bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of ethnicity in high-level obstetric clinical incidents: a review of cases from a large UK NHS maternity unit
Authors: Farrant Kimberley , Faluyi David , Watson Kylie , Vause Sarah , Birds Heather , Rowbotham Shirley , Heazell Alexander EP
Published: November 2022

Introduction

Women from ethnic minority groups are at more risk of adverse outcomes in pregnancy compared with those from white British groups; suboptimal care may contribute to this increased risk. This study aimed to examine serious clinical incidents at two maternity units to explore causative factors for women from ethnic minorities and determine whether these differed from white women.

Methods

A retrospective review was conducted of all serious incidents (n=36) occurring in a large National Health Service maternity provider (~14 000 births per annum) between 2018 and 2020. Data were collected from case records for variables which could mediate the association between ethnicity and adverse outcome. The incident reviews were blinded and reviewed by two independent investigators and data regarding root causes and contributory factors were extracted.

Results

Fourteen of the 36 incidents (39%) occurred in women from minority ethnic groups, which is comparable to the maternity population. Women involved in serious clinical incidents frequently had pre-existing medical or obstetric complications. Booking after 12 weeks’ gestation occurred more frequently in women from minority ethnic groups than in the background population. There were differences in root causes of serious incidents between groups, a lack of situational awareness was the most frequent cause in white women and staff workload was most frequent in women from minority ethnic groups. Communication issues and detection of deterioration were similar between the two groups.

Discussion

Although there was no difference in the proportion of serious incidents between the groups, there were differences in medical and pregnancy-related risk factors between groups and in the root causes identified. Efforts are needed to ensure equity of early access to antenatal care and to ensure that there is adequate staffing to ensure that women’s needs are met; this is particularly cogent when there are complex medical or social needs.
X-linked variations inSHROOM4are implicated in congenital anomalies of the urinary tract and the anorectal, cardiovascular and central nervous systems
Authors: Kolvenbach Caroline M , Felger Tim , Schierbaum Luca , Thiffault Isabelle , Pastinen Tomi , Szczepańska Maria , Zaniew Marcin , Adamczyk Piotr , Bayat Allan , Yilmaz Öznur , Lindenberg Tobias T , Thiele Holger , Hildebrandt Friedhelm , Hinderhofer Katrin , Moog Ute , Hilger Alina C , Sullivan Bonnie , Bartik Lauren , Gnyś Piotr , Grote Phillip , Odermatt Benjamin , Reutter Heiko M , Dworschak Gabriel C
Published: November 2022

Background

SHROOM4is thought to play an important role in cytoskeletal modification and development of the early nervous system. Previously, single-nucleotide variants (SNVs) or copy number variations (CNVs) inSHROOM4have been associated with the neurodevelopmental disorder Stocco dos Santos syndrome, but not with congenital anomalies of the urinary tract and the visceral or the cardiovascular system.

Methods

Here, exome sequencing and CNV analyses besides expression studies in zebrafish and mouse andknockdown(KD) experiments using a splice blocking morpholino in zebrafish were performed to study the role ofSHROOM4during embryonic development.

Results

In this study, we identified putative disease-causing SNVs and CNVs inSHROOM4in six individuals from four families with congenital anomalies of the urinary tract and the anorectal, cardiovascular and central nervous systems (CNS). Embryonic mouse and zebrafish expression studies showedShroom4expression in the upper and lower urinary tract, the developing cloaca, the heart and the cerebral CNS. KD studies in zebrafish larvae revealed pronephric cysts, anomalies of the cloaca and the heart, decreased eye-to-head ratio and higher mortality compared with controls. These phenotypes could be rescued by co-injection of human wild-typeSHROOM4mRNA and morpholino.

Conclusion

The identified SNVs and CNVs in affected individuals with congenital anomalies of the urinary tract, the anorectal, the cardiovascular and the central nervous systems, and subsequent embryonic mouse and zebrafish studies suggestSHROOM4as a developmental gene for different organ systems.
Characterising heart rhythm abnormalities associated with Xp22.31 deletion
Authors: Wren Georgina , Baker Emily , Underwood Jack , Humby Trevor , Thompson Andrew , Kirov George , Escott-Price Valentina , Davies William
Published: November 2022

Background

Genetic deletions at Xp22.31 are associated with the skin condition X linked ichthyosis (XLI), and with a substantially increased risk of atrial fibrillation/flutter (AF), in males. AF is associated with elevated thrombosis, heart failure, stroke and dementia risk.

Methods

Through: (a) examining deletion carriers with a diagnosis of AF in UK Biobank, (b) undertaking an online survey regarding abnormal heart rhythms (AHRs) in men/boys with XLI and female carriers of XLI-associated deletions and (c) screening for association between common genetic variants within Xp22.31 and idiopathic AF-related conditions in UK Biobank, we have investigated how AHRs manifest in deletion carriers, and have identified associated risk factors/comorbidities and candidate gene(s). Finally, we examined attitudes towards heart screening in deletion carriers.

Results

We show that AHRs may affect up to 35% of deletion carriers (compared with <20% of age-matched non-carriers), show no consistent pattern of onset but may be precipitated by stress, and typically resolve quickly and respond well to intervention. Gastrointestinal (GI) conditions and asthma/anaemia were the most strongly associated comorbidities in male and female deletion carriers with AHR, respectively. Genetic analysis indicated significant enrichment of common AF risk variants aroundSTS(7 065 298–7 272 682 bp in GRCh37/hg19 genome build) in males, and of common GI disorder and asthma/anaemia risk variants aroundPNPLA4(7 866 804–7 895 780 bp) in males and females, respectively. Deletion carriers were overwhelmingly in favour of cardiac screening implementation.

