emergence delirium occurred in 11.8% (91/771) and 13.2% (102/774) of the EEG-guided care and usual care groups, respectively (risk ratio: 0.90; 95% confidence interval: 0.69-1.17; P=0.41). Three patients from each group reported intraoperative awareness.

Conclusions:

Compared with usual care, SedLine spectral edge frequency-guided and patient state index-guided propofol-remifentanil anesthetic care neither alters anesthetic delivery nor decreases the unexpected low incidence of POD in relatively young Chinese patients undergoing laparoscopic surgery.
Osteoarticular Salmonella infections in healthy children
Authors: Wang Hongmei , Lei Min , Huang Baoxing , Deng Jikui , Zheng Lei , Wang Qian
Published: December 2021

Introduction:

Osteoarticular infections caused by Salmonella spp. are rare. Salmonella osteomyelitis is more common in children with underlying chronic diseases or immunodeficiency, but is rare in previously healthy children.

Patient concerns:

Six previously healthy children with Salmonella osteoarticular infections were admitted to our hospital. Identification and characterization of the isolates were also performed and correlated with the clinical findings.

Diagnosis:

The predominant symptoms were fever, pain, and swelling. Three patients were diagnosed with osteomyelitis (including 2 with left humerus, 1 with left tibia), 1 patient with osteoarthritis (elbow, right), and 2 patients with septic arthritis (knee joint, right).

Interventions:

Surgical drainage was performed in all children, and the aspirates were subsequently cultured. Intravenous antibiotic therapy combined with surgical drainage of purulent material is necessary to eradicate the infection.

Outcomes:

A 2-year follow-up showed good healing in all six children after clinical interventions.

Conclusion:

Osteoarticular infections caused by Salmonella have no distinctive features, clinical manifestations, or radiological characteristics. Intravenous antibiotics combined with surgical debridement/drainage are necessary for eradication of the bacteria.
Transoral Endoscopic Thyroidectomy by Vestibular Approach for Differentiated Thyroid Cancer Intraoperatively Invading Strap Muscle
Authors: Nguyen Xuan Hau , Nguyen Xuan Hien , Nguyen Thanh Long , Pham Tuan Dat , Le Van Quang
Published: December 2021

Background:

Transoral endoscopic thyroidectomy vestibular approach (TOETVA) has become increasingly popular in the surgical treatment of thyroid cancer. However, its application in T3b disease has not been well-defined.

Methods:

We conducted a quasi-experimental study on patients with an intraoperative diagnosis of T3bN0M0 differentiated thyroid carcinoma from January 2019 to January 2021 in our institution. Surgical and early oncological outcomes were assessed.

Results:

Among 326 patients who underwent TOETVA for thyroid cancer, 12 cases had T3bN0M0 disease intraoperatively. The mean operation time was 136.67±7.32 minutes, with 7.17±0.83 mL of blood loss. No patients reported symptoms of postoperatively transient hypoparathyroidism, mental nerve, or recurrent laryngeal nerve injury. After radioactive iodine therapy, all patients had undetectable thyroglobulin, negative antithyroglobulin, and normal neck ultrasound.

Conclusions:

TOETVA seems to be a surgically and oncological safe method for differentiated thyroid cancer patients with small tumors invading strap muscle intraoperatively. The patients can be well-managed with endoscopic total thyroidectomy and postoperative radioactive iodine therapy. Further studies with a larger sample size and longer follow-up are needed to provide more solid evidence.
Minimally Invasive Management of Acute Cholecystitis and Frailty Assessment in Geriatric Patients
Authors: Zygomalas Apollon N. , Katsanos Konstantinos , Skroubis George
Published: December 2021

The aim was to compare laparoscopic cholecystectomy (LC) with the percutaneous cholecystostomy (PC) for the management of acute lithiasic cholecystitis in geriatric patients and investigate the decision-making using frailty assessment. A retrospective analysis was performed in all patients aged over 65 years who were treated for acute cholecystitis at our hospital in a period of 5 years. Patients were divided in LC and PC groups. In total, 111 (54.1%) patients were subjected to LC and 94 (45.9%) to PC. The American Society of Anesthesiologists (ASA) and the Clinical Frailty Score were lower for the LC group. However, for patients over 85 years of age, frailty scores between groups were not statistically different. Morbidity and mortality between groups were not statistically different. Both LC and PC are safe and efficient in geriatric patients. Frailty score may better drive the selection of patients to be managed laparoscopically.
A Leak-Free Head-Out Plethysmography System to Accurately Assess Lung Function in Mice
Authors: Bruggink Stephanie , Kentch Kyle , Kronenfeld Jason , Renquist Benjamin J.
Published: December 2021

