bluuebunny/crossref_metadata_2025 huggingface dataset:
Prehospital identification of acute ischaemic stroke with large vessel occlusion: a retrospective study from western Norway
Authors: Leto Nedim , Bjørshol Conrad Arnfinn , Kurz Martin , Østerås Øyvind , Fromm Annette , Lindner Thomas Werner
Published: November 2023

Background

In 2019, the emergency medical services (EMS) covering the western Norway Regional Health Authority area implemented its version of the prehospital clinical criteria G-FAST (Gaze deviation, Facial palsy, Arm weakness, Visual loss, Speech disturbance) to detect acute ischaemic stroke (AIS) with large vessel occlusion (LVO). For patients with gaze deviation and at least one other G-FAST symptom, a primary stroke centre (PSC) may be bypassed and the patient taken directly to a comprehensive stroke centre (CSC) for rapid endovascular treatment (EVT) evaluation. The study aim was to investigate the efficacy of the G-FAST criteria for LVO patient selection and direct transfer to a CSC.

Methods

This retrospective study included patients with code-red emergency medical communication centre (EMCC) stroke suspicion ambulance dispatch between August to December 2020. Stroke suspicion was defined as having at least one G-FAST symptom at EMS arrival. We obtained patient data from dispatches from EMCCs, EMS records and local EVT registries. Clinical features, CT images, and reperfusion treatment were recorded. The test characteristics for gaze deviation plus one other G-FAST symptom in detecting LVO were determined.

Results

Among 643 patients, 59 were diagnosed with LVO at hospital arrival. In this group, seven fulfilled the G-FAST criteria for direct transport to a CSC at EMS arrival on scene, resulting in a sensitivity of 12% (95% CI 5% to 23%). The specificity was 99.66% (95% CI 98.77% to 99.96%), the positive predictive value 78%, and the negative predictive value 92%. EVT was performed in 64% (38/59) of LVO cases. Median time from PSC arrival to start of EVT at a CSC was 163 min.

Conclusion

The use of local G-FAST prehospital criteria by EMS personnel to identify patients with AIS with LVO is not suitable for selection of patients with LVO for direct transfer to a CSC.
Spatial transcriptomics reveals a low extent of transcriptionally active hepatitis B virus integration in patients with HBsAg loss
Authors: Yu Xiaoqi , Gong Qiming , Yu Demin , Chen Yongyan , Jing Ying , Zoulim Fabien , Zhang Xinxin
Published: November 2023

Objective

Hepatitis B virus (HBV) can integrate into the chromosomes of infected hepatocytes, contributing to the production of hepatitis B surface antigen (HBsAg) and to hepatocarcinogenesis. In this study, we aimed to explore whether transcriptionally active HBV integration events spread throughout the liver tissue in different phases of chronic HBV infection, especially in patients with HBsAg loss.

Design

We constructed high-resolution spatial transcriptomes of liver biopsies containing 13 059 tissue spots from 18 patients with chronic HBV infection to analyse the occurrence and relative distribution of transcriptionally active viral integration events. Immunohistochemistry was performed to evaluate the expression of HBsAg and HBV core antigen. Intrahepatic covalently closed circular DNA (cccDNA) levels were quantified by real-time qPCR.

Results

Spatial transcriptome sequencing identified the presence of 13 154 virus-host chimeric reads in 7.86% (1026 of 13 059) of liver tissue spots in all patients, including three patients with HBsAg loss. These HBV integration sites were randomly distributed on chromosomes and can localise in host genes involved in hepatocarcinogenesis, such as
ALB, CLU
and
APOB
. Patients who were receiving or had received antiviral treatment had a significantly lower percentage of viral integration-containing spots and significantly fewer chimeric reads than treatment-naïve patients. Intrahepatic cccDNA levels correlated well with viral integration events.

Conclusion

Transcriptionally active HBV integration occurred in chronically HBV-infected patients at different phases, including in patients with HBsAg loss. Antiviral treatment was associated with a decreased number and extent of transcriptionally active viral integrations, implying that early treatment intervention may further reduce the number of viral integration events.
Navigating parental requests: considering the relational potential standard in paediatric end-of-life care in the paediatric intensive care unit
Authors: Kingsley Jenny , Clark Jonna , Lewis-Newby Mithya , Dudzinski Denise Marie , Diekema Douglas
Published: November 2023

Families and clinicians approaching a child’s death in the paediatric intensive care unit (PICU) frequently encounter questions surrounding medical decision-making at the end of life (EOL), including defining what is in the child’s best interest, finding an optimal balance of benefit over harm, and sometimes addressing potential futility and moral distress. The best interest standard (BIS) is often marshalled by clinicians to help navigate these dilemmas and focuses on a clinician’s primary ethical duty to the paediatric patient. This approach does not consider a clinician’s potential duty to the patient’s family. This paper argues that when a child is dying in the PICU, the physician has a duty to serve both the patient and the family, and that in some circumstances, the duty to serve the family becomes as important as that owed to the child. We detail the limitations of the BIS in paediatric EOL care and propose the relational potential standard as an additional ethical framework to guide our decisions.
Dementia prevention: the Mendelian randomisation perspective
Authors: Anderson Emma Louise , Davies Neil M , Korologou-Linden Roxanna , Kivimäki Mika
Published: November 2023

Understanding the causes of Alzheimer’s disease and related dementias remains a challenge. Observational studies investigating dementia risk factors are limited by the pervasive issues of confounding, reverse causation and selection biases. Conducting randomised controlled trials for dementia prevention is often impractical due to the long prodromal phase and the inability to randomise many potential risk factors. In this essay, we introduce Mendelian randomisation as an alternative approach to examine factors that may prevent or delay Alzheimer’s disease. Mendelian randomisation is a causal inference method that has successfully identified risk factors and treatments in various other fields. However, applying this method to dementia risk factors has yielded unexpected findings. Here, we consider five potential explanations and provide recommendations to enhance causal inference from Mendelian randomisation studies on dementia. By employing these strategies, we can better understand factors affecting dementia risk.
Energetic costs of mounting an immune response in a coral reef damselfish (Pomacentrus amboinensis)
Authors: Levet Marie , Roche Dominique G. , Killen Shaun S. , Colosio Simona , Bshary Redouan , Miest Joanna J. , Binning Sandra A.
Published: November 2023

