bluuebunny/crossref_metadata_2025 huggingface dataset:
Disentangling the interactions between nasopharyngeal and gut microbiome and their involvement in the modulation of COVID-19 infection
Authors: Mancabelli Leonardo , Taurino Giuseppe , Ticinesi Andrea , Ciociola Tecla , Vacondio Federica , Milani Christian , Fontana Federico , Lugli Gabriele Andrea , Tarracchini Chiara , Alessandri Giulia , Viappiani Alice , Bianchi Massimiliano , Nouvenne Antonio , Chetta Alfredo Antonio , Turroni Francesca , Meschi Tiziana , Mor Marco , Bussolati Ovidio , Ventura Marco
Published: September 2023

The human organism is inhabited by trillions of microorganisms, known as microbiota, which are considered to exploit a pivotal role in the regulation of host health and immunity. Recent investigations have suggested a relationship between the composition of the human microbiota and COVID-19 infection, highlighting a possible role of bacterial communities in the modulation of the disease severity. In this study, we performed a shotgun metagenomics analysis to explore and compare the nasopharyngeal microbiota of 38 hospitalized Italian patients with and without COVID-19 infection during the third and fourth pandemic waves. In detail, the metagenomic analysis combined with specific correlation analyses suggested a positive association of several microbial species, such as
S. parasanguinis
and
P. melaninogenica
, with the severity of COVID-19 infection. Furthermore, the comparison of the microbiota composition between the nasopharyngeal and their respective fecal samples highlighted an association between these different compartments represented by a sharing of several bacterial species. Additionally, lipidomic and deep-shotgun functional analyses of the fecal samples suggested a metabolic impact of the microbiome on the host’s immune response, indicating the presence of key metabolic compounds in COVID-19 patients, such as lipid oxidation end products, potentially related to the inflammatory state. Conversely, the patients without COVID-19 displayed enzymatic patterns associated with the biosynthesis and degradation of specific compounds like lysine (synthesis) and phenylalanine (degradation) that could positively impact disease severity and contribute to modulating COVID-19 infection.

IMPORTANCE

The human microbiota is reported to play a major role in the regulation of host health and immunity, suggesting a possible impact on the severity of COVID-19 disease. This preliminary study investigated the possible correlation between nasopharyngeal microbiota and COVID-19 infection. In detail, the analysis of the nasopharyngeal microbiota of hospitalized Italian patients with and without COVID-19 infection suggested a positive association of several microbial species with the severity of the disease and highlighted a sharing of several bacteria species with the respective fecal samples. Moreover, the metabolic analyses suggested a possible impact of the microbiome on the host's immune response and the disease severity.
Efficient screening of adsorbed receptors for
Salmonella
phage LP31 and identification of receptor-binding protein
Authors: Ge Haojie , Ye Ling , Cai Yueyi , Guo Huimin , Gu Dan , Xu Zhengzhong , Hu Maozhi , Allison Heather E. , Jiao Xin'an , Chen Xiang
Published: September 2023

The adsorption process is the first step in the lifecycle of phages and plays a decisive role in the entire infection process. Identifying the adsorption mechanism of phages not only makes phage therapy more precise and efficient but also enables the exploration of other potential applications and modifications of phages. Phage LP31 can lyse multiple
Salmonella
serotypes, efficiently clearing biofilms formed by
Salmonella enterica
serovar Enteritidis (
S
. Enteritidis) and significantly reducing the concentration of
S
. Enteritidis in chicken feces. Therefore, LP31 has great potential for many practical applications. In this study, we established an efficient screening method for phage infection-related genes and identified a total of 10 genes related to the adsorption process of phage LP31. After the construction of strain C50041Δ
rfaL
58−358
, it was found that the knockout strain had a rough phenotype as an O-antigen-deficient strain. Adsorption rate and transmission electron microscopy experiments showed that the receptor for phage LP31 was the O
9
antigen of
S
. Enteritidis. Homology comparison and adsorption experiments confirmed that the tail fiber protein Lp35 of phage LP31 participated in the adsorption process as a receptor-binding protein.