Mice are a valuable model for elegant studies of complex, systems-dependent diseases, including pulmonary diseases. Current tools to assess lung function in mice are either terminal or lack accuracy. We set out to develop a low-cost, accurate, head-out variable-pressure plethysmography system to allow for repeated, non-terminal measurements of lung function in mice. Current head-out plethysmography systems are limited by air leaks that prevent accurate measures of volume and flow. We designed an inflatable cuff that encompasses the mouse’s neck preventing air leak. We wrote corresponding software to collect and analyze the data, remove movement artifacts, and automatically calibrate each dataset. This software calculates inspiratory/expiratory volume, inspiratory/expiratory time, breaths per minute, enhanced pause, mid-expiratory flow, and end-inspiratory pause. To validate the use, we established our plethysmography system accurately measured tidal breathing, the bronchoconstrictive response to methacholine, sex and age associated changes in breathing, and breathing changes associated with house dust mite sensitization. Our estimates of volume, flow, and timing of breaths are in line with published estimates, we observed dose-dependent decreases in volume and flow in response to methacholine (P < 0.05), increased lung volume and decreased breathing rate with aging (P < 0.05), and that house dust mite sensitization decreased tidal volume and flow (P <0.05) while exacerbating the methacholine induced increases in inspiratory and expiratory time (P < 0.05). We describe an accurate, sensitive, low-cost, head-out plethysmography system that allows for longitudinal studies of pulmonary disease in mice.

New & Noteworthy

We describe a variable-pressure head-out plethysmography system that can be used to assess lung function in mice. A balloon cuff that inflates around the mouse’s neck prevents air leak, allowing for accurate measurements of lung volume and air flow. Custom software facilitates system calibration, removes movement artifacts, and eases data analysis. The system was validated by measuring tidal breathing, responses to methacholine, and changes associated with house dust mite sensitization, sex, and aging.

Contributions to Study

Stephanie Bruggink: development of head-out plethysmography chamber, measurement of breathing, data analysis, prepared manuscript

Kyle Kentch: development of head-out plethysmography chamber, programmed software to collect and analyze data, prepared manuscript

Jason Kronenfeld: development of tools to analyze data, analysis of data

Benjamin Renquist: development of head-out plethysmography chamber, statistical analysis, prepared manuscript
Genomic dissection of the bacterial population underlyingKlebsiella pneumoniaeinfections in hospital patients: insights into an opportunistic pathogen
Authors: Gorrie Claire L. , Mirceta Mirjana , Wick Ryan R. , Judd Louise M. , Lam Margaret M. C. , Gomi Ryota , Abbott Iain J. , Thomson Nicholas R. , Strugnell Richard A. , Pratt Nigel F. , Garlick Jill S. , Watson Kerrie M. , Hunter Peter C. , Pilcher David V. , McGloughlin Steve A. , Spelman Denis W. , Wyres Kelly L. , Jenney Adam W. J. , Holt Kathryn E.
Published: December 2021