While immune responses can be energetically costly, quantifying these costs is challenging. We tested the metabolic costs of immune activation in damselfish ( Pomacentrus amboinensis Bleeker, 1868) following a mass-adjusted injection of lipopolysaccharide (LPS) endotoxin. Fish were divided into eight treatments: two controls (handling and saline injection) and six LPS groups with concentrations ranging from 3 to 100 mg kg−1. We used intermittent flow respirometry to measure differences in oxygen uptake (delta ṀO2) 20 h before versus 20 h after LPS injection and changes in metabolic traits (lowest, routine, and peak metabolic rates) as proxies of the aerobic costs of metabolism. Spleen somatic index (SSI) and gene expression in spleens were measured to assess immune activation. We found no difference in metabolic traits or SSI but observed different nonlinear patterns of delta ṀO2 in fish exposed to 50 and 100 mg kg−1 LPS compared to lower doses and controls. Fish exposed to high doses of LPS also had lower residual aerobic scope compared to controls and lower LPS doses. Fish exposed to doses of 3, 50, and 100 mg kg−1 showed altered gene expression compared to the handling control. Overall, our results suggest that immune activation has measurable effects on metabolic traits that are both dose- and time-dependent.
Production of $${^{180\textrm{m}}}$$Hf in photoproton reaction $${^{181}}$$Ta$$(\gamma ,p)$$ at energy $$E_{\mathrm{\gamma max}} = 35$$–95 MeV
Authors: Timchenko I. S. , Deiev O. S. , Olejnik S. N. , Potin S. M. , Korda L. P. , Kushnir V. A. , Mytrochenko V. V. , Perezhogin S. A. , Herzáň A.
Published: November 2023

The production of the $$^{180\textrm{m}}\textrm{Hf}$$

180
m

Hf

nuclei in the photoproton reaction $${^{181}\textrm{Ta}}(\gamma ,p)$$

181

Ta

(
γ
,
p
)

was studied at end-point bremsstrahlung energies $$E_{\mathrm{\gamma max}}=35$$

E

γ
max

=
35

–95 MeV. The experiment was performed at the electron linear accelerator LUE-40 NSC KIPT with the use of the $$\gamma $$
γ
activation and off-line $$\gamma $$
γ
-ray spectroscopy. The experimental values of the bremsstrahlung flux-averaged cross-sections $$\langle {\sigma (E_{\mathrm{\gamma max}})}\rangle _{\textrm{m}}$$

⟨

σ
(

E

γ
max

)

⟩

m

for the $${^{181}\textrm{Ta}}(\gamma ,p)^{180\textrm{m}}\textrm{Hf}$$

181

Ta

(
γ
,
p
)

180
m

Hf

reaction were determined, and at $$E_{\mathrm{\gamma max}} > 55$$

E

γ
max

>
55

 MeV obtained for the first time. The measured values, as well as the literature data, significantly (by more that an order of magnitude) exceed the theoretical flux-averaged cross-sections $$\langle {\sigma (E_{\mathrm{\gamma max}})}\rangle _{\textrm{th}}$$

⟨

σ
(

E

γ
max

)

⟩

th

. The $$\langle {\sigma (E_{\mathrm{\gamma max}})}\rangle _{\textrm{th}}$$

⟨

σ
(

E

γ
max

)

⟩

th

values were calculated using the cross-section $$\sigma (E)$$

σ
(
E
)

computed with the TALYS1.95 code for six different level density models. A comparative analysis of the calculated total cross-sections from the TALYS computation for the reactions $${^{181}\textrm{Ta}}(\gamma ,p)^{180}\textrm{Hf}$$

181

Ta

(
γ
,
p
)

180

Hf

and $${^{181}\textrm{Ta}}(\gamma ,n)^{180}\textrm{Ta}$$

181

Ta

(
γ
,
n
)

180

Ta

was performed. It was shown that the photoproton $$(\gamma ,p)$$

(
γ
,
p
)

to photoneutron $$(\gamma ,n)$$

(
γ
,
n
)

strength ratio is consistent with the estimates based on the isospin selection rules and the value from the $$(e,e'p)$$

(
e
,

e
′

p
)

experiment.
New mass limit of a strange star admitting a colour flavor locked equation of state
Authors: Goswami K. B. , Saha A. , Chattopadhyay P. K. , Karmakar S.
Published: November 2023

A class of strange stars is analysed in the present article in hydrostatic equilibrium, whose state is defined by a CFL phase equation of state. We have compared our results with those obtained from the MIT equation of state for strange quark matter, which is regarded as free particles. We have noted that if we consider quarks to form a cooper pair and if their description is made by the CFL equation of state, the maximum mass of strange star reaches a value as high as 3.61 $$M_{\odot }$$

M
⊙

. This value is well above the value of 2.03 $$M_{\odot }$$

M
⊙

obtained by using the MIT bag equation of state for massless free quarks. Both the maximum masses are determined by solving the TOV equation for different values of the strange quark mass $$m_s$$

m
s

. Thus, the inclusion of the possibility of quark pair formation in the theory permits us to accommodate a wider class of compact objects such as PSR J1614-2230, PSR J0740+6620, PSR J0952-0607 etc. and the mass of the companion star in the GW190814 event in our model. The consideration of such a high value of mass is hardly theoretically obtainable from normal strange star models in general relativity even with a fast rotation effect. The object PSR J0952-0607 is found to be the fastest and heaviest pulsar in the disk of Milky Way Galaxy, having a mass of 2.35 $$M_{\odot }$$