Conclusion

Our data suggest AHRs are frequently associated with Xp22.31 deletion, and highlight subgroups of deletion carriers that may be prioritised for screening. Examining cardiac function further in deletion carriers, and in model systems lacking steroid sulfatase, may clarify AF pathophysiology.
Goals of care changes after acute ischaemic stroke: decision frequency and predictors
Authors: Hausammann Raphaela , Maslias Errikos , Amiguet Michael , Jox Ralf J , Borasio Gian Domenico , Michel Patrik
Published: November 2022

Objectives

Little is known about the factors leading to a change in goals of care (CGC) in patients with an acute ischaemic stroke (AIS). Our aim was to analyse the proportion and outcome of such patients and identify medical predictors of a CGC during acute hospitalisation.

Methods

We retrospectively reviewed all patients who had an AIS over a 13-year period from the prospectively constructed Acute Stroke Registry and Analysis of Lausanne. We compared patients with a CGC during the acute hospital phase to all other patients and identified associated clinical and radiological variables using logistic regression analysis.

Results

A CGC decision was taken in 440/4264 (10.3%) consecutive patients who had an AIS. The most powerful acute phase predictors of a CGC were transit through the intensive care unit, older age, pre-existing disability, higher stroke severity and initial decreased level of consciousness. Adding subacute phase variables, we also identified active oncological disease, fever and poor recanalisation as predictors. 76.6% of the CGC patients died in the stroke unit and 1.0% of other patients, and 30.5% of patients with a CGC received a palliative care consultation. At 12 months, 93.6% of patients with CGC had died, compared with 10.1% of non-CGC patients.

Conclusions

Over three-quarters of AIS patients with CGC died in hospital, but less than a third received a palliative care consultation. The identified clinical and radiological predictors of a CGC may allow physicians to initiate timely the decision-making process for a possible CGC.
Venous thromboembolism among Medicare acute ischaemic stroke patients with and without COVID-19
Authors: Tong Xin , Yang Quanhe , Asaithambi Ganesh , Merritt Robert K
Published: November 2022

Background

COVID-19 is associated with an increased risk of venous thromboembolism (VTE). This study examined the prevalence of VTE among acute ischaemic stroke (AIS) patients with and without a history of COVID-19.

Methods

We identified AIS hospitalisations of Medicare fee-for-service (FFS) beneficiaries aged ≥65 years from 1 April 2020 to 31 March 2022. We compared the prevalence and adjusted prevalence ratio of VTE among AIS patients with and without a history of COVID-19.

Results

Among 283 034 Medicare FFS beneficiaries with AIS hospitalisations, the prevalence of VTE was 4.51%, 2.96% and 2.61% among those with a history of hospitalised COVID-19, non-hospitalised COVID-19 and without COVID-19, respectively. As compared with patients without a history of COVID-19, the prevalence of VTE among patients with a history of hospitalised or non-hospitalised COVID-19 were 1.62 (95% CI 1.54 to 1.70) and 1.13 (95% CI 1.03 to 1.23) times greater, respectively.

Conclusions

There appeared to be a notably higher prevalence of VTE among Medicare beneficiaries with AIS accompanied by a current or prior COVID-19. Early recognition of coagulation abnormalities and appropriate interventions may help improve patients’ clinical outcomes.
A molecular dynamics simulation investigation on the effects of Ser/Cys exchange in the Ser–cisSer–Lys catalytic triad of malonamidase E2
Authors: Roy Anupom , Gauld James W.
Published: November 2022

The enzyme malonamidase E2 catalytically hydrolyzes malonamate (MLA) into malonate and ammonia. Its active site contains an uncommon Ser– cisSer–Lys catalytic triad that is critical to its functioning. Mutations of the residues in this triad can not only provide insight into its key features but also potentially identify how it may be influenced or adapted, i.e., decreased or increased. In this study, the effects of single and double Ser/Cys exchanges on the wild-type Ser155– cisSer131–Lys62 catalytic triad (i.e., Cys155– cisSer131–Lys62 (S155C), Ser155– cisCys131–Lys62 (S131C), and Cys155– cisCys131–Lys62 (S131C/S155C)) were examined. In particular, the dynamics and stability of the resulting substituted triads were examined along with their inter-triad residue hydrogen bonding interactions as well as those with other nearby residues and the MLA substrate. The present results suggest that some mutations are more impactful than others. Indeed, mutation of cisSer131 to cisCys131 disrupts the triad and causes inconsistent hydrogen bonding interactions among the triad residues (i.e., Ser155, Cys131, and Lys62). In contrast, in the double mutant Cys155– cisCys131–Lys62, the triad's residues appear to exhibit greater conformation stability with more consistent hydrogen bond interactions, though not necessarily as in the wild type.
CompOSE reference manual
Authors:   CompOSE Core Team, Typel S. , Oertel M. , Klähn T. , Chatterjee D. , Dexheimer V. , Ishizuka C. , Mancini M. , Novak J. , Pais H. , Providência C. , R. Raduta Ad. , Servillat M. , Tolos L.
Published: November 2022

CompOSE (CompStar Online Supernovae Equations of State) is an online repository of equations of state (EoS) for use in nuclear physics and astrophysics, e.g., in the description of compact stars or the simulation of core-collapse supernovae and neutron-star mergers, see . The main services, offered via the website, are: a collection of data tables in a flexible and easily extendable data format for different EoS types and related physical quantities with extensive documentation and referencing; software for download to extract and to interpolate these data and to calculate additional quantities; webtools to generate EoS tables that are customized to the needs of the users and to illustrate dependencies of various EoS quantities in graphical form. This manual is an update of previous versions that are available on the CompOSE website, at , and that was originally published in the journal “Physics of Particles and Nuclei” with . It contains a detailed description of the service, containing a general introduction as well as instructions for potential contributors and for users. Short versions of the manual for EoS users and providers will also be available as separate publications.

