bluuebunny/crossref_metadata_2025 huggingface dataset:
Improving HLA typing imputation accuracy and eplet identification with local next‐generation sequencing training data
Authors: Lhotte Romain , Letort Véronique , Usureau Cédric , Jorge‐Cordeiro Debora ,   PHRC Acorghla Consortium, Siemowski Jérémy , Gabet Lionel , Cournede Paul‐Henry , Taupin Jean‐Luc
Published: September 2023

Assessing donor/recipient HLA compatibility at the eplet level requires second field DNA typings but these are not always available. These can be estimated from lower‐resolution data either manually or with computational tools currently relying, at best, on data containing typing ambiguities. We gathered NGS typing data from 61,393 individuals in 17 French laboratories, for loci A, B, and C (100% of typings), DRB1 and DQB1 (95.5%), DQA1 (39.6%), DRB3/4/5, DPB1, and DPA1 (10.5%). We developed HaploSFHI, a modified iterative maximum likelihood algorithm, to impute second field HLA typings from low‐ or intermediate‐resolution ones. Compared with the reference tools HaploStats, HLA‐EMMA, and HLA‐Upgrade, HaploSFHI provided more accurate predictions across all loci on two French test sets and four European‐independent test sets. Only HaploSFHI could impute DQA1, and solely HaploSFHI and HaploStats provided DRB3/4/5 imputations. The improved performance of HaploSFHI was due to our local and nonambiguous data. We provided explanations for the most common imputation errors and pinpointed the variability of a low number of low‐resolution haplotypes. We thus provided guidance to select individuals for whom sequencing would optimize incompatibility assessment and cost‐effectiveness of HLA typing, considering not only well‐imputed second field typing(s) but also well‐imputed eplets.
Therapeutic trial of fluvastatin in a cell line xenograft model of canine mammary gland cancer
Authors: Atmane Mohamed Issam , Vigneau Anne‐Laurence , Beaudry Francis , Rico Charlène , Boerboom Derek , Paquet Marilène
Published: September 2023

The Hippo signalling pathway is involved in breast cancer and canine mammary tumour (CMT). This study sought to evaluate the efficacy of fluvastatin on the Hippo pathway and its main effectors, YAP and TAZ, in vivo in a murine CMT cell line xenograft model. On treatment day 1, mice were divided into four groups: vehicle, fluvastatin, doxorubicin or a combination therapy. Tumour volumes were monitored with callipers and tissues harvested on day 28th of treatment. Histopathological examination of tumour tissues and major organs was performed as well as tumour evaluation of necrosis, apoptosis, cellular proliferation, expression of YAP, TAZ and the mRNA levels of four of their target genes (CTGF, CYR61, ANKRD1 and RHAMM2). Results showed a statistically significant variation in tumour volumes only for the combination therapy and final tumour weight only for the doxorubicin group compared to control. There was no significant difference in tumour necrosis, expression of CC3, ki‐67, YAP and TAZ measured by immunohistochemistry and in the mRNA levels of the target genes. Unexpectedly, lung metastases were found in the control group (9) and not in the fluvastatin treated group (7). In addition, mass spectrometry‐based quantification of fluvastatin reveals concentrations comparable to levels reported to exert therapeutic effects. This study shows that fluvastatin tumours concentration reached therapeutic levels without having an effect on the hippo pathway or various tumour parameters. Interestingly, only the control group had lung metastases. This study is the first to explore the repurposing of statins for cancer treatment in veterinary medicine.
Can Instagram Be Adopted as an Innovative Tool for Developing Self-Esteem? An Evaluation of Self-Esteem through Social Media User-Experience
Authors: Ligaraba Neo , Chuchu Tinashe
Published: September 2023

Instagram has emerged as one of the most popular social media platforms. This study examined Instagram usage of young adults in an emerging market, South Africa. The research sought to establish the extent to which Instagram usage may affect self-esteem among young consumers in emerging markets. A conceptual model has been developed based on identified factors such as Instagram usage, emotional investment in Instagram, self-efficacy, sense of community and self-esteem. 361 active Instagram users were selected through convenience sampling and the feedback they provided was processed for insights. Descriptive statistics and structural equation modeling (SEM) were used to investigate the interrelationships between the constructs. Implications for marketers include promoting adequate use of Instagram and making users aware of the potential threats of its excessive usage.
Experiences with remote communication in adult intensive care units during the COVID-19 pandemic: a systematic review protocol
Authors: Cardoso Ana Filipa , Pires Miguel Grilo , Cioga Elisabete , Abalroado Inês , Santos Diana , Duque Filipa Margarida , Loureiro Ricardo , Felizardo Helena , Fernandes António Manuel , Silva Rosa , Ventura Filipa , Santana Elaine , Cardoso Daniela , Loureiro Luís
Published: September 2023

Objective:

The objective of this review is to explore the lived experiences of critically ill adults, their families, or health care professionals with remote communication in intensive care units (ICUs) during the COVID-19 pandemic.

Introduction:

Family visiting restrictions in ICUs during the COVID-19 pandemic imposed significant challenges to communication between critically ill adults, their families, and the health care team. Evidence shows that several communication strategies were developed and implemented in ICUs during the COVID-19 pandemic to promote family engagement; however, the experiences of critically ill adults, their families, and health care professionals with these strategies are scattered across primary qualitative studies.

Inclusion criteria:

This review will consider qualitative studies that include critically ill adults, their families, or health care professionals, focusing on their experiences with remote communication strategies in ICUs during the COVID-19 pandemic.

