bluuebunny/crossref_metadata_2025 huggingface dataset:
Cosmic microwave background constraints on extended dark matter objects
Authors: Croon Djuna , Muñoz Sergio Sevillano
Published: July 2024

Primordially formed extended dark objects would accrete baryonic matter and impact the ionisation history of the Universe. Insisting on consistency with the anisotropies of the cosmic microwave background, we derive constraints on the dark matter fraction for various classes of objects, of different sizes. We introduce a novel scaling technique to speed up numerical calculations and release our calculation framework in the form of a Mathematica notebook. Conservatively, we focus on spherical accretion and collisional ionisation. We find strong constraints limiting the dark matter fraction to subpercent level for objects of up to 104 AU in size.
Precession and split of tilted, geometrically thin accretion disk: an analytical study
Authors: Shen Ye , Chen Bin
Published: July 2024

It has been observed that many relativistic jets display a kind of cork-screw-like
precession. Numerical simulations has suggested that such kind of precession may originate from
the precession of the disk. In this work, we introduce an analytical model to describe the
precession and split of a tilted, geometrically thin disk. We consider the Lense-Thirring effect
from the central (primary) black hole (BH) and the gravitational effect from the companion
(secondary) BH far away from the center, both of which could induce the precession of the
accretion disk around the spin axis of central black hole. We propose the splitting conditions
that when the rate of viscous diffusion cannot catch up with the dynamical frequency at a certain
layer of fluid, the disk would split into two parts which precess independently. We presume that
the precessions of the inner and outer disks are in accord with the rotation and precession of
jet, respectively. By matching the frequencies of the disks to the observed frequencies of jet in
the cork-screw-like precession and considering the splitting condition, we are allowed to read
four parameters, the innermost radius (r
in), the outermost radius (r
out) of the
disk, the initial splitting radius (r
sp,0), and the inflow speed magnitude (β), of
the disk. We apply this model to OJ 287. Moreover, considering the inward shrinking of the disks,
we find the time variation of the precession angle of jet. This time variation presents a unique
feature of our model, which could be distinguishable in the future observation.
Assessment of the impact of fuelling puff location on divertor impurity compression and enrichment in STEP
Authors: Osawa R.T. , Newton S.L. , Moulton D. , Henderson S.S. , Badicel V. , Hudoba A.
Published: July 2024

In order to achieve a compatible solution between the divertors and the core, SOLPS-ITER simulations were performed in a Spherical Tokamak for Energy Production (STEP) connected double-null geometry to investigate the possibility of using deuterium (

D

2

) puff locations as an actuator for divertor argon (Ar) compression/enrichment. It was found that puffing

D

2

from the inner-midplane (IMP)

D

2

puff enhanced Ar compression and enrichment on the high-field-side (HFS) and lowered the required upstream Ar fraction to achieve acceptable target conditions. An interesting link was found between argon compression and the number of stagnation points of the middle-charge-state Ar ions in the HFS SOL,

N

st

; significantly improved compression and enrichment were obtained for

N

st

=
1

(corresponding mostly to the cases with IMP puff) compared to

N

st

=
3

(corresponding mostly to the cases without IMP puff). An intermediate compression and enrichment was obtained when

N

st

=
5

. The change of

N

st

from 3 to 1 (or 5) was achieved by a combination of

D

+

outflow, high collision frequency, and flipped temperature gradients around the IMP. Given a possible drawback of

Γ

D

OMP

+

IMP

, that is a direct effect on the upstream main plasma density and temperature, we propose

Γ

D

PFR

+

IMP

as the best solution, balancing the negative and positive effects of private-flux-region and IMP

D

2

puffs. Further studies will be carried out both experimentally and numerically.
Formation and culture of cell spheroids by using magnetic nanostructures resembling a crown of thorns
Authors: Li Shijiao , Qiu Jingjiang , Guo Zhongwei , Gao Qiulei , Huang Chen-Yu , Hao Yilin , Hu Yifan , Liang Tianshui , Zhai Ming , Zhang Yudong , Nie Bangbang , Chang Wei-Jen , Wang Wen , Xi Rui , Wei Ronghan
Published: July 2024

In contrast to traditional two-dimensional cell-culture conditions, three-dimensional (3D) cell-culture models closely mimic complex in vivo conditions. However, constructing 3D cell culture models still faces challenges. In this paper, by using micro/nano fabrication method, including lithography, deposition, etching, and lift-off, we designed magnetic nanostructures resembling a crown of thorns. This magnetic crown of thorns (MCT) nanostructure enables the isolation of cells that have endocytosed magnetic particles. To assess the utility of this nanostructure, we used high-flux acquisition of Jurkat cells, an acute-leukemia cell line exhibiting the native phenotype, as an example. The novel structure enabled Jurkat cells to form spheroids within just 30 min by leveraging mild magnetic forces to bring together endocytosed magnetic particles. The size, volume, and arrangement of these spheroids were precisely regulated by the dimensions of the MCT nanostructure and the array configuration. The resulting magnetic cell clusters were uniform in size and reached saturation after 1400 s. Notably, these cell clusters could be easily separated from the MCT nanostructure through enzymatic digestion while maintaining their integrity. These clusters displayed a strong proliferation rate and survival capabilities, lasting for an impressive 96 h. Compared with existing 3D cell-culture models, the approach presented in this study offers the advantage of rapid formation of uniform spheroids that can mimic in vivo microenvironments. These findings underscore the high potential of the MCT in cell-culture models and magnetic tissue enginerring.
Robust and customizable spheroid culture system for regenerative medicine
Authors: Park Kyoung Hwan , Truong Thuy Trang , Park Jae-Hyun , Park Yujin , Kim Hyeok , Hyun Sung-Ae , Shim Hye-Eun , Mallick Sudipta , Park Hun-Jun , Huh Kang Moo , Kang Sun-Woong
Published: July 2024