M
⊙

, which may be predicted in our model, as observational evidence supports the existence of strange quark matter in its composition.
FRACTAL CHARACTERISTICS OF DIFFERENT-SCALE STRUCTURES IN WATER INJECTION COAL AND THEIR CONTROL MECHANISM ON DYNAMIC WATER MIGRATION
Authors: LIU ZHEN , YU ZEHAN , YANG HE , ZHU MUYAO , SUN SHUYANG , YAO MEIRU , DONG SHUAI , LI ZHENG
Published: November 2023

Clarifying the control mechanism of structures in water injection coal on dynamic water transport is fundamental for improving the effect of pre-wetting and dust reduction. Using nuclear magnetic resonance experimental system, we simulated realistic water injection coal seam conditions. We obtained the real mechanical environment of water injection coal seam, the [Formula: see text] spectrum curves of the pore structure at different scales, realized a fine measurement of liquid permeability, proposed a method for calculating the fractal dimension of the specific surface area which combined a tortuosity fractal dimension algorithm, delineated micro-holes and medium–large holes, clarified the quantitative relationships between the structural porosity, the specific surface area, tortuosity, and permeability, and investigated the control mechanism of structural characteristics on the dynamic water transport process. The results showed that, under different mechanical environments, the fractal dimension of the specific surface area of micro–small pores was close to 2, while that of medium–large pores was close to 3. The former fractal dimension increased more obviously, indicating that medium–large pores are more easily compressed than micro–small ones. Under such conditions, the complexity of pore size distribution increased. Additionally, the fractal dimension increase of tortuosity was higher for medium–large pores than for micro–small pores, indicating that the hydraulic reconstruction process was more obvious at a large scale. According to the quantitative relationship between structural porosity, the specific surface area, tortuosity, and permeability, medium–large pores control most of the dynamic water migration in the coal bodies of Daliuta Coal Mine, while the whole pore size range has an important influence on dynamic water migration in the coal bodies of Luling Coal Mine. Our findings provide a solid scientific basis for the development of hydraulic permeability technologies for difficult-to-penetrate coal seams.
Vibration Analysis of Internally Perforated Annular Plate with Discontinuous Boundary Conditions
Authors: Liu Junfeng , Lou Jingjun , Chai Kai , Yang Qingchao , Chu Jiawen
Published: November 2023

Because of the introduction of modal coupling, discontinuous boundaries have a significant impact on the vibration characteristics of annular plates. Based on the spectral element method (SEM) and parametric equivalent method (PEM), the vibration calculation and analysis of internally perforated annular plate with discontinuous boundary are explained. Firstly, a uniform annular plate is regarded as a spectral element, and the vibration response of an annular plate with general elastic boundaries is obtained based on the motion equation of the annular plate and the virtual spring method (VSM). The displacement solution is described by the Bessel function, and a fitting method of discontinuous spring stiffness coefficient based on the weighted least square norm least square method is proposed. Based on the force equilibrium condition, the vibration response of an annular plate with a discontinuous boundary is derived, and the reasons for the change of vibration characteristics with a discontinuous boundary are explained from modal superposition. The dynamic stiffness matrix method is used to establish the vibration equation of an annular plate with a discontinuous boundary, and the influence of internal openings on the vibration characteristics of an annular plate is effectively calculated by the parametric equivalent method. Finally, a finite element simulation model is established to test the accuracy and stability of the proposed method. The influence of general discontinuous boundary conditions on structural dynamic behavior is analyzed by numerical examples, which provides useful guidance for structural vibration analysis with discontinuous boundary conditions.
Equivariant formality of the isotropy action on (ℤ2 ⊕ ℤ2)-symmetric spaces
Authors: Amann Manuel , Kollross Andreas
Published: November 2023

Compact symmetric spaces are probably one of the most prominent class of formal spaces, i.e. of spaces where the rational homotopy type is a formal consequence of the rational cohomology algebra. As a generalization, it is even known that their isotropy action is equivariantly formal. In this paper, we show that [Formula: see text]-symmetric spaces are equivariantly formal and formal in the sense of Sullivan, in particular. Moreover, we give a short alternative proof of equivariant formality in the case of symmetric spaces with our new approach.
Structure invariant properties of the hierarchically hyperbolic boundary
Authors: Abbott Carolyn , Behrstock Jason , Russell Jacob
Published: November 2023

We prove several topological and dynamical properties of the boundary of a hierarchically hyperbolic group are independent of the specific hierarchically hyperbolic structure. This is accomplished by proving that the boundary is invariant under a “maximization” procedure introduced by the first two authors and Durham.
Growth rate of Dehn twist lattice points in Teichmüller space
Authors: Han Jiawei
Published: November 2023

Athreya et al. [Lattice point asymptotics and volume growth on Teichmüller space, Duke Math. J. 161 (2012) 1055–1111] have shown the number of mapping class group lattice points intersecting a closed ball of radius [Formula: see text] in Teichmüller space is asymptotic to [Formula: see text], where [Formula: see text] is the dimension of the Teichmüller space. In contrast we show the number of Dehn twist lattice points intersecting a closed ball of radius [Formula: see text] is coarsely asymptotic to [Formula: see text]. Moreover, we show the number multi-twist lattice points intersecting a closed ball of radius [Formula: see text] grows coarsely at least at the rate of [Formula: see text].
Indole Substrates to Carbazole Targets: An Update in the Discovery of an Ideal Synthetic Methodology
Authors: Behera Priyanka , Ramakrishna D. S. , Mohapatra Suhasini , Praveen P. Lakshmi , Kothakapu Sridhar Reddy
Published: November 2023