Methods:

This review will be conducted in accordance with JBI methodology. The search strategy will aim to locate both published and unpublished qualitative studies in English, Spanish, and Portuguese. Studies published after January 2020 will be included. Study selection, critical appraisal, and data extraction will be performed independently by 2 reviewers. Data will be presented in narrative format and synthesized using the JBI meta-aggregation process. A ConQual Summary of Findings will be presented.

Review registration:

PROSPERO CRD42022383603
Gut check: Unveiling the influence of acute exercise on the gut microbiota
Authors: Grosicki Gregory J. , Langan Sean P. , Bagley James R. , Galpin Andrew J. , Garner Dan , Hampton‐Marcell Jarrad T. , Allen Jacob M. , Robinson Austin T.
Published: September 2023

The human gastrointestinal microbiota and its unique metabolites regulate a diverse array of physiological processes with substantial implications for human health and performance. Chronic exercise training positively modulates the gut microbiota and its metabolic output. The benefits of chronic exercise for the gut microbiota may be influenced by acute changes in microbial community structure and function that follow a single exercise bout (i.e., acute exercise). Thus, an improved understanding of changes in the gut microbiota that occur with acute exercise could aid in the development of evidence‐based exercise training strategies to target the gut microbiota more effectively. In this review, we provide a comprehensive summary of the existing literature on the acute and very short‐term (<3 weeks) exercise responses of the gut microbiota and faecal metabolites in humans. We conclude by highlighting gaps in the literature and providing recommendations for future research in this area.
Metal-pattern preparation based on selective deposition using soft organofluorine surfaces
Authors: Tsujioka Tsuyoshi
Published: September 2023

Metal-pattern formation using vacuum evaporation is a critical process from basic research to industrial mass-production. Selective metal deposition using metal-atom desorption from an organic surface is a promising metal-patterning method by maskless vacuum deposition. In this study, we demonstrate metal-pattern formation by maskless deposition for various metal species using a vacuum-depositable and printable perfluoropolyether (PFPE) based material. A PFPE-based film has a low dispersion component of surface free energy and surface softness, and its surface has the ability to efficiently desorb for various metals. This method, which enables metal-pattern formation using maskless vacuum deposition for a variety of metal species with a high melting point and low intrinsic vapor pressure, including Ag, Cr, and Ni, can be applied to such applications as electrode-pattern formations.
Building water resilience in the face of cascading wildfire risks
Authors: Belongia Megan F. , Hammond Wagner Courtney , Seipp Kimberly Quesnel , Ajami Newsha K.
Published: September 2023

Severe wildfire is altering the natural and the built environment and posing risks to environmental and societal health and well-being, including cascading impacts to water systems and built water infrastructure. Research on wildfire-resilient water systems is growing but not keeping pace with the scale and severity of wildfire impacts, despite their intensifying threat. In this study, we evaluate the state of knowledge regarding wildfire-related hazards to water systems. We propose a holistic framework to assess interactions and feedback loops between water quality, quantity, and infrastructure hazards as determinants of post-fire water availability and access. Efforts to address the evolving threat of wildfires to water systems will require more interdisciplinary research on the complex relationships shaping wildfire’s threat to water availability and access. To support this, we need reliable long-term data availability, consistent metrics, greater research in shared contexts, more extensive research beyond the burn area, and multistakeholder collaboration on wildfire risks to water systems.
3D architecture and a bicellular mechanism of touch detection in mechanosensory corpuscle
Authors: Nikolaev Yury A. , Ziolkowski Luke H. , Pang Song , Li Wei-Ping , Feketa Viktor V. , Xu C. Shan , Gracheva Elena O. , Bagriantsev Sviatoslav N.
Published: September 2023

Mechanosensory corpuscles detect transient touch and vibration in the skin of vertebrates, enabling precise sensation of the physical environment. The corpuscle contains a mechanoreceptor afferent surrounded by lamellar cells (LCs), but corpuscular ultrastructure and the role of LCs in touch detection are unknown. We report the three-dimensional architecture of the avian Meissner (Grandry) corpuscle acquired using enhanced focused ion beam scanning electron microscopy and machine learning-based segmentation. The corpuscle comprises a stack of LCs interdigitated with terminal endings from two afferents. Simultaneous electrophysiological recordings from both cell types revealed that mechanosensitive LCs use calcium influx to trigger action potentials in the afferent and thus serve as physiological touch sensors in the skin. The elaborate architecture and bicellular sensory mechanism in the corpuscles, which comprises the afferents and LCs, create the capacity for nuanced encoding of the submodalities of touch.
Shear-reversible clusters of HIV-1 in solution: stabilized by antibodies, dispersed by mucin
Authors: Ogundiran Ayobami I. , Chang Tzu-Lan , Ivanov Andrey , Kumari Namita , Nekhai Sergei , Chandran Preethi L.
Published: September 2023

HIV-1 has eluded vaccine therapy for the past 40 years. The virus mutates rapidly and is protected by a shifting glycan shield of mannose sugars, which has hindered the broad neutralization of the virus by antibodies (Abs). Studies have shown that mannose residues are self-adhesive, but it is not known if these adhesions drive HIV-1 to aggregate in solution, further complicating Ab neutralization. The behavior of HIV-1 in culture media was monitored using Dynamic Light Scattering and complementary atomic force microscopy (AFM) imaging in the presence of anti-gp120 Abs, lectins, mannosidase, and mucin. After accounting for the serum contribution from the culture media, HIV-1 was found to be diffusing in solution in 400–700 nm clusters. These clusters could be sheared into single virus particles by filtration, but the dispersed particles clustered back within a short time frame. Sample preparation prior to AFM and transmission electron microscopy (TEM) imaging appears to disperse clusters, but the clusters become visible in AFM when they are stabilized by Abs in solution. The clustered form of the virus appears to restrict access of Abs, lectins, and glycosidases to surfaces within the cluster. Mannosidase treatment following virus dispersion by filtration prevented clustering, suggesting that the mannose glycan shield is involved in cluster formation. Dispersed HIV-1 particles that were bound by Abs did not re-cluster back. Free mucin molecules (porcine gastric mucin) effectively dispersed HIV-1 clusters, even those stabilized by Abs. HIV-1-loaded mucin dried on the AFM surface with a fern-like fractal pattern, similar to that seen clinically in cervical mucin during the more penetrable ovulation stage.

