bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of novel hierarchical designs for skin graft simulants with high expansion potential
Authors: Gupta Vivek , Singh Gurpreet , Chanda Arnab
Published: March 2023

Skin graft designs play an essential role in healing severe burn injuries. Split-thickness skin grafting (STSG) is one of the commonly used techniques for treating large burn injuries. In STSG, parallel cuts are projected onto a small portion of excised healthy skin for expansion and covering a larger burn area. To date, expansions reported for STSG are very low and insufficient to cover large burn areas. In this work, novel traditional and auxetic hierarchical cuts were designed on skin graft simulants, which were mechanically tested to study their expansion potential. Additive manufacturing and a two-part polymeric material were employed to fabricate the skin graft simulants. The nonlinear mechanical behavior of the hierarchical skin graft simulants was characterized using hyperelastic models. The effective Poisson’s ratio, meshing ratios, and induced stresses in first and second-order hierarchical cut patterns were estimated across all skin graft simulants for up to 300% strain. Also, Statistical analysis was performed to calculate the significance among the groups. From the analysis, the skin graft simulants with second-order auxetic incision patterns were found to exhibit the lowest induced stresses and maximum expansion of approximately four times, at 300% strain. To date, traditional skin grafts have only been able to achieve up to three times expansion. Therefore, the expansions realized with the novel hierarchical skin graft simulants is unprecedented, with the potential to generate ground-breaking advances in burn injury treatment.
Key factors and performance criteria of wearable strain sensors based on polymer nanocomposites
Authors: Zhagiparova Aliya , Kalimuldina Gulnur , Diaby Abdullatif Lacina , Abbassi Fethi , Ali Md Hazrat , Araby Sherif
Published: March 2023

Recently, there has been growing demand for wearable electronic devices/strain sensors in soft robotics, body-health monitoring, human–machine interfaces, and human motion detection. Wearable strain sensors feature fast and multistimuli sensitivity, high flexibility, ultrastretchability, and biocompatibility. Although progress in flexible strain sensors is exponential, the production of wearable sensors faces several challenges, such as reliability and reproducibility. An in-depth understanding of the sensing mechanisms of flexible strain sensors based on’ polymeric nanocomposites is needed to fabricate reliable and reproducible sensors and move from the prototype phase into the industry phase. In this review, types of strain sensors and key parameters such as linearity, gauge factor (sensitivity), hysteresis, and durability are explained in the context of recently published work. In addition, current challenges and perspectives in relation to wearable strain sensors are delineated.
Principal strategies for designing graphdiyne-based catalyst toward green hydrogen production from water electrolysis
Authors: Yu Huidi , Jin Xu , Li Yiheng , Zhang Lin , Yang Meng , Li Jianming
Published: March 2023

Water electrolysis has attracted significant attention for large-scale production of green hydrogen as next-generation clean fuels. Recently, the development of graphdiyne (GDY), a new member of carbon allotropes, has been promisingly offering novel alternatives for acquisition of inexpensive and efficient catalysts in the water electrolyzer. The unique atomic arrangement in GDY architecture leads to coexistence of sp– and sp2–C, correspondingly brings numerous intriguing features such as heterogeneous electron distribution, wide tailorable natural bandgap, rapid electron/mass transport and rich chemical bonds. These unique intrinsic natures of GDY provide brilliant inspirations for scientists to design new-concept electrocatalyst toward cathodic hydrogen evolution reaction, anodic oxygen evolution reaction and the overall water-splitting. Based on the immense progress, in this short perspective, current principal design strategies of GDY-based catalysts are systematically summarized, including interface engineering, individual atom fixation, induced constrained growth and bottom-up fabrication. With abundant implementation examples for achieving highly efficient water electrolysis, in particular we focus on clarifying the decisive role of GDY on these design strategies with comprehensive theoretical and experimental evidences. The future direction in developing GDY-based electrocatalysts in hydrogen energy field is also depicted with the urgent anticipation of deeper understanding of structure-performance relationship and catalytic mechanism, especially those in real industry water electrolyzers.
Nanowire-based synaptic devices for neuromorphic computing
Authors: Chen Xue , Chen Bingkun , Zhao Pengfei , Roy Vellaisamy A L , Han Su-Ting , Zhou Ye
Published: March 2023

The traditional von Neumann structure computers cannot meet the demands of high-speed big data processing; therefore, neuromorphic computing has received a lot of interest in recent years. Brain-inspired neuromorphic computing has the advantages of low power consumption, high speed and high accuracy. In human brains, the data transmission and processing are realized through synapses. Artificial synaptic devices can be adopted to mimic the biological synaptic functionalities. Nanowire (NW) is an important building block for nanoelectronics and optoelectronics, and many efforts have been made to promote the application of NW-based synaptic devices for neuromorphic computing. Here, we will introduce the current progress of NW-based synaptic memristors and synaptic transistors. The applications of NW-based synaptic devices for neuromorphic computing will be discussed. The challenges faced by NW-based synaptic devices will be proposed. We hope this perspective will be beneficial for the application of NW-based synaptic devices in neuromorphic systems.
Existence of quasiconformal mappings in a given Hardy space
Authors: Bouchala Ondřej , Koskela Pekka
Published: March 2023

Let

Ω
\Omega

be a simply connected domain in

C

\mathbb {C}

and let

0
>
p
>
∞

0>p>\infty

. We show that there is a quasiconformal mapping

f
f

from the unit disk

D

\mathbb {D}

onto

Ω
\Omega

which is in the Hardy space

H
p

H^p

.