Carbazole compounds have been proven to exhibit vital photophysical and biological applications. Even simple carbazole derivatives were showing attractive biological activities such as antimicrobacterial activity (Glycozoline), antiproliferative activity (Mukonine), free radical scavenger (Carazostatin), etc. In case of photophysical applications, carbazole derivatives were utilized in organic semiconductors, photoconducting polymers, Green host material in phosphorescent organic light-emitting diodes (OLEDs), hole-transporting material in OLEDs and organic light emitting materials. An account of different synthetic methodologies involved in the synthesis of natural and synthetic carbazole derivatives was evaluated based on the usage of commercially available cheap starting materials such as derivatives of Indole. This paper takes into account the time from 2011 to 2023. The advanced methods were developed based on the 12 principles of Green chemistry such as Multistep domino reactions, Atom & Step economy reactions, protection-free reactions, mild reaction conditions, open atmosphere reactions, harmless by-products and photochemical transformations.
Transition System Representation of Boolean Control Networks
Authors: Cheng Daizhan , Zhang Xiao , Ji Zhengping
Published: November 2023

In this paper, we propose a transition system (TS) framework for the analysis and design of logical networks. The formula for calculating the fixed points and cycles of a TS is first provided. Then, the TS representation of Boolean networks (BNs) and Boolean control networks (BCNs) is introduced. The first kind of representation is state-based, which converts a BCN into a TS with either distinguished controls or undistinguished ones. The second representation is output-based, which is also called the simulation of the original BCN. Finally, after introducing the notion of output simulation, our method is applied to design output robust controls of logical networks.
Effect of Different Drying Techniques on the Functionality and Digestibility of Yellow-Fleshed Cassava Flour and Its Performance in Food Application
Authors: Akonor P. T. , Tutu C. Osei , Affrifah N. S. , Budu A. S. , Saalia F. K.
Published: November 2023

The impact of different drying techniques on the properties of yellow cassava flour and its food application was investigated in this study. Flour was made from three cultivars of yellow cassava by solar-, hot air oven-, or drum- drying. Their functionality was determined by standard methods, and their digestibility was evaluated in vitro. The flours were used in the preparation of fufu, which was evaluated by sensorial and instrumental methods. The digestibility of drum-dried flours was higher (69.4–79.7%) than solar- (60.4–70.7%) or air oven-dried flours (60.3–70.4%), whereas β-carotene concentration was higher in air oven-dried samples compared to the others. Significant differences (

p
<
0.05

) due to cultivar and/or drying technique were observed in the hydration and pasting properties of the flours. Instrumental texture analysis of fufu made from yellow cassava flours showed both drying technique and cultivar to affect the hardness, adhesiveness, and cohesiveness of the product. Acceptability scores for the fufu ranged from 4 to 6, with a decisive preference for samples produced from drum-dried flours. The study has shown the successful utilization of different drying techniques in the production of flour from yellow cassava variants for the preparation of fufu.
Supplementary Tables 1-14 from Ultra-Deep Sequencing Reveals the Mutational Landscape of Classical Hodgkin Lymphoma
Authors: Gomez Felicia , Fisk Bryan , McMichael Joshua F. , Mosior Matthew , Foltz Jennifer A. , Skidmore Zachary L. , Duncavage Eric J. , Miller Christopher A. , Abel Haley , Li Yi-Shan , Russler-Germain David A. , Krysiak Kilannin , Watkins Marcus P. , Ramirez Cody A. , Schmidt Alina , Martins Rodrigues Fernanda , Trani Lee , Khanna Ajay , Wagner Julia A. , Fulton Robert S. , Fronick Catrina C. , O'Laughlin Michelle D. , Schappe Timothy , Cashen Amanda F. , Mehta-Shah Neha , Kahl Brad S. , Walker Jason , Bartlett Nancy L. , Griffith Malachi , Fehniger Todd A. , Griffith Obi L.
Published: November 2023

Supplemental Tables 1-14
Supplementary Figure 6 from Ultra-Deep Sequencing Reveals the Mutational Landscape of Classical Hodgkin Lymphoma
Authors: Gomez Felicia , Fisk Bryan , McMichael Joshua F. , Mosior Matthew , Foltz Jennifer A. , Skidmore Zachary L. , Duncavage Eric J. , Miller Christopher A. , Abel Haley , Li Yi-Shan , Russler-Germain David A. , Krysiak Kilannin , Watkins Marcus P. , Ramirez Cody A. , Schmidt Alina , Martins Rodrigues Fernanda , Trani Lee , Khanna Ajay , Wagner Julia A. , Fulton Robert S. , Fronick Catrina C. , O'Laughlin Michelle D. , Schappe Timothy , Cashen Amanda F. , Mehta-Shah Neha , Kahl Brad S. , Walker Jason , Bartlett Nancy L. , Griffith Malachi , Fehniger Todd A. , Griffith Obi L.
Published: November 2023

Coverage Summary Across Sites that Passed and Failed Validation
Supplementary Figure 17 from Ultra-Deep Sequencing Reveals the Mutational Landscape of Classical Hodgkin Lymphoma
Authors: Gomez Felicia , Fisk Bryan , McMichael Joshua F. , Mosior Matthew , Foltz Jennifer A. , Skidmore Zachary L. , Duncavage Eric J. , Miller Christopher A. , Abel Haley , Li Yi-Shan , Russler-Germain David A. , Krysiak Kilannin , Watkins Marcus P. , Ramirez Cody A. , Schmidt Alina , Martins Rodrigues Fernanda , Trani Lee , Khanna Ajay , Wagner Julia A. , Fulton Robert S. , Fronick Catrina C. , O'Laughlin Michelle D. , Schappe Timothy , Cashen Amanda F. , Mehta-Shah Neha , Kahl Brad S. , Walker Jason , Bartlett Nancy L. , Griffith Malachi , Fehniger Todd A. , Griffith Obi L.
Published: November 2023