Graphical Abstract
The solution to the ‘1/2 vs 3/2’ puzzle
Authors: Wang Guo-Li , Li Qiang , Wang Tianhong , Feng Tai-Fu , Wu Xing-Gang , Chang Chao-Hsi
Published: November 2022

Using an almost complete relativistic method based on the Bethe–Salpeter equation, we study the mixing angle $$\theta $$
θ
, the mass splitting $$\bigtriangleup M$$

△
M

, the strong decay widths $$\Gamma (D^{({\prime })}_1)$$

Γ
(

D
1

(
′
)

)

and the weak production rates $$Br(B\rightarrow D^{({\prime })}_1\ell \nu _{\ell })$$

B
r
(
B
→

D
1

(
′
)

ℓ

ν
ℓ

)

of the $$D_1(2420)$$

D
1

(
2420
)

and $$D_1^{\prime }(2430)$$

D
1
′

(
2430
)

. We find there is the strong cancellation between the $$^1P_1$$

1

P
1

and $$^3P_1$$

3

P
1

partial waves in $$D_1^{\prime }(2430)$$

D
1
′

(
2430
)

with $$\theta \sim -\,35.3^{\circ }$$

θ
∼
-

35
.

3
∘

, which leads to the ‘1/2 vs 3/2’ puzzle. The puzzle can not be overcome by adding only relativistic corrections since in a large parameter range where $$\bigtriangleup M$$

△
M

is linear varying and not small, the $$\theta $$
θ
, $$\Gamma (D^{({\prime })}_1)$$

Γ
(

D
1

(
′
)

)

and $$Br(B\rightarrow D^{({\prime })}_1\ell \nu _{\ell })$$

B
r
(
B
→

D
1

(
′
)

ℓ

ν
ℓ

)

remain almost unchanged but conflict with data. While in a special range around the mass inverse point where $$\bigtriangleup M=0$$

△
M
=
0

and $$\theta =\pm \, 90^{\circ }$$

θ
=
±

90
∘

, they change rapidly but we find the windows where $$\bigtriangleup M$$

△
M

, $$\Gamma (D^{({\prime })}_1)$$

Γ
(

D
1

(
′
)

)

and $$Br(B\rightarrow D^{({\prime })}_1\ell \nu _{\ell })$$

B
r
(
B
→

D
1

(
′
)

ℓ

ν
ℓ

)

are all consistent with data. The small $$\bigtriangleup M$$

△
M

confirmed by experiment, is crucial to solve the ‘1/2 vs 3/2’ puzzle.
The role of density inhomogeneity and anisotropy in the final outcome of dissipative collapse
Authors: Zitha Vusi M. , Govender Wesley , Govender Megandhren
Published: November 2022

In this work, we employ the “horizon” function introduced by Ivanov (Int J Mod Phys D 25:1650049, 2016b) to study radiating stellar models with a generalized Vaidya exterior. Since the star is dissipating energy in the form of a radial heat flux, the radial pressure at the boundary is non-vanishing. We study the boundary condition which encodes the temporal behaviour of the model. Utilizing a scheme developed by Ivanov, we provide several solutions to the modified junction condition. We show that the presence of strings, allow for the collapse to a black hole or the complete burning of a star.
Time-Variant Satellite Vegetation Classification Enabled by Hybrid Metaheuristic-Based Adaptive Time-Weighted Dynamic Time Warping
Authors: Kumawat Manisha , Khaparde Arti
Published: November 2022

Land cover data is very significant for designing the earth system, managing the natural resources, and also for performing conservation planning. Time-series data are captured with their dynamic vegetation behavior using remote sensing technology, which is broadly utilized in land cover mapping. Most of the Vegetation Index (VI) such as the Enhanced Vegetation Index (EVI) and Normalized Difference Vegetation Index (NDVI) comprises commonly employed features that are obtained from the time-series spectral data. But, these VIs are not validated as the optimal techniques for generating the temporal profiles. Recent researches highly depend on optical satellite imagery for performing these above-mentioned tasks. Dynamic Time Warping (DTW) is said to be an effective optimal solution for solving the existing challenges, especially the improved version of DTW named Time-Weighted Dynamic Time Warping (TWDTW) is used for time-series analysis regarding the time-series vegetation classification. Yet, the TWDTW efficiency is not shown with other comparative machine learning approaches owing to the classification of vegetation type in the mountain areas. The major goal of this paper is to research and create a novel approach for distinguishing the kind of vegetation in a farm region near Ujani Dam in Solapur District, Maharashtra using time-series analysis. For time-series analysis employing satellite images, the suggested model offers a unique Adaptive Time-Weighted Dynamic Time Warping (ATWDTW). The farm’s satellite images are first pre-processed before being sent to ATWDTW for examination. The TWDTW idea is optimized for classification performance using a new hybrid metaheuristic technique named Adaptive Coyote Crow Search Optimization (ACCSO). From the experimental results, the performance of the suggested ACCSO-ATWDTW correspondingly provides superior performance to the traditional approaches, where the designed model using ACCSO-ATWDTW provides 7.2%, 5.2%, 9.9%, 4.55%, and 2.33% higher MCC than the MFO-ATWDTW, BSA-ATWDTW, MF-BSA-ATWDTW, CSA-ATWDTW, and COA-ATWDTW at the maximum iteration of 200. This proved the robustness and less sensitivity to training samples of the TWDTW method when applied to mountain vegetation-type classifications.
Equitable critical graphs
Authors: Jency Loura , Raj Benedict Michael
Published: November 2022

