bluuebunny/crossref_metadata_2025 huggingface dataset:
Preliminary evaluation of a flow cytometric assay with microsphere controls for the detection of platelet‐bound antibodies in canine immune thrombocytopenia
Authors: Brooks Marjory B. , Maruyama Haruhiko , Cremer Signe E. , Goggs Robert , Forman Marnin A. , Koch Michael , Merriam Julia , Makielski Kelly , Viall Austin , LeVine Dana N.
Published: March 2022

Background

Canine immune thrombocytopenia (ITP) ranges from a mild to severe bleeding disorder, and platelet counts do not reliably predict clinical disease course. The detection of platelet autoantibodies may further define the disease phenotype, but variability in assay configurations and a lack of well‐characterized controls limit the diagnostic utility of anti‐platelet antibody assays.

Objectives

We aimed to develop control reagents to facilitate the characterization of canine platelet surface‐associated immunoglobulin (PSAIg) in flow cytometric assays.

Methods

Silica microspheres were coated with canine IgG and IgM to assess the reactivity of goat and rabbit origin anti‐canine immunoglobulin reagents. They were also used as positive controls in the PSAIg assay. Preliminary assay evaluation and determination of sample stability used PRP isolated from seven healthy dogs and 26 dogs newly diagnosed with thrombocytopenia.

Results

Blood sample stability was established for up to a 48‐hour storage time. The conjugated positive control microspheres demonstrated stable fluorescent labeling over a 2‐year observation period. Rabbit and goat origin anti‐dog IgM fluorescent antibody labels reacted nonspecifically with canine IgG. Rabbit origin anti‐dog IgG antibody demonstrated greater class specificity for canine IgG than a goat origin antibody. Thrombocytopenic dogs had a broad range of membrane‐bound immunoglobulin. Median PSAIgG for dogs with primary or secondary ITP (18.4%, 34.1%, respectively) were significantly higher than controls (3.8%,P < .05).

Conclusions

The described assay reagents and procedures provide positive controls and allow consistent thresholding to define a positive test result, suitable for any flow cytometer. A rabbit anti‐dog IgG fluorescent label demonstrated specificity for canine IgG and was useful for the detection of PSAIgG in thrombocytopenic dogs.
Medical management and resolution of perinatal bilateral exophthalmia and secondary corneal ulcers in an Antillean manatee (Trichechus manatus manatus) neonate from Puerto Rico
Authors: Cabrias‐Contreras Lesly J. , Bras Dineli , de Ángel‐Ramírez José E. , Escobar‐Torres Sylma M. , Fernández‐Martínez Ricardo , Hernández‐Lara Edward , Rivera‐Guzmán Antonio L. , Rivera‐Pérez Carla I. , Mignucci‐Giannoni Antonio A.
Published: March 2022

Objective

To present a novel case of perinatal bilateral exophthalmos and corneal ulcers in a neonate Antillean manatee and describe the medical treatment that led to the resolution of the observed clinical signs and vision restoration.

Animal studied

A manatee stranded alone in Puerto Rico on July 5, 2020.

Results

The manatee was found in critical condition with pronounced exophthalmos, lagophthalmos, and corneal opacification of both eyes (OU). Vision impairment was evident due to the lack of ocular menace reflex and bumping into the tank's walls. Biomicroscopy revealed conjunctival hyperemia and chemosis, limited third eyelid movement, but had viscous tears present OU. Dense, full‐thickness, white to cream‐colored cellular infiltrates affected 70% of the cornea with peripheral active vascularization OU. Rubeosis iridis was also present OU. Treatment consisted of supportive medical management, including nutritional support and topical treatment for ulcerative keratitis. Resolution of the corneal ulcers and functional vision were achieved after 6 weeks of therapy. Currently, bilateral, mild, intermittent exophthalmos is observed with no adverse clinical signs, and the calf is in good health.

Conclusions

The extent of bilateral corneal disease on a neonatal calf may be a result of an intrauterine infection or possible trauma at or right after birth. While the latter may have led to exophthalmia and consequent corneal disease, the exact cause could not be determined. Supportive therapy and medical management of infectious keratitis were successful and led to vision recovery. This is the first report of ocular pathology in a neonatal manatee.
Determination of cutoff values on computed tomography and magnetic resonance images for the diagnosis of atlantoaxial instability in small‐breed dogs
Authors: Planchamp Bastien , Forterre Franck , Vidondo Beatriz , Hernandez‐Guerra Angel M. , Plessas Ioannis N. , Schmidt Martin J. , Waschk Maja A. , Precht Christina
Published: March 2022

Objective

To determine cutoff values for the diagnosis of atlantoaxial instability (AAI) based on cross‐sectional imaging in small‐breed dogs.

Study design

Retrospective multicenter study.

Sample population

Client‐owned dogs (n = 123) and 28 cadavers.

Methods

Dogs were assigned to three groups: a control group, a “potentially unstable” group, and an AAI‐affected group, according to imaging findings and clinical signs. The ventral compression index (VCI), cranial translation ratio (CTR), C1‐C2 overlap, C1‐C2 angle, atlantoaxial distance, basion‐dens interval, dens‐to‐axis length ratio (DALR), power ratio, and clivus canal angles were measured on CT or T2‐weighted magnetic resonance (MR) images. Receiver operating characteristic (ROC) analysis was performed to define cutoff values in flexed (≥25°) and extended (<25°) head positions.