We furthermore show that either all quasiconformal mappings from

D

\mathbb {D}

onto

Ω
\Omega

are in 

H
p

H^p

for every

p
p

, or for every

0
>
p
>
∞

0>p>\infty

there is a quasiconformal mapping

f
:

D

→
Ω

f\colon \mathbb {D}\to \Omega

with

f
∉

H
p

f\notin H^p

.
Isometries of combinatorial Tsirelson spaces
Authors: Maślany Natalia
Published: March 2023

We extend existing results that characterize isometries on the Tsirelson-type spaces

T

[

1
n

,

S

1

]

T\big [\frac {1}{n}, \mathcal {S}_1\big ]

(

n
∈

N

,
n
⩾
2

n\in \mathbb {N}, n\geqslant 2

) to the class

T
[
θ
,

S

α

]

T[\theta , \mathcal {S}_{\alpha }]

(

θ
∈

(

0
,

1
2

]

\big (\theta \in \big (0, \frac {1}{2}\big ]

,

1
⩽
α
>

ω
1

1\leqslant \alpha > \omega _1

\big), where

S

α

\mathcal {S}_{\alpha }

denote the Schreier families of order

α
\alpha

. We prove that every isometry on

T
[
θ
,

S

1

]

T[\theta , \mathcal {S}_1]

\big(

θ
∈

(

0
,

1
2

]

\theta \in \big (0, \frac {1}{2}\big ]

\big) is determined by a permutation of the first

⌈

θ

−
1

⌉

\lceil {\theta }^{-1} \rceil

elements of the canonical unit basis followed by a possible sign-change of the corresponding coordinates together with a sign-change of the remaining coordinates. Moreover, we show that for the spaces

T
[
θ
,

S

α

]

T[\theta , \mathcal {S}_{\alpha }]

\big(

θ
∈

(

0
,

1
2

]

\theta \in \big (0, \frac {1}{2}\big ]

,

2
⩽
α
>

ω
1

2\leqslant \alpha > \omega _1

\big) the isometries exhibit a more rigid character, namely, they are all implemented by a sign-change operation of the vector coordinates.
A note on the integrality of volumes of representations
Authors: Kim Sungwoon
Published: March 2023

Let

Γ
\Gamma

be a torsion-free, non-uniform lattice in

S
O

(
2
n
,
1
)

\mathrm {SO}(2n,1)

. We present an elementary, combinatorial–geometrical proof of a theorem of Bucher, Burger, and Iozzi [Math. Ann. 381 (2021), pp. 209–242] which states that the volume of a representation

ρ
:
Γ
→

S
O

(
2
n
,
1
)

\rho :\Gamma \to \mathrm {SO}(2n,1)

, properly normalized, is an integer if

n
n

is greater than or equal to

2
2

.
One dimensional 𝖱𝖢𝖣 spaces always satisfy the regular Weyl’s law
Authors: Iwahashi Akemi , Kitabeppu Yu , Yonekura Akari
Published: March 2023

Ambrosio, Honda, and Tewodrose proved that the regular Weyl’s law is equivalent to a mild condition related to the infinitesimal behavior of the measure of balls in compact finite dimensional

R
C
D

\mathsf {RCD}

spaces. Though that condition is seemed to always hold for any such spaces, however, Dai, Honda, Pan, and Wei recently showed that for any integer

n
n

at least 2, there exists a compact

R
C
D

\mathsf {RCD}

space of

n
n

dimension fails to satisfy the regular Weyl’s law. In this short article we prove that one dimensional

R
C
D

\mathsf {RCD}

spaces always satisfy the regular Weyl’s law.
Automorphisms of algebraic varieties and infinite transitivity
Authors: Arzhantsev I.
Published: March 2023

This is a survey of recent results on multiple transitivity for automorphism groups of affine algebraic varieties. The property of infinite transitivity of the special automorphism group is treated, which is equivalent to the flexibility of the corresponding affine variety. These properties have important algebraic and geometric consequences. At the same time they are fulfilled for wide classes of varieties. Also, the situations are studied where infinite transitivity occurs for automorphism groups generated by finitely many one-parameter subgroups. In the appendices to the paper, the results on infinitely transitive actions in complex analysis and in combinatorial group theory are discussed.
Approximating diamond principles on products at an inaccessible cardinal
Authors: Ben-Neria Omer , Zhang Jing
Published: March 2023

We isolatethe approximating diamond principles, which are consequences of the diamond principle at an inaccessible cardinal. We use these principles to find new methods for negating the diamond principle at large cardinals. Most notably, we demonstrate, using Gitik’s overlapping extenders forcing, a new method to get the consistency of the failure of the diamond principle at a large cardinalθ\thetawithout changing cofinalities or adding fast clubs toθ\theta. In addition, we show that the approximating diamond principles necessarily hold at a weakly compact cardinal. This result, combined with the fact that in all known models where the diamond principle fails the approximating diamond principles also fail at an inaccessible cardinal, exhibits essential combinatorial obstacles to make the diamond principle fail at a weakly compact cardinal.
Higher-Order Evidence in Aesthetics
Authors: Whiting Daniel
Published: March 2023