Diagram of observed mutated components of the PI3K signaling cascade
Supplementary Figure 16 from Ultra-Deep Sequencing Reveals the Mutational Landscape of Classical Hodgkin Lymphoma
Authors: Gomez Felicia , Fisk Bryan , McMichael Joshua F. , Mosior Matthew , Foltz Jennifer A. , Skidmore Zachary L. , Duncavage Eric J. , Miller Christopher A. , Abel Haley , Li Yi-Shan , Russler-Germain David A. , Krysiak Kilannin , Watkins Marcus P. , Ramirez Cody A. , Schmidt Alina , Martins Rodrigues Fernanda , Trani Lee , Khanna Ajay , Wagner Julia A. , Fulton Robert S. , Fronick Catrina C. , O'Laughlin Michelle D. , Schappe Timothy , Cashen Amanda F. , Mehta-Shah Neha , Kahl Brad S. , Walker Jason , Bartlett Nancy L. , Griffith Malachi , Fehniger Todd A. , Griffith Obi L.
Published: November 2023

Diagram of observed mutated components of the MAPK signaling cascade
Supplementary Figure 1 from Ultra-Deep Sequencing Reveals the Mutational Landscape of Classical Hodgkin Lymphoma
Authors: Gomez Felicia , Fisk Bryan , McMichael Joshua F. , Mosior Matthew , Foltz Jennifer A. , Skidmore Zachary L. , Duncavage Eric J. , Miller Christopher A. , Abel Haley , Lee Yi-Shan , Russler-Germain David A. , Krysiak Kilannin , Watkins Marcus P. , Ramirez Cody A. , Schmidt Alina , Martins Rodrigues Fernanda , Trani Lee , Khanna Ajay , Wagner Julia A. , Fulton Robert S. , Fronick Catrina C. , O'Laughlin Michelle D. , Schappe Timothy , Cashen Amanda F. , Mehta-Shah Neha , Kahl Brad S. , Walker Jason , Bartlett Nancy L. , Griffith Malachi , Fehniger Todd A. , Griffith Obi L.
Published: November 2023

Exome VAF and Depth of Coverage
Supplementary Figure 1 from Ultra-Deep Sequencing Reveals the Mutational Landscape of Classical Hodgkin Lymphoma
Authors: Gomez Felicia , Fisk Bryan , McMichael Joshua F. , Mosior Matthew , Foltz Jennifer A. , Skidmore Zachary L. , Duncavage Eric J. , Miller Christopher A. , Abel Haley , Li Yi-Shan , Russler-Germain David A. , Krysiak Kilannin , Watkins Marcus P. , Ramirez Cody A. , Schmidt Alina , Martins Rodrigues Fernanda , Trani Lee , Khanna Ajay , Wagner Julia A. , Fulton Robert S. , Fronick Catrina C. , O'Laughlin Michelle D. , Schappe Timothy , Cashen Amanda F. , Mehta-Shah Neha , Kahl Brad S. , Walker Jason , Bartlett Nancy L. , Griffith Malachi , Fehniger Todd A. , Griffith Obi L.
Published: November 2023

Exome VAF and Depth of Coverage
FIGURE 6 from Ultra-Deep Sequencing Reveals the Mutational Landscape of Classical Hodgkin Lymphoma
Authors: Gomez Felicia , Fisk Bryan , McMichael Joshua F. , Mosior Matthew , Foltz Jennifer A. , Skidmore Zachary L. , Duncavage Eric J. , Miller Christopher A. , Abel Haley , Lee Yi-Shan , Russler-Germain David A. , Krysiak Kilannin , Watkins Marcus P. , Ramirez Cody A. , Schmidt Alina , Martins Rodrigues Fernanda , Trani Lee , Khanna Ajay , Wagner Julia A. , Fulton Robert S. , Fronick Catrina C. , O'Laughlin Michelle D. , Schappe Timothy , Cashen Amanda F. , Mehta-Shah Neha , Kahl Brad S. , Walker Jason , Bartlett Nancy L. , Griffith Malachi , Fehniger Todd A. , Griffith Obi L.
Published: November 2023

Regulating Hippo. A, Diagram of pathways that regulate Hippo signaling. Identified SMGs are shown in red; genes mutated in at least one non-hypermutated sample are shown in yellow; genes only mutated in the hypermutated sample (HL-513) are shown in orange. The gene mutation frequency across the cohort is shown as a percent. The pathways labeled in green indicate larger pathways not shown in this diagram. B, The total number and type of mutation observed are shown in the inset bar chart. C, Lolliplot of CDH5; mutations identified in the current study are shown on the top and COSMIC mutations found in lymphoid tissue on the bottom. D, Lolliplot of mutations identified at GNA13; mutations identified in the current study are shown on the top and COSMIC mutations found in lymphoid tissue on the bottom.
FIGURE 1 from Ultra-Deep Sequencing Reveals the Mutational Landscape of Classical Hodgkin Lymphoma
Authors: Gomez Felicia , Fisk Bryan , McMichael Joshua F. , Mosior Matthew , Foltz Jennifer A. , Skidmore Zachary L. , Duncavage Eric J. , Miller Christopher A. , Abel Haley , Li Yi-Shan , Russler-Germain David A. , Krysiak Kilannin , Watkins Marcus P. , Ramirez Cody A. , Schmidt Alina , Martins Rodrigues Fernanda , Trani Lee , Khanna Ajay , Wagner Julia A. , Fulton Robert S. , Fronick Catrina C. , O'Laughlin Michelle D. , Schappe Timothy , Cashen Amanda F. , Mehta-Shah Neha , Kahl Brad S. , Walker Jason , Bartlett Nancy L. , Griffith Malachi , Fehniger Todd A. , Griffith Obi L.
Published: November 2023