Results

Cutoff values for the VCI of ≥0.16 in extended and ≥0.2 in flexed head positions were diagnostic for AAI (sensitivity of 100% and 100%, specificity of 94.54% and 96.67%, respectively). Cutoff values for the other measurements were defined with a lower sensitivity (75%‐96%) and specificity (70%‐97%). A combination of the measurements did not increase the sensitivity and specificity compared with the VCI as single measurement.

Conclusion

Cutoff values for several imaging measurements were established with good sensitivity and specificity. The VCI, defined as the ratio between the ventral and dorsal atlantodental interval, had the highest sensitivity and specificity in both head positions.

Clinical significance

The use of defined cutoff values allows an objective diagnosis of AAI in small‐breed dogs. The decision for surgical intervention, however, should remain based on a combination of clinical and imaging findings.
A SEM ANALYSIS OF THE IMPACT OF UNETHICAL STAKEHOLDER BEHAVIORS ON CONSTRUCTION PROJECT FAILURES: AN OIL AND GAS INDUSTRY STUDY
Authors: Gomarn Pittayaporn , Pongpeng Jakrapong
Published: March 2022

Continued unethical behavior by stakeholders within the oil and gas construction industry has a possible impact on the failure of many projects. This study therefore aims to investigate the impact of this type of behavior on the oil and gas construction industry. A conceptual framework was developed from both a literature review and interviews with 8 experts working on oil and gas construction projects in Myanmar, Malaysia and Thailand. A 31-item questionnaire was used to measure the 304 responses, from which a confirmatory factor analysis and structural equation model (SEM) were developed to investigate this impact. The results revealed that the most significant direct impact on a project’s failure was a main contractor’s unethical behavior. Furthermore, the study determined that the unethical behaviors of the consultant and designer had no direct impact on a project’s failure but that there was an impact of the owner’s unethical behavior. Ranked in order of importance, the indicators of a project failure are as follows: stakeholders' dissatisfaction; cost overrun; time overrun; negative effects on health, safety and environment; quality defects; and dispute and litigation. The results provide a guideline for developing a code of ethics to conduct unethical behavior investigations, which will help decrease future project failures
KANSEI-BASED DESIGN FOR AN INDONESIAN TRADITIONAL FOOD PACKAGING
Authors: Fithri Prima , Zadry Hilma Raimona , Turrahmi Ulfa Nadia
Published: March 2022

One of the traditional specialties in Pariaman, West Sumatra, which is very famous, is sala lauak. Sala lauak is a dish in the shape of a thumb-sized lump made of fish dough that is mashed and collected with flour. Sala lauak specialties are in great demand by people within the region and outside the region. According to the Pariaman City government, sala lauak can be a souvenir for tourists with this potential. Pariaman City Government plans to develop sala lauak packaging. One way is to provide frozen sala lauak. However, currently, the frozen sala lauak packaging has not been developed by the Pariaman City Government. Whereas, unique, save, and attractive packaging is very important to increase the consumer purchasing power. Thus, this study designs frozen sala lauak packaging using a psychological approach based on consumers' feelings and emotions, namely Kansei Engineering. The design of frozen sala lauak packaging using the Kansei Engineering method uses 198 Kansei words, which are simplified into 19 Kansei words. The resulting packaging design consists of two design alternatives. Based on the design evaluation results using the Analytical Hierarchy Process (AHP) method, a design for frozen sala lauak packaging was selected. The packaging design chosen is in the form of a flat pouch in red, complete with product information and packaging attributes. The flat bottom packaging design gets a positive emotional response from consumers, so it is expected to increase consumer interest in buying sala lauak, especially as a tourist souvenir
ASSESSMENT OF CORROSION RESISTANT ALLOY (CRA) CLAD MATERIAL FOR GEOTHERMAL WELLHEAD PIPING SYSTEM
Authors: Tayactac Reylina Garcia , Ang Edward B.O
Published: March 2022

The geothermal power industry has reported a wide range of corrosion problems. Given the extremely corrosive conditions to be treated in the geothermal sector and the benefits of reduced unplanned downtime when used, operating cost savings would be expected if more CRAs clad products were used. The selection of suitable Corrosion Resistant Alloy (CRA) material is vital for plant operability, especially in challenging well conditions with low pH value and carbon dioxide, hydrogen sulphide, and hydrogen chloride content. The primary examined material alloy 625 given its exceptional erosion and corrosion resistance. Alloy 625 was selected based on a preliminary material selection review of its mechanical and chemical properties to withstand a corrosive environment. The study method emphasizes selected material from dissimilar alloying steel grades (e.g. Backing Steel + CRA material) based on its mechanical properties, chemical composition, macro and micro examination, and corrosion resistance using the common industrial standards. The study focuses on using Alloy 625 cladding using the overlay method to determine the weld overlay's suitability for the geothermal production system. The weld overlay cladding is performed to increase the components' life and as a replacement using an expensive corrosion resistant solid material. In many cases, only the surface of the material requires corrosion resistance and carbon or alloy steel can be clad with a more corrosion-resistant alloy. Up to 50% of the cost of using the solid alloy can be saved by cladding. This study also describes the technical and economic advantages of using Alloy 625 clad material in the present condition
POWER LOSS REDUCTION OF DISTRIBUTION NETWORK IN DENSELY INDUSTRIALIZED COASTAL BELT BY DEVELOPMENT OF HYDROPHOBIC COATING APPLYING ACCELERATED AGING FOR CERAMIC INSULATOR
Authors: Ali Basit , Khan Abdul Attayyab , Ali Ahsan , Maqsood Marya , Nisha Rohma
Published: March 2022

