bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a HiBiT-tagged reporter hepatitis E virus and its utility as an antiviral drug screening platform
Authors: Nagashima Shigeo , Primadharsini Putu Prathiwi , Nishiyama Takashi , Takahashi Masaharu , Murata Kazumoto , Okamoto Hiroaki 
Published: September 2023

ABSTRACT
Previously, we developed an infectious hepatitis E virus (HEV) harboring the nanoKAZ gene in the hypervariable region of the open reading frame 1 (ORF1) of the HEV3b (JE03-1760F/P10) genome and demonstrated the usefulness for screening anti-HEV drugs that inhibit the early infection process. In the present study, we constructed another reporter HEV (HEV3b-HiBiT) by placing a minimized HiBiT tag derived from NanoLuc luciferase at the 3′-end of the viral capsid (ORF2) coding sequence. It replicated efficiently in PLC/PRF/5 cells, produced membrane-associated particles identical to those of the parental virus, and was genetically stable and infectious. The HiBiT tag was fused to both secreted ORF2s (ORF2s-HiBiT) and ORF2c capsid protein (ORF2c-HiBiT). The ORF2c-HiBiT formed membrane-associated HEV particles (eHEV3b-HiBiT). By treating these particles with digitonin, we demonstrated that the HiBiT tag was expressed on the surface of capsid and was present inside the lipid membrane. To simplify the measurement of luciferase activity and provide a more convenient screening platform, we constructed an ORF2s-defective mutant (HEV3b-HiBiT/ΔORF2s) in which the secreted ORF2s are suppressed. We used this system to evaluate the effects of introducing small interfering RNAs and treatment with an inhibitor or accelerator of exosomal release on HEV egress and demonstrated that the effects on virus release can readily be analyzed. Therefore, HEV3b-HiBiT and HEV3b-HiBiT/ΔORF2s reporters may be useful for investigating the virus life cycle and can serve as a more convenient screening platform to search for candidate drugs targeting the late stage of HEV infection such as particle formation and release.

IMPORTANCE

The construction of recombinant infectious viruses harboring a stable luminescence reporter gene is essential for investigations of the viral life cycle, such as viral replication and pathogenesis, and the development of novel antiviral drugs. However, it is difficult to maintain the stability of a large foreign gene inserted into the viral genome. In the present study, we successfully generated a recombinant HEV harboring the 11‐amino acid HiBiT tag in the ORF2 coding region and demonstrated the infectivity, efficient virus growth, particle morphology, and genetic stability, suggesting that this recombinant HEV is useful for
in vitro
assays. Furthermore, this system can serve as a more convenient screening platform for anti-HEV drugs. Thus, an infectious recombinant HEV is a powerful approach not only for elucidating the molecular mechanisms of the viral life cycle but also for the screening and development of novel antiviral agents.
Predicting COVID-19 prognosis in hospitalized patients based on early status
Authors: Natanov David , Avihai Byron , McDonnell Erin , Lee Eileen , Cook Brennan , Altomare Nicole , Ko Tomohiro , Chaia Angelo , Munoz Carolayn , Ouellette Samantha , Nyalakonda Suraj , Cederbaum Vanessa , Parikh Payal D. , Blaser Martin J. 
Published: September 2023

ABSTRACT

Predicting which patients are at greatest risk of severe disease from COVID-19 has the potential to improve patient outcomes and improve resource allocation. We developed machine learning models for predicting COVID-19 prognosis from a retrospective chart review of 969 hospitalized COVID-19 patients at Robert Wood Johnson University Hospital during the first pandemic wave in the United States, focusing on 77 variables from patients’ first day of hospital admission. Our best 77-variable model was better able to predict mortality (receiver operating characteristic area under the curve [ROC AUC] = 0.808) than CURB-65, a commonly used clinical prediction rule for pneumonia severity (ROC AUC = 0.722). After identifying highly predictive variables in our full models using
Sh
apley
a
dditive ex
p
lanations values, we generated two models, platelet count, lactate, age, blood urea nitrogen, aspartate aminotransferase, and C-reactive protein (PLABAC) and platelet count, red blood cell distribution width, age, blood urea nitrogen, lactate, and eosinophil count (PRABLE), that use age and five common laboratory tests to predict mortality (PLABAC: ROC AUC = 0.796, PRABLE: ROC AUC = 0.793), which also outperformed CURB-65. We externally validated PLABAC using data from the National COVID Cohort Collaborative Data Enclave from 7901 hospitalized COVID-19 patients from the pre-vaccination period and 1547 from the vaccination period, yielding ROC AUCs of 0.755 and 0.766, respectively. This study demonstrates that our models can accurately predict COVID-19 outcomes from a small number of variables obtained early in a patient’s hospital stay in patients from institutions around the United States after the initial pandemic wave. These models can serve as a clinical prediction aid and accurately capture a patient’s prognosis using a small number of routinely obtained laboratory values.