IMPORTANCE

A full understanding of the interaction between phages and their receptors can help with the development of phage-related products. Phages like LP31 with the tail fiber protein Lp35, or a closely related protein, have been reported to effectively recognize and infect multiple
Salmonella
serotypes. However, the role of these proteins in phage infection has not been previously described. In this study, we established an efficient screening method to detect phage adsorption to host receptors. We found that phage LP31 can utilize its tail fiber protein Lp35 to adsorb to the O
9
antigen of
S.
Enteritidis, initiating the infection process. This study provides a great model system for further studies of how a phage-encoded receptor-binding protein (RBP) interacts with its host's RBP binding target, and this new model offers opportunities for further theoretical and experimental studies to understand the infection mechanism of phages.
Supplemental Material: Strength of the winter North Atlantic jet stream has deviated from its natural trend under anthropogenic warming
Authors: Cai Binggui , Marković Slobodan , Guo Zhengtang , al. et
Published: September 2023

Cave site, methods, supplemental discussion, Figures S1–S14, Table S1, and data sets S1–S3.  
Triceps injury in non-bowling arm in cricket: an unusual mechanism
Authors: Jagadevan Mohanakrishnan , Anbazhagan Sathiaprabhu , Barathi Deepak , Kuppusamy Balaji
Published: September 2023

Cricket is a non-contact sport that is popular worldwide and consists of repetitive throwing, bowling and fielding. Fast bowlers are prone to injury to the bowling arm due to repetitive stress, but this case study focuses on the damage caused to the bowler’s non-bowling arm. This individual was a right-handed fast bowler who developed pain and dysfunction in his left arm after competing in more than 20 cricket tournaments. Following the stipulated bowling spell, he had severe pain in the posterior aspect of his left arm. On the field, he was managed with ice compression. Ecchymosis was seen on the distal part of his posteromedial arm. Diagnostic ultrasound revealed an acute triceps injury. The pain lasted 2 weeks and was gradually relieved with analgesics and anti-inflammatory medications. This observation led to the recommendation that elbow flexion of the non-bowling arm be checked for and avoided.
Widening rural–urban gap in life expectancy in China since COVID-19
Authors: Han Shasha , Su Binbin , Zhao Yihao , Chen Chen , Zheng Xiaoying
Published: September 2023

Introduction

Disparities in life expectancy between rural and urban populations are well established but how it varies with epidemics and pandemics remains poorly understood. We aimed to quantify the rural–urban differences in the mortality burden of COVID-19 and to contribute to understanding the disparity trends in life expectancy between 1987 and 2021 in China.

Methods

We used monthly death counts from death registration systems. Rural–urban gap estimation and decomposition were carried out using period life tables to calculate life expectancy, the Arriaga decomposition technique to break down into age-specific and cause-specific mortality, and the Lee-Carter forecasts to estimate the expected gap.

Results

The rural–urban gap increased to 22.7 months (95% credible interval (CI) 19.6 to 25.8) in 2020 and further to 23.7 months (95% CI 19.6 to 26.7) in 2021, and was larger than expected under the continuation of the prepandemic trends. Compared with that in the recent 2003 SARS-CoV-2 epidemic and the 2009 influenza epidemic, excess rural–urban gaps in the COVID-19 pandemic changed from urban disadvantage to rural disadvantage, and the contributions shifted toward old age groups and circulatory diseases. Variations in the rural–urban gap since 1987 were positively correlated with the rural–urban disparity in public health expenditures, especially among ages <60 (p values <0.005).