IMPORTANCE

The phenomenon of reversible clustering is expected to further nuance HIV immune stealth because virus surfaces can escape interaction with antibodies (Abs) by hiding temporarily within clusters. It is well known that mucin reduces HIV virulence, and the current perspective is that mucin aggregates HIV-1 to reduce infections. Our findings, however, suggest that mucin is dispersing HIV clusters. The study proposes a new paradigm for how HIV-1 may broadly evade Ab recognition with reversible clustering and why mucin effectively neutralizes HIV-1.
Multi-integrated approach for unraveling small open reading frames potentially associated with secondary metabolism in
Streptomyces
Authors: Fan Si-Min , Li Ze-Qi , Zhang Shi-Zhe , Chen Liang-Yu , Wei Xi-Ying , Liang Jian , Zhao Xin-Qing , Su Chun
Published: September 2023

Small open reading frames (smORFs) are widely distributed in various living organisms. However, their functions remain largely unexplored. In addition, annotation and detection of smORFs are limited using existing methods and hindered by their specific properties. In this study, we systematically investigated smORFs and smORF-encoded peptides (SEPs) in
Streptomyces
, which are well-known bacterial producers of diverse bioactive secondary metabolites. We established a peptidogenomic workflow based on multi-integrated comprehensive database search and database-independent
de novo
sequencing to identify smORFs in
Streptomyces xinghaiensis
NRRL B-24674
T
(S187). In addition, we described SEPome related to the secondary metabolism, which include 68 novel SEPs and 79 common smORFs with
Streptomyces coelicolor
A3 (2). Functional analysis of universal smORFs revealed enrichment in biosynthetic processes, stress response, ribosomes, and nucleic acid binding. Meanwhile, 5 Cryptic smORF-encoded Peptides (CSEPs) distributed in non-annotated regions of the genome, and non-coding RNAs could encode for CSEPs. A total of 66 new RNAs, including 32 non-coding RNAs (ncRNAs) were revealed, and 4 ncRNA-encoded peptides were identified. Furthermore, an investigation of carbon metabolism showed that NagE functions in spore formation and secondary metabolism in
Streptomyces
. Particularly, NagE was observed to function in the biosynthesis of anti-complement agents in
S. xinghaiensis,
suggesting a novel role of the phosphoenolpyruvate phosphotransferase system in microbial secondary metabolism. We thus provide an effective strategy for analyzing public data sets of model strains to identify smORFs for non-model species. The ncRNAs and SEPs present rich sources for engineering streptomycetes to produce bioactive compounds.

Importance

Due to their small size and special chemical features, small open reading frame (smORF)-encoding peptides (SEPs) are often neglected. However, they may play critical roles in regulating gene expression, enzyme activity, and metabolite production. Studies on bacterial microproteins have mainly focused on pathogenic bacteria, which are importance to systematically investigate SEPs in streptomycetes and are rich sources of bioactive secondary metabolites. Our study is the first to perform a global identification of smORFs in streptomycetes. We established a peptidogenomic workflow for non-model microbial strains and identified multiple novel smORFs that are potentially linked to secondary metabolism in streptomycetes. Our multi-integrated approach in this study is meaningful to improve the quality and quantity of the detected smORFs. Ultimately, the workflow we established could be extended to other organisms and would benefit the genome mining of microproteins with critical functions for regulation and engineering useful microorganisms.
QRS complex and T wave planarity for the efficacy prediction of automatic implantable defibrillators
Authors: Hnatkova Katerina , Andršová Irena , Novotný Tomáš , Vanderberk Bert , Sprenkeler David , Junttila Juhani , Reichlin Tobias , Schlögl Simon , Vos Marc A , Friede Tim , Bauer Axel , Huikuri Heikki V , Willems Rik , Schmidt Georg , Sticherling Christian , Zabel Markus , Malik Marek
Published: September 2023

Objective

To test the hypothesis that in recipients of primary prophylactic implantable cardioverter-defibrillators (ICDs), the non-planarity of ECG vector loops predicts (a) deaths despite ICD protection and (b) appropriate ICD shocks.

Methods

Digital pre-implant ECGs were collected in 1948 ICD recipients: 21.4% females, median age 65 years, 61.5% ischaemic heart disease (IHD). QRS and T wave three-dimensional loops were constructed using singular value decomposition that allowed to measure the vector loop planarity. The non-planarity, that is, the twist of the three-dimensional loops out of a single plane, was related to all-cause mortality (n=294; 15.3% females; 68.7% IHD) and appropriate ICD shocks (n=162; 10.5% females; 87.7% IHD) during 5-year follow-up after device implantation. Using multivariable Cox regression, the predictive power of QRS and T wave non-planarity was compared with that of age, heart rate, left ventricular ejection fraction, QRS duration, spatial QRS-T angle, QTc interval and T-peak to T-end interval.

Results

QRS non-planarity was significantly (p<0.001) associated with follow-up deaths despite ICD protection with HR of 1.339 (95% CI 1.165 to 1.540) but was only univariably associated with appropriate ICD shocks. Non-planarity of the T wave loop was the only ECG-derived index significantly (p<0.001) associated with appropriate ICD shocks with multivariable Cox regression HR of 1.364 (1.180 to 1.576) but was not associated with follow-up mortality.