In this introduction, I explain the notion of higher-order evidence and explore its bearing on aesthetic judgement. I start by illustrating how reflection on cases involving higher-order evidence engages with well-established concerns in aesthetics—specifically, how it might reveal tensions within and between widely recognized aesthetic ideals governing aesthetic judgement. Next, I show how attention to higher-order evidence in relation to aesthetic judgement might expose limitations or assumptions of theories in epistemology, where the nature and significance of higher-order evidence with respect to belief is the focus of much recent attention. The aim is not to resolve the issues but to demonstrate the significance of higher-order evidence in aesthetics and, in doing so, encourage work on the topic in and across aesthetics and epistemology.
Correcting Coal Miner Respirator Total Inward Leakage Values for Respiratory Tract Deposition
Authors: Nicas Mark
Published: March 2023

The great majority of workplace respirator efficacy studies have measured total inward leakage (TIL) for particulate contaminants. One of the first such studies, designated the Harris study, was conducted in the early 1970s in US underground coal mines. As in other particle-based studies, inside-the-facepiece dust sampling was continuously conducted across the inhalation and exhalation phases of the breathing cycle, although unlike in other studies, respirable dust cyclones were used in air sampling. Because exhaled air was partially depleted of dust particles due to deposition in the respiratory tract, the measured time-averaged dust concentration inside the facepiece underestimated the time-averaged dust concentration inspired into the facepiece. In turn, the reported TIL values underestimated the true TIL values experienced, which is to say, overestimated respirator efficacy. This paper describes a method to correct the Harris study’s reported TIL values for respiratory tract deposition while accounting for particle size-selective sampling by the cyclone devices. Given the estimated coal mine particle size distribution outside the respirator, it is shown that the reported TIL values should be increased by the multiplicative factor 1.69. This paper also discusses the assigned protection factor (APF) of five for the quartermask respirator class and shows that 4/5 quartermasks in the Harris study did not meet the criterion for complying with this APF value when using the corrected TIL values.
Prioritizing prognostic-associated subpopulations and individualized recurrence risk signatures from single-cell transcriptomes of colorectal cancer
Authors: Tong Mengsha , Lin Yuxiang , Yang Wenxian , Song Jinsheng , Zhang Zheyang , Xie Jiajing , Tian Jingyi , Luo Shijie , Liang Chenyu , Huang Jialiang , Yu Rongshan
Published: March 2023

Colorectal cancer (CRC) is one of the most common gastrointestinal malignancies. There are few recurrence risk signatures for CRC patients. Single-cell RNA-sequencing (scRNA-seq) provides a high-resolution platform for prognostic signature detection. However, scRNA-seq is not practical in large cohorts due to its high cost and most single-cell experiments lack clinical phenotype information. Few studies have been reported to use external bulk transcriptome with survival time to guide the detection of key cell subtypes in scRNA-seq data. We proposed scRankXMBD, a computational framework to prioritize prognostic-associated cell subpopulations based on within-cell relative expression orderings of gene pairs from single-cell transcriptomes. scRankXMBD achieves higher precision and concordance compared with five existing methods. Moreover, we developed single-cell gene pair signatures to predict recurrence risk for patients individually. Our work facilitates the application of the rank-based method in scRNA-seq data for prognostic biomarker discovery and precision oncology. scRankXMBD is available at https://github.com/xmuyulab/scRank-XMBD. (XMBD:Xiamen Big Data, a biomedical open software initiative in the National Institute for Data Science in Health and Medicine, Xiamen University, China.)
Safety of guselkumab in patients with psoriasis with a history of malignancy: 5-year results from the VOYAGE 1 and VOYAGE 2 trials
Authors: Blauvelt Andrew , Thaçi Diamant , Papp Kim A , Ho Vincent , Ghoreschi Kamran , Kim Byung Soo , Miller Megan , Shen Yaung-Kaung , You Yin , Chan Daphne , Yu Jenny , Yang Ya-Wen , Lebwohl Mark G , Gottlieb Alice B , Crowley Jeffrey , Foley Peter
Published: March 2023

The VOYAGE 1 and 2 studies of guselkumab in moderate-to-severe psoriasis are among the first studies of biologics to include patients with a history of malignancy. In these studies, 18 guselkumab-treated patients had a history of malignancy (excluding nonmelanoma skin cancer) > 5 years prior to enrolment. These 18 patients were exposed to guselkumab for up to 5 years; during this time, one patient had a recurrence of bronchial carcinoma, and three patients developed new malignancies (breast cancer, melanoma and sebaceous carcinoma). All patients with new or recurrent malignancies had underlying risk factors for malignancy. Overall, the results of this analysis in a small population of patients with a history of malignancy support the favourable long-term safety profile of guselkumab.
A preclinical randomized controlled multi-centre trial of anti-interleukin-17A treatment for acute ischaemic stroke
Authors: Gelderblom Mathias , Koch Simon , Strecker Jan-Kolja , Jørgensen Carina , Garcia-Bonilla Lidia , Ludewig Peter , Schädlich Ines Sophie , Piepke Marius , Degenhardt Karoline , Bernreuther Christian , Pinnschmidt Hans , Arumugam Thiruma V , Thomalla Götz , Faber Cornelius , Sedlacik Jan , Gerloff Christian , Minnerup Jens , Clausen Bettina H , Anrather Josef , Magnus Tim
Published: March 2023