IMPORTANCE
COVID-19 remains the fourth leading cause of death in the United States. Predicting COVID-19 patient prognosis is essential to help efficiently allocate resources, including ventilators and intensive care unit beds, particularly when hospital systems are strained. Our PLABAC and PRABLE models are unique because they accurately assess a COVID-19 patient’s risk of death from only age and five commonly ordered laboratory tests. This simple design is important because it allows these models to be used by clinicians to rapidly assess a patient’s risk of decompensation and serve as a real-time aid when discussing difficult, life-altering decisions for patients. Our models have also shown generalizability to external populations across the United States. In short, these models are practical, efficient tools to assess and communicate COVID-19 prognosis.
Svalbox Digital Model Database: A geoscientific window into the High Arctic
Authors: Betlem Peter , Rodés Nil , Birchall Thomas , Dahlin Anders , Smyrak-Sikora Aleksandra , Senger Kim 
Published: September 2023

Abstract
Digital outcrop models (DOMs) have revolutionized the way twenty-first century geoscientists work. DOMs are georeferenced three-dimensional (3-D) digital representations of outcrops that facilitate quantitative work on outcrops at various scales. Outcrop digitalization has been traditionally conducted using laser scanners, but in the past decade, it has seen an exponential growth because of efficient and consumer-friendly structure-from-motion (SfM) algorithms concurrent with the rapid development of cost-effective aerial drones with high-resolution onboard cameras. While DOMs are routinely used in geoscientific research, education, and industry, enhanced DOM usage is restricted because raw data (e.g., photographs) and metadata are often incomplete and/or unavailable. In this contribution, we present the Svalbox Digital Model Database (Svalbox DMDb), a database of metadata and openly available data packages for individual DOMs. The Svalbox DMDb is a regional DOM database geographically constrained to the Norwegian High Arctic archipelago of Svalbard at 74°N–81°N and 10°E–35°E. Svalbard offers exceptional-quality, vegetation-free outcrops with a wide range of lithologies and tectono-magmatic styles, including extension, compression, and magmatism. Data and metadata of the systematically digitalized outcrops across Svalbard are shared according to FAIR principles through the Svalbox DMDb. Fully open-access and downloadable DOMs include not just the DOMs themselves, but also the input data, processing reports and projects, and other data products such as footprints and orthomosaics. Rich metadata for each DOM include both the technical and geological parameters (metadata), enabling visualization and integration with regional geoscientific data available through the Norwegian Polar Institute and the Svalbox online portal. The current release of Svalbox DMDb, documented in this contribution, covers 135 DOMs cumulatively covering 114 km of Proterozoic to Cenozoic stratigraphy.
Geoscience academic hiring networks reinforce historic patterns of inequity
Authors: Dahl Robyn Mieko 
Published: September 2023

Abstract
An analysis of the academic hiring networks in geoscience reveals a severe imbalance that favors graduates from a small handful of institutions. In this study, social network analysis was conducted on a database consisting of every individual with a Ph.D. working in a geoscience degree-granting program in the United States (n = 6694) between 2015 and 2021. Individuals were mapped from the institution where they earned their Ph.D. to the institution where they currently work. Of the 895 geoscience degree-granting institutions included in the database, 10 alone produced nearly a quarter (24.6%) of the entire academic geoscience workforce. Network analysis also identified a small, closed network consisting of five of the top-10 institutions, which suggests that these networks hire more frequently from one another than from other institutions in the network. When academic rank was used to analyze the network for change over time, no significant shift in the hiring patterns was found. These imbalances in faculty production disadvantage scientists who are educated at programs other than the top-placing institutions and ultimately reinforces longstanding inequities in the field, such as the underrepresentation of people who are Black, Indigenous, People of Color (BIPOC), and first-generation college students in geoscience faculty. These patterns of inequity have also been shown to limit the spread of new scientific ideas throughout research communities.
The Application of Raw Chickpeas and Nuts in the Development of Plant-Based Cheese Snack: Ideal Nutrition and Texture Properties
Authors: Nie Ying , Liu Yaqun , Luo Qiulan , Huang Yisheng , Hu Lei , Zou Xianghui , Zheng Yuzhong , Li Biansheng , Huang Yongping 
Published: September 2023