Conclusions

The analysed data suggest that QRS and T wave non-planarity might offer distinction between patients who are at greater risk of death despite ICD protection and those who are likely to use the defibrillator protection.
Complete response to immunotherapy in a patient with high-risk stage III colorectal cancer after ctDNA-guided detection of early adjuvant treatment failure
Authors: Lucchesi Nicholas , Ally Jenna M , Reilley Matthew J
Published: September 2023

The standard of care for stage III colorectal cancer (CRC) is curative resection with adjuvant chemotherapy (ACT). There is a high risk of recurrence particularly for high-risk patients with stage III disease, making close disease monitoring vital. Circulating tumor DNA (ctDNA) is now established as an effective method of early detection of disease relapse as well as postoperative risk stratification. However there remains a lack of established protocol for using ctDNA to assess response to ACT and in using that data to alter therapy in real time. A case is described of a patient with high-risk stage III CRC in whom failure of ACT was detected early and therapy was quickly changed based on rising ctDNA levels. The described patient had complete radiologic and clinical response to checkpoint inhibitor immunotherapy and remains free of disease after 18 months. This case demonstrates a promising example of how ctDNA can be used to both assess effectiveness of ongoing therapy and drive real-time change in treatment while sparing unnecessary chemotherapy toxicities.
Semantic Segmentation of Images Based on Multi-Feature Fusion and Convolutional Neural Networks
Authors: Wang Zhenyu , Xiao Juan , Zhang Shuai , Qi Baoqiang
Published: September 2023

Image semantic segmentation technology is one of the core research contents in the field of computer vision. With the improvement of computer performance and the continuous development of deep learning technology, researchers have more and more enthusiasm to study the actual effect and performance of image semantic segmentation. The results of deep semantic segmentation allow computers to have a more detailed and accurate understanding of images, and have a wide range of application needs in the fields of autonomous driving, intelligent security, medical imaging, remote sensing images, etc. However, the existing image semantic segmentation algorithms have the disadvantages of easy discontinuous results and insufficient prediction accuracy. In this paper, we take deep learning-based image semantic segmentation technology as the research object to explore the improvement of the image semantic segmentation algorithm and its application in road scenarios. First, this paper proposes MCU-Net method based on residual fusion and multi-scale contextual information. MCU-Net uses residual fusion module to deepen the network structure and improve the ability of U-Net to acquire deeper features. Then a top-down and bottom-up path is constructed for feature information between different levels, and the spatial and semantic information contained in shallow and deep features in the network is fully utilized by fusing features from different levels. In addition, an enhanced void space pyramid pooling module is added for feature information between the same levels, which enables the output features to have a larger range of semantic information. Second, this paper proposes the DAMCU-Net method based on attention mechanism and edge detection based on MCU-Net. DAMCU-Net extracts global contextual information by the attention mechanism optimization module, while fusing features using dense jump connections to facilitate the network to recover more spatial detail information during upsampling, and uses the FReLU activation function to improve the segmentation capability of the network for complex targets. For the edge information lost in the feature extraction process, the edge detection branch is added to supplement the feature information of the main path by feature fusion to achieve the optimization of the edge information.
Milnor’s triple linking number and Gauss diagram formulas of 3-bouquet graphs
Authors: Ito Noboru , Oyamaguchi Natsumi
Published: September 2023

The space of Gauss diagram formulas that are knot invariants is introduced by Goussarov–Polyak–Viro in 2000; it is extended to nanophrases by Gibson–Ito in 2011. However, known invariants in concrete presentations of Gauss diagram formulas are very limited, even in the one-component case. This paper gives a recipe to obtain explicit forms of Gauss diagram formulas that are invariants of virtual links with base points or tangles. As an application, we introduce a new construction of Gauss diagram formulas of [Formula: see text]-bouquets and how to give link invariants that do not change with base point moves, including a reconstruction of the Milnor’s triple linking number.
ANALYTIC SOLUTION OF ONE-DIMENSIONAL FRACTIONAL GLYCOLYSIS MODEL
Authors: KHAN FAIZ MUHAMMAD , ALI AMJAD , ABDULLAH  , KHAN ILYAS , SINGH ABHA , ELDIN SAYED M.
Published: September 2023

Glycolysis, which occurs in the cytoplasm of both prokaryotic and eukaryotic cells, is regarded to be the primary step employed in the breakdown of glucose to extract energy. As it is utilized by all living things on the planet, it was likely one of the first metabolic routes to emerge. It is a cytoplasmic mechanism that converts glucose into carbon molecules while also producing energy. The enzyme hexokinase aids in the phosphorylation of glucose. Hexokinase is inhibited by this mechanism, which generates glucose-6-P from adenosine triphosphate (ATP). This paper’s primary goal is to quantitatively examine the general reaction–diffusion Glycolysis system. Since the Glycolysis model shows a positive result as the unknown variables represent chemical substance concentration, therefore, to evaluate the behavior of the model for the non-integral order derivative of both independent variables, we expanded the concept of the conventional order Glycolysis model to the fractional Glycolysis model. The nonlinearity of the model is decomposed through an Adomian polynomial for evaluation. More precisely, we used the iterative Laplace Adomian decomposition method (LADM) to determine the numerical solution for the underlying model. The model’s necessary analytical/numerical solution was found by adding the first few iterations. Finally, we have presented numerical examples and graphical representations to explain the dynamics of the considered model to ensure the scheme’s validity.
INVESTIGATION OF NEW SOLITARY WAVE SOLUTIONS OF THE GILSON–PICKERING EQUATION USING ADVANCED COMPUTATIONAL TECHNIQUES
Authors: KHATER MOSTAFA M. A. , ATTIA RAGHDA A. M.
Published: September 2023