Klebsiella pneumoniaeis a major cause of opportunistic healthcare-associated infections, which are increasingly complicated by the presence of extended-spectrum beta-lactamases (ESBLs) and carbapenem resistance. We conducted a year-long prospective surveillance study ofK. pneumoniaeclinical isolates identified in a hospital microbiological diagnostic laboratory. Disease burden was two-thirds urinary tract infections (UTI; associated with female sex and age), followed by pneumonia (15%), wound (10%) and disseminated infections/sepsis (10%). Whole-genome sequencing (WGS) revealed a diverse pathogen population, including other species within theK. pneumoniaecomplex (18%). Several infections were caused byK. variicola/K. pneumoniaespecies hybrids, one of which showed evidence of nosocomial transmission, indicating fitness to transmit and cause disease despite a lack of acquired antimicrobial resistance (AMR). A wide range of AMR phenotypes were observed and, in most cases, corresponding mechanisms were identified in the genomes, mainly in the form of plasmid-borne genes. ESBLs were correlated with presence of other acquired AMR genes (median 10). Bacterial genomic features associated with nosocomial onset of disease were ESBL genes (OR 2.34, p=0.015) and rhamnose-positive capsules (OR 3.12, p<0.001). Virulence plasmid-encoded features (aerobactin, hypermucoidy) were rare (<3%), and mostly present in community-onset cases. WGS-confirmed nosocomial transmission was rare (10% of cases) but strongly associated with ESBLs (OR 21, p<1×10-11). We estimate 28% risk of onward nosocomial transmission for ESBL-positive strains vs 1.7% for ESBL-negative strains. These data indicate the underlying burden ofK. pneumoniaedisease in hospitalised patients is due largely to opportunistic infections with diverse strains. However, we also identified several successful lineages that were overrepresented but not due to nosocomial transmission. These lineages were associated with ESBL, yersiniabactin, mannose+ K loci and rhamnose- K loci; most are also common in public clinical genome collections, suggesting enhanced propensity for colonisation and spread in the human population.
Wide Diversity of Recombinant Noroviruses Circulating in Spain, 2016 to 2020
Authors: Navarro-Lleó Noemi , Santiso-Bellón Cristina , Vila-Vicent Susana , Carmona-Vicente Noelia , Gozalbo-Rovira Roberto , Rodríguez-Díaz Jesús , Buesa Javier
Published: December 2021

Noroviruses are the leading cause of sporadic cases and outbreaks of viral gastroenteritis. For more than 20 years most norovirus infections have been caused by the pandemic genotype GII.4, yet recent studies have reported the emergence of recombinant strains in many countries. In the present study, 4,950 stool samples collected between January 2016 and April 2020 in Valencia (Spain) from patients with acute gastroenteritis were analyzed to investigate the etiological agent. Norovirus was the most frequently detected enteric virus with a positive rate of 9.5% (471/4,950). Among 224 norovirus strains characterized, 175 belonged to genogroup GII and 49 to genogroup GI. Using dual genotyping based on sequencing the ORF1/ORF2 junction region we detected 25 different capsid-polymerase type associations. The most common GII capsid genotype was GII.4 Sydney 2012, followed by GII.2, GII.3, GII.6 and GII.17. A high prevalence of recombinant strains (90.4%) was observed among GII infections between 2018 and 2020. GII.4 Sydney[P16] was the predominant genotype from 2019 to 2020. In addition, GII.P16 polymerase was found harboring within six different capsid genes. A new subcluster of GII.4 Sydney associated with the P31 polymerase was identified by phylogenetic analysis. GI.4 and GI.3 were the predominant genotypes in genogroup GI, in which recombinant strains were also found, such as GI.3[P10], GI.3[P13] and GI.5[P4]. Interestingly, the GI.3[P10] strain could represent a new capsid genotype. This study shows the extensive diversity of recombinant noroviruses circulating in Spain and highlights the role of recombination events in the spread of noroviruses.
Trial-by-trial fluctuations in amygdala activity track motivational enhancement of desirable sensory evidence during perceptual decision-making
Authors: Paterson Ren , Lyu Yizhou , Leong Yuan Chang
Published: December 2021

People are biased towards seeing outcomes that they are motivated to see. For example, sports fans often perceive the same ambiguous foul in favor of the team they support. Here, we test the hypothesis that motivational biases in perceptual decision-making arise from amygdala-dependent biases in sensory processing. Human participants were rewarded for correctly categorizing an ambiguous image into one of two categories while undergoing fMRI. On each trial, we used a financial bonus to motivate participants to see one category over another. The reward maximizing strategy was to perform the categorizations accurately, but participants were biased towards categorizing the images as the category we motivated them to see. Heightened amygdala activity was associated with motivation consistent categorizations, and tracked trial-by-trial enhancement of neural activity in sensory cortices that was specific to the desirable category. Analyses using a drift diffusion model provide converging evidence that trial-by-trial amygdala activity was associated with stronger biases in the accumulation of sensory evidence. Prior work examining biases in perceptual decision-making have focused on the role of frontoparietal regions. Our work highlights an important contribution of the amygdala. When people are motivated to see one outcome over another, the amygdala biases perceptual decisions towards those outcomes.
I-M-150847, a novel GLP-1 and GIP receptor dual agonist, improves glycemic control and reduces obesity in the rodent model of type 2 diabetes and obesity
Authors: Bauri Rathin , Bele Shilpak , Edelli Jhansi , Reddy Neelesh C. , Kurukuti Sreenivasulu , Devasia Tom , Ibrahim Ahamed , Rai Vishal , Mitra Prasenjit
Published: December 2021