Three-dimensional cell spheroids show promise for the reconstruction of native tissues. Herein, we report a sophisticated, uniform, and highly reproducible spheroid culture system for tissue reconstruction. A mesh-integrated culture system was designed to precisely control the uniformity and reproducibility of spheroid formation. Furthermore, we synthesized hexanoyl glycol chitosan, a material with ultralow cell adhesion properties, to further improve spheroid formation efficiency and biological function. Our results demonstrate improved biological function in various types of cells and ability to generate spheroids with complex structures composed of multiple cell types. In conclusion, our spheroid culture system offers a highly effective and widely applicable approach to generating customized spheroids with desired structural and biological features for a variety of biomedical applications.
Single-atom nickel on defective g-C4N3 as a promising bifunctional electrocatalyst for the OER and ORR: a first-principles analysis
Authors: Gao Teng fei , Wu Xiao-Kuan , Bo wen Deng , kun Xin Zhi , Yu Fang , Wang Liang , Zhang Jie , Yun Jimmy
Published: July 2024

Searching for inexpensive and highly active materials to replace noble metals for oxygen evolution reaction (OER) and oxygen reduction reaction (ORR) is an important challenge. The two-dimensional semi-metallic carbon nitride g-C4N3 is an excellent candidate for electrochemical reactions owing to its eminent conductivity and stability. Here, using density functional theory (DFT) a series of low-budget non-noble transition metal single-atom (SAC) loaded on the g-C4N3 (named as TM@C4N3, TM = Cr, Mn, Fe, Co, Ni, Cu) were investigated as electrocatalysts for OER and ORR. Ni@C4N3 shows an enormous application potential as electrode material, with OER and ORR overpotentials of 0.59 V and 0.23 V, respectively. The second lowest binding energy between Ni and support g-C4N3 indicates that Ni@C4N3 possesses good overall stability. The d-band center as well as metal valence as the descriptor exhibit good agreement with the adsorption energy of the intermediate. A linear relationship exists among the adsorption energies of the three intermediates O, OH, and OOH, given the similarity that they are all bonded to the metal through one oxygen atom. By adjusting the adsorption energy of these intermediates, the catalytic activity of electrocatalysts can be tuned for OER and ORR. This study confirmed that Ni@C4N3 is a good bifunctional catalyst and provides important guidance for the design of bifunctional electrocatalysts for OER and ORR.
Enhanced mechanical and tribological properties of ultrasonically assisted stir-cast AA7075 metal matrix composites in challenging corrosive environments
Authors: N Murugan , K S Jayakumar , Raj R Ashok , D Antony Prabu
Published: July 2024

Aluminum-based metal matrix composites (AMMCs) find extensive applications in aerospace, defence, automotive, and various sectors on account of remarkable mechanical properties, lightweight nature, and excellent dimensional stability. In this research, AA7075 matrix material was reinforced with tungsten carbide ceramic particles with various 0, 5, 10, 15 and 20 weight percentages (wt%) with the use of Ultrasonic assisted stir casing setup. The stir casted AA7075 MMCs were subjected to XRD, SEM, and density test to investigate the presence of elements, microstructure and density. The tensile, micro hardness, and wear test were performed on AL7075 based MMCs after conducting NaCl based spray test at the condition of spray pressure of 1.2 kg cm−2, spray duration of 120 h and PH value of 8.2 to determine the wear resistance, micro hardness and Ultimate Tensile Strength. The XRD test confirmed the presence of secondary phases such as Al2Cu, W2C, and MgZn2 with Al and WC phases. The SEM test confirmed the uniform dispersion and no more cluster formation upto 15 wt% WC addition and agglomeration of WC was occurred in the addition of 20 wt% of WC. The enhancing of wt% of WC improved the corrosion resistance, Micro hardness, UTS, wear and up to 15 wt% addition and decreases by the 20 wt% WC addition. The higher tensile strength 312 MPa was obtained from AA7075/15 wt%WC composite. The lower wear rate 0.11 mg m−1 was obtained from AA7075/15 wt%WC at 1000 m sliding distance with 1.2 m s−1 sliding velocity. The improved mechanical and tribological properties were mainly depended on strengthening mechanisms such as load transfer mechanism and dislocation strengthening mechanism.
Graphene-enhanced manganese dioxide functional ink infused with polyaniline for high-performance screen-printed micro supercapacitor
Authors: Shetty Shilpa , Saquib Mohammad , Selvakumar M , Firouzi Hadi , Nayak Ramakrishna
Published: July 2024