This study focuses on employing recent and accurate computational techniques, specifically the Sardar-sub equation [Formula: see text] method, to explore novel solitary wave solutions of the Gilson–Pickering [Formula: see text] equation. The GP equation is a mathematical model with implications in fluid dynamics and wave phenomena. It describes the behavior of solitary waves, which are localized disturbances propagating through a medium without changing shape. The physical significance of the [Formula: see text] equation lies in its ability to capture the dynamics of solitary waves in various systems, including water waves, optical fibers, and nonlinear acoustic waves. The study’s findings contribute to the advancement of mathematical modeling approaches and offer valuable insights into solitary wave phenomena. The stability of the constructed solutions is investigated using the properties of the Hamiltonian system. The accuracy of the computational solutions is demonstrated by comparing them with approximate solutions obtained through He’s variational iteration [Formula: see text] method. Furthermore, the effectiveness of the employed computational techniques is validated through comparisons with other existing methods.
Thermality of the zero-point length and gravitational selfduality
Authors: De Córdoba P. Fernández , Isidro J. M. , Roy Rudranil
Published: September 2023

It has been argued that the existence of a zero-point length is the hallmark of quantum gravity. In this paper, we suggest a thermal mechanism whereby this quantum of length arises in flat, Euclidean spacetime [Formula: see text]. For this, we consider the infinite sequence of all flat, Euclidean spacetimes [Formula: see text] with [Formula: see text], and postulate a probability distribution for each [Formula: see text] to occur. The distribution considered is that of a canonical ensemble at temperature [Formula: see text], the energy levels those of a 1-dimensional harmonic oscillator. Since both the harmonic energy levels and the spacetime dimensions are evenly spaced, one can identify the canonical distribution of harmonic-oscillator eigenvalues with that of dimensions [Formula: see text]. The state describing this statistical ensemble has a mean square deviation in the position operator, that can be interpreted as a quantum of length. Thus, placing an oscillator in thermal equilibrium with a bath provides a thermal mechanism whereby a zero-point length is generated. The quantum-gravitational implications of this construction are then discussed. In particular, a model is presented that realizes a conjectured duality between a weakly gravitational, strongly quantum system and a weakly quantum, strongly gravitational system.
Factors Affecting Stem Cell–Based Regenerative Approaches in Retinal Degeneration
Authors: Patel Sachin H. , Lamba Deepak A.
Published: September 2023

Inherited and age-associated vision loss is often associated with degeneration of the cells of the retina, the light-sensitive layer at the back of the eye. The mammalian retina, being a postmitotic neural tissue, does not have the capacity to repair itself through endogenous regeneration. There has been considerable excitement for the development of cell replacement approaches since the isolation and development of culture methods for human pluripotent stem cells, as well as the generation of induced pluripotent stem cells. This has now been combined with novel three-dimensional organoid culture systems that closely mimic human retinal development in vitro. In this review, we cover the current state of the field, with emphasis on the cell delivery challenges, role of the recipient immunological microenvironment, and challenges related to connectivity between transplanted cells and host circuitry both locally and centrally to the different areas of the brain.
Risk Factors Contributing to Highly Pathogenic Avian Influenza H5N6 in China, 2014–2021: Based on a MaxEnt Model
Authors: Sun Zhuo , Li Yue-peng , An Qi , Gao Xiang , Wang Hong-bin
Published: September 2023

Highly pathogenic avian influenza H5N6, an acute infectious poultry disease, has appeared in China since 2014. The serious HPAI H5N6 epidemic has caused substantial economic losses to the poultry industry and seriously threatened public health. This study developed two maximum entropy models based on highly pathogenic avian influenza virus H5N6 surveillance data obtained through China’s national surveillance program and HPAI H5N6 outbreak data in China, identified risk factors for the disease and developed risk prediction maps. Both models had a good predictive performance with area under the receiver operating characteristic curves of 0.931 and 0.892. Our study considered 26 variables from bioclimate, geographical, and socioeconomic factors. After the screening, 14 variables were retained and incorporated into the construction of the two models. HPAIV H5N6 presence was related to population density, road density, poultry market density, mean diurnal range, and chicken density. HPAI H5N6 poultry outbreaks were associated with population density, road density, mean diurnal range, precipitation of the driest month, and chicken density. Overall, Southern China was the high-risk area for HPAIV H5N6 maintenance and H5N6 outbreak. The risk factors and maps associated with the HPAIV H5N6 presence and HPAI H5N6 outbreak identified in our study will help develop appropriate HPAIV H5N6 control measures to reduce the risk of infection and morbidity in poultry and humans.
Research on Railway Passenger Volume Forecast Based on the Spline Interpolation and IPSO-Gradient Difference Acceleration Rule
Authors: Fan Dingyuan , Yang Fei , Ji Jinghao , Zhang Zexi
Published: September 2023