Deep exome coverage, validation rate, final variant count, and VAF per sample. A, Average per base coverage for targeted regions across each tumor and normal sample. B, A targeted orthogonal sequencing strategy (HaloPlex; Agilent) was used to validate all variants that passed filtering strategies for all samples (except for the hypermutated sample, for which a subset of variants were selected for validation—see Materials and Methods). The count of assayed variants that passed, failed, or were validated only in the HaloPlex tumor sample, is shown by sample as well as the number for which validation was not possible due to low tumor coverage or amplicon design failure. The overall count of variants that passed, failed, or received a “tumor only” validation status, excluding variants from HL-513 is shown at the right. Note: One patient (HL-584) did not have any variants pass filtering and review, therefore 30/31 patients were included in validation. C, Comparison of exome VAF and HaloPlex VAF is shown for samples with two or more variants. D, VAF and variant count for all variants across all samples used in all further analyses. Following each sample number is the number of HaloPlex discovered variants and exome discovered variants. In addition, a colored rectangle indicating the EBV stats (assessed using competitive alignment) is shown. Note: Variants from one patient failed validation (HL-157) and no further variants were called in de novo exercises. This patient was removed from all further analyses. In addition, the patient who did not have variants to validate, gained two variants in the de novo exercise and was included in the final cohort (HL-584).
Data from Ultra-Deep Sequencing Reveals the Mutational Landscape of Classical Hodgkin Lymphoma
Authors: Gomez Felicia , Fisk Bryan , McMichael Joshua F. , Mosior Matthew , Foltz Jennifer A. , Skidmore Zachary L. , Duncavage Eric J. , Miller Christopher A. , Abel Haley , Li Yi-Shan , Russler-Germain David A. , Krysiak Kilannin , Watkins Marcus P. , Ramirez Cody A. , Schmidt Alina , Martins Rodrigues Fernanda , Trani Lee , Khanna Ajay , Wagner Julia A. , Fulton Robert S. , Fronick Catrina C. , O'Laughlin Michelle D. , Schappe Timothy , Cashen Amanda F. , Mehta-Shah Neha , Kahl Brad S. , Walker Jason , Bartlett Nancy L. , Griffith Malachi , Fehniger Todd A. , Griffith Obi L.
Published: November 2023

Abstract
The malignant Hodgkin and Reed Sternberg (HRS) cells of classical Hodgkin lymphoma (cHL) are scarce in affected lymph nodes, creating a challenge to detect driver somatic mutations. As an alternative to cell purification techniques, we hypothesized that ultra-deep exome sequencing would allow genomic study of HRS cells, thereby streamlining analysis and avoiding technical pitfalls. To test this, 31 cHL tumor/normal pairs were exome sequenced to approximately 1,000× median depth of coverage. An orthogonal error-corrected sequencing approach verified >95% of the discovered mutations. We identified mutations in genes novel to cHL including: CDH5 and PCDH7, novel stop gain mutations in IL4R, and a novel pattern of recurrent mutations in pathways regulating Hippo signaling. As a further application of our exome sequencing, we attempted to identify expressed somatic single-nucleotide variants (SNV) in single-nuclei RNA sequencing (snRNA-seq) data generated from a patient in our cohort. Our snRNA analysis identified a clear cluster of cells containing a somatic SNV identified in our deep exome data. This cluster has differentially expressed genes that are consistent with genes known to be dysregulated in HRS cells (e.g., PIM1 and PIM3). The cluster also contains cells with an expanded B-cell clonotype further supporting a malignant phenotype. This study provides proof-of-principle that ultra-deep exome sequencing can be utilized to identify recurrent mutations in HRS cells and demonstrates the feasibility of snRNA-seq in the context of cHL. These studies provide the foundation for the further analysis of genomic variants in large cohorts of patients with cHL.
Significance:
Our data demonstrate the utility of ultra-deep exome sequencing in uncovering somatic variants in Hodgkin lymphoma, creating new opportunities to define the genes that are recurrently mutated in this disease. We also show for the first time the successful application of snRNA-seq in Hodgkin lymphoma and describe the expression profile of a putative cluster of HRS cells in a single patient.
Gut Frailty: Its Concept and Pathogenesis
Authors: Naito Yuji
Published: November 2023

Background: There is still a considerable gap between average life expectancy and healthy life expectancy in Japan. Recent research has revealed that gut frailty may be a worsening factor for various diseases, a cause of chronic inflammation, and a precursor to frailty. Summary: Among self-reported symptoms, constipation is particularly significant as one of the key symptoms of gut frailty. Studies have demonstrated that individuals with constipation have significantly lower survival rates and are also at a higher risk of developing various diseases such as chronic kidney disease, cardiovascular diseases, and neurodegenerative disorders like Parkinson’s disease. Various molecular mechanisms could contribute to gut frailty, and the decrease in mucus secretion is an extremely early-stage pathology. Dysbiosis of gut microbiota has a major impact on many conditions associated with gut frailty. Prebiotics, probiotics, post-biotics, and fecal microbiota transplantation are under investigation as a treatment option for gut frailty. Key Message: Although the concept of gut frailty has not yet gained widespread recognition, we hope to propose more practical screening methods, diagnostic approaches, and specific interventions in the future.
Bag-Valve-Mask Ventilation and Survival From Out-of-Hospital Cardiac Arrest: A Multicenter Study
Authors: Idris Ahamed H. , Aramendi Ecenarro Elisabete , Leroux Brian , Jaureguibeitia Xabier , Yang Betty Y. , Shaver Sarah , Chang Mary P. , Rea Tom , Kudenchuk Peter , Christenson Jim , Vaillancourt Christian , Callaway Clifton , Salcido David , Carson Jonas , Blackwood Jennifer , Wang Henry E.
Published: November 2023

BACKGROUND:

Few studies have measured ventilation during early cardiopulmonary resuscitation (CPR) before advanced airway placement. Resuscitation guidelines recommend pauses after every 30 chest compressions to deliver ventilations. The effectiveness of bag-valve-mask ventilation delivered during the pause in chest compressions is unknown. We sought to determine: (1) the incidence of lung inflation with bag-valve-mask ventilation during 30:2 CPR; and (2) the association of ventilation with outcomes after out-of-hospital cardiac arrest.