In the world of miniature advancements in technology, a current champion has emerged: the micro supercapacitors. In order to fabricate these micro-supercapacitors, we have developed a promising and user-friendly approach for printing a conductive functional ink containing a ternary composite of manganese dioxide (MnO2) nanoparticles, Graphene, and polyaniline (PANI) as a dopant. Screen-printing technique was employed to fabricate micro-supercapacitors using the nanocomposite conductive ink. The performance of the energy storage device was examined using flexible symmetric and asymmetric, with an aqueous 1 M KOH electrolyte. According to this strategy, the characterisation and electrochemical study results revealed that doping PANI into both symmetric and asymmetric devices significantly increased the material’s capacitive performance of areal capacitance 167 mFcm−2 for MnO2/Graphene/PANI-5 composite (MGP-5) and 292.5 mFcm−2 for asymmetric supercapacitor (ASSC) at 5 mVs−1. Furthermore, the asymmetric supercapacitor displayed outstanding cyclic stability, retaining 93.6% of its capacitance after 10000 cycles. This underscores the possibility of incorporating polyaniline (PANI) into MnO2 and graphene matrices as efficient blueprints for the development of superior electrode materials. The improvement represents a significant step forward, opening avenues for the future development of novel devices and their integration into top-of-the-line flexible energy storage systems.
Dynamic reconstruction for digital tomosynthesis: a phantom proof of concept for breast care
Authors: Barbieri Matteo , Jailin Clément , Vancamberg Laurence , Roux Stéphane
Published: July 2024

Objective. Digital tomosynthesis (DTS) is a type of limited-angle Computed Tomography (CT) used in orthopedic and oncology care to provide a pseudo-3D reconstructed volume of a body part from multiple x-ray projections. Patient motion during acquisitions results in artifacts which affect screening and diagnostic performances. Hence, accurate reconstruction of moving body parts from a tomosynthesis projection series is addressed in this paper, with a particular focus on the breast. The aim of this paper is to assess the feasibility of a novel dynamic reconstruction technique for DTS and evaluate its accuracy compared to an available ground truth. Approach. The proposed method is a combination of a 4D dynamic tomography strategy leveraging the formalism of Projection-based Digital Volume Correlation (P-DVC) with a multiscale approach to estimate and correct patient motion. Iterations of two operations are performed: (i) a motion-corrected reconstruction based on the Simultaneous Iterative Reconstruction Technique (SIRT) algorithm and (ii) a motion estimation from projection residuals, to obtain motion-free volumes. Performance is evaluated on a synthetic Digital Breast Tomosynthesis (DBT) case. Three slabs of a CIRS breast phantom are imaged on a Senographe PristinaTM, under plate-wise rigid body motions with amplitudes ranging up to 10 mm so that an independent measurement of the motion can be accessed. Results. Results show a motion estimation average precision down to 0.183 mm (1.83 voxels), when compared to the independent measurement. Moreover, an 84.2% improvement on the mean residual error and a 59.9% improvement on the root mean square error (RMSE) with the original static reconstruction are obtained. Significance. Visual and quantitative assessments of the dynamically reconstructed volumes show that the proposed method fully restores conspicuity for important clinical features contained in the phantom.
Vehicle scrappage policies for transportation decarbonization
Authors: Woody Maxwell , Stolper Samuel , Vaishnav Parth , Keoleian Gregory A
Published: July 2024

Vehicle electrification is one of the primary strategies being pursued for the decarbonization of the transportation sector. But to meet emissions reduction goals for that sector, the current vehicle replacement rate is insufficient. Vehicle scrappage policies can accelerate fleet turnover by providing an incentive to retire a vehicle before its natural end of life and simultaneously replace it with a more efficient or less polluting alternative. Previous scrappage programs, like the United States’ Cash for Clunkers, have had limited success as decarbonization policies; however, most of these programs ended before the widespread availability of electric vehicles and did not have decarbonization as a primary policy goal. Here we explain why scrappage policies may be necessary to meet climate goals, review historic vehicle scrappage policies from a variety of countries, highlight the successes and failures of those policies, and establish policy design considerations that could help ensure that future scrappage programs are more successful than previous efforts.
Surfaces in which every point sounds the same
Authors: Wang Feng , Wyman Emmett , Xi Yakun
Published: July 2024

We address a maximally structured case of the question, “Can you hear your location on a manifold,” posed by Wyman and Xi [Can you hear your location on a manifold?, https://arxiv.org/abs/2304.04659, 2023] for dimension

2
2

. In short, we show that if a compact surface without a boundary sounds the same at every point, then the surface has a transitive action by the isometry group. In the process, we show that you can hear your location on Klein bottles and that you can hear the lengths and multiplicities of looping geodesics on compact hyperbolic quotients.
Risk of age-related macular degeneration in men receiving 5α-reductase inhibitors: a population-based cohort study
Authors: Su Yu-Chen , Shen Chin-Yao , Shao Shih-Chieh , Lai Chi-Chun , Hsu Sheng-Min , Lee Chaw-Ning , Liu Chan-Jung , Hung Jia-Horung , Lai Edward Chia-Cheng
Published: July 2024

Background

Recent studies suggest that 5α-reductase inhibitors (5ARIs) for benign prostate hyperplasia (BPH) result in abnormal retinal anatomical alteration.

Objective

To compare age-related macular degeneration (AMD) incidence in BPH patients receiving 5ARIs or tamsulosin.

Design

Retrospective, population-based cohort study using new-user and active-comparator design.