Conclusions

Our findings identified a widening rural–urban gap in life expectancy since COVID-19, and a shifting trend towards old ages and circulatory diseases, disrupting the diminishing trend of the gap over 35 years. The findings highlight the unequal impact of the pandemic on different communities in terms of mortality burdens.
The carbon footprint of clinical trials: a global survey on the status quo and current regulatory guidance
Authors: Hoffmann Jean-Marc , Bauer Annina , Grossmann Regina
Published: September 2023

Introduction

All economic sectors including the service sector, along with healthcare, education and research, need to reduce their greenhouse gas emissions to limit global temperature increases. In this study, we aim to globally assess the awareness and current actions taken by Academic Research Institutions (ARIs) or governments regarding the reduction of carbon dioxide equivalent (CO2e) emissions for clinical research.

Methods

We designed a cross-sectional survey-based study, which was distributed within the International Clinical Trials Center Network (ICN). The survey population comprised representatives of the ICN who had extensive experience in academic clinical research and profound knowledge and understanding of the local context.

Results

The response rate was 80%. Responding ARIs were from 15 different countries and 4 continents. Around half of the ARIs reported that almost none of their research projects considered reducing their carbon footprint. The other half of the ARIs were not familiar with this subject at all. According to 60% of the respondents, greenhouse gas emissions are not assessed by Institutional Review Boards (IRBs)/Ethics Committees (ECs) or competent authorities, while 40% did not know. Neither IRBs/ECs nor competent authorities currently advise sponsors and investigators on reducing the carbon footprint of their clinical research projects. As for reducing greenhouse gas emissions in clinical research, virtual conferences and meetings were the most commonly implemented measures by ARIs across all regions. Finally, we have put together an action plan/checklist advising researchers on carbon footprint reduction for clinical trials.

Conclusion

Currently, greenhouse gas emissions are neglected during the planning phase of a research project, and they are not yet addressed or assessed by default during the approval procedures by IRBs/ECs or competent authorities. Thus, all involved stakeholders within clinical research need to be made aware of it through advice from ARIs and IRBs/ECs, among others.
Empowering telemetry technicians and enhancing communication to improve in-hospital cardiac arrest survival
Authors: McCoy Cody , Keshvani Neil , Warsi Maryam , Brown L Steven , Girod Carlos , Chu Eugene S , Hegde Anita A
Published: September 2023

Delays in treatment of in-hospital cardiac arrests (IHCAs) are associated with worsened survival. We sought to assess the impact of a bundled intervention on IHCA survival in patients on centralised telemetry. A retrospective quality improvement study was performed of a bundled intervention which incorporated (1) a telemetry hotline for telemetry technicians to reach nursing staff; (2) empowerment of telemetry technicians to directly activate the IHCA response team and (3) a standardised escalation system for automated critical alerts within the nursing mobile phone system. In the 4-year study period, there were 75 IHCAs, including 20 preintervention and 55 postintervention. Cox proportional hazard regression predicts postintervention individuals have a 74% reduced the risk of death (HR 0.26, 95% CI 0.08 to 0.84) during a code and a 55% reduced risk of death (HR 0.45, 95% CI 0.23 to 0.89) prior to hospital discharge. Overall code survival improved from 60.0% to 83.6% (p=0.031) with an improvement in ventricular tachycardia/ventricular fibrillation (VT/VF) code survival from 50.0% to 100.0% (p=0.035). There was no difference in non-telemetry code survival preintervention and postintervention (71.4% vs 71.3%, p=0.999). The bundled intervention, including improved communication between telemetry technicians and nurses as well as empowerment of telemetry technicians to directly activate the IHCA response team, may improve IHCA survival, specifically for VT/VF arrests.
Socio-economic factors associated with open defecation among agricultural households: a cross-sectional study in Haiti
Authors: Paul Bénédique
Published: September 2023

Background

Open defecation (OD) is recognised as an important public health challenge in low-income and middle-income countries. Although agriculture is the main occupation in these countries, few if any study on OD has focused on agricultural households. In order to enhance the prevention of OD and contribute to a better understanding of this health-threatening behaviour, this paper analyses the socio-economic factors associated with OD practice among agricultural households in Haiti.