Human and global health would be greatly improved by replacing animal-based foods with plant-based alternatives. This transition would be facilitated when more affordable, convenient, sustainable, nutritious, and tasty plant-based foods are available on the market. Interest in related research has surged these years, and dozens of plant-based cheese (PBC) products have been introduced to the market. However, studies found that most PBCs are far from comparable with dairy cheese in nutritional value, and the texture and sensory properties are still hurdles to the widespread consumption of PBCs. This paper focused on the “tissue disruption route” and adopted chickpeas and nuts as the main ingredients to form a cheese snack. Test results showed that our samples were high of nourishment value compared to the cheese sample and even healthier than the cheese in the terms of energy (

709.37
±
1.35

vs.

865.63
±
0.49

kJ/100 g,

p
<
0.01

), K/Na ratio (

142.00
±
0.82

/

13.33
±
0.12

mg/100 g vs.

121.67
±
2.05

/

44.23
±
0.05

mg/100 g,

p
<
0.01

), DF (

6.99
±
0.01

g/100 g vs. N/A,

p
<
0.01

), and cholesterol (

8.81
±
0.25

vs.

207.30
±
3.35

mg/100 g,

p
<
0.01

). From the order of magnitude, the PBC samples are similar to the cheese sample in the aspects of cohesiveness (

p
<
0.05

) in texture test, and the fermentation process improved the imitation of texture properties in terms of hardness and cohesiveness (both

p
<
0.05

). The volatile compounds were similar between the two PBC samples; however, the fermentation process could increase the species of the volatile compounds and make the PBC a little more similar to the dairy cheese. Overall, the observed properties of our PBC snack using raw chickpeas and nuts make the “plant-based cheese substitutes” extremely promising because of their nutritional value, sensory, and texture properties.
Association Between Alcohol Consumption and Ectopic Fat in the Multi‐Ethnic Study of Atherosclerosis
Authors: Kazibwe Richard , Chevli Parag A. , Evans Joni K. , Allison Matthew , Michos Erin D. , Wood Alexis C. , Ding Jingzhong , Shapiro Michael D. , Mongraw‐Chaffin Morgana 
Published: September 2023

Background
The relationship between alcohol consumption and ectopic fat distribution, both known factors for cardiovascular disease, remains understudied. Therefore, we aimed to examine the association between alcohol consumption and ectopic adiposity in adults at risk for cardiovascular disease.

Methods and Results
In this cross‐sectional analysis, we categorized alcohol intake among participants in MESA (Multi‐Ethnic Study of Atherosclerosis) as follows (drinks/day): <1 (light drinking), 1 to 2 (moderate drinking), >2 (heavy drinking), former drinking, and lifetime abstention. Binge drinking was defined as consuming ≥5 drinks on 1 occasion in the past month. Visceral, subcutaneous, and intermuscular fat area, pericardial fat volume, and hepatic fat attenuation were measured using noncontrast computed tomography. Using multivariable linear regression, we examined the associations between categories of alcohol consumption and natural log‐transformed fat in ectopic depots. We included 6756 MESA participants (62.1±10.2 years; 47.2% women), of whom 6734 and 1934 had chest computed tomography (pericardial and hepatic fat) and abdominal computed tomography (subcutaneous, intermuscular, and visceral fat), respectively. In adjusted analysis, heavy drinking, relative to lifetime abstention, was associated with a higher (relative percent difference) pericardial 15.1 [95% CI, 7.1–27.7], hepatic 3.4 [95% CI, 0.1–6.8], visceral 2.5 [95% CI, −10.4 to 17.2], and intermuscular 5.2 [95% CI, −6.6 to 18.4] fat but lower subcutaneous fat −3.5 [95% CI, −15.5 to 10.2]). The associations between alcohol consumption and ectopic adiposity exhibited a J‐shaped pattern. Binge drinking, relative to light‐to‐moderate drinking, was also associated with higher ectopic fat.