A proper vertex coloring of a graph [Formula: see text] is equitable if the sizes of any two color classes differ by at most one. The equitable chromatic number of a graph [Formula: see text], denoted by [Formula: see text], is the minimum [Formula: see text] such that [Formula: see text] is equitably [Formula: see text]-colorable. In this paper, we discuss some basic properties of equitable critical graphs as well as equitable [Formula: see text]-critical graphs. A graph [Formula: see text] is called equitable critical if [Formula: see text] for every proper subgraph [Formula: see text] of [Formula: see text]. [Formula: see text] is called equitable [Formula: see text]-critical if it is equitable [Formula: see text]-chromatic and equitable critical.

Furthermore, we discuss that equitable vertex (edge) critical, equitable critical vertex (edge) graphs.
Vertex neighborhood restricted edge achromatic sums of graphs
Authors: Joseph Anu , Dominic Charles
Published: November 2022

The vertex induced 2-edge coloring number [Formula: see text] of a graph [Formula: see text] is the highest number of colors that can occur in an edge coloring of a graph [Formula: see text] such that not more than two colors can be used to color the edges in the induced subgraph [Formula: see text] generated by the closed neighborhood [Formula: see text] of a vertex [Formula: see text] in [Formula: see text]. The vertex induced 2-edge coloring sum of a graph [Formula: see text] denoted as [Formula: see text], is the greatest sum among all the vertex induced 2-edge coloring of a graph [Formula: see text] which concedes [Formula: see text] colors. The vertex incident 2-edge coloring number of a graph [Formula: see text] is the highest number of colors required to color the edges of a graph [Formula: see text] such that not more than two colors can be ceded to the edges incident at the vertex [Formula: see text] of [Formula: see text]. The vertex incident 2-edge coloring sum of a graph [Formula: see text] denoted as [Formula: see text], is the maximum sum among all the vertex incident 2-edge coloring of graph [Formula: see text] which receives maximum [Formula: see text] colors. In this paper, we initiate a study on the vertex induced 2-edge coloring sum and vertex incident 2-edge coloring sum concepts and apply the same to some graph classes. Besides finding the exact values of these parameters, we also obtain some bounds and a few comparative results.
Automatic Computation of Meaning in Authored Images Such as Artworks: A Grand Challenge for AI
Authors: G. Stork David
Published: November 2022

We discuss preliminary successes and major outstanding challenges in extracting messages, stories, morals, and especially
meaning
in crafted or “authored” images, such as artworks. Traditional semantic image understanding seeks to summarize an image (such as through a caption), or to answer basic questions expressed in free-text natural language, but can neither infer plausible
reasons
the creator made the artwork nor compute a high-level message or meaning it conveys. Such meaning is often abstract, dependent upon genre, period, and art movement, and exploits visual conventions such as special objects and signs (“signifiers”), composition, and possibly non-realistic style. Several of these properties have no counterpart in the natural photographs that are studied in most semantic image analysis, nor in the application-specific image analysis applied to robotics, autonomous driving, medical diagnosis, or remote sensing. For such reasons, the extraction of meaning from works in a variety of styles and subjects will be both a tool for art scholars and a grand challenge to artificial intelligence research.
All the Tau We Cannot See
Authors: Hyman Bradley
Published: November 2022

Alzheimer's disease (AD) was described in 1906 as a dementing disease marked by the presence of two types of fibrillar aggregates in the brain: neurofibrillary tangles and senile plaques. The process of aggregation and formation of the aggregates has been a major focus of investigation ever since the discoveries that the tau protein is the predominant protein in tangles and amyloid β is the predominant protein in plaques. The idea that smaller, oligomeric species of amyloid may also be bioactive has now been clearly established. This review examines the possibility that soluble, nonfibrillar, bioactive forms of tau—the “tau we cannot see”—comprise a dominant driver of neurodegeneration in AD.
Carbon Microspheres Composite PbO2 Anode to Enhance Electrode Activity for Degradation of Isopropylantipyrine: Kinetics and Mechanism
Authors: Tao Qibin , Lan Hao , Wei Lanlan , Chen Lu , Weng Mili , Dai Qizhou
Published: November 2022

An innovative CMS-PbO2 electrode was fabricated by combining hydrothermally synthesized carbon microspheres (CMS) on a PbO2 electrode by electrodeposition. Using the CMS-PbO2 electrode, the main factors affecting Isopropylantipyrine (PRP) degradation were studied. Under optimum process conditions, the concentration of PRP was 50 mg l−1, the applied current density was 30 mA cm−2, the electrolyte (Na2SO4) concentration was 0.1 mol l−1, and pH was 7. The PRP degradation rate reached 100%, and chemical oxygen demand (COD) removal rate reached 43.42% after 120 min of electrochemical oxidation. Using field-emission scanning electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, cyclic voltammetry, linear sweep voltammetry, and electrochemical impedance spectroscopy, the electrochemical performance of the two electrodes was discussed. The composite of carbon microspheres successfully improved the electrochemical activity of the electrode and its conductivity. Furthermore, the ability of the two electrodes to generate hydroxyl radicals was compared and the possible degradation pathway of PRP was considered. In addition, electrode stability and safety were evaluated by accelerated lifetime experiments and detection of lead ions in solution after electrochemical oxidation. The CMS-electrode was more stable and safer than the PbO2 electrode. The CMS-PbO2 electrode provides a new strategy for the treatment of pharmaceutical wastewater.
Cubic Bi2O3-Based Electrochemical Nitric Oxide Sensor Using Double Perovskite Oxide Electrodes
Authors: Bhardwaj Aman , Bae Hohan , Mathur Lakshya , Mathur Sanjay , Song Sun-Ju
Published: November 2022