In order to solve the problem that the railway passenger volume data are abnormal due to holidays and major events interfering with the prediction accuracy, the spline interpolation method is introduced to replace the abnormal passenger volume data. In addition, an improved particle swarm optimization (IPSO) is proposed to optimize the gradient difference acceleration law to combine and improve the predicted value and further improve the prediction accuracy of the railway passenger traffic. Finally, taking Beijing as the research object, the Holt exponential smoothing method and the BP neural network are selected to verify the effect of spline interpolation and IPSO-gradient difference acceleration law on prediction accuracy. The research results show that the spline interpolation method has a better prediction effect after processing abnormal passenger traffic data, and the improved particle swarm algorithm also shows better optimization ability and convergence speed when solving the double difference postulate. In comparison with the BP neural network, Holt exponential smoothing, simple averaging, and conventional redifference approaches, the IPSO-redifference acceleration method achieves a superior prediction performance, and the absolute values of the forecast error are reduced by 3.320%, 1.518%, 2.419%, and 0.602%.
Investigating Peer Advisors’ Strategies to Promote Cancer Prevention and Early Detection in Swedish Communities with Challenging Socioeconomic Conditions
Authors: Efremius Simon , Eriksson Lars E. , Kleijberg Max
Published: September 2023

Worse socioeconomic conditions (e.g., having a migration background, lower income, and lower educational level) may lead to barriers for cancer prevention and early detection. Community-based initiatives providing tailored and accessible information are found to increase cancer screening participation and improve health outcomes for people with challenging socioeconomic conditions. To inform such initiatives, more research is needed from the perspective of those working with them. This article focuses on the Swedish “peer advisor project” in which the Regional Cancer Centre Stockholm Gotland (RCC) collaborates with community-based peer advisors to reduce cancer inequities in areas with challenging socioeconomic conditions. We aim to investigate the perspectives of people working with the peer advisor project in relation to challenges they face, strategies they use, and forms of impact they perceive their work to have. We used a participatory action research approach, involving 12 peer advisor representatives and three RCC representatives. Underlying data (interviews and participant observations) were qualitatively analyzed. Findings are presented in relation to three themes: (1) Peer advisors bridge a gap between the cancer care system and communities through dialogues with communities and RCC representatives. (2) Peer advisors navigate culturally based sensitivities through efforts to create safe spaces for discussing cancer prevention and early detection. (3) Peer advisor and RCC representatives described forms of impact in relation to personal contexts, community contexts, RCC’s organizational context, and societal context. Sustainability and structural challenges may limit the peer advisor project to create impact. We discuss that peer advisors may act as cultural brokers through dialogues with communities and the cancer care system, thereby increasing an understanding of communities’ contexts and needs. Findings from this study can inform development and implementation of similar community-based peer-to-peer initiatives in other contexts. More research is needed to investigate the long-term impact of the project including community-based perspectives.
Figure S3 from ESRRB Inhibits the TGFβ Signaling Pathway to Drive Cell Proliferation in Cervical Cancer
Authors: Li Qin-Shu , Zheng Peng-Sheng
Published: September 2023

Fig. S3 describes the wide field diagram of ICC
Supplementary Data from Oncogenic ASPM Is a Regulatory Hub of Developmental and Stemness Signaling in Cancers
Authors: Tsai Kelvin K. , Bae Byoung-Il , Hsu Chung-Chi , Cheng Li-Hsin , Shaked Yuval
Published: September 2023

This file contains Supplementary Figures 1-5, Supplementary Tables 1-2, and Supplementary Materials and Methods.
Supplementary methods from Intratumoral Microbiota Composition Regulates Chemoimmunotherapy Response in Esophageal Squamous Cell Carcinoma
Authors: Wu Hong , Leng Xuefeng , Liu Qianshi , Mao Tianqin , Jiang Tao , Liu Yiqiang , Li Feifei , Cao Chenhui , Fan Jun , Chen Liang , Chen Yaqi , Yao Quan , Lu Shun , Liang Renchuan , Hu Lanlin , Liu Mingxin , Wan Yejian , Li Zhaoshen , Peng Jun , Luo Qiyu , Zhou Hang , Yin Jun , Xu Ke , Lan Mei , Peng Xinhao , Lan Haitao , Li Gang , Han Yongtao , Zhang Xia , Xiao Zhi-Xiong Jim , Lang Jinyi , Wang Guihua , Xu Chuan
Published: September 2023

Supplementary methods
Supplementary figure legend from Intratumoral Microbiota Composition Regulates Chemoimmunotherapy Response in Esophageal Squamous Cell Carcinoma
Authors: Wu Hong , Leng Xuefeng , Liu Qianshi , Mao Tianqin , Jiang Tao , Liu Yiqiang , Li Feifei , Cao Chenhui , Fan Jun , Chen Liang , Chen Yaqi , Yao Quan , Lu Shun , Liang Renchuan , Hu Lanlin , Liu Mingxin , Wan Yejian , Li Zhaoshen , Peng Jun , Luo Qiyu , Zhou Hang , Yin Jun , Xu Ke , Lan Mei , Peng Xinhao , Lan Haitao , Li Gang , Han Yongtao , Zhang Xia , Xiao Zhi-Xiong Jim , Lang Jinyi , Wang Guihua , Xu Chuan
Published: September 2023

Supplementary figure legend
Figure S6 from Intratumoral Microbiota Composition Regulates Chemoimmunotherapy Response in Esophageal Squamous Cell Carcinoma
Authors: Wu Hong , Leng Xuefeng , Liu Qianshi , Mao Tianqin , Jiang Tao , Liu Yiqiang , Li Feifei , Cao Chenhui , Fan Jun , Chen Liang , Chen Yaqi , Yao Quan , Lu Shun , Liang Renchuan , Hu Lanlin , Liu Mingxin , Wan Yejian , Li Zhaoshen , Peng Jun , Luo Qiyu , Zhou Hang , Yin Jun , Xu Ke , Lan Mei , Peng Xinhao , Lan Haitao , Li Gang , Han Yongtao , Zhang Xia , Xiao Zhi-Xiong Jim , Lang Jinyi , Wang Guihua , Xu Chuan
Published: September 2023