Methods

The study used primary data from 1269 households selected in 5 out of 10 geographic departments of Haiti surveyed in 2020–2021. Descriptive statistics and bivariate analysis were used to identify households’ characteristics that were significantly associated with OD. In addition, a multivariate analysis was performed using binary logistic regression to study the factors associated with the probability to defecate in the open.

Results

Findings show that one out of five (20.1%) agricultural households in Haiti practices OD. More than 26% of the households did not have any member with secondary school education level. Multivariate analysis revealed that in addition to the location, the probability of OD practices among agricultural households was correlated with socio-economic factors such as education, access to the media, plot number and livestock, level of specialisation in the agriculture, agricultural income and participation in local organisations.

Conclusion

While Haiti is struggling with cholera among other health issues, this paper sheds light on factors associated with OD, a health-threatening and unsustainable sanitation behaviour. According to the results, in addition to toilet acquisition subsidies, awareness campaigns need to make use of mass media and local organisations particularly women and community ones. Elimination of OD among agricultural households is of great significance for better quality of foods and vegetables at watershed level.
The 2020 US cancer screening deficit and the timing of adults’ most recent screen: a population-based cross-sectional study
Authors: Semprini Jason , Ranganathan Radhika
Published: September 2023

Objective

In 2020, cancer screenings declined, resulting in a cancer screening deficit. The significance of this deficit, however, has yet to be quantified from a population health perspective. Our study addresses this evidence gap by examining how the pandemic changed the timing of American adults’ most recent cancer screen.

Methodology

We obtained population-based, cancer screening data from the Behavioural Risk Factor Surveillance System (BRFSS) (2010, 2012, 2014, 2016, 2018, 2020). Mammograms, pap smears and colonoscopies were each specified as a variable of mutually exclusive categories to indicate the timing since the most recent screening (never, 0–1 years, 1–2 years, 3+ years). Our cross-sectional, quasi-experimental design restricts the sample to adults surveyed in January, February or March. We then leverage a quirk in the BRFSS implementation and consider adults surveyed in the second year of the 2020 survey wave as exposed to the COVID-19 pandemic. Respondents surveyed in January 2020–March 2020 were considered unexposed. To estimate the impact of exposure to the COVID-19 pandemic on the timing of recent cancer screenings, we constructed linear and logistic regression models which control for sociodemographic characteristics associated with screening patterns, and state fixed effects and temporal trend fixed effects to control for confounding.

Results

In 2020, the cancer screening deficit was largely due to a 1 year delay among adults who receive annual screening, as the proportion of adults reporting a cancer screen in the past year declined by a nearly identical proportion of adults reporting their most recent cancer screen 1–2 years ago (3%–4% points). However, the relative change was higher for mammograms and pap smears (17%) than colonoscopies (4%). We also found some evidence that the proportion of women reporting never having completed a mammogram declined in 2020, but the mechanisms for this finding should be further explored with the release of future data.

Conclusion

Our estimates for the pandemic’s effect on cancer screening rates are smaller than prior studies. Because we account for temporal trends, we believe prior studies overestimated the effect of the pandemic and underestimated the overall downward trend in cancer screenings across the country leading up to 2020.
Comparative transcriptomic and proteomic analyses provide insights into the key genes involved in muscle growth in the large Diqing Tibetan pig
Authors: Nie Jingru , Zhang Bo , Ma Li , Yan Dawei , Zhang Hao , Bai Ying , Liu Shiyi , Dong Xinxing
Published: September 2023