For achieving a sustainable energy future, energy consumption through renewable sources needs to be maximized and greenhouse emissions should be radically reduced. Automotive exhausts sharing the largest global NOX emissions must meet regulated standards by after-treatment systems (ATS) equipped with smart electronic feedback loops through on-board NOX monitoring. Herein, we demonstrate an efficient (Dy, W) co-doped Bi2O3-based electrochemical sensing architecture equipped with Ln2NiMnO6 double perovskite oxides (DPOs) as electrode materials for selective nitric oxides (NO) detection. The sensor configuration facilitates operation in a wide temperature range (325 °C–500 °C) with high sensitivity of 50 mV/decade, a response time below 60 sec. and detection abilities as low as 200 ppb. While investigating the impact of rare-Earth cations, a predominant Ni3+–O–Mn3+ interaction and acquisition of optimal eg
1 electron configuration of transition metal atoms in La2NiMnO6 was found responsible for improved electrocatalytic and redox chemical activity that substantiates the sensing behavior. The study carefully scrutinizes the sensing mechanism to abide by the mixed-potential model. Moreover, the durability assessed over a month of operation supported the applicability of presented sensing elements in on-board NOX monitoring systems.
Rational Design of NiSe/ReSe2Nanocomposite For Efficient Electrochemical Hydrogen Evolution Reaction
Authors: Sultana Fozia , Mushtaq Muhammad , Althahban Sultan , Ferdous Tabassum , Firdous Samreena , Zaman Abid , Azeem Muhammad , Yang Qing
Published: November 2022

The hydrogen evolution reaction (HER) in renewable energy systems has long been a fascinating process, but designing highly efficient and ultrastable electrocatalysts is challenging. Transition metal-based heterostructure nanohybrids are currently drawing more interest in the field of electrolysis because nanohybids can optimize kinetic processes while simultaneously lowering charge transfer resistance and increasing the electrochemically active electrode’s surface area at the reaction interface. Here, we propose a concept for a two-step colloidal hot injection electrocatalyst based on NiSe/ReSe2nanocomposites that is extremely effective for hydrogen evolution under acidic conditions. The as-obtained nanocomposite material worked efficiently, attaining a current density of 10 mA cm−2at a substantially lower over-potential of 120 mV vs RHE as compared to each of the individual components i.e. NiSe nanoparticles and ReSe2nanosheets. As single component catalysts, ReSe2nanosheets and NiSe nanoparticles, however, achieved current densities of 10 mA cm−2at higher overpotentials of 172 mV and 221 mV, respectively. Even more intriguingly, the NiS/ReSe2nanocomposite is believed to give a faster kinetic process for HER, as evidenced by a Tafel slope of 115 mV dec−1, which certainly is lower than that of the 179 mV dec−1and 190 mV dec−1for pure NiSe and ReSe2, respectively. NiSe nanocrystallites and ReSe2nanosheets were assumed to be working in a synergistic manner to generate the electronic structural modification that led to the noticeably increased electrocatalytic properties. In order to make highly tuned electrocatalysts in solids, we anticipate that the fabrication of hybrid structures will be a successful strategy.
Ag-Doped Cu2Se: Tunability of Structural, Optical, and Electrical Properties
Authors: Gad S. A. , Shaban H. , Saleh Hisham A. , Hameed Talaat A.
Published: November 2022

A successful synthesis of high-purity Cu2−xAgxSe nanopowders (x = 0.03, 0.06, and 0.0.9 mole) was realized through a direct fusion approach. The XRD measurements uncovered the existence of two phases in the Cu2−xAgxSe nanopowders with dominant orientation along the(101) plane.The (101) reflection displayed a monotonical shift towards 2θ angles due to small disfigurement of unit cell originating from the replacement of Cu with Ag. The optical parameters such as absorption coefficient (α), energy band gaps (Eg), extinction coefficients (k), and the refractive index (n) were thoroughly investigated. The values of the energy band gap were found to be 0.78 to 1.5 eV. The increase in the band gap may be due to the decrease in grain size, or the increase in strains. Scanning and transmission electron microscope (SEM) and TEM were used to investigate the morphology of the samples. Cu0.97Ag0.03Se exhibits distinguishable particles and a clear grain boundary, while Cu0.91Ag0.09Se exhibits particles with tetragonal and monoclinic shapes, which supported the presence of two phases-tetragonal CuAgSe and monoclinic −Cu2Se-found in the XRD data. The presence of Ag, Cu, and Se was confirmed by the energy-dispersive X-ray analysis (EDAX). The dielectric characteristics, ac conductivity, and the complex electric modulus were investigated in the frequency range from 0.1 Hz to 10 MHz at temperatures 30 °C and 150 °C.
Formation of Li10Zn4O9, Li2MoO3, and ZnSeO3 Nanophases: Roles in Electrical Conductivity and Electrochemical Stability in Lithium Ion Conductors and their Crystalline Counterparts
Authors: Sengupta Aditi , Chamuah Anil , Ram Rakesh , Ghosh Chandan Kumar , Diyali Sanghraj , Biswas Bhaskar , Ali Mir Sahidul , Bhattacharya Sanjib
Published: November 2022