METHODS:

We studied patients with out-of-hospital cardiac arrest from 6 sites of the Resuscitation Outcomes Consortium CCC study (Trial of Continuous Compressions versus Standard CPR in Patients with Out-of-Hospital Cardiac Arrest). We analyzed patients assigned to the 30:2 CPR arm with ≥2 minutes of thoracic bioimpedance signal recorded with a cardiac defibrillator/monitor. Detectable ventilation waveforms were defined as having a bioimpedance amplitude ≥0.5 Ω (corresponding to ≥250 mL V
T
) and a duration ≥1 s. We defined a chest compression pause as a 3- to 15-s break in chest compressions. We compared the incidence of ventilation and outcomes in 2 groups: patients with ventilation waveforms in <50% of pauses (group 1) versus those with waveforms in ≥50% of pauses (group 2).

RESULTS:

Among 1976 patients, the mean age was 65 years; 66% were male. From the start of chest compressions until advanced airway placement, mean±SD duration of 30:2 CPR was 9.8±4.9 minutes. During this period, we identified 26 861 pauses in chest compressions; 60% of patients had ventilation waveforms in <50% of pauses (group 1, n=1177), and 40% had waveforms in ≥50% of pauses (group 2, n=799). Group 1 had a median of 12 pauses and 2 ventilations per patient versus group 2, which had 12 pauses and 12 ventilations per patient. Group 2 had higher rates of prehospital return of spontaneous circulation (40.7% versus 25.2%;
P
<0.0001), survival to hospital discharge (13.5% versus 4.1%;
P
<0.0001), and survival with favorable neurological outcome (10.6% versus 2.4%;
P
<0.0001). These associations persisted after adjustment for confounders.

CONCLUSIONS:

In this study, lung inflation occurred infrequently with bag-valve-mask ventilation during 30:2 CPR. Lung inflation in ≥50% of pauses was associated with improved return of spontaneous circulation, survival, and survival with favorable neurological outcome.
Raising NAD
+
Level Stimulates Short-Chain Dehydrogenase/Reductase Proteins to Alleviate Heart Failure Independent of Mitochondrial Protein Deacetylation
Authors: Walker Matthew A. , Chen Hongye , Yadav Aprajita , Ritterhoff Julia , Villet Outi , McMillen Tim , Wang Yuliang , Purcell Hayley , Djukovic Danijel , Raftery Daniel , Isoherranen Nina , Tian Rong
Published: November 2023

BACKGROUND:

Strategies to increase cellular NAD
+
(oxidized nicotinamide adenine dinucleotide) level have prevented cardiac dysfunction in multiple models of heart failure, but molecular mechanisms remain unclear. Little is known about the benefits of NAD
+
-based therapies in failing hearts after the symptoms of heart failure have appeared. Most pretreatment regimens suggested mechanisms involving activation of sirtuin, especially Sirt3 (sirtuin 3), and mitochondrial protein acetylation.

METHODS:

We induced cardiac dysfunction by pressure overload in SIRT3-deficient (knockout) mice and compared their response with nicotinamide riboside chloride treatment with wild-type mice. To model a therapeutic approach, we initiated the treatment in mice with established cardiac dysfunction.

RESULTS:

We found nicotinamide riboside chloride improved mitochondrial function and blunted heart failure progression. Similar benefits were observed in wild-type and knockout mice. Boosting NAD
+
level improved the function of NAD(H) redox-sensitive SDR (short-chain dehydrogenase/reductase) family proteins. Upregulation of Mrpp2 (mitochondrial ribonuclease P protein 2), a multifunctional SDR protein and a subunit of mitochondrial ribonuclease P, improves mitochondrial DNA transcripts processing and electron transport chain function. Activation of SDRs in the retinol metabolism pathway stimulates RXRα (retinoid X receptor α)/PPARα (proliferator-activated receptor α) signaling and restores mitochondrial oxidative metabolism. Downregulation of Mrpp2 and impaired mitochondrial ribonuclease P were found in human failing hearts, suggesting a shared mechanism of defective mitochondrial biogenesis in mouse and human heart failure.

CONCLUSIONS:

These findings identify SDR proteins as important regulators of mitochondrial function and molecular targets of NAD
+
-based therapy. Furthermore, the benefit is observed regardless of Sirt3-mediated mitochondrial protein deacetylation, a widely held mechanism for NAD
+
-based therapy for heart failure. The data also show that NAD
+
-based therapy can be useful in pre-existing heart failure.
Direct Oral Anticoagulants for Stroke Prevention in Patients With Device-Detected Atrial Fibrillation: A Study-Level Meta-Analysis of the NOAH-AFNET 6 and ARTESiA Trials
Authors: McIntyre William F. , Benz Alexander P. , Becher Nina , Healey Jeffrey S. , Granger Christopher B. , Rivard Lena , Camm A. John , Goette Andreas , Zapf Antonia , Alings Marco , Connolly Stuart J. , Kirchhof Paulus , Lopes Renato D.
Published: November 2023

BACKGROUND:

Device-detected atrial fibrillation (also known as subclinical atrial fibrillation or atrial high-rate episodes) is a common finding in patients with an implanted cardiac rhythm device and is associated with an increased risk of ischemic stroke. Whether oral anticoagulation is effective and safe in this patient population is unclear.

METHODS:

We performed a systematic review of MEDLINE and Embase for randomized trials comparing oral anticoagulation with antiplatelet or no antithrombotic therapy in adults with device-detected atrial fibrillation recorded by a pacemaker, implantable cardioverter defibrillator, cardiac resynchronization therapy device, or implanted cardiac monitor. We used random-effects models for meta-analysis and rated the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation framework (GRADE). The review was preregistered (PROSPERO CRD42023463212).