This paper aims to reduce the power losses by improving the hydrophobic strength of ceramic insulators for densely industrialized coastal areas to save them from flashover due to contamination. The hydrophobic strength of ceramic insulators must increase to resolve the contamination occurrence and power losses problem. The system progresses by creating an artificial chamber to provide five different environmental conditions heat, rain, fog, dust, and humidity. The testing part of the system includes taking readings for rain happened, temperature, humidity, and pH for five years using data from reliable sources and creating acidic rain, temperature, dust, and fog artificially to obtain results more accurately. The Coating includes nitrocellulose material dissolved in a solvent mixture of diacetone alcohol, Hexa hydro phenol, ethyl acetate, benzol, and toluene in a spray form to apply on the insulators. The coated insulator was tested in an artificial aging chamber by applying all the environmental effects of the coastal areas for five years using accelerated testing. After performing tests, the results show a 7% decrease in contamination development on the ceramic insulator surface. Hence improving its hydrophobic strength and losses of the power system minimized.
ALKALI SILICA REACTION OF RECYCLED GLASS AGGREGATE MORTAR USING FLY ASH UNDER STEAM CURING
Authors: Mien Tran Van , NAWA Toyoharu , Stitmannaithum Boonchai , Tuan Anh Nguyen Duc
Published: March 2022

Utilization of recycled glass as fine and coarse aggregates in concrete materials can give significant economical and environmental benefits, especially in the case of developing countries. However, alkali-silica reaction (ASR) will be a serious problem when the recycled glass is used as concrete aggregates. This paper shows an investigation of the alkali-silica reaction of glass sand mortar under steam curing. The test for ASR expansion follows ASTM C1567. Type F fly ash (FA) is used together with Ordinary Portland cement (OPC) mixing with mixed color glass sand. FA contents are of 20%, 30%, 40% and 50% as OPC replacement. Steam curing accelerating FA reaction is used to contribute to the mitigation of ASR by strength improvement of the mortar. Under steam curing, the results show that the recommended contents of FA to use are of 20% to 30% to ensure expansion lower than the threshold of ASTM. Moreover, steam curing increases the expansion of the glass sand mortar in compared to the moist curing, and expansion crack appears at the interface between glass sand and cementitious matrix, not in the glass sand. In comparison with glass sand mortar under moist curing, expansion of glass sand mortar using fly ash under steam curing is contributed primarily by: (1) delayed ettringite formation, (2) reducing ion transportation, (3) increasing tensile strength of fly ash glass sand mortar and (4) reducing glass sand dissolution rate in rich alkalinity solution.
Stakeholders’ Involvement in Organisational Governance Structure of State Islamic Religious Council
Authors: Ismail Abdul Ghafar , Mohd Shafiai Mohd Hakimi , Ahmad Muhammad Adli
Published: March 2022

The State Islamic Religious Council (SIRC) is to advise the Sultan on all questions concerning Islam in the state. In this study, we raise three research questions – how are the works’ of (SIRC) organised? who are the people that become board member of SIRC? and does the organisational governance structure follow the best practices? Hence, the objective of this study is to examine the involvement of stakeholders in preserving their interest in SIRC. By examining the Federal Constitution of Malaysia, selected state law and selected web of SIRC, the results of this study are: first, the constitution provides the separation of power for each layer of government in relation to revenues; second, the hierarchy within SIRC has identified each job, its function and where it reports to within SIRC; and third; the sample of SIRC has adopted differently the organisational structure.
Maternal and foetal physiological response of sacral surface electrical stimulation during pregnancy: A preliminary study
Authors: Katsura Daisuke , Tsuji Shunichiro , Hayashi Kaori , Tokoro Shinsuke , Hoshiyama Takako , Kita Nobuyuki , Murakami Takashi
Published: March 2022

New Findings

What is the central question of this study?

The physiological response to sacral neuromodulation by pregnant women and foetuses has not been previously explored.

What is the main finding and its importance?

Sacral surface electrical stimulation had no adverse effect on pregnant women and foetuses at least 36 weeks of gestation. It may cause uterine relaxation resulting from decreased uterine artery pulsatility index and increased umbilical venous flow volume and thereby improve utero‐placental perfusion and improve lower back pain.

This study aimed to examine the impact of sacral surface electrical stimulation on maternal and foetal physiology during pregnancy. Ten pregnant women at 36 weeks of gestation without multiple gestations, foetuses with malformations, foetal growth restriction, hypertensive disorders, polyhydramnios, or oligohydramnios were enrolled. This prospective study monitored maternal and foetal physiological responses before and after sacral surface electrical stimulation for single pregnancies. Sacral surface electrical stimulation was performed once per patient. Each parameter was measured directly before and then immediately after stimulation. Follow‐up measurements were conducted at 12 h, 1 day, 2 days and 7 days after stimulation. Variables of interest were compared before and after the stimulation. Regarding the foetal Doppler measurements, significant differences were not found in the umbilical and middle cerebral artery pulsatility index. However, foetuses showed a significant increase in the umbilical venous flow volume. The uterine contraction frequency and the maternal uterine artery pulsatility index significantly decreased. Pregnancy outcomes, and rates of caesarean section, foetal distress, and neonatal asphyxia were not confirmed. In conclusion, sacral surface electrical stimulation had no adverse effects on pregnant women or foetuses at 36 weeks of gestation and might improve utero‐placental perfusion and lower back pain.
Estimation of Regional Pulmonary Compliance in Idiopathic Pulmonary Fibrosis Based on Personalized Lung Poromechanical Modeling
Authors: Patte Cécile , Brillet Pierre-Yves , Fetita Catalin , Bernaudin Jean-François , Gille Thomas , Nunes Hilario , Chapelle Dominique , Genet Martin
Published: March 2022