Pig growth involves multiple genes and coordinated regulatory mechanisms. The large Diqing Tibetan pigs (TPs) are a unique plateau pig breed in China. Data on the mechanisms of muscle growth and development in TPs are limited, and its transcriptional regulation mechanism remains unclear. This study identifies important genes and proteins involved in muscle growth in TPs. We obtained transcriptomic and proteomic data from the longissimus dorsi muscle tissues of TPs and Duroc pigs (DPs) via RNA-seq and isobaric tags for relative and absolute quantitation analyses, respectively. Comparative analyses of TPs and DPs yielded 557 differentially expressed genes (DEGs) and 56 differentially abundant proteins (DAPs). Functional annotation of these DEGs and DAPs was enriched in metabolic processes, metabolic pathways, cytoskeletal protein binding, AMPK signaling pathway, insulin signaling pathway, PPAR signaling pathway, and other related pathways. Ten genes were identified as key candidate regulators ( FASN, PPARG, PCK1, ACTA2, TXN, SNU13, APOA1, ATP8, ALDH2, and IGFN1) that may play important roles in the muscle growth traits of TPs. This study provides a reference for analyzing the genetic regulation mechanism underlying muscle growth in pigs and improving the meat yield of TPs via molecular marker-assisted selection.
Effect of Arrhenius activation energy on two-phase nanofluid flow and heat transport inside a circular segment with convective boundary conditions: Optimization and sensitivity analysis
Authors: Panda Subhajit , Ontela Surender , Mishra S. R. , Thumma Thirupathi
Published: September 2023

This paper analyzes the heat transport phenomena of two-phase nanofluid within a permeable circular segment with an interaction of Arrhenius activation energy and, examines the interaction of convective boundary conditions affecting the flow characteristics. The pre-exponential factor of the Arrhenius equation deals with the collision between molecules, and it has significant applications for getting the rate of a chemical reaction and is used to estimate material properties with changes in temperature and energy. To a greater extent, the external uniform heat source encourages thermal properties on account of the behavior of Brownian and thermophoresis parameters. The transformation of the standard nondimensional form of the governing equations is obtained for the assumption of appropriate similarity variables and stream function. The set of these transformed equations is tackled numerically with the shooting technique. The characteristics of physical parameters on the flow phenomena are presented graphically and the validation with earlier research displays a strong correlation for the specific case. The special attraction of the present investigation is the regression analysis for the simulated results of heat and solutal transfer rates using Response Surface Methodology considering various characterizing parameters like heat source, thermal radiation, curvature, activation energy, thermal and solutal Biot numbers within certain range.
Photoelectric properties of Pb ions adsorbed on black phosphorene in water
Authors: Jiao Gan , Liu Guili , Zhao Jing Wei , Wei Lin , Zhang Guoying
Published: September 2023

Using density functional theory, the effects of Pb[Formula: see text] coverage and Fe modification on the electronic properties of black phosphorus in water were calculated. The investigation found that the increasing of Pb[Formula: see text] coverage improves the stability of the structure and the adsorption height, and makes the bond length of the P–P bond continuously increase, and the modification of Fe further increases the adsorption height of the system. Black phosphorene has a direct bandgap semiconductor structure in water, with a bandgap value of 0.759[Formula: see text]eV, and the adsorption of Pb[Formula: see text] makes it a metal structure, and the modification of Fe makes the bandgap reopened and becomes a direct bandgap semiconductor structure. Intrinsic black phosphorus has strong sp orbital hybridization, s orbital and p orbital make great contributions to the conduction band and valence band, the adsorption of Pb[Formula: see text] makes the total density of states increase, and the value of the density of states at the Fermi level increases, the density of states crosses the Fermi level, and the system exhibits metallicity. It can be seen that the adsorption of Pb ions and the modification of Fe have changed the structural properties of the black phosphene system in aqueous solution, and the structural stability of the system has been continuously improved, which has important guiding significance for removing Pb ions in water, purifying water quality, protecting ecological environment and human life and health.
A Simple Model of Tumor-Immune Interaction: The Effect of Antigen Delay
Authors: Li Jianquan , Chen Yuming , Cao Hui , Zhang Dian , Zhang Peijun
Published: September 2023