Figure S6 shows immune cell clusters and signatures revealed by single-cell RNA sequencing in patients with ESCC.
Figure S5 from Intratumoral Microbiota Composition Regulates Chemoimmunotherapy Response in Esophageal Squamous Cell Carcinoma
Authors: Wu Hong , Leng Xuefeng , Liu Qianshi , Mao Tianqin , Jiang Tao , Liu Yiqiang , Li Feifei , Cao Chenhui , Fan Jun , Chen Liang , Chen Yaqi , Yao Quan , Lu Shun , Liang Renchuan , Hu Lanlin , Liu Mingxin , Wan Yejian , Li Zhaoshen , Peng Jun , Luo Qiyu , Zhou Hang , Yin Jun , Xu Ke , Lan Mei , Peng Xinhao , Lan Haitao , Li Gang , Han Yongtao , Zhang Xia , Xiao Zhi-Xiong Jim , Lang Jinyi , Wang Guihua , Xu Chuan
Published: September 2023

Figure S5 shows intra-tumoral Microbiota associated with activated immune cell infiltration.
Supplementary Data from N6-methyladenosine Modification of FZR1 mRNA Promotes Gemcitabine Resistance in Pancreatic Cancer
Authors: Su Jiachun , Li Rui , Chen Ziming , Liu Shaoqiu , Zhao Hongzhe , Deng Shuang , Zeng Lingxing , Xu Zilan , Zhao Sihan , Zhou Yifan , Li Mei , He Xiaowei , Liu Ji , Xue Chunling , Bai Ruihong , Zhuang Lisha , Zhou Quanbo , Zhang Shaoping , Chen Rufu , Huang Xudong , Lin Dongxin , Zheng Jian , Zhang Jialiang
Published: September 2023

Supplementary Figures 1-6 and supplementary Tables 1-7.
Figure S1 from Intratumoral Microbiota Composition Regulates Chemoimmunotherapy Response in Esophageal Squamous Cell Carcinoma
Authors: Wu Hong , Leng Xuefeng , Liu Qianshi , Mao Tianqin , Jiang Tao , Liu Yiqiang , Li Feifei , Cao Chenhui , Fan Jun , Chen Liang , Chen Yaqi , Yao Quan , Lu Shun , Liang Renchuan , Hu Lanlin , Liu Mingxin , Wan Yejian , Li Zhaoshen , Peng Jun , Luo Qiyu , Zhou Hang , Yin Jun , Xu Ke , Lan Mei , Peng Xinhao , Lan Haitao , Li Gang , Han Yongtao , Zhang Xia , Xiao Zhi-Xiong Jim , Lang Jinyi , Wang Guihua , Xu Chuan
Published: September 2023

Figure S1 shows detection of intra-tumoral microbiota in the ESCC tissues.
Supplementary Table 2 from Apolipoprotein E2 Stimulates Protein Synthesis and Promotes Melanoma Progression and Metastasis
Authors: Adaku Nneoma , Ostendorf Benjamin N. , Mei Wenbin , Tavazoie Sohail F.
Published: September 2023

Full GSEA results tail vein injection
Table S2 from Dual Inhibition of KRASG12D and Pan-ERBB Is Synergistic in Pancreatic Ductal Adenocarcinoma
Authors: Gulay Kevin Christian Montecillo , Zhang Xinlian , Pantazopoulou Vasiliki , Patel Jay , Esparza Edgar , Pran Babu Deepa Sheik , Ogawa Satoshi , Weitz Jonathan , Ng Isabella , Mose Evangeline S. , Pu Minya , Engle Dannielle D. , Lowy Andrew M. , Tiriac Hervé
Published: September 2023

Table S2. List of antibodies used in this study.
Supplementary Data from Plasma Membrane Channel TRPM4 Mediates Immunogenic Therapy–Induced Necrosis
Authors: Ghosh Santanu , Yang Rachel , Duraki Darjan , Zhu Junyao , Kim Ji Eun , Jabeen Musarrat , Mao Chengjian , Dai Xinyi , Livezey Mara R. , Boudreau Matthew W. , Park Ben H. , Nelson Erik R. , Hergenrother Paul J. , Shapiro David J.
Published: September 2023

Supplementary Movie 1
Supplementary Data from Plasma Membrane Channel TRPM4 Mediates Immunogenic Therapy–Induced Necrosis
Authors: Ghosh Santanu , Yang Rachel , Duraki Darjan , Zhu Junyao , Kim Ji Eun , Jabeen Musarrat , Mao Chengjian , Dai Xinyi , Livezey Mara R. , Boudreau Matthew W. , Park Ben H. , Nelson Erik R. , Hergenrother Paul J. , Shapiro David J.
Published: September 2023

Supplementary Movie 2
Supplementary Data from Plasma Membrane Channel TRPM4 Mediates Immunogenic Therapy–Induced Necrosis
Authors: Ghosh Santanu , Yang Rachel , Duraki Darjan , Zhu Junyao , Kim Ji Eun , Jabeen Musarrat , Mao Chengjian , Dai Xinyi , Livezey Mara R. , Boudreau Matthew W. , Park Ben H. , Nelson Erik R. , Hergenrother Paul J. , Shapiro David J.
Published: September 2023