Pulmonary function is tightly linked to the lung mechanical behavior, especially large deformation during breathing. Interstitial lung diseases, such as idiopathic pulmonary fibrosis (IPF), have an impact on the pulmonary mechanics and consequently alter lung function. However, IPF remains poorly understood, poorly diagnosed, and poorly treated. Currently, the mechanical impact of such diseases is assessed by pressure–volume curves, giving only global information. We developed a poromechanical model of the lung that can be personalized to a patient based on routine clinical data. The personalization pipeline uses clinical data, mainly computed tomography (CT) images at two time steps and involves the formulation of an inverse problem to estimate regional compliances. The estimation problem can be formulated both in terms of “effective”, i.e., without considering the mixture porosity, or “rescaled,” i.e., where the first-order effect of the porosity has been taken into account, compliances. Regional compliances are estimated for one control subject and three IPF patients, allowing to quantify the IPF-induced tissue stiffening. This personalized model could be used in the clinic as an objective and quantitative tool for IPF diagnosis.
Nonlinear Dynamics in Mechanics: State of the Art and Expected Future Developments
Authors: Rega Giuseppe
Published: March 2022

Starting from a recent classification of the development stages of nonlinear dynamics in mechanics, this review builds on the idea that the level of scientific maturity of the area is now such as to involve a gradual shift of its core interests from the inherent theoretical and practical findings to the application benefits that they can bring to solving dynamic problems in a variety of technological environments. First, an overview of the current state of knowledge and the achievements of the community of relevant scholars in about the last ten years is presented, distinguishing between traditional and emerging themes fully inherent to mechanics, and more hybridized scientific contexts. Then, a “vision” of expected future developments is attempted, by organizing the presentation along some main lines. (i) Identifying modeling, methodological, and computational advancements needed to address challenging, new or updated, research issues, with a view to deepening and further expanding the ranges of theoretical development and practical interest of nonlinear dynamics. (ii) Overviewing directions toward which promoting full exploitation of intrinsic or intentionally added nonlinearities, to the aim of improving and possibly optimizing specific behaviors and general operating conditions of actual systems/structures in a variety of dynamic environments, by also referring to the uncertainty quantification issue. (iii) Pursuing “novel” lines of developments of nonlinear dynamics in a fully hybridized and cross-disciplinary framework, with also possible expectation of new related phenomenologies.
Role of Suction/Injection on Free Convective Flow in a Vertical Channel in the Presence of Point/Line Heat Source/Sink
Authors: Jha Basant K. , Altine Muhammad M. , Hussaini Ayyub M.
Published: March 2022

This research work investigates the effect of point/line heat source/sink on free convection flow between two vertical channels with suction/injection. The Heaviside step function is used to model the constant heat source/sink, which is then transformed into line source/sink. The governing equations describing flow formation and heat transfer are obtained and solved using the Laplace transform approach. The effect of physical parameters such as suction/injection, Prandtl number, and heat source/sink on velocity and temperature fields are studied graphically, while the skin friction, Nusselt number, and mass flowrate are analyzed through tabular representation. Results indicate that as the value of point/line source parameters rise, velocity and temperature profile of fluid flow are enhanced.
Extreme material parameters accessible by active acoustic metamaterials with Willis coupling
Authors: Craig Steven R. , Wang Bohan , Su Xiaoshi , Banerjee Debasish , Welch Phoebe J. , Yip Mighten C. , Hu Yuhang , Shi Chengzhi
Published: March 2022

Active acoustic metamaterials incorporate electric circuit elements that input energy into an otherwise passive medium to aptly modulate the effective material properties. Here, we propose an active acoustic metamaterial with Willis coupling to drastically extend the tunability of the effective density and bulk modulus with the accessible parameter range enlarged by at least two orders of magnitude compared to that of a non-Willis metamaterial. Traditional active metamaterial designs are based on local resonances without considering the Willis coupling that limit their accessible effective material parameter range. Our design adopts a unit cell structure with two sensor-transducer pairs coupling the acoustic response on both sides of the metamaterial by detecting incident waves and driving active signals asymmetrically superimposed onto the passive response of the material. The Willis coupling results from feedback control circuits with unequal gains. These asymmetric feedback control circuits use Willis coupling to expand the accessible range of the effective density and bulk modulus of the metamaterial. The extreme effective material parameters realizable by the metamaterials will remarkably broaden their applications in biomedical imaging, noise control, and transformation acoustics-based cloaking.
Evaluating and Characterizing an Individually-Tailored Community Exercise Program for Older Adults With Chronic Neurological Conditions: A Mixed-Methods Study
Authors: Coomaran Vithusha , Khan Ali , Tyson Erin , Bardutz Holly , Hopper Tristan D. , Mang Cameron S.
Published: March 2022