Multiple consensus statements have called for preclinical randomized controlled trials to improve translation in stroke research. We investigated the efficacy of an interleukin-17A neutralizing antibody in a multi-centre preclinical randomized controlled trial using a murine ischaemia reperfusion stroke model. Twelve-week-old male C57BL/6 mice were subjected to 45 min of transient middle cerebral artery occlusion in four centres. Mice were randomly assigned (1:1) to receive either an anti-interleukin-17A (500 µg) or isotype antibody (500 µg) intravenously 1 h after reperfusion. The primary endpoint was infarct volume measured by magnetic resonance imaging three days after transient middle cerebral artery occlusion. Secondary analysis included mortality, neurological score, neutrophil infiltration and the impact of the gut microbiome on treatment effects. Out of 136 mice, 109 mice were included in the analysis of the primary endpoint. Mixed model analysis revealed that interleukin-17A neutralization significantly reduced infarct sizes (anti-interleukin-17A: 61.77 ± 31.04 mm3; IgG control: 75.66 ± 34.79 mm3; P = 0.01). Secondary outcome measures showed a decrease in mortality (hazard ratio = 3.43, 95% confidence interval = 1.157–10.18; P = 0.04) and neutrophil invasion into ischaemic cortices (anti-interleukin-17A: 7222 ± 6108 cells; IgG control: 28 153 ± 23 206 cells; P < 0.01). There was no difference in Bederson score. The analysis of the gut microbiome showed significant heterogeneity between centres (R = 0.78, P < 0.001, n = 40). Taken together, neutralization of interleukin-17A in a therapeutic time window resulted in a significant reduction of infarct sizes and mortality compared with isotype control. It suggests interleukin-17A neutralization as a potential therapeutic target in stroke.
Tc-99m labelled bone scintigraphy in suspected cardiac amyloidosis
Authors: Rauf Muhammad Umaid , Hawkins Philip N , Cappelli Francesco , Perfetto Federico , Zampieri Mattia , Argiro Alessia , Petrie Aviva , Law Steven , Porcari Aldostefano , Razvi Yousuf , Bomsztyk Joshua , Ravichandran Sriram , Ioannou Adam , Patel Rishi , Starr Neasa , Hutt David F , Mahmood Shameem , Wisniowski Brendan , Martinez–Naharro Ana , Venneri Lucia , Whelan Carol , Roczenio Dorota , Gilbertson Janet , Lachmann Helen J , Wechalekar Ashutosh D , Rapezzi Claudio , Serenelli Matteo , Massa Paolo , Caponetti Angelo Giuseppe , Ponziani Alberto , Accietto Antonella , Giovannetti Alessandro , Saturi Giulia , Sguazzotti Maurizio , Gagliardi Christian , Biagini Elena , Longhi Simone , Fontana Marianna , Gillmore Julian D
Published: March 2023

Aims

To perform evaluation of widely embraced bone scintigraphy-based non-biopsy diagnostic criteria (NBDC) for ATTR amyloid cardiomyopathy (ATTR-CM) in clinical practice, and to refine serum free light chain (sFLC) ratio cut-offs that reliably exclude monoclonal gammopathy (MG) in chronic kidney disease.

Methods and results

A multi-national retrospective study of 3354 patients with suspected or histologically proven cardiac amyloidosis (CA) referred to specialist centres from 2015 to 2021; evaluations included radionuclide bone scintigraphy, serum and urine immunofixation, sFLC assay, eGFR measurement and echocardiography. Seventy-nine percent (1636/2080) of patients with Perugini grade 2 or 3 radionuclide scans fulfilled NBDC for ATTR-CM through absence of a serum or urine monoclonal protein on immunofixation together with a sFLC ratio falling within revised cut-offs incorporating eGFR; 403 of these patients had amyloid on biopsy, all of which were ATTR type, and their survival was comparable to non-biopsied ATTR-CM patients (p = 0.10). Grade 0 radionuclide scans were present in 1091 patients, of whom 284 (26%) had CA, confirmed as AL type (AL-CA) in 276 (97%) and as ATTR-CM in only one case with an extremely rare TTR variant. Among 183 patients with grade 1 radionuclide scans, 122 had MG of whom 106 (87%) had AL-CA; 60/61 (98%) without MG had ATTR-CM.

Conclusion

The NBDC for ATTR-CM are highly specific [97% (95% CI 0.91-0.99)] in clinical setting, and diagnostic performance was further refined here using new cut-offs for sFLC ratio in patients with CKD. A grade 0 radionuclide scan all but excludes ATTR-CM but occurs in most patients with AL-CA. Grade 1 scans in patients with CA and no MG are strongly suggestive of early ATTR-type, but require urgent histologic corroboration.
Association of long-term time in target range for systolic blood pressure with cardiovascular risk in the elderly: a Chinese veteran cohort study
Authors: Lin Zhongqiu , Xiao Zhiwen , Chen Wei , Xu Wenlong , Huang Chixiong , Xie Jingfang , Jin Ming , Wei Xiaomin , He Sisi , Xie Zhiquan , Liao Wangjun , Liao Yulin , Feng Weijing , Chen Yanmei , Bin Jianping
Published: March 2023

Aims

Short-term blood pressure (BP) time in target range (TTR) independently predicts cardiovascular (CV) outcomes in adults. However, there are limited data regarding long-term TTR for BP among elderly participants. We aimed to determine whether future CV risk varies for those who can maintain a long-term systolic BP (SBP) target range by assessing TTR in elderly individuals with hypertension.