Conclusions
Alcohol consumption had a J‐shaped association with ectopic adiposity. Both heavy alcohol intake and binge alcohol drinking were associated with higher ectopic fat.
Statin Treatment in Patients With Stroke With Low‐Density Lipoprotein Cholesterol Levels Below 70 mg/dL
Authors: Kim Joon‐Tae , Lee Ji Sung , Kim Beom Joon , Kang Jihoon , Lee Keon‐Joo , Park Jong‐Moo , Kang Kyusik , Lee Soo Joo , Kim Jae Guk , Cha Jae‐Kwan , Kim Dae‐Hyun , Park Tai Hwan , Lee Kyungbok , Lee Jun , Hong Keun‐Sik , Cho Yong‐Jin , Park Hong‐Kyun , Lee Byung‐Chul , Yu Kyung‐Ho , Oh Mi Sun , Kim Dong‐Eog , Ryu Wi‐Sun , Choi Jay Chol , Kwon Jee‐Hyun , Kim Wook‐Joo , Shin Dong‐Ick , Yum Kyu Sun , Sohn Sung Il , Hong Jeong‐Ho , Lee Sang‐Hwa , Park Man‐Seok , Choi Kang‐Ho , Lee Juneyoung , Park Kwang‐Yeol , Bae Hee‐Joon 
Published: September 2023

Background
It is unclear whether statin treatment could reduce the risk of early vascular events when baseline low‐density lipoprotein cholesterol (LDL‐C) levels are already low, at <70 mg/dL, at the time of the index stroke.

Methods and Results

This study was an analysis of a prospective, multicenter, nationwide registry of consecutive patients with first‐ever acute ischemic stroke with baseline low‐density lipoprotein cholesterol levels <70 mg/dL and without statin pretreatment. An inverse probabilities of treatment weights method was applied to control for imbalances in baseline characteristics. The primary outcome was a composite of stroke (either hemorrhagic or ischemic), myocardial infarction, and all‐cause death within 3 months. A total of 2850 patients (age, 69.5±13.4 years; men, 63.5%) were analyzed for this study. In‐hospital statin treatment was used for 74.2% of patients. The primary composite outcome within 3 months occurred in 21.5% of patients in the nonstatin group and 6.7% of patients in the statin group (
P
<0.001), but the rates of stroke (2.65% versus 2.33%), hemorrhagic stroke (0.16% versus 0.10%), and myocardial infarction (0.73% versus 0.19%) were not significantly different between the 2 groups. After inverse probability of treatment weighting analysis, the primary composite outcome was significantly reduced in patients with statin therapy (weighted hazard ratio [HR], 0.54 [95% CI, 0.42–0.69]). However, statin treatment did not increase the risk of hemorrhagic stroke (weighted HR, 1.11 [95% CI, 0.10–12.28]).

Conclusions
Approximately three‐quarters of the patients with first‐ever ischemic stroke with baseline low‐density lipoprotein cholesterol levels <70 mg/dL received in‐hospital statin treatment. Statin treatment, compared with no statin treatment, was significantly associated with a reduced risk of the 3‐month primary composite outcomes and all‐cause death but did not alter the rate of stroke recurrence.
Bridging Diverse Delusions of Time
Authors: Hancock P.A. 
Published: September 2023

Abstract
Efforts continue to determine how many differing forms of time connote reality. These numbers range from the many to the few. The most common integer is two. Here, one represents a property of externality and the other a property of internality, or more colloquially a characteristic of mind. Attempts to weld this dyad into a “grand unified theory of time” are legion. However, since the essentially unquestioned foundational premise, viz the reality of time, is false, all subsequent theorizing, however well-meaning, proves vacuous. The unacceptable alternative is to embrace the delusion of time. However, this assertion of zero-time theory is so repugnant to the deeply entrenched belief in time by living systems that this answer proves unpalatable at best and rejected forthwith in virtually all instances. Explanations of time predicated upon the premises of duality and reality prove intriguing but eventually fruitless paths to pursue.
Bathymetry-Aware Mesoscale Eddy Parameterizations across Upwelling Slope Fronts: A Machine Learning–Augmented Approach
Authors: Xie Chenyue , Wei Huaiyu , Wang Yan 
Published: September 2023