Li2O doped glass-nanocomposites and their crystalline counterparts have been developed and analyzed on the light of DC conductivity and cyclic-voltammetic (CV) studies. Micro-structural study reveals the distribution of Li10Zn4O9, Li2Zn2(MoO4)3, ZnMoO4, Zn(MoO2)2, Li2Mo6O7 and Li2MoO3 nanophases in the glassy matrices. Crystalline counterparts exhibit an enhancement in crystallites’ sizes. As the crystalline counterpart is formed by controlled cooling, ZnSeO3 chain structure is expected to break by increasing dimensions of molybdate rod-like structures. In the present study, crystalline counterpart shows better electrochemical stability. Interconnected ZnSeO3 nanophases have to initiate structural stability as they play pivotal role in the formation of structure. Formation of Li10Zn4O9 and Li2MoO3 nanophases are supposed to be responsible for higher conductivity in the glassy system.
Analysis of Two-Dimensional Heat Transfer Problem Using the Boundary Integral Equation
Authors: Kebeba Nimona Ketema , Haifo Gizaw Debito
Published: November 2022

In this paper, we examine the problem of two-dimensional heat equations with certain initial and boundary conditions being considered. In a two-dimensional heat transport problem, the boundary integral equation technique was applied. The problem is expressed by an integral equation using the fundamental solution in Green’s identity. In this study, we transform the boundary value problem for the steady-state heat transfer problem into a boundary integral equation and drive the solution of the two-dimensional heat transfer problem using the boundary integral equation for the mixed boundary value problem by using Green’s identity and fundamental solution.
Recurrent Catatonia due to Episodic Obsessive-Compulsive Disorder
Authors: Das Soumitra , Prasad Sakshi , Fichadia Palak Atul , Shrestha Abhigan Babu , Amuk Williams Ozge C. , Bachu Anil
Published: November 2022

Background. Catatonia is regarded as a diverse type of motor dysregulation syndrome that includes mutism, immobility, catalepsy, negativism, stereotypies, and echo phenomena. Catatonia is known to coexist with a wide range of physical and mental health conditions, including mood disorders, schizophrenia, autoimmune disorders, and metabolic abnormalities. Albeit, the association between obsessive-compulsive disorder (OCD) and catatonia is underreported, and mechanisms are not well elucidated. Study. In this study, we present a case of a 36-year-old woman who developed episodes of catatonia during the course of her obsessive-compulsive disorder (OCD). Success rates have been recorded with both benzodiazepines and electroconvulsive therapy (ECT). Gauging the severity of her symptoms and poor drug compliance, the patient was opted for and successfully treated with ECT. She was also educated about OCD through a series of therapy sessions and exposure and response prevention (ERP) principles. She was maintained on ERP and adjunctive clonazepam upon discharge. On subsequent follow-ups, the patient seemed to be doing well and was eager to begin her job again. Conclusion. Our study shows a possible link between OCD and catatonia. Additionally, robust studies are needed in order to determine the pathophysiology of catatonia and the mechanism of ECT so that more beneficial therapeutics can be developed. A combination of ECT and antidepressants with ERP therapy for recurrent catatonia with OCD could be effective as a therapeutic modality.
Comparison of Endogenous Endophthalmitis in Patients with and Without COVID-19 Infection
Authors: Namvar Ehsan , Moallem Mehdi , Afarid Mehrdad , Bolkheir Alireza
Published: November 2022

Introduction. Endogenous endophthalmitis (EE) is an ophthalmic emergency that can have severe sight-threatening complications. Prompt diagnosis and aggressive treatment are central to the successful management of EE. In recent years, a significant increase has occurred in the number of cases of EE. Some of these individuals had a COVID-19 infection. The current study compared EE in patients with and without COVID-19 infection. Methods. All cases of EE admitted to Khalili Hospital between April 2020 and September 2021 were included in this prospective case-control study. Patients were divided into 2 groups: (i) the case group (EE patients with confirmed COVID-19 infection; n = 7) and (ii) the control group (EE patients without a history or evidence of COVID-19 infection; n = 7). Age, sex, presenting and final visual acuity, systemic diseases and risk factors for EE, anterior segment and fundus findings, hospitalization due to COVID-19, intensive care unit (ICU) admission, systemic steroid therapy, results of the sepsis workup, causative microorganism, types of treatment (pars plana vitrectomy vs. intravitreal or antifungal antibiotics), and follow-up period were recorded. Results. Twenty-four eyes of the 14 patients were included in this study, of which 9 were female. The mean age was 49.57 years. Follow-ups ranged from 1 month to 20 months (mean, 8 months). There were no statistically significant differences in age (P = 0.653), mean follow-up (P = 0.943), gender (P = 0.313), and clinical presentation (P = 0.409) between the case and control groups. Seven patients (50%) had positive intraocular culture results. Two out of 7 patients had a history of COVID-19 infection. The most common causative microorganism was Candida (4 patients [28.57%]; 6 eyes [25%]). No statistically significant differences were observed between the 2 groups in the need for vitrectomy (P = 1.000). The visual outcome between the 2 groups was similar (P = 0.179). Conclusion. The COVID-19 infection does not seem to affect the severity, visual outcomes, improvement rate, or vitrectomy rate of EE. Early diagnosis and management, especially pars plana vitrectomy, can prevent serious complications and save many eyes.
Abstract A004: Repetitive elements and viral mimicry co-evolve in pancreatic cancer
Authors: Sun Siyu
Published: November 2022