We propose a simple model of tumor-immune interactions, which involves effector cells and tumor cells. In the model, the stimulation delay of tumor antigen in the immune system is incorporated. We investigate the dynamical behavior of the model via theoretic analysis and numerical simulations. The saddle-node bifurcation can occur in both cases with and without delay. In contrast to the case without delay, stimulation delay may result in some complex dynamical behaviors and biological phenomena. In the presence of delay, conditions on absolute/conditional stability of equilibria and the existence of Hopf bifurcations are obtained. We further discuss the effect of the tumor on the switch between absolute stability and conditional stability. Numerical simulations also show the existence of homoclinic bifurcation and the dependence of the asymptotic state of the tumor progression on initial conditions for different delay values. Effects of delay on the dynamics of the model and on the region of tumor extinction are illustrated by simulations with different sets of parameter values. Finally, the corresponding biological implications are demonstrated.
Blitz Innovation Framework — From Innovation to Ecosystem for Software Startups
Authors: Shanbhag Narendranath , Pardede Eric
Published: September 2023

Start-ups and established organisations alike create business models around value propositions. This would make value propositions the core offering of value, around which business model efforts are based on. Products are created following successful validation of any identified value proposition. This research proposes a holistic approach to value proposition development, with the aim of helping software start-ups to quickly develop and scale their product development efforts. The proposed framework takes a process-based approach while remaining user-centric. It covers the whole spectrum of the value proposition development process ranging from the study of the user to managing growth-related aspects of the product and monitoring performance via the identification of key metrics. This end-to-end approach can help inexperienced start-up teams during their early development efforts and therefore lower the barriers of entry for the software startup space. Validation for the proposed framework is done using a case study approach of a successful value proposition by a former start-up.
FedEgo: Privacy-preserving Personalized Federated Graph Learning with Ego-graphs
Authors: Zhang Taolin , Mai Chengyuan , Chang Yaomin , Chen Chuan , Shu Lin , Zheng Zibin
Published: September 2023

As special information carriers containing both structure and feature information, graphs are widely used in graph mining, e.g., Graph Neural Networks (GNNs). However, graph data are stored separately in multiple distributed parties in some practical scenarios, which may not be directly shared due to conflicts of interest. Hence, federated graph neural networks are proposed to address such data silo issues while preserving each party’s privacy (or client). Nevertheless, different graph data distributions of various parties, which is known as the statistical heterogeneity, may degrade the performance of naive federated learning algorithms like FedAvg. In this article, we propose FedEgo, a federated graph learning framework based on ego-graphs to tackle the challenges above, in which each client will train their local models while also contributing to the training of a global model. FedEgo applies GraphSAGE over ego-graphs to make full use of the structure information and utilizes Mixup for privacy concerns. To deal with the statistical heterogeneity, we integrate personalization into learning and propose an adaptive mixing coefficient strategy that enables clients to achieve their optimal personalization. Extensive experimental results and in-depth analysis demonstrate the effectiveness of FedEgo.
Advancing Direct Convolution Using Convolution Slicing Optimization and ISA Extensions
Authors: Ferrari Victor , Sousa Rafael , Pereira Marcio , L. De Carvalho João P. , Amaral José Nelson , Moreira José , Araujo Guido
Published: September 2023

Convolution is one of the most computationally intensive operations that must be performed for machine learning model inference. A traditional approach to computing convolutions is known as the Im2Col + BLAS method. This article proposes SConv: a direct-convolution algorithm based on an MLIR/LLVM code-generation toolchain that can be integrated into machine-learning compilers. This algorithm introduces: (a) Convolution Slicing Analysis (CSA)—a convolution-specific 3D cache-blocking analysis pass that focuses on tile reuse over the cache hierarchy; (b) Convolution Slicing Optimization—a code-generation pass that uses CSA to generate a tiled direct-convolution macro-kernel; and (c) Vector-based Packing—an architecture-specific optimized input-tensor packing solution based on vector-register shift instructions for convolutions with unitary stride. Experiments conducted on 393 convolutions from full ONNX-MLIR machine learning models indicate that the elimination of the Im2Col transformation and the use of fast packing routines result in a total packing time reduction, on full model inference, of 2.3×–4.0× on Intel x86 and 3.3×–5.9× on IBM POWER10. The speed-up over an Im2Col + BLAS method based on current BLAS implementations for end-to-end machine-learning model inference is in the range of 11