We report the discovery of a novel unimolecular glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor dual agonist that exhibits potent glycemic control and weight loss in diet-induced obese mice. The dual agonism of GLP-1 and GIP receptor was achieved by replacing the tryptophan cage of exendin-4 with the C-terminal undecapeptide sequence of oxyntomodulin along with a single amino acid substitution from histidine to tyrosine at the amino terminus of the peptide. The structural modification places lysine 30 of the novel incretin agonist in frame with the corresponding lysine residue in the native GIP sequence. The novel incretin receptor dual agonist, named I-M-150847, induces rapid redistribution of GLP-1R at the plasma membrane following activation ensuring the maintenance of the receptor in a sensitized state. I-M-150847 promotes glucose-stimulated insulin exocytosis in cultured pancreatic beta cells and augments insulin-stimulated glucose uptake in mouse adipocytes. Chronic administration of I-M-150847 enhances insulin sensitivity, improves glycemic control, and achieves significant weight loss relative to the control or exendin-4-treated DIO-mice demonstrating the therapeutic efficacy of dual agonist in ameliorating type 2 Diabetes and Obesity.

Significance statement.

Replacement of the Trp-cage with the C-terminal oxyntomodulin undecapeptide along with the tyrosine substitution at the amino terminus converts the selective GLP-1R agonist exendin-4 to a novel GLP-1R and GIPR dual agonist I-M-150847.

The GLP-1R and GIPR dual agonist I-M-150847 induces the expeditious redistribution of GLP-1R at the plasma membrane following initial activation thereby maintaining the receptor in a sensitized state.

The incretin receptor dual agonist I-M-150847 enhances insulin sensitivity and delivers superior glycemic control and weight loss compared to exendin-4 in the rodent model of diabetes and obesity.

Graphical Abstract:
Development of CuidaTEXT: a text message intervention to support Latino dementia family caregivers
Authors: Perales-Puchalt Jaime , Acosta-Rullán Mariola , Ramírez-Mantilla Mariana , Espinoza-Kissell Paul , Vidoni Eric D. , Niedens Michelle , Ellerbeck Edward F. , Hinton Ladson , Loera Linda , Ramírez A. Susana , Lara Esther , Watts Amber , Williams Kristine , Resendez Jason , Burns Jeffrey
Published: December 2021

Objectives

To describe the development of CuidaTEXT: a tailored text message intervention to support Latino dementia family caregivers.

Methods

CuidaTEXT is informed by the Stress Process Framework and Social Cognitive Theory. We developed and refined CuidaTEXT using a mixed-method approach that included thematic analysis and descriptive statistics. We followed six user-centered design stages, including the selection of design principles, software vendor collaboration, evidence-based foundation, caregiver and research/clinical advisory board guidance, sketching and prototyping, and usability testing among five Latino caregivers.

Results

CuidaTEXT is a bilingual 6-month long intervention tailored to caregiver needs that includes: 1) 1-3 daily automatic messages (n=244) about logistics, dementia education, self-care, social support, end-of-life, care of the person with dementia, behavioral symptoms and problem-solving strategies; 2) 783 keyword-driven text messages for further help with the above topics; 3) live chat interaction with a coach for further help; 4) a 19-page reference booklet summarizing the purpose and functions of the intervention. CuidaTEXT’s prototype scored 97 out of 100 in the System Usability Scale.

Conclusions

CuidaTEXT’s prototype demonstrated high usability among Latino caregivers. CuidaTEXT’s feasibility is ready to be tested.

Clinical Implications

CuidaTEXT’s usability and its potential for widespread implementation holds promise in supporting Latino caregivers.