Overexpression of repetitive DNA is an emerging hallmark of human cancers and several repeats, such as SINE elements and satellite, transcribe immunostimulatory RNA that mimic features associated with viral infection. However, the extent to which specific repeat families affect tumor evolution and the immune microenvironment in a pro-or anti-tumorigenic manner remains poorly understood. We present an integrated, evolutionary multi-omic analysis pf repeat evolution in multiregion-sampled human metastatic and primary pancreatic cancers for the first time. We found that LINE-1 (L1) somatic insertion location coincides with tumor evolution. Moreover, we found L1 activity is negatively correlated with immunogenic SINE element expression. Two orthogonal metrics were used in quantifying immunogenicity of SINE elements: IFN signature and capability of forming dsRNA, where both methods revealed that evolutionary young SINE elements have stronger correlation with IFN signatures and are more likely to form dsRNAs. Moreover, the anti-correlation between L1 activity and SINE expression is validated through both immunohistological analysis of human samples and pancreatic cancer cell lines. In the end, we proposed that the model of hypoactive L1 is beneficial for tumors by suppression of immunogenic SINE elements through either their direct reverse transcription or accelerating their degradation. Our analysis therefore sheds light on the evolutionary role of dark matter repeats in a tumor’s adaptation to immunogenic vulnerabilities.

Citation Format: Siyu Sun. Repetitive elements and viral mimicry co-evolve in pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr A004.
Abstract A015: Rationale for the use of pulsed rather than continual dosing of the novel Focal Adhesion Kinase inhibitor AMP945 in pancreatic cancer
Authors: Lambert John , Devine Mark , Bishop Anthony
Published: November 2022

Amplia Therapeutics Limited is developing AMP945, a highly selective inhibitor of Focal adhesion kinase (FAK) for the treatment of pancreatic cancer in combination with standard of care gemcitabine and nab-paclitaxel.1 FAK has been associated with the activity of myofibroblasts and collagen deposition and remodeling in PDAC. In preclinical studies, AMP945 displays potent anti-fibrotic activity in vitro and in vivo. In mouse models of PDAC, pulsed dosing of AMP945 added to gemcitabine and nab-paclitaxel inhibited collagen deposition and cross-linking and potentiated the effect of chemotherapy leading to increased survival.2A Phase 1 trial of AMP945 has been completed in which AMP945 showed excellent safety, tolerability, and pharmacokinetic properties as well as pharmacodynamic evidence of target engagement. Amplia’s recently initiated Phase 1b/2a clinical trial AMP945-PC-2013 (ACCENT) will assess a pulse dosing regimen of AMP945 in combination with gemcitabine and nab-paclitaxel as first-line therapy in patients with advanced pancreatic cancer. In ACCENT, patients will undergo a one-week oral loading dose of AMP945 and will be pulse dosed for four days prior to IV administration of gemcitabine and nab-paclitaxel, given according to a standard treatment schedule. Once daily oral dosing has anticipated benefits in terms of limitation of risk of acquired resistance, minimal potential for drug-drug interactions, adherence to therapy, and allows patients to self-administer AMP945 with the aim of potentiating response to standard of care chemotherapy. This abstract presentation will report on AMP945’s development status and the clinical rationale and status of the ACCENT trial. 1. Von Hoff et al., N Engl J Med 2013; 369:1691-1703 2. Murphy KJ et al. Sci Adv. 2021 Oct;7(40):eabh0363. 3. https://clinicaltrials.gov/ct2/show/NCT05355298

Citation Format: John Lambert, Mark Devine, Anthony Bishop. Rationale for the use of pulsed rather than continual dosing of the novel Focal Adhesion Kinase inhibitor AMP945 in pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr A015.
Abstract A075: NCOA4-mediated ferritinophagy is a pancreatic cancer dependency via maintenance of iron bioavailability for iron-sulfur cluster proteins
Authors: Santana-Codina Naiara , Zhang Huan , del Rey Maria Quiles , Kapner Kevin S. , Gikandi Ajami , Malcolm Callum , Poupault Clara , Kuljanin Miljan , John Kristen , Biancur Douglas E. , Chen Brandon , Das Nupur , Lowder Kristen , Hennessey Connor J. , Huang Wesley , Yang Annan , Shah Yatrik M. , Nowak Jonathan A. , Aguirre Andrew J. , Mancias Joseph D.
Published: November 2022

Pancreatic ductal adenocarcinomas (PDAC) depend on autophagy for survival; however, the metabolic substrates that autophagy provides to drive PDAC progression are unclear. Ferritin, the cellular iron storage complex, is targeted for lysosomal degradation (ferritinophagy) by the selective autophagy adaptor Nuclear receptor coactivator 4 (NCOA4), resulting in release of iron for cellular utilization. Using patient-derived and genetically engineered murine models of PDAC we now demonstrate that ferritinophagy is upregulated in PDAC to sustain iron availability thereby promoting tumor progression. Mass spectrometry-based quantitative proteomics reveals that ferritinophagy fuels iron-sulfur cluster protein synthesis to support mitochondrial homeostasis. Targeting NCOA4 leads to tumor growth delay and prolonged survival but with development of compensatory iron acquisition pathways. Finally, enhanced ferritinophagy accelerates PDAC tumorigenesis, and an elevated ferritinophagy expression signature predicts for poor prognosis in PDAC patients. Together, our data reveal that maintenance of iron homeostasis is a critical function of PDAC autophagy, and we define NCOA4-mediated ferritinophagy as a therapeutic target in PDAC.