A mixed-methods approach was used to study an individually-tailored community exercise program for people with a range of chronic neurological conditions (e.g., stroke, spinal cord injury, brain injury, multiple sclerosis, Parkinson’s disease) and abilities. The program was delivered to older adults (mean age: 62 ± 9 years) with chronic neurological conditions across a 12-week and an 8-week term. Participants attended 88% of sessions and completed 89% of prescribed exercises in those sessions. There were no adverse events. Clinically important improvements were achieved by all evaluated participants (n = 8) in at least one testing domain (grip strength, lower-extremity strength, aerobic endurance, and balance). Interviews with participants identified key program elements as support through supervision, social connection, individualized programming, and experiential learning. Findings provide insight into elements that enable a community exercise program to meet the needs of a complex and varied group. Further study will support positive long-term outcomes for people aging with neurological conditions.
Improving SABRE hyperpolarization with highly nonintuitive pulse sequences: Moving beyond avoided crossings to describe dynamics
Authors: Eriksson Shannon L. , Lindale Jacob R. , Li Xiaoqing , Warren Warren S.
Published: March 2022

Signal amplification by reversible exchange (SABRE) creates “hyperpolarization” (large spin magnetization) using a transition metal catalyst and parahydrogen, addressing the sensitivity limitations of magnetic resonance. SABRE and its heteronuclear variant X-SABRE are simple, fast, and general, but to date have not produced polarization levels as large as more established methods. We show here that the commonly used theoretical framework for these applications, which focuses on avoided crossings (also called level anticrossings or LACs), steer current SABRE and X-SABRE experiments away from optimal solutions. Accurate simulations show astonishingly rich and unexpected dynamics in SABRE/X-SABRE, which we explain with a combination of perturbation theory and average Hamiltonian approaches. This theoretical picture predicts simple pulse sequences with field values far from LACs (both instantaneously and on average) using different terms in the effective Hamiltonian to strategically control evolution and improve polarization transfer. Substantial signal enhancements under such highly nonintuitive conditions are verified experimentally.
SARS-CoV-2 receptor binding domain displayed on HBsAg virus–like particles elicits protective immunity in macaques
Authors: Dalvie Neil C. , Tostanoski Lisa H. , Rodriguez-Aponte Sergio A. , Kaur Kawaljit , Bajoria Sakshi , Kumru Ozan S. , Martinot Amanda J. , Chandrashekar Abishek , McMahan Katherine , Mercado Noe B. , Yu Jingyou , Chang Aiquan , Giffin Victoria M. , Nampanya Felix , Patel Shivani , Bowman Lesley , Naranjo Christopher A. , Yun Dongsoo , Flinchbaugh Zach , Pessaint Laurent , Brown Renita , Velasco Jason , Teow Elyse , Cook Anthony , Andersen Hanne , Lewis Mark G. , Camp Danielle L. , Silverman Judith Maxwell , Nagar Gaurav S. , Rao Harish D. , Lothe Rakesh R. , Chandrasekharan Rahul , Rajurkar Meghraj P. , Shaligram Umesh S. , Kleanthous Harry , Joshi Sangeeta B. , Volkin David B. , Biswas Sumi , Love J. Christopher , Barouch Dan H.
Published: March 2022

Authorized vaccines against SARS-CoV-2 remain less available in low- and middle-income countries due to insufficient supply, high costs, and storage requirements. Global immunity could still benefit from new vaccines using widely available, safe adjuvants, such as alum and protein subunits, suited to low-cost production in existing manufacturing facilities. Here, a clinical-stage vaccine candidate comprising a SARS-CoV-2 receptor binding domain–hepatitis B surface antigen virus–like particle elicited protective immunity in cynomolgus macaques. Titers of neutralizing antibodies (>10
4
) induced by this candidate were above the range of protection for other licensed vaccines in nonhuman primates. Including CpG 1018 did not significantly improve the immunological responses. Vaccinated animals challenged with SARS-CoV-2 showed reduced median viral loads in bronchoalveolar lavage (~3.4 log
10
) and nasal mucosa (~2.9 log
10
) versus sham controls. These data support the potential benefit of this design for a low-cost modular vaccine platform for SARS-CoV-2 and other variants of concern or betacoronaviruses.
Trips and neurotransmitters: Discovering principled patterns across 6850 hallucinogenic experiences
Authors: Ballentine Galen , Friedman Samuel Freesun , Bzdok Danilo
Published: March 2022

Psychedelics probably alter states of consciousness by disrupting how the higher association cortex governs bottom-up sensory signals. Individual hallucinogenic drugs are usually studied in participants in controlled laboratory settings. Here, we have explored word usage in 6850 free-form testimonials about 27 drugs through the prism of 40 neurotransmitter receptor subtypes, which were then mapped to three-dimensional coordinates in the brain via their gene transcription levels from invasive tissue probes. Despite high interindividual variability, our pattern-learning approach delineated how drug-induced changes of conscious awareness are linked to cortex-wide anatomical distributions of receptor density proxies. Each discovered receptor-experience factor spanned between a higher-level association pole and a sensory input pole, which may relate to the previously reported collapse of hierarchical order among large-scale networks. Coanalyzing many psychoactive molecules and thousands of natural language descriptions of drug experiences, our analytical framework finds the underlying semantic structure and maps it directly to the brain.
Predicting nonlinear physical aging of glasses from equilibrium relaxation via the material time
Authors: Riechers Birte , Roed Lisa A. , Mehri Saeed , Ingebrigtsen Trond S. , Hecksher Tina , Dyre Jeppe C. , Niss Kristine
Published: March 2022