Methods and results

The Chinese veteran cohort study included 943 elderly participants with hypertension aged over 75 years. The primary outcome was the first occurrence of CV events during annual visits. Time in target range was estimated over 15 years of follow-up using linear interpolation. The target range was defined as 120–140 mmHg according to guidelines. The association between SBP TTR and CV outcomes was estimated using multivariable Cox proportional hazards models. During the 15 year follow-up, the probability of CV events gradually decreased with increasing TTR for SBP. After multivariable adjustment for traditional CV risk factors and mean BP, comparing the highest vs. lowest quartiles of TTR for SBP, the hazard ratios (HRs) [95% confidence intervals (CIs)] were 0.424 (0.289–0.624) for the primary outcome. For each 1 SD increase in TTR, the risk of the primary outcome decreased by 25.4% (HR: 0.746; 95% CI: 0.666–0.834). Consistent findings were observed in sensitivity analyses.

Conclusion

Greater long-term TTR for SBP was associated with a decreased risk of CV events in elderly individuals independent of mean BP, suggesting that SBP TTR might serve as a modifiable risk factor for future CV health in elderly patients with hypertension.

Lay Summary

This ongoing Chinese veteran cohort study adds to the understanding of the relationship between higher long-term systolic blood pressure (SBP) time in target range (TTR) and cardiovascular benefits among elderly individuals with hypertension.
Refining the Treatment of Pancreatic Cancer From Big Data to Improved Individual Survival
Authors: Bailey Peter , Zhou Xu , An Jingyu , Peccerella Teresa , Hu Kai , Springfeld Christoph , Büchler Markus , Neoptolemos John P
Published: March 2023

Pancreatic cancer is one of the most lethal cancers worldwide, most notably in Europe and North America. Great strides have been made in combining the most effective conventional therapies to improve survival at least in the short and medium term. The start of treatment can only be made once a diagnosis is made, which at this point, the tumor volume is already very high in the primary cancer and systemically. If caught at the earliest opportunity (in circa 20% patients) surgical resection of the primary followed by combination chemotherapy can achieve 5-year overall survival rates of 30%–50%. A delay in detection of even a few months after symptom onset will result in the tumor having only borderline resectabilty (in 20%–30% of patients), in which case the best survival is achieved by using short-course chemotherapy before tumor resection as well as adjuvant chemotherapy. Once metastases become visible (in 40%–60% of patients), cure is not possible, palliative cytotoxics only being able to prolong life by few months. Even in apparently successful therapy in resected and borderline resectable patients, the recurrence rate is very high. Considerable efforts to understand the nature of pancreatic cancer through large-scale genomics, transcriptomics, and digital profiling, combined with functional preclinical models, using genetically engineered mouse models and patient derived organoids, have identified the critical role of the tumor microenvironment in determining the nature of chemo- and immuno-resistance. This functional understanding has powered fresh and exciting approaches for the treatment of this cancer.
Similarity characteristics of qualitative and quantitative regulation for adjustable ejector
Authors: Yang Yong , Ren Xiaotong , Li Yiqiao , Wang Ning , Zhang Kun , Shen Shengqiang
Published: March 2023

In the new era of ejector technology entering into system scale from device scale. The methodology of regulation mode of an adjustable ejector has been summarized in this paper. The similarity in characteristics of qualitative and quantitative regulation under different operating modes are researched. The results show that both qualitative and quantitative regulation have the characteristics of ‘constant capacity’. Three different ‘constant-capacity’ phenomena in ejectors have been found, and the similarity indicates that the turbulent flow in ejectors has some statistical invariances in the form of mass flow rate of jetting flow. The ejector has the similar entrainment ability by increasing primary pressure by 43% in the qualitative regulation mode or enlarging the nozzle throat opening by 47% in the quantitative regulation mode under critical mode with similar underexpanded state. The advantages of adjustable ejectors have been promoted, in particular ±5% regulation accuracy or constant regulation ability, discharging improved ability by 80% in flow rate or 10% in pressure lifting ability in subcritical mode or primary flow rate saving ability by 25% or 13% in pressure lifting ability in critical mode.
Aztreonam/avibactam activity against a large collection of carbapenem-resistant Enterobacterales (CRE) collected in hospitals from Europe, Asia and Latin America (2019–21)
Authors: Sader Helio S , Castanheira Mariana , Kimbrough John H , Kantro Valerie , Mendes Rodrigo E
Published: March 2023

Background

Aztreonam/avibactam is under development to treat infections caused by Gram-negative bacteria. We evaluated the in vitro activities of aztreonam/avibactam and comparators against a global collection of carbapenem-resistant Enterobacterales (CRE), including ceftazidime/avibactam-resistant isolates.

Methods

Isolates were consecutively collected (24 924; 1/patient) from 69 medical centres in 36 countries during 2019–21. Isolates were susceptibility tested by CLSI broth microdilution. All CRE isolates (n = 1098; 4.4%) were in silico screened for carbapenemase (CPE) genes after genome sequencing. CRE susceptibility results were stratified by CPE, geography and resistance phenotype.

Results

Aztreonam/avibactam inhibited 99.6% of CREs at ≤8 mg/L (MIC50/90, 0.25/0.5 mg/L), including 98.9% (345/349) of ceftazidime/avibactam-resistant isolates. Aztreonam/avibactam activity was consistent across geographical regions (98.9%–100.0% inhibited at ≤8 mg/L), but susceptibility to comparators varied markedly. Susceptibility (CLSI criteria) for ceftazidime/avibactam and meropenem/vaborbactam ranged from 80.2% and 77.5% in Western Europe to 39.5% and 40.3% in the Asia-Pacific region, respectively. Aztreonam/avibactam retained activity against isolates non-susceptible to colistin (99.7% inhibited at ≤8 mg/L) or tigecycline (98.6% inhibited at ≤8 mg/L). A CPE gene was identified in 972 CRE isolates (88.5%). The most common CPEs were KPC (43.1% of CREs), NDM (26.6%) and OXA-48–like (18.7%); 57 isolates (5.2%) had >1 CPE gene. Aztreonam/avibactam inhibited 99.9% of CPE producers at ≤8 mg/L, whereas ceftazidime/avibactam and meropenem/vaborbactam exhibited limited activity against isolates producing MBL and/or OXA-48-like enzymes.