Citation Format: Naiara Santana-Codina, Huan Zhang, Maria Quiles del Rey, Kevin S. Kapner, Ajami Gikandi, Callum Malcolm, Clara Poupault, Miljan Kuljanin, Kristen John, Douglas E. Biancur, Brandon Chen, Nupur Das, Kristen Lowder, Connor J. Hennessey, Wesley Huang, Annan Yang, Yatrik M. Shah, Jonathan A. Nowak, Andrew J. Aguirre, Joseph D. Mancias. NCOA4-mediated ferritinophagy is a pancreatic cancer dependency via maintenance of iron bioavailability for iron-sulfur cluster proteins [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr A075.
Abstract A077: PancreaCult™ Organoid Medium Kits support the robust establishment and expansion of human pancreatic duct organoids
Authors: Quiskamp Nina , Tsai Angela , Pan Joanna , Hasan Misha , Chang George , Tai Isabella T. , Eaves Allen C. , Louis Sharon A. , Conder Ryan K.
Published: November 2022

Organoid culture is a novel in vitro culture method that promotes the growth of primary and PSC-derived cells in three-dimensional culture to generate structures that recapitulate tissue morphology. We have developed PancreaCult™ Organoid Medium Kits (Human), which combine PancreaCult™ Organoid Initiation Medium (OIM) and serum-free PancreaCult™ Organoid Growth Medium (OGM) into a robust and standardized workflow for the establishment and expansion of pancreatic duct organoids. To establish organoids, fresh or cryopreserved islet-depleted exocrine tissue was seeded in Corning® Matrigel® domes and cultured in PancreaCult™ OIM. After 3 days, the medium was changed to PancreaCult™ OGM and the organoids were passaged and maintained in this medium thereafter, and passaged as fragments every 4 - 7 days. Organoids were successfully established from all 5 donors with a 2- to 6-fold expansion in cell numbers every 7 - 14 days. Real-time PCR and immunocytochemistry demonstrated that these organoids express pancreatic duct markers (PDX1, SOX9, KRT19, CFTR, CA2, and MUC1), as well as proliferation and stem cell markers, Ki-67 and LGR5, respectively. Pancreatic duct organoids could be maintained for at least 10 passages (n = 3) and cryopreserved as fragments that could be used for rapid re-establishment of cultures at later time points. Organoids could also be dissociated and re-seeded in Prostaglandin E2-free PancreaCult™ OGM supplemented with ROCK inhibitor, Y-27632 and 10% FBS on Transwell® inserts to create 2D monolayers. In addition to normal pancreatic duct cultures, PancreaCult™ OGM supported the efficient long-term expansion of 4 pre-established pancreatic ductal adenocarcinoma (PDAC) organoid lines and maintained the mutational profile of the parent line after 5 passages, as determined through whole exome sequencing of 29 cancer-associated genes. Through the optional removal of epidermal growth factor (EGF), PancreaCult™ OGM can be modified to suppress normal cell growth to select for tumor cells with activating KRAS mutations. Our results demonstrate that PancreaCult™ Organoid Medium Kits provide a robust and flexible in vitro culture system for the establishment and expansion of normal pancreatic duct cells, as well as the long-term expansion of PDAC organoids.

Citation Format: Nina Quiskamp, Angela Tsai, Joanna Pan, Misha Hasan, George Chang, Isabella T. Tai, Allen C. Eaves, Sharon A. Louis, Ryan K. Conder. PancreaCult™ Organoid Medium Kits support the robust establishment and expansion of human pancreatic duct organoids [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr A077.
Abstract B009: Multi-omics analysis of glutathione S-transferase P1 (GSTP1) knockdown model suggests role in pancreatic ductal adenocarcinoma (PDAC) cell metabolism
Authors: Duttenhefner Jenna , Reindl Katie M.
Published: November 2022

GSTP1 belongs to a large family of detoxification enzymes essential for cellular homeostasis in healthy cells. GSTP1 is overexpressed in many cancers and is associated with poor survival in PDAC patients. Studies in glioblastoma and breast cancer have suggested crucial roles of GST family members in metabolism through increased lactate dehydrogenase A and increased GAPDH activity, respectively. The mechanisms underlying the action of GSTP1 in PDAC metabolism and cell proliferation are not well studied. To begin characterizing the diverse functions of GSTP1 in cancer cells, we knocked down GSTP1 expression in three different PDAC cell lines. We revealed unique changes in the global transcriptomic, proteomic, and metabolomic signatures associated with GSTP1 knockdown compared to control cells through multi-omics techniques, real-time ATP production assays, and comprehensive hydrophilic metabolite and phospholipid panels. Through preliminary transcriptomic and proteomic analyses, we found 461 genes and 57 proteins differentially expressed in our GSTP1 knockdown MIA PaCa-2 cells. Among these, 41 were similarly upregulated or downregulated at the mRNA and protein levels. Pathway analysis of these changes revealed profound effects on energy production and lipid metabolism in GSTP1 knockdown cells. Hydrophilic metabolite and phospholipid panels and real-time ATP production assays supported our findings. Our results indicate that GSTP1 knockdown may directly influence mitochondrial dysfunction and lipid peroxidation pathways through associated reductions in ALDH7A1, GLUT3, and SLC7A11 levels. Continued research to further elucidate precise mechanisms and understand GSTP1’s role in driving cancer cell metabolism will aid in establishing GSTP1 targeting as a therapeutic opportunity for PDAC treatment.

Citation Format: Jenna Duttenhefner, Katie M. Reindl. Multi-omics analysis of glutathione S-transferase P1 (GSTP1) knockdown model suggests role in pancreatic ductal adenocarcinoma (PDAC) cell metabolism [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr B009.