The noncrystalline glassy state of matter plays a role in virtually all fields of materials science and offers complementary properties to those of the crystalline counterpart. The caveat of the glassy state is that it is out of equilibrium and therefore exhibits physical aging, i.e., material properties change over time. For half a century, the physical aging of glasses has been known to be described well by the material-time concept, although the existence of a material time has never been directly validated. We do this here by successfully predicting the aging of the molecular glass 4-vinyl-1,3-dioxolan-2-one from its linear relaxation behavior. This establishes the defining property of the material time. Via the fluctuation-dissipation theorem, our results imply that physical aging can be predicted from thermal-equilibrium fluctuation data, which is confirmed by computer simulations of a binary liquid mixture.
Hematopoietic stem cells temporally transition to thrombopoietin dependence in the fetal liver
Authors: Lee Yeojin , DiMaulo-Milk Emily , Leslie Juliana , Ding Lei
Published: March 2022

Tissue stem cells temporally change intrinsic mechanisms to meet physiological demands. However, little is known whether and how stem cells rely on distinct extrinsic maintenance mechanisms over time. Here, we found that hematopoietic stem cells (HSCs) temporally transition to depend on thrombopoietin (TPO), a key extrinsic factor, from E16.5 onward in the developing liver. Deletion of
Tpo
reduced mTOR activity, induced differentiation gene expression, and preferentially depleted metabolically active HSCs. Ectopic activation of the JAK2 or MAPK pathway did not rescue HSCs in

Tpo
−/−

mice. Enforced activation of the mTOR pathway by conditionally deleting
Tsc1
significantly rescued HSCs and their gene expression in

Tpo
−/−

mice.
Lin28b
intrinsically promoted mTOR activation in HSCs, and its expression diminished over time. Conditional deletion of
Lin28b
further reduced mTOR activity and strongly exacerbated HSC depletion in

Tpo
−/−

mice. Therefore, HSCs temporally transition from intrinsic LIN28B-dependent to extrinsic TPO-dependent maintenance in the developing liver.
The doors of precision: Reenergizing psychiatric drug development with psychedelics and open access computational tools
Authors: Barron Daniel S. , Friedman Richard A.
Published: March 2022

Psychedelics paired with new applications of computational tools might help bypass the imprecision of psychiatric diagnosis and connect measures of behavior to specific physiologic targets.
Metabolic adaptation of ovarian tumors in patients treated with an IDO1 inhibitor constrains antitumor immune responses
Authors: Odunsi Kunle , Qian Feng , Lugade Amit A. , Yu Han , Geller Melissa A. , Fling Steven P. , Kaiser Judith C. , Lacroix Andreanne M. , D’Amico Leonard , Ramchurren Nirasha , Morishima Chihiro , Disis Mary L. , Dennis Lucas , Danaher Patrick , Warren Sarah , Nguyen Van Anh , Ravi Sudharshan , Tsuji Takemasa , Rosario Spencer , Zha Wenjuan , Hutson Alan , Liu Song , Lele Shashikant , Zsiros Emese , McGray A. J. Robert , Chiello Jessie , Koya Richard , Chodon Thinle , Morrison Carl D. , Putluri Vasanta , Putluri Nagireddy , Mager Donald E. , Gunawan Rudiyanto , Cheever Martin A. , Battaglia Sebastiano , Matsuzaki Junko
Published: March 2022

To uncover underlying mechanisms associated with failure of indoleamine 2,3-dioxygenase 1 (IDO1) blockade in clinical trials, we conducted a pilot, window-of-opportunity clinical study in 17 patients with newly diagnosed advanced high-grade serous ovarian cancer before their standard tumor debulking surgery. Patients were treated with the IDO1 inhibitor epacadostat, and immunologic, transcriptomic, and metabolomic characterization of the tumor microenvironment was undertaken in baseline and posttreatment tumor biopsies. IDO1 inhibition resulted in efficient blockade of the kynurenine pathway of tryptophan degradation and was accompanied by a metabolic adaptation that shunted tryptophan catabolism toward the serotonin pathway. This resulted in elevated nicotinamide adenine dinucleotide (NAD
+
), which reduced T cell proliferation and function. Because NAD
+
metabolites could be ligands for purinergic receptors, we investigated the impact of blocking purinergic receptors in the presence or absence of NAD
+
on T cell proliferation and function in our mouse model. We demonstrated that A2a and A2b purinergic receptor antagonists, SCH58261 or PSB1115, respectively, rescued NAD
+
-mediated suppression of T cell proliferation and function. Combining IDO1 inhibition and A2a/A2b receptor blockade improved survival and boosted the antitumor immune signature in mice with IDO1 overexpressing ovarian cancer. These findings elucidate the downstream adaptive metabolic consequences of IDO1 blockade in ovarian cancers that may undermine antitumor T cell responses in the tumor microenvironment.
Optimizing Vancomycin Dosing and Monitoring in Neonates and Infants Using Population Pharmacokinetic Modeling
Authors: Jarugula Praneeth , Akcan-Arikan Ayse , Munoz-Rivas Flor , Moffett Brady S. , Ivaturi Vijay , Rios Danielle
Published: March 2022

We determined optimal vancomycin starting dose regimens in infants ≤180 days of age to achieve the highest probability of target attainment with an area under the concentration-time curve for 24 h (AUC
24
) of ≥400 using population pharmacokinetic (PK) modeling. Secondarily, determination of the relationship between serum creatinine (SCR) and vancomycin clearance in neonates was done.
Anti-HIV Drugs Cause Mitochondrial Dysfunction in Monocyte-Derived Macrophages
Authors: Wallace Jennillee , Gonzalez Hemil , Rajan Reshma , Narasipura Srinivas D. , Virdi Amber K. , Olali Arnold Z. , Naqib Ankur , Arbieva Zarema , Maienschein-Cline Mark , Al-Harthi Lena
Published: March 2022