Conclusions

Aztreonam/avibactam activity was not adversely affected by clinically relevant CPEs. Our results support aztreonam/avibactam development to treat infections caused by CRE, including MBL producers.
Comparative Analysis and Structure Identification of Oxidative Metabolites and Hydrogenation Metabolite Enantiomers for 2-Fluorodeschloroketamine
Authors: Luo Xuan , Zhang Di , Zhang Fang , Luo Qiulian , Huang Kejian , Liu Xiaofeng , Yang Ning , Li Junbo , Qiao Wentao , Yang Lan
Published: March 2023

In this study, we used solid-phase extraction with liquid chromatography–ion trap time-of-flight mass spectrometry (LC–IT-TOF-MS) to analyze 2-fluorodeschloroketamine (2-FDCK) metabolites in human urine. The complete set of oxidative metabolites was identified, with 17 compounds divided into four groups. Furthermore, we examined the hydroxy substitution site after oxidative metabolism with theoretical calculation and 2-FDCK nuclear magnetic resonance (NMR) data. We clarified the correlation of the oxidative metabolic sites with the electron cloud density in the structure. Additionally, two enantiomers of dihydro-2-fluorodeschloroketamine (dihydro-2-FDCK) were determined by using a laboratory-made dihydro-2-FDCK hydrochloride reference substance. Their configurations were determined via NMR spectrometry data prediction of the ACD Labs-Structure Elucidator Suite software and theoretical calculation. Moreover, the stereoselectivity of the related enzymes in hydrogenation metabolism in vivo was clarified. These findings provide an important reference for analyzing other oxidative metabolites, laying the foundation for future analysis, prediction, elucidation and identification of the latest ketamine-type new psychoactive substance metabolites.
Automated topology design to improve the susceptibility of naval ships using geometric deep learning
Authors: Hwang Joon-Tae , Hong Suk-Yoon , Song Jee-Hun
Published: March 2023

The survivability of a naval ship is defined as its ability to evade or withstand a hostile environment while performing a given mission. Stealth technology, which reduces the probability of detection by enemy detection equipment using a highly advanced detection system, is one of the most important technologies to improve the survivability of naval ships. Moreover, radar cross-section (RCS) reduction is a very important factor in stealth technology because a small RCS, which is the main parameter determining susceptibility, improves the ability of ships to evade enemy detection equipment. In this study, an automated topology design for reducing susceptibility was developed by combining geometric deep learning and topology optimization. A convolutional neural network model was used as the geometric deep-learning model, and the triangular meshes of the naval ship models and equipment models were used as datasets. To compensate for the lack of training data, randomly generated meshes were additionally used as datasets. To express the feature data of the mesh as a matrix, points at equal intervals were projected orthogonally and the distance between the plane and point was set as a matrix value. The label data were defined as the highest RCS values excluding the cardinal points. After realizing the topology design for reducing susceptibility using the developed system, verification was performed through RCS analysis of the original model and the topology-designed model.
Effects of the surface irregularity of termite tunnels on food transport efficiency: a simulation study
Authors: Lee Sang-Hee , Park Cheol-Min , Lee Sang-Bin
Published: March 2023

Termites are believed to have evolved in a way that optimizes their foraging efficiency, which involves both searching for food and transporting it efficiently. Although the search efficiency has been well-studied through tunnel pattern analysis, transport efficiency has received limited attention due to the challenges of directly observing behavior that is highly influenced by environmental conditions. In this study, we introduce an individual-based model to simulate transport behavior and examine transport efficiency (E) by considering the tunnel surface irregularities and curvature, which are critical environmental factors. The model is characterized by four control variables: tunnel curvature (k1), termite stopping time at irregularity sites (k2), irregularity distribution (k3), and irregularity density (k4). The simulation results indicate that as k1 increases, E decreases, while k3 has little impact on E. The impact of k4 on E is decisive; when k4 ≤ 6, an increase in k4 results in increased traffic jam frequency and a faster reduction in E. However, when k4 > 6, the jamming frequency is not significantly affected, reducing the decrease in E. k2 strongly contributes to reducing E without significantly affecting the frequency. In the discussion section, we explore potential mechanisms that termites use to maintain transport efficiency in heterogeneous soils, and discuss how to improve the model to better reflect real-termite systems.
Comparison of ectoparasite communities of sylvatic and urban wild mesomammals and unowned community cats in north-central Florida
Authors: Mays Maestas S E , Campbell L P , Wisely S M , Dingman P A , Reeves L E , Kaufman P E
Published: March 2023