Setting

General population.

Subjects

Males with BPH, newly receiving 5ARIs or tamsulosin from 2010 to 2018.

Methods

Data were extracted from Taiwan’s National Health Insurance Research Database. We used Cox proportional hazards model with 1:4 propensity score (PS) matching, based on intention-to-treat analysis to determine the risk of incident AMD. Sensitivity analyses included an as-treated approach and weighting-based PS methods. We also separately reported the risks of incident AMD in patients receiving finasteride and dutasteride to determine risk differences among different 5ARIs.

Results

We included 13 586 5ARIs users (mean age: 69 years) and 54 344 tamsulosin users (mean age: 68.37 years). After a mean follow-up of 3.7 years, no differences were observed in the risk of incident AMD between 5ARIs and tamsulosin users [hazard ratio (HR): 1.06; 95% confidence intervals (95% CI): 0.98–1.15], with similar results from sensitivity analyses. However, increased risk of incident age-related macular degeneration was observed in patients receiving dutasteride [HR: 1.13; 95% CI: 1.02–1.25], but not in those receiving finasteride [HR: 0.99; 95% CI: 0.87–1.12], in the subgroup analyses.

Conclusions

We found no difference between 5ARIs and tamsulosin regarding the incidence of AMD in BPH patients. However, the risk profiles for AMD differed slightly between dutasteride and finasteride, suggesting that the potency of androgen inhibition is a factor related to AMD incidence.
New horizons in clinical practice guidelines for use with older people
Authors: Martin Finbarr C , Quinn Terence J , Straus Sharon E , Anand Sonia , van der Velde Nathalie , Harwood Rowan H
Published: July 2024

Globally, more people are living into advanced old age, with age-associated frailty, disability and multimorbidity. Achieving equity for all ages necessitates adapting healthcare systems. Clinical practice guidelines (CPGs) have an important place in adapting evidence-based medicine and clinical care to reflect these changing needs. CPGs can facilitate better and more systematic care for older people. But they can also present a challenge to patient-centred care and shared decision-making when clinical and/or socioeconomic heterogeneity or personal priorities are not reflected in recommendations or in their application. Indeed, evidence is often lacking to enable this variability to be reflected in guidance. Evidence is more likely to be lacking about some sections of the population. Many older adults are at the intersection of many factors associated with exclusion from traditional clinical evidence sources with higher incidence of multimorbidity and disability compounded by poorer healthcare access and ultimately worse outcomes. We describe these challenges and illustrate how they can adversely affect CPG scope, the evidence available and its summation, the content of CPG recommendations and their patient-centred implementation. In all of this, we take older adults as our focus, but much of what we say will be applicable to other marginalised groups. Then, using the established process of formulating a CPG as a framework, we consider how these challenges can be mitigated, with particular attention to applicability and implementation. We consider why CPG recommendations on the same clinical areas may be inconsistent and describe approaches to ensuring that CPGs remain up to date.
Invited commentary: target trial emulation—a call for more widespread use
Authors: Anderson Amanda Hyre
Published: July 2024

Causal inference methods intended for use with observational data have been widely available for decades, but barriers to their widespread adoption exist. These likely include lack of familiarity with several methodological techniques often used in combination in these investigations, such as inverse probability of treatment weighting and g-estimation, and the intensity of computational effort needed to employ these techniques. Even with these methods, critical design flaws undermine the ability to make valid causal inference in some studies. Identification of the need to explicitly pair study design elements with these causal inference methods led to development of a methodological approach recently termed target trial emulation. This approach requires that investigators define a hypothetical randomized trial, emulate that hypothetical protocol in assembling the cohort and defining study elements, and then conduct an analysis that attempts to mirror random treatment assignment. In the accompanying article by Heindel et al (Am J Epidemiol. 2024;XXX(XX):XXX-XXX), the authors successfully emulate a target trial of systemic heparin during arteriovenous fistula creation on short-term endpoints by utilizing data from 2 existing randomized trials with key confounders available. Target trial emulation provides a framework with which to promote valid inference and generate high-quality contributions to the literature, and its use should be expanded.
Participation in physical, cognitive, and social activities and the association with mobility disability transitions in older adults
Authors: Lange-Maia Brittney S , Wang Tianhao , Poole Victoria N , Lamar Melissa , Shah Raj C , Barnes Lisa L , James Bryan D
Published: July 2024

Development of late-life mobility disability is a dynamic process of transitions between worsening and improving. We tested associations between participation in physical, social, and cognitive activity with mobility disability transitions. Participants (n = 2758, age 78.1 years [SD, 7.7]) from 2 Rush Alzheimer’s Disease Center cohorts completed annual mobility disability questionnaires for 7.6 (SD, 4.4) years. First-order Markov transition models tested associations between baseline self-reported physical, social, and cognitive activity with bidirectional transitions in mobility disability score increases (worsening) and decreases (improving) between consecutive visits. Overall, 75.5% of participants experienced ≥1 transition among 18 318 pairs of consecutive visits—4174 of which were worsening and 2606 were improving transitions. Adjusting for covariates, higher participation in each activity type was associated with lower odds of worsening (physical odds ratio [OR], 0.71; 95% CI, 0.67-0.75; social OR, 0.64; 95% CI, 0.58-0.70; and cognitive OR, 0.79; 95% CI, 0.74-0.85), and higher odds of improving (physical OR, 1.20; 95% CI, 1.11-1.28; social OR, 1.45; 95% CI, 1.30-1.61; and cognitive OR, 1.12; 95% CI, 1.03-1.22) in separate models. In combined models, physical and social activity remained associated with worsening and improving; cognitive activity was only associated with worsening. Physical, social, and cognitive activity engagement contributes to lower odds of worsening mobility disability and may promote recovery.
Association between Dietary Practices and Growth Trajectories in Preschool Children
Authors: Jones-Antwi Rebecca E , Narayan K M Venkat , Cunningham Solveig A
Published: July 2024

Objectives

To estimate the association of dietary practices with early life weight among children born in 2001 in the U.S.