RESULTS:

From 785 citations, we identified 2 randomized trials with relevant clinical outcome data: NOAH-AFNET 6 (Non–Vitamin K Antagonist Oral Anticoagulants in Patients With Atrial High Rate Episodes; 2536 participants) evaluated edoxaban, and ARTESiA (Apixaban for the Reduction of Thrombo-Embolism in Patients With Device-Detected Sub-Clinical Atrial Fibrillation; 4012 participants) evaluated apixaban. Meta-analysis demonstrated that oral anticoagulation with these agents reduced ischemic stroke (relative risk [RR], 0.68 [95% CI, 0.50–0.92]; high-quality evidence). The results from the 2 trials were consistent (I
2
statistic for heterogeneity=0%). Oral anticoagulation also reduced a composite of cardiovascular death, all-cause stroke, peripheral arterial embolism, myocardial infarction, or pulmonary embolism (RR, 0.85 [95% CI, 0.73–0.99]; I
2
=0%; moderate-quality evidence). There was no reduction in cardiovascular death (RR, 0.95 [95% CI, 0.76–1.17]; I
2
=0%; moderate-quality evidence) or all-cause mortality (RR, 1.08 [95% CI, 0.96–1.21]; I
2
=0%; moderate-quality evidence). Oral anticoagulation increased major bleeding (RR, 1.62 [95% CI, 1.05–2.50]; I²=61%; high-quality evidence).

CONCLUSIONS:

The results of the NOAH-AFNET 6 and ARTESiA trials are consistent with each other. Meta-analysis of these 2 large randomized trials provides high-quality evidence that oral anticoagulation with edoxaban or apixaban reduces the risk of stroke in patients with device-detected atrial fibrillation and increases the risk of major bleeding.
Universal Generation for Optimality Theory Is PSPACE-Complete
Authors: Hao Sophie
Published: November 2023

This article shows that the universal generation problem for Optimality Theory (OT) is PSPACE-complete. While prior work has shown that universal generation is at least NP-hard and at most EXPSPACE-hard, our results place universal generation in between those two classes, assuming that NP ≠ PSPACE. We additionally show that when the number of constraints is bounded in advance, universal generation is at least NL-hard and at most NPNP-hard. Our proofs rely on a close connection between OT and the intersection non-emptiness problem for finite automata, which is PSPACE-complete in general and NL-complete when the number of automata is bounded. Our analysis shows that constraint interaction is the main contributor to the complexity of OT: The ability to factor transformations into simple, interacting constraints allows OT to furnish compact descriptions of intricate phonological phenomena.
It‘s all in the name: Another new Cyrtodactylus Gray (Squamata: Gekkonidae) from northern Mizoram, North-east India
Authors: LALREMSANGA HMAR TLAWMTE , COLNEY ZOSIAMLIANA , VABEIRYUREILAI MATHIPI , MALSAWMDAWNGLIANA FANAI , BOHRA SANATH CHANDRA , BIAKZUALA LAL , MUANSANGA LAL , DAS MADHURIMA , PURKAYASTHA JAYADITYA
Published: November 2023

A new species of Cyrtodactylus is described from Vairengte town, situated in the Kolasib District of Mizoram State, north-eastern India. The new species is found to be a member of Indo-Burman Cyrtodactylus khasiensis clade based on ND2 gene sequences and morphological parameters, such as number of precloacal pores, mid-ventral scale rows, paravertebral tubercles on the trunk, dorsal tubercle rows, subdigital lamellae on pes and subcaudal scalation, making it the sixth endemic Cyrtodactylus from Mizoram and twenty second from north-east India. Moreover, phylogenetic evidence suggests the new species to be sister to the recently described C. aaronbaueri, and morphological analyses also reveal marginal separation between the two species based on the PCA of infralabials, lamellae on fingers and toes, paravertebral tubercles on the trunk, and dorsal tubercle rows.
Description of one new species of the genus Gymnogryllus (Orthoptera, Gryllidae, Gryllinae) from Cameroon with a key for African species
Authors: NYOBE PHILENE CORINNE AUDE UM , NGOUTE CHARLY OUMAROU , RICHARD NZOKO FIEMAPONG ARMAND , ROBILLARD TONY , MA LIBIN , KEKEUNOU SEVILOR
Published: November 2023

During a Gryllidae survey in the Southern Cameroonian Plateau, one new species of the genus Gymnogryllus (Orthoptera, Gryllidae, Gryllinae) was discovered and described, namely Gymnogryllus bilongi Um Nyobe & Kekeunou sp. nov. This finding extends the number of species known of this genus in Cameroon at two and proposes a key for African species.
Design and Comparative Analysis of Silicon and GaAs MOSFET for Low Power Applications
Authors: Kaur Sidhu Rajdevinder , Ubhi Jagpal Singh , Agarwal Alpana , Raj Balwinder
Published: November 2023

The demand for low power consumption in modern electronic devices has led to the development of various technologies, including usage of different materials such as Si and GaAs. In this paper, we present a design and comparative analysis of Si and GaAs MOSFETs for low power applications.
The analysis includes the electrical characteristics, performance parameters, and power consumption of both devices. The Si MOSFET and GaAs MOSFET are simulated and analyzed using TCAD tools, and the results are compared. The simulation results show that the GaAs MOSFET has a higher transconductance
(gm) compared to the Si MOSFET. However, the Si MOSFET has a lower gate leakage current (Ig) and lower power consumption at low operating frequencies. We also investigate the effect of scaling on the performance and power consumption of both MOSFETs. The results show that scaling improves
the performance of both devices, but the power consumption increases as the device dimensions are reduced. The comparative analysis of Si and GaAs MOSFETs for low power applications provides useful insights into the selection of suitable MOSFET technology for specific applications. The results
show that both Si and GaAs MOSFETs have their advantages and disadvantages, and the choice depends on the application requirements.