The adaptation of wildlife species to urban environments can drive changes in the ecology of ectoparasites and vector-borne disease. To better understand ectoparasite dynamics in an urban environment, we investigated the ectoparasite communities of 183 sylvatic and urban opossums and raccoons captured across four seasons at a rural research station and within the city of Gainesville, FL, and of 115 community cats from the Gainesville, FL area. Amblyomma americanum (L.) (Acari: Ixodidae), Dermacentor variabilis (Say), and Ixodes texanus Banks were collected from raccoons, A. americanum, D. variabilis, and Ixodes scapularis Say from opossums, and A. americanum from cats. Few ticks were collected from urban animals, although species richness of ectoparasites was similar between urban and sylvatic habitats. Ctenocephalides felis (Bouché) (Siphonaptera: Pulicidae) was collected from all sampled host species, but was particularly abundant on opossums. Additionally, Orchopeas howardi (Baker) (Siphonaptera: Ceratophyllidae) was collected from raccoons, and O. howardi and Polygenis gwyni (Fox) (Siphonaptera: Rhopalopsyllidae) from opossums. Only raccoons were infested with raccoon lice, and only cats were infested with cat lice. Primarily opossums were infested with mites. Ectoparasite community composition varied by habitat, host species, and season; seasonal variation in ectoparasite communities differed between the sylvatic and urban habitats. While urban mesomammals did not appear to play an important role in supporting tick populations in an urban habitat, urban opossums appear to serve as an alternate host for large numbers of cat fleas, which may be an important consideration for treatment and control efforts against ectoparasites of companion animals.
Breast exam use during the protracted COVID-19 pandemic, by age, race, and geography
Authors: Butler Eboneé N , Benefield Thad , Henderson Louise , Kuzmiak Cherie , Pritchard Michael , Nyante Sarah
Published: March 2023

In this study we analyzed data collected from the onset of the COVID-19 pandemic through March 31, 2022, to identify temporal shifts in breast exam volume. Screening mammography volume stabilized toward the end of the study period, and diagnostic exam volume varied over time and by age. Older women experienced a decline in diagnostic exam volume between August 2020 and April 2021 that was not observed among women aged younger than 50 years (50-69 years: monthly percentage change [MPC] = −6.5%; and 70 years and older: MPC = −15.7%). With respect to breast biopsy volume, women aged younger than 70 years had increased exam volume beginning in April 2020 and June 2020, whereas a corresponding increase among older women was delayed until April 2021 (70 years and older: MPC = 9.3%). Findings from our study suggest a temporal shift in the use of breast exams that could result in differential detection of breast cancer by age.
Otherwise than teaching by artificial intelligence
Authors: Lee Sang-Eun
Published: March 2023

Advances in digital technology are changing the methods of teaching and learning. In the course of this stream of changes, the emergence of artificial intelligence (AI) has become a topic of great interest and concern. The development of teaching AIs (artificial intelligences that teach), which can provide adaptive and personalized dialogue with students, has shifted the relationship between teachers and students, and has raised new questions regarding the role of teachers. The purpose of this paper is to rethink the meaning of the act of teaching, without denying its variety, and to reflect on the role of teachers in the relatively unfamiliar situation created by the emergence of AI teaching machines. To this end, I attempt, first, to re-examine the nature of teaching by considering two possible orientations: teaching as a return to homogeneity and teaching as exposure to heterogeneity. My purpose is to consider the characteristics and limitations of the teaching implemented by AI and to discuss the role of human teachers in overcoming these limitations. Second, I seek to reveal what it is for the teacher to speak, which is often understood as the most important aspect of teaching, again by way of two characterizations: the closed conversation, which converges on a conclusion, and the open conversation, oriented towards ethical responsibility. In doing this, I shall examine critically some characteristics of language used by AI teaching machines and suggest alternatives that might constitute openness to an ethical conversation. In furtherance of this, I shall consider the account of teaching that is central to the philosophy of Emmanuel Levinas.
Peripheral vascular bypass with cadaveric arterial allograft in a toddler with femoral mycotic aneurysm
Authors: Huerta Carlos Theodore , Quinn Kirby , Restrepo Ricardo , Mas Madeleen , Patel Bhavi , Melnick Steven J , Sola Juan E , Velazquez Omaida C , Thorson Chad M
Published: March 2023

Mycotic aneurysms are exceedingly rare in the pediatric population. The optimal surgical treatment for children with this disease is unclear as aneurysm resection and vascular reconstruction are uncommonly performed in young children. We present a unique case of a 21-month-old child with a complex cardiac history who presented with limb ischemia and was discovered to have thrombosis of the common femoral and superficial femoral artery. Groin exploration revealed a left common femoral and superficial femoral artery mycotic aneurysm that was successfully repaired with excision of the mycotic aneurysm, external iliac to profunda femoral artery vascular bypass using cryopreserved arterial allograft and femoral vein reconstruction. This case demonstrates successful vascular reconstruction can be performed in a young child with an Aspergillus mycotic aneurysm using cadaveric arterial allograft.
An Assessment of Quaternary Structure Functionality in Homomer Protein Complexes
Authors: Abrusán György , Foguet Carles
Published: March 2023