Methods

The Early Childhood Longitudinal Study (ECLS-B) is a population-based cohort followed from 9 months to Kindergarten entry (n~5000). We employed an auto-regressive cross-lagged model to assess the impacts of dietary practices on weight stability over time. We calculated age- and sex-standardized BMI z-scores using WHO growth curves.

Results

BMI z-scores had a stable increase over time. Later age of solid food introduction was associated with lower BMI z-score at age 2y [-0.03(-0.05,-0.004)]; having dinners more times per week with family at age 2y was associated with higher BMI z-score at 4y [0.03(0.01,0.05)]. These changes, of <0.05 BMI z-score, are small. Children with higher birthweight were introduced to solid foods at younger ages [-0.39 months(-0.45,-0.32)] and were breast fed longer [0.13 months(0.04,0.22)]. For girls, having dinner at a regular time at ages 2y and 4y was associated with lower BMI at ages 4y and 5y.

Conclusions

Dietary practices in early childhood affect weight trajectories. However, these effects are small and are largely overshadowed by prior weight. Children’s weight in infancy is associated with subsequent dietary practices but also small effects.
Invited commentary: dispersal policies, neighborhood disadvantage, and refugee health in a Nordic context
Authors: Rostila Mikael
Published: July 2024

In this issue of the Journal, Kim et al (Am J Epidemiol 2024;XXX(XX):XXX-XXX) examine whether neighborhood disadvantage is associated with cardiovascular disease risk in Denmark. A potential contribution of their article is the study of mediators (cumulative income, unstable employment, and poor mental health) underlying the association using a quasi-experimental design based on a Danish refugee dispersal policy. In this commentary, I draw attention to some potential limitations involving use of refugee dispersal policies as natural experiments. I further discuss the extent to which the mediators studied by Kim et al contribute to our overall understanding of mechanisms linking neighborhood disadvantage and cardiovascular disease risk. However, because a similar dispersal policy was introduced during the same time period in a country neighboring Denmark—Sweden—I also take the opportunity to give an account of the background of dispersal policies in the two countries and offer some general reflections on their consequences for refugee integration and well-being there.
Modeling package size–conscious automated dispensing cabinet replenishment to improve efficiency
Authors: Rodgers John Killian L , Braun Randy , Rowe Erinn , Kruszewski Kristen M , Colmenares Evan W
Published: July 2024

Purpose

Optimization of automated dispensing cabinets (ADCs) has traditionally focused on modifying the inventory within these devices and ignored the replenishment process itself. Rounding replenishment quantities to the nearest package size, termed package size–conscious replenishment (PSCR), was investigated as a way to optimize labor needs for ADC replenishment.

Methods

A simulation of PSCR for a subset of medications stocked in ADCs at the University of North Carolina Medical Center was conducted. The simulation utilized real-world vend data and rounding factors to model the impact of PSCR on key ADC metrics. The final simulation utilized 2 months of ADC transactions across 410 medications in 149 ADCs. Four replenishment methodologies were simulated: standard replenishment and 3 PSCR strategies, including rounding down, rounding any direction, and rounding up.

Results

All 3 PSCR methodologies had significantly lower stockout frequencies than standard replenishment at 0.722% (P = 0.026) for rounding down, 0.698% (P = 0.024) for rounding any direction, and 0.680% (P = 0.024) for rounding up vs 0.773% for standard replenishment. PSCR methods were associated with significant time savings for both technician and pharmacist activities (P < 0.001 for all 3 strategies), with a savings of up to 0.27 technician and 0.52 pharmacist full-time equivalents estimated for the rounding-up methodology. Maximum carrying cost was higher for all 3 PSCR methodologies.

Conclusion

PSCR was modeled to significantly decrease both pharmacist and technician time needed to replenish ADCs while also decreasing stockout frequency. Modest increases in maximum carrying cost were also shown. The simulation created for this evaluation could also be utilized to model other components of the ADC replenishment process.
Where is the Muranów Lily? Unearthing Traces of Queer Jewishness in Contemporary Warsaw
Authors: Gajowy Aleksandra
Published: July 2024