Abstract
Mesoscale eddy buoyancy fluxes across continental slopes profoundly modulate the boundary current dynamics and shelf–ocean exchanges but have yet to be appropriately parameterized via the Gent–McWilliams (GM) scheme in predictive ocean models. In this work, we test the prognostic performance of multiple GM variants in noneddying simulations of upwelling slope fronts that are commonly found along the subtropical continental margins. The tested GM variants range from a set of constant eddy buoyancy diffusivities to recently developed energetically constrained, bathymetry-aware diffusivities, whose implementation is augmented by an artificial neural network (ANN) serving to predict the mesoscale eddy energy based on the topographic and mean flow quantities online. In addition, an ANN is employed to parameterize the cross-slope eddy momentum flux (EMF) that maintains a barotropic flow field analogous to that in an eddy-resolving model. Our tests reveal that noneddying simulations employing the bathymetry-aware forms of the Rhines scale–based scheme and GEOMETRIC scheme can most accurately reproduce the heat contents and along-slope baroclinic transports as those in the eddy-resolving simulations. Further analyses reveal certain degrees of physical consistency in the ANN-inferred eddy energy, which tends to grow (decay) as isopycnal slopes are steepened (flattened), and in the parameterized EMF, which exhibits the correct strength of shaping the flow baroclinicity if a bathymetry-aware GM variant is jointly used. These findings provide a recipe of GM variants for use in noneddying simulations with continental slopes and highlight the potential of machine learning techniques to augment physics-based mesoscale eddy parameterization schemes.

Significance Statement
This study evaluates the predictive skill of parameterization schemes of water mass transports induced by ocean mesoscale eddies across continental slopes. Correctly parameterizing these transports in noneddying ocean models (e.g., ocean climate models) is crucial for predicting the ocean circulation and shelf–ocean exchanges. This work highlights the importance of bathymetric effects on eddy transports, as parameterization schemes that account for the influence of a sloping seafloor outperform those developed specifically for a flat-bottomed ocean. This work also highlights the efficacy of machine learning techniques to augment physics-based mesoscale eddy parameterization schemes, for instance, by estimating the mesoscale eddy energy online to realize energy-dependent parameterization schemes in noneddying simulations.
Biomechanical Analysis of Meniscotibial Ligament Tenodesis to Treat Meniscal Extrusion in the Setting of Posterior Medial Meniscus Root Repair
Authors: Doan Kent , Dey Hazra Maria Else , Brown Justin R. , Hollenbeck Justin F.M. , Dey Hazra Rony-Orijit , Johnson Donovan , Fossum Bradley , Vidal Armando 
Published: September 2023

Background: Meniscal extrusion often persists after a medial meniscus root repair. If the meniscus is extruded, the function of the meniscus as a load-sharing device and secondary knee stabilizer is compromised. Hypothesis: It was hypothesized that repairing the meniscotibial ligament (MTL) would decrease meniscal extrusion in the settings of both an isolated MTL tear and a repaired medial meniscus root while also improving medial compartment contact mechanics. Study Design: Controlled laboratory study. Methods: Ten fresh-frozen cadaveric knees (mean age, 50.5 years) were tested in 5 conditions: intact, MTL deficiency, MTL deficiency + posterior medial meniscus root deficiency, MTL deficiency + posterior medial meniscus root repair, and MTL tenodesis + posterior medial meniscus root repair. Specimens were mounted to a load frame that applied a 1000-N axial load. Joint contact pressures were measured using thin pressure sensors, and the peak and mean pressures were analyzed. Ultrasound was used to measure meniscal extrusion. Results: The MTL tear in isolation resulted in significant meniscal extrusion compared with the intact state ( P = 0.035) without a detectable difference in medial compartment pressures. The addition of a root tear to the MTL tear state resulted in significantly more extrusion ( P = 0.001) and significant increases in medial compartment pressure ( P = .030) compared to the MTL tear state. Root repair alone restored extrusion, mean contact pressure, and peak contact pressure back to the intact state ( P > .05). Conclusion: This study showed that MTL disruption led to increased meniscal extrusion in a cadaveric model. Unlike the root tear state, MTL disruption did not change contact mechanics. Furthermore, root repair alone was sufficient in restoring intact biomechanics and extrusion. Clinical Relevance: This study may help clinicians understand the origin of medial meniscus root tears and aid in the decision-making process for whether to add an MTL tenodesis in the setting of root repair.