It has been recently suggested that a significant fraction of homomer protein–protein interfaces evolve neutrally, without contributing to function, due to a hydrophobic bias in missense mutations. However, the fraction of such gratuitous complexes is currently unknown. Here, we quantified the fraction of homodimers where multimerization is unlikely to contribute to their biochemical function. We show that: 1) ligand binding-site structure predicts whether a homomer is functional or not; the vast majority of homodimers with multichain binding-sites (MBS) are likely to be functional, while in homodimers with single-chain binding-sites (SBS) and small to medium interfaces, quaternary structure is unlikely to be functional in a significant fraction—35%, even up to 42%—of complexes; 2) the hydrophobicity of interfaces changes little with the strength of selection, and the amino acid composition of interfaces is shaped by the “hydrophobic ratchet” in both types, but they are not in a strict equilibrium with mutations; particularly cysteines are much more abundant in mutations than in interfaces or surfaces; 3) in MBS homomers, the interfaces are conserved, while in a high fraction of SBS homomers, the interface is not more conserved than the solvent-accessible surface; and 4) MBS homomer interfaces coevolve more strongly with ligand binding sites than the interfaces of SBS homomers, and MBS complexes have higher capacity to transfer information from ligands across the interfaces than SBS homomers, explaining the enrichment of allostery in the former.
HIV-1 DNA Testing in Viremic Patients Identifies More Drug Resistance Than HIV-1 RNA Testing
Authors: Curanovic Dusica , Martens Sharon K , Rodriguez Milka A , Hammill Hunter A , Petropoulos Christos J , Walworth Charles M
Published: March 2023

Background

The Department of Health and Human Services HIV-1 Treatment Guidelines recommend drug resistance testing in HIV-1 RNA to guide the selection of antiretroviral therapy in patients with viremia. However, resistance-associated mutations (RAMs) in HIV-1 RNA may reflect only the patient’s current regimen and can be lost during prolonged absence of therapy. We determined if HIV-1 DNA testing can provide drug resistance information beyond that identified in contemporaneous plasma virus.

Methods

This was a retrospective database review of results obtained for patients with viremia for whom commercial HIV-1 RNA and HIV-1 DNA drug resistance testing was ordered on the same day. Resistance-associated mutations and drug susceptibility calls were compared between paired tests, and the effect of HIV-1 viral load (VL) on test concordance was assessed using Spearmen’s rho correlation.

Results

Among 124 paired tests, more RAMs were identified in HIV-1 DNA in 63 (50.8%) cases, and in HIV-1 RNA in 11 (8.87%) cases. HIV-1 DNA testing captured all contemporaneous plasma virus RAMs in 101/117 (86.3%) cases and identified additional RAMs in 63/117 (53.8%) cases. There was a significant positive correlation between the viral load at the time of resistance testing and the percentage of plasma virus RAMs detected in HIV-1 DNA (rs = 0.317; P < .001). In 67 test pairs demonstrating pan-sensitive plasma virus, resistance in HIV-1 DNA was seen in 13 (19.4%) cases.

Conclusions

HIV-1 DNA testing identified more resistance than HIV-1 RNA testing in most patients with viremia and may be informative in patients whose plasma virus reverts to wild-type following therapy discontinuation.
AI and the Bomb
Authors: Johnson James
Published: March 2023

Will AI make accidental nuclear war more likely? If so, how might these risks be reduced? AI and the Bomb provides a coherent, innovative, and multidisciplinary examination of the potential effects of AI technology on nuclear strategy and escalation risk. The book addresses a gap in the international relations and strategic studies literature that considers how AI might influence nuclear security and future warfare. Its findings have significant theoretical and policy ramifications for using AI technology in the nuclear enterprise. AI and the Bomb advances an innovative theoretical framework to consider AI technology and atomic risk, drawing on insights from political psychology, neuroscience, computer science, and strategic studies. This multidisciplinary study unpacks the seminal cognitive-psychological features of the Cold War-era scholarship, offering a novel explanation for why these matter for AI applications and nuclear strategic thinking; thus ensuring the research’s policy relevance and contribution to the literature that considers the impact of military force and technological change.
The Metaphysics of Light in the Hexaemeral Literature
Authors: Katsos Isidoros C.
Published: March 2023

This work rethinks critically what (we think) we know about the nature of light in the ancient sources. It contests the prevalent view in the history of optics that premodernity theorized light as subordinate to sight (‘oculocentrism’) by examining in depth the contrary textual evidence found in early Christian sources. It shows that, from Philo of Alexandria and Origen to Basil of Caesarea and Gregory of Nyssa, the Jewish-Christian commentary tradition on the biblical creation narrative (‘hexaemeral literature’) reflected deeply on the nature and physicality of light for the purposes of understanding the structure and purpose of material creation. Contemplation of nature allowed early Christian thinkers to conceptualize light as the explanatory principle of vision rather than as subordinated to it. Contrary to the prevalent view, the hexaemeral literature necessitates a ‘luminocentric’ interpretation of the theory of light of the Timaeus in its reception history in the context of late antique cosmology. The hexaemeral luminocentrism invites the reader of Scripture to grasp not only the sensible properties of light but also their causal principle as the first manifestation of the divine logos in creation. The hexaemeral metaphysics of light thus provides the missing ground of meaning of the early Christian language of light.
‘From Sight to Light’
Authors: Katsos Isidoros C.
Published: March 2023

This chapter discusses and confronts the widespread view in the history of optics that the physics of light was born in the seventeenth century with the scientific revolution. It lays out the ‘oculocentric’ epistemic foundations of this view and examines its verifiability through three possible hexaemeral hypotheses: the spiritual vision of noetic beings; the cosmic vision of the universe; and the anthropocentric theory of vision of the Timaeus. The close reading of the sources shows that the hexaemeral optical paradigm is not oculocentric but luminocentric. This textual evidence overturns the oculocentric narrative and necessitates a new enquiry into the nature of light. It is shown that at the heart of hexaemeral luminocentrism lies the anagogical journey of the reader of Scripture from the physics to the metaphysics of light.