In this essay I explore the possibility of an embodied, desiring encounter with traces of queer Jewishness in contemporary Warsaw. Examining Benny Nemer’s 2015 experimental audioguide Lilia z Muranowa (The Muranów Lily), commissioned by POLIN, the Museum of the History of Polish Jews, I propose a line of enquiry following a dybbuk-like haunting that the audioguide performs. In doing so, I investigate how desiring, affective speculation, legends and rumours might enable an encounter with history, if we allow ourselves to be haunted by them. I provide a landscape which the listener or the performer of Nemer’s experimental tale may engender with their desire, their body and their fantasy, in order to restore lives lost and forgotten in the archives, through the desiring archival subject: a queer Polish Jew.
Compound-SNE: comparative alignment of t-SNEs for multiple single-cell omics data visualization
Authors: Cess Colin G , Haghverdi Laleh
Published: July 2024

One of the first steps in single-cell omics data analysis is visualization, which allows researchers to see how well-separated cell-types are from each other. When visualizing multiple datasets at once, data integration/batch correction methods are used to merge the datasets. While needed for downstream analyses, these methods modify features space (e.g. gene expression)/PCA space in order to mix cell-types between batches as well as possible. This obscures sample-specific features and breaks down local embedding structures that can be seen when a sample is embedded alone. Therefore, in order to improve in visual comparisons between large numbers of samples (e.g. multiple patients, omic modalities, different time points), we introduce Compound-SNE, which performs what we term a soft alignment of samples in embedding space. We show that Compound-SNE is able to align cell-types in embedding space across samples, while preserving local embedding structures from when samples are embedded independently.

Availability and implementation

Python code for Compound-SNE is available for download at https://github.com/HaghverdiLab/Compound-SNE.
MuCoCP: a priori chemical knowledge-based multimodal contrastive learning pre-trained neural network for the prediction of cyclic peptide membrane penetration ability
Authors: Yu Yunxiang , Gu Mengyun , Guo Hai , Deng Yabo , Chen Danna , Wang Jianwei , Wang Caixia , Liu Xia , Yan Wenjin , Huang Jinqi
Published: July 2024

Motivation

There has been a burgeoning interest in cyclic peptide therapeutics due to their various outstanding advantages and strong potential for drug formation. However, it is undoubtedly costly and inefficient to use traditional wet lab methods to clarify their biological activities. Using artificial intelligence instead is a more energy-efficient and faster approach. MuCoCP aims to build a complete pre-trained model for extracting potential features of cyclic peptides, which can be fine-tuned to accurately predict cyclic peptide bioactivity on various downstream tasks. To maximize its effectiveness, we use a novel data augmentation method based on a priori chemical knowledge and multiple unsupervised training objective functions to greatly improve the information-grabbing ability of the model.

Results

To assay the efficacy of the model, we conducted validation on the membrane-permeability of cyclic peptides which achieved an accuracy of 0.87 and R-squared of 0.503 on CycPeptMPDB using semi-supervised training and obtained an accuracy of 0.84 and R-squared of 0.384 using a model with frozen parameters on an external dataset. This result has achieved state-of-the-art, which substantiates the stability and generalization capability of MuCoCP. It means that MuCoCP can fully explore the high-dimensional information of cyclic peptides and make accurate predictions on downstream bioactivity tasks, which will serve as a guide for the future de novo design of cyclic peptide drugs and promote the development of cyclic peptide drugs.

Availability and implementation

All code used in our proposed method can be found at https://github.com/lennonyu11234/MuCoCP.
BELHD: improving biomedical entity linking with homonym disambiguation
Authors: Garda Samuele , Leser Ulf
Published: July 2024

Motivation

Biomedical entity linking (BEL) is the task of grounding entity mentions to a given knowledge base (KB). Recently, neural name-based methods, system identifying the most appropriate name in the KB for a given mention using neural network (either via dense retrieval or autoregressive modeling), achieved remarkable results for the task, without requiring manual tuning or definition of domain/entity-specific rules. However, as name-based methods directly return KB names, they cannot cope with homonyms, i.e. different KB entities sharing the exact same name. This significantly affects their performance for KBs where homonyms account for a large amount of entity mentions (e.g. UMLS and NCBI Gene).

Results

We present BELHD (Biomedical Entity Linking with Homonym Disambiguation), a new name-based method that copes with this challenge. BELHD builds upon the BioSyn model with two crucial extensions. First, it performs pre-processing of the KB, during which it expands homonyms with a specifically constructed disambiguating string, thus enforcing unique linking decisions. Second, it introduces candidate sharing, a novel strategy that strengthens the overall training signal by including similar mentions from the same document as positive or negative examples, according to their corresponding KB identifier. Experiments with 10 corpora and 5 entity types show that BELHD improves upon current neural state-of-the-art approaches, achieving the best results in 6 out of 10 corpora with an average improvement of 4.55pp recall@1. Furthermore, the KB preprocessing is orthogonal to the prediction model and thus can also improve other neural methods, which we exemplify for GenBioEL, a generative name-based BEL approach.