Combination antiretroviral therapy (cART) dramatically changed the face of the HIV/AIDS pandemic, making it one of the most prominent medical breakthroughs of the past 3 decades. However, as the life span of persons living with HIV (PLWH) continues to approach that of the general population, the same cannot be said regarding their quality of life.
Interdependence of Shigella flexneri O Antigen and Enterobacterial Common Antigen Biosynthetic Pathways
Authors: Maczuga Nicholas , Tran Elizabeth N. H. , Qin Jilong , Morona Renato
Published: March 2022

Bacterial outer membrane polysaccharides play key roles in a range of bacterial activities from homeostasis to virulence. Two such OM polysaccharide populations are ECA and LPS Oag, which are synthesized by separate homologs of the Wzy-dependent pathway.
The Impact of Implementing the Virtuo Blood Culture System on the Characteristics and Management of Patients with Staphylococcus aureus Bacteremia
Authors: Chavez Miguel A. , Munigala Satish , Burnham Carey-Ann D. , Yarbrough Melanie L. , Warren David K.
Published: March 2022

Persistent
Staphylococcus aureus
bacteremia (SAB) has been associated with increased mortality. Enhanced microbial detection with new blood culture technology may improve detection of
S. aureus
in patients with SAB.
Host Cells Actively Resist Porcine Reproductive and Respiratory Syndrome Virus Infection via the IRF8-MicroRNA-10a-SRP14 Regulatory Pathway
Authors: Zheng Zifang , Fu Xiali , Ling Xue , Sun Huanhuan , Li Yang , Ma Zhiqian , Wei Bingjie , Zheng Haixue , Xiao Shuqi
Published: March 2022

Porcine reproductive and respiratory syndrome virus (PRRSV) has rapidly spread to the global pig industry and caused incalculable economic damage since first discovered in the 1980s. However, conventional vaccines do not provide satisfactory protection.
SARS-CoV-2 Evolution: On the Sudden Appearance of the Omicron Variant
Authors: Berkhout Ben , Herrera-Carrillo Elena
Published: March 2022

The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spreads rapidly and harbors many mutations in the spike protein, but the origin of this virus variant remains unclear. We address the role of unusual virus evolution mechanisms such as hypermutation, out-of-frame reading, and recombination.
Swapping Metagenomics Preprocessing Pipeline Components Offers Speed and Sensitivity Increases
Authors: Armstrong George , Martino Cameron , Morris Justin , Khaleghi Behnam , Kang Jaeyoung , DeReus Jeff , Zhu Qiyun , Roush Daniel , McDonald Daniel , Gonazlez Antonio , Shaffer Justin P. , Carpenter Carolina , Estaki Mehrbod , Wandro Stephen , Eilert Sean , Akel Ameen , Eno Justin , Curewitz Ken , Swafford Austin D. , Moshiri Niema , Rosing Tajana , Knight Rob
Published: March 2022

In shotgun metagenomics studies that seek to relate changes in microbial DNA across samples, processing the data on a computer often takes longer than obtaining the data from the sequencing instrument. Recently developed software packages that perform individual steps in the pipeline of data processing in principle offer speed advantages, but in practice they may contain pitfalls that prevent their use, for example, they may make approximations that introduce unacceptable errors in the data.
Mutation of MtrA at the Predicted Phosphorylation Site Abrogates Its Role as a Global Regulator in Streptomyces venezuelae
Authors: Lu Ting , Zhu Yanping , Ni Xue , Zhang Xia , Liu Yang , Cui Xiqing , Pang Xiuhua
Published: March 2022

Although phosphorylation has been shown to be essential for the activation of many response regulator proteins of two-component systems, the role of the phosphorylation site in the function of the global regulator MtrA in the genusStreptomyceshas not been reported. In this study, we generatedStreptomycesmutants that had amino acid substitutions at the predicted phosphorylation site of MtrA, and the effects of the substitutions were investigated by comparing the phenotypes of the resulting strains and their gene expression patterns with those of the wild-type strain and an MtrA deletion mutant.
The Type IV Pilus of Plasmid TP114 Displays Adhesins Conferring Conjugation Specificity and Is Important for DNA Transfer in the Mouse Gut Microbiota
Authors: Allard Nancy , Neil Kevin , Grenier Frédéric , Rodrigue Sébastien
Published: March 2022

Conjugative plasmids are involved in horizontal gene transfer in the gut microbiota, which constitutes an important antibiotic resistance gene reservoir. However, the molecular mechanisms used by conjugative plasmids to select recipient bacteria and transfer at high rates in the mouse gut microbiota remain poorly characterized.
Large-scale, flat-lying mafic intrusions in the Baltican crust and their influence on basement deformation during the Caledonian orogeny
Authors: Lescoutre Rodolphe , Almqvist Bjarne , Koyi Hemin , Berthet Théo , Hedin Peter , Galland Olivier , Brahimi Sonia , Lorenz Henning , Juhlin Christopher
Published: March 2022