Supplement corrected to show label: 1 Supplementary Table
Data from Intratumoral Microbiota Composition Regulates Chemoimmunotherapy Response in Esophageal Squamous Cell Carcinoma
Authors: Wu Hong , Leng Xuefeng , Liu Qianshi , Mao Tianqin , Jiang Tao , Liu Yiqiang , Li Feifei , Cao Chenhui , Fan Jun , Chen Liang , Chen Yaqi , Yao Quan , Lu Shun , Liang Renchuan , Hu Lanlin , Liu Mingxin , Wan Yejian , Li Zhaoshen , Peng Jun , Luo Qiyu , Zhou Hang , Yin Jun , Xu Ke , Lan Mei , Peng Xinhao , Lan Haitao , Li Gang , Han Yongtao , Zhang Xia , Xiao Zhi-Xiong Jim , Lang Jinyi , Wang Guihua , Xu Chuan
Published: September 2023

Abstract
Neoadjuvant chemoimmunotherapy (NACI) has shown promise in the treatment of resectable esophageal squamous cell carcinoma (ESCC). The microbiomes of patients can impact therapy response, and previous studies have demonstrated that intestinal microbiota influences cancer immunotherapy by activating gut immunity. Here, we investigated the effects of intratumoral microbiota on the response of patients with ESCC to NACI. Intratumoral microbiota signatures of β-diversity were disparate and predicted the treatment efficiency of NACI. The enrichment of Streptococcus positively correlated with GrzB+ and CD8+ T-cell infiltration in tumor tissues. The abundance of Streptococcus could predict prolonged disease-free survival in ESCC. Single-cell RNA sequencing demonstrated that responders displayed a higher proportion of CD8+ effector memory T cells but a lower proportion of CD4+ regulatory T cells. Mice that underwent fecal microbial transplantation or intestinal colonization with Streptococcus from responders showed enrichment of Streptococcus in tumor tissues, elevated tumor-infiltrating CD8+ T cells, and a favorable response to anti-PD-1 treatment. Collectively, this study suggests that intratumoral Streptococcus signatures could predict NACI response and sheds light on the potential clinical utility of intratumoral microbiota for cancer immunotherapy.
Significance:
Analysis of intratumoral microbiota in patients with esophageal cancer identifies a microbiota signature that is associated with chemoimmunotherapy response and reveals that Streptococcus induces a favorable response by stimulating CD8+ T-cell infiltration.

See related commentary by Sfanos, p. 2985
Data from N6-methyladenosine modification of FZR1 mRNA promotes gemcitabine resistance in pancreatic cancer
Authors: Su Jiachun , Li Rui , Chen Ziming , Liu Shaoqiu , Zhao Hongzhe , Deng Shuang , Zeng Lingxing , Xu Zilan , Zhao Sihan , Zhou Yifan , Li Mei , He Xiaowei , Liu Ji , Xue Chunling , Bai Ruihong , Zhuang Lisha , Zhou Quanbo , Zhang Shaoping , Chen Rufu , Huang Xudong , Lin Dongxin , Zheng Jian , Zhang Jialiang
Published: September 2023

Abstract
The therapeutic options for treating pancreatic ductal adenocarcinoma (PDAC) are limited, and resistance to gemcitabine, a cornerstone of PDAC chemotherapy regimens, remains a major challenge. N6-methyladenosine (m6A) is a prevalent modification in mRNA that has been linked to diverse biological processes in human diseases. Herein, by characterizing the global m6A profile in a panel of gemcitabine-sensitive and gemcitabine-insensitive PDAC cells, we identified a key role for elevated m6A modification of the master G0/G1 regulator FZR1 in regulating gemcitabine sensitivity. Targeting FZR1 m6A modification augmented the response to gemcitabine treatment in gemcitabine-resistant PDAC cells both in vitro and in vivo. Mechanistically, GEMIN5 was identified as a novel m6A mediator that specifically bound to m6A-modified FZR1 and recruited the eIF3 translation initiation complex to accelerate FZR1 translation. FZR1 upregulation maintained the G0/G1 quiescent state and suppressed gemcitabine sensitivity in PDAC cells. Clinical analysis further demonstrated that both high levels of FZR1 m6A modification and FZR1 protein corresponded to poor response to gemcitabine. These findings reveal the critical function of m6A modification in regulating gemcitabine sensitivity in PDAC and identify the FZR1/GEMIN5 axis as a potential target to enhance gemcitabine response.
Data from Apolipoprotein E2 Stimulates Protein Synthesis and Promotes Melanoma Progression and Metastasis
Authors: Adaku Nneoma , Ostendorf Benjamin N. , Mei Wenbin , Tavazoie Sohail F.
Published: September 2023

Abstract
The secreted lipid transporter apolipoprotein E (APOE) plays important roles in atherosclerosis and Alzheimer's disease and has been implicated as a suppressor of melanoma progression. The APOE germline genotype predicts human melanoma outcomes, with APOE4 and APOE2 allele carriers exhibiting prolonged and reduced survival, respectively, relative to APOE3 homozygotes. While the APOE4 variant was recently shown to suppress melanoma progression by enhancing antitumor immunity, further work is needed to fully characterize the melanoma cell-intrinsic effects of APOE variants on cancer progression. Using a genetically engineered mouse model, we showed that human germline APOE genetic variants differentially modulate melanoma growth and metastasis in an APOE2>APOE3>APOE4 manner. The low-density lipoprotein receptor-related protein 1 (LRP1) receptor mediated the cell-intrinsic effects of APOE variants on melanoma progression. Protein synthesis was a tumor cell-intrinsic process differentially modulated by APOE variants, with APOE2 promoting translation via LRP1. These findings reveal a gain-of-function role for the APOE2 variant in melanoma progression, which may aid in predicting melanoma patient outcomes and understanding the protective effect of APOE2 in Alzheimer's disease.
Significance:
APOE germline variants impact melanoma progression through disparate mechanisms, such as the protein synthesis–promoting function of the APOE2 variant, indicating that germline genetic variants are causal contributors to metastatic outcomes.