Availability and implementation

The code to reproduce our experiments can be found at: https://github.com/sg-wbi/belhd.
Karyotype diversity and genome size in the Cyphomandra clade of Solanum L. (Solanaceae)
Authors: Mesquita Amanda T , Braz Guilherme T , Shimizu Gustavo H , Machado Raquel M , Romero-da Cruz Maria V , Forni-Martins Eliana R
Published: July 2024

The Cyphomandra clade, a distinct group within the Solanum L. genus, is characterized by remarkable traits, including large chromosomes and big genome sizes. We aimed to investigate whether these features are conserved within the Cyphomandra clade and how they differentiate this group from other Solanum species. We elaborated karyotypes based on CMA/DAPI banding and rDNA fluorescence in situ hybridization (FISH) and estimated the genome size from 12 species, eight belonging to Cyphomandra and four from related clades. All species showed metacentric or submetacentric chromosomes and symmetrical karyotypes, with 2n = 24, except S. mammosum L. (2n = 22). CMA/DAPI banding in combination with rDNA FISH revealed three distinct patterns of heterochromatin distribution (number and position of bands, all CMA+). Most species showed one pair of 35S and 5S rDNA on different chromosomes, except S. mammosum (one of the two pairs was observed in the same chromosome). Notable, the Cyphomandra clade species showed larger chromosomes and genome sizes than other species of Solanum, corroborating that these karyotype attributes are valuable to characterize the clade. The number of CMA/DAPI bands and rDNA sites does not justify the differences in the genome size. Therefore, the accumulation and dispersion of other repetitive sequences, like transposable elements, may be associated with the karyotype changes.
A trip of a bamboo lifetime: tracing the origin and evolution of Chusquea (Poaceae, Bambusoideae, Bambuseae) in Patagonia, southernmost South America
Authors: Guerreiro Carolina , Brignone Nicolás F , Clark Lynn G , Vega Andrea S
Published: July 2024

We performed a phylogenetic analysis with estimated clade ages and an ancestral-range estimation focused on the Patagonian species of Chusquea, i.e. the Chusquea culeou clade, to unravel their biogeographical history. Phylogenetic analyses were conducted with sequence data from four plastid markers, using maximum parsimony and Bayesian inference approaches. The complete sampling and addition of the Patagonian Chusquea species into a phylogenetic framework revealed the most likely origin and evolutionary history of the Chusquea culeou clade. The Patagonian Chusquea originated roughly 11.35 Mya, most likely from a common ancestor from the Atlantic Forest region, when this lineage underwent in situ diversification and its species evolved sympatrically. All the extant species have arisen in the last 8 Myr. Moreover, according to the present sampling, the most recent common ancestor of subtribe Chusqueinae originated in the Northern Andes, which is also the most common source area of the estimated dispersal events. Some other preliminary insights on the biogeographic history of the genus are included.
The ageing central nervous system in multiple sclerosis: the imaging perspective
Authors: Filippi Massimo , Preziosa Paolo , Barkhof Frederik , Ciccarelli Olga , Cossarizza Andrea , De Stefano Nicola , Gasperini Claudio , Geraldes Ruth , Granziera Cristina , Haider Lukas , Lassmann Hans , Margoni Monica , Pontillo Giuseppe , Ropele Stefan , Rovira Àlex , Sastre-Garriga Jaume , Yousry Tarek A , Rocca Maria A
Published: July 2024

The interaction between ageing and multiple sclerosis is complex and carries significant implications for patient care. Managing multiple sclerosis effectively requires an understanding of how ageing and multiple sclerosis impact brain structure and function. Ageing inherently induces brain changes, including reduced plasticity, diminished grey matter volume, and ischaemic lesion accumulation. When combined with multiple sclerosis pathology, these age-related alterations may worsen clinical disability. Ageing may also influence the response of multiple sclerosis patients to therapies and/or their side effects, highlighting the importance of adjusted treatment considerations. MRI is highly sensitive to age- and multiple sclerosis-related processes. Accordingly, MRI can provide insights into the relationship between ageing and multiple sclerosis, enabling a better understanding of their pathophysiological interplay and informing treatment selection. This review summarizes current knowledge on the immunopathological and MRI aspects of ageing in the CNS in the context of multiple sclerosis. Starting from immunosenescence, ageing-related pathological mechanisms and specific features like enlarged Virchow-Robin spaces, this review then explores clinical aspects, including late-onset multiple sclerosis, the influence of age on diagnostic criteria, and comorbidity effects on imaging features. The role of MRI in understanding neurodegeneration, iron dynamics and myelin changes influenced by ageing and how MRI can contribute to defining treatment effects in ageing multiple sclerosis patients, are also discussed.
Cryotherapy for the treatment of cutaneous intestinal metaplasia
Authors: Coltart George Stewart , Scott Joseph , Sommerlad Matthew , Healy Eugene
Published: July 2024

Cutaneous intestinal metaplasia (CIM) is a rare complication affecting long-term stomas. We review the management of cases present in the literature and report on the successful use of cryotherapy as a treatment for CIM.
Top-down and bottom-up oscillatory dynamics regulate implicit visuomotor sequence learning
Authors: Lum Jarrad A G , Barham Michael P , Hyde Christian , Hill Aron T , White David J , Hughes Matthew E , Clark Gillian M
Published: July 2024