The Fennoscandian Shield in central Sweden displays a complex structural and compositional architecture that is mainly related to the Proterozoic history of the Baltica paleocontinent. In its western parts, the Precambrian basement is covered by the allochthonous rocks of the Caledonide orogen, and direct information about the underlying crust is restricted to a few unevenly distributed basement windows in western Sweden and Norway. In this study, we use preliminary results from the second borehole of the Collisional Orogeny in the Scandinavian Caledonides project (COSC-2), new gravity data, forward gravity, and magnetic modeling and interpretation of seismic reflection profiles to assess the 3-D architecture of the basement. Our results reveal a wide (~100 km) and dense network of mainly flat-lying and saucer-shaped dolerites intruding the volcanic and granitic upper crustal rocks of the Transscandinavian Igneous Belt. Similar intrusion geometries related to 1.2 Ga dolerites can be recognized in the Fennoscandian Shield. We discuss that the formation of these sill complexes occurred in a lithologically and structurally heterogeneous crust during transtension, which is in disagreement with the current understanding of sill emplacement that involves crustal shortening, layering, or anisotropy of the host rock. Our seismic interpretation and the structural observations from the COSC-2 drilling show that part of the Caledonian-related basement deformation was localized along the margins of the dolerite sheets. We propose that the dolerite intrusion geometry, akin to a flat-ramp geometry, guided the basement deformation during the Caledonian orogeny.
Assessing the effect of melt extraction from mushy reservoirs on compositions of granitoids: From a global database to a single batholith
Authors: Cornet J. , Bachmann O. , Ganne J. , Fiedrich A. , Huber C. , Deering C.D. , Feng X.
Published: March 2022

Mafic and ultramafic plutonic rocks are often considered to be crystal cumulates (i.e., they are melt-depleted), but such a classification is much more contentious for intermediate to silicic granitoids (e.g., tonalite, granodiorite, granite, and syenite). Whether or not a given plutonic rock has lost melt to feed shallower subvolcanic intrusive bodies or volcanic edifices has key implications for understanding igneous processes occurring within the crust throughout the evolution of the Earth. We use statistical analyses of a global volcanic and plutonic rock database to show that most mafic to felsic plutonic rock compositions can be interpreted as melt-depleted (i.e., most of the minerals analyzed are more evolved than their bulk-rock compositions would allow). To illustrate the application of the method to natural samples (from the Tertiary Adamello Batholith in the southern Alps), we estimate the degree of melt depletion using a combination of magmatic textures, bulk-rock chemistry, modal mineralogy, distributions of plagioclase composition (using scanning electron microscope phase mapping/electron microprobe analyses), and thermodynamic modeling. We find that melt depletion correlates with the magmatic foliation and is accompanied by bulk depletion in incompatible elements, low amounts of near-solidus minerals, and mineral compositions that are too evolved (i.e., depleted in Ca or Mg, depending on the mineral) to be in equilibrium with their bulk-rock chemistry. The analytical and modeling workflow proposed in this study provides a path to quantifying melt depletion in any plutonic samples.

Most plutons cannot be assumed to represent liquids; degree of crystal-liquid separation must be a major consideration in their interpretation, whether or not cumulate textures are obvious. (Bacon and Druitt, 1988, p. 253) Igneous rocks, especially plutonic rocks, rarely represent quenched melts. (Miller et al., 2003, p. 529)
Bolide impact effects on the West Florida Platform, Gulf of Mexico: End Cretaceous and late Eocene
Authors: Poag C. Wylie
Published: March 2022

This study documents seismic reflection evidence that two different bolide impacts significantly disrupted stratigraphic and depositional processes on the West Florida Platform (Gulf of Mexico). The first impact terminated the Late Cretaceous Epoch (Chicxulub impact, Mexico; ca. 66 Ma; end-Maastrichtian age). The second took place in the late Eocene (Chesapeake Bay impact, Virginia, USA, portion of the Chesapeake Bay; ca. 35 Ma; Priabonian age). Both impacts produced far-reaching seismic shaking and ground roll followed by an impact-generated tsunami, the effects of which are evident in the seismostratigraphic record. The Chicxulub seismic shaking caused collapse and shoreward retreat of the Florida Escarpment and widely disrupted (faulting, folding, slumping) normal flat-lying shelf beds. The associated tsunami currents redistributed these shelf deposits and mixed them together with collapse debris from the escarpment to form a thick wedge of sediments along the base of the escarpment. The Chesapeake Bay impact created a mounded sedimentary deposit near the outer edge of the late Eocene ramp slope. This deposit also has a bipartite origin. A lower layer is marked by en echelon faulting created in situ by seismic shaking, whereas an upper layer represents sediments redistributed from the late Eocene shelf and upper ramp slope by tsunami-driven bottom currents (debris flows, contour currents, slumps). This is the first report of seismic effects from the Chesapeake Bay impact in the Gulf of Mexico. These results further demonstrate that large-scale marine bolide impacts have widespread effects on the stratigraphic and depositional record of Earth.
Recent advances in the diagnosis and management of cluster headache
Authors: Schindler Emmanuelle A D , Burish Mark J
Published: March 2022

Cluster headache, a primary headache disorder, consists of short (15-180 minutes), frequent (up to eight a day), unilateral attacks of facial pain with associated ipsilateral autonomic features and restlessness. The attacks are suspected to be one of the most painful human experiences, and the disorder is associated with a high rate of suicidal ideation. Proper diagnosis is key, as some of the most effective treatments, such as high flow oxygen gas, are rarely used in other headache disorders. Yet diagnostic delay is typically years for this disorder, as it is often confused with migraine and trigeminal neuralgia, and secondary causes may be overlooked. This review covers the clinical, pathophysiologic, and therapeutic features of cluster headache. Recent updates in diagnosis include the redefinition of chronic cluster headache (remission periods lasting less than three months instead of the previous one month), and recent advances in management include new treatments for episodic cluster headache (galcanezumab and non-invasive vagus nerve stimulation).