Implicit visuomotor sequence learning is crucial for acquiring skills that result in automated behaviors. The oscillatory dynamics underpinning this learning process are not well understood. To address this gap, the current study employed electroencephalography with a medium-density array (64 electrodes) to investigate oscillatory activity associated with implicit visuomotor sequence learning in the Serial Reaction Time task. In the task, participants unknowingly learn a series of finger movements. Eighty-five healthy adults participated in the study. Analyses revealed that theta activity at the vertex and alpha/beta activity over the motor areas decreased over the course of learning. No associations between alpha/beta and theta power were observed. These findings are interpreted within a dual-process framework: midline theta activity is posited to regulate top-down attentional processes, whereas beta activity from motor areas underlies the bottom-up encoding of sensory information from movement. From this model, we suggest that during implicit visuomotor sequence learning, top-down processes become disengaged (indicated by a reduction in theta activity), and modality specific bottom-up processes encode the motor sequence (indicated by a reduction in alpha/beta activity).
Frontal pole–precuneus connectivity is associated with a discrepancy between self-rated and observer-rated depression severity in mood disorders: a resting-state functional magnetic resonance imaging study
Authors: Kawakami Shintaro , Okada Naohiro , Satomura Yoshihiro , Shoji Eimu , Mori Shunsuke , Kiyota Masahiro , Omileke Favour , Hamamoto Yu , Morita Susumu , Koshiyama Daisuke , Yamagishi Mika , Sakakibara Eisuke , Koike Shinsuke , Kasai Kiyoto
Published: July 2024

Discrepancies in self-rated and observer-rated depression severity may underlie the basis for biological heterogeneity in depressive disorders and be an important predictor of outcomes and indicators to optimize intervention strategies. However, the neural mechanisms underlying this discrepancy have been understudied. This study aimed to examine the brain networks that represent the neural basis of the discrepancy between self-rated and observer-rated depression severity using resting-state functional MRI. To examine the discrepancy between self-rated and observer-rated depression severity, self- and observer-ratings discrepancy (SOD) was defined, and the higher and lower SOD groups were selected from depressed patients as participants showing extreme deviation. Resting-state functional MRI analysis was performed to examine regions with significant differences in functional connectivity in the two groups. The results showed that, in the higher SOD group compared to the lower SOD group, there was increased functional connectivity between the frontal pole and precuneus, both of which are subregions of the default mode network that have been reported to be associated with ruminative and self-referential thinking. These results provide insight into the association of brain circuitry with discrepancies between self- and observer-rated depression severity and may lead to more treatment-oriented diagnostic reclassification in the future.
Disentangling transcriptomic heterogeneity within the human subgenual anterior cingulate cortex
Authors: Jenkins Aaron K , Shelton Micah A , Yin RuoFei , Gorczyca Michael T , Zong Wei , Glausier Jill R , Lewis David A , Tseng George C , Seney Marianne L , McClung Colleen A
Published: July 2024

The subgenual anterior cingulate cortex (sgACC) is a critical site for understanding the neural correlates of affect and emotion. While the activity of the sgACC is functionally homogenous, it is comprised of multiple Brodmann Areas (BAs) that possess different cytoarchitectures. In some sgACC BAs, Layer 5 is sublaminated into L5a and L5b which has implications for its projection targets. To understand how the transcriptional profile differs between the BAs, layers, and sublayers of human sgACC, we collected layer strips using laser capture microdissection followed by RNA sequencing. We found no significant differences in transcript expression in these specific cortical layers between BAs within the sgACC. In contrast, we identified striking differences between Layers 3 and 5a or 5b that were concordant across sgACC BAs. We found that sublayers 5a and 5b were transcriptionally similar. Pathway analyses of L3 and L5 revealed overlapping biological processes related to synaptic function. However, L3 was enriched for pathways related to cell-to-cell junction and dendritic spines whereas L5 was enriched for pathways related to brain development and presynaptic function, indicating potential functional differences across layers. Our study provides important insight into normative transcriptional features of the sgACC.
US Food and Drug Administration, Centers for Disease Control and Prevention, and National Institutes of Health Co-Sponsored Public Workshop Summary—Development Considerations of Antimicrobial Drugs for the Treatment of Gonorrhea
Authors: Hiruy Hiwot , Bala Shukal , Byrne James M , Roche Kerian Grande , Jang Seong H , Kim Peter , Nambiar Sumathi , Rubin Dan , Yasinskaya Yuliya , Bachmann Laura H , Bernstein Kyle , Botgros Radu , Cammarata Sue , Chaves Ricardo L , Deal Carolyn D , Drusano George L , Duffy Erin M , Eakin Ann E , Gelone Steve , Hiltke Thomas , Hook Edward W , Jerse Ann E , McNeil Candice J , Newman Lori , O’Brien Seamus , Perry Caroline , Reno Hilary E L , Romaguera Raul A , Sato Junko , Unemo Magnus , Wi Teodora E C , Workowski Kimberly , O’May Graeme A , Shukla Sunita J , Farley John J
Published: July 2024

There is an unmet need for developing drugs for the treatment of gonorrhea due to rapidly evolving resistance of Neisseria gonorrhoeae against antimicrobial drugs used for empiric therapy, an increase in globally reported multidrug-resistant cases, and the limited available therapeutic options. Furthermore, few drugs are under development. Development of antimicrobials is hampered by challenges in clinical trial design, limitations of available diagnostics, changes in and varying standards of care, lack of robust animal models, and clinically relevant pharmacodynamic targets. On 23 April 2021, the US Food and Drug Administration, Centers for Disease Control and Prevention, and National Institute of Allergy and Infectious Diseases of the National Institutes of Health co-sponsored a workshop with stakeholders from academia, industry, and regulatory agencies to discuss the challenges and strategies, including potential collaborations and incentives, to facilitate the development of drugs for the treatment of gonorrhea. This article provides a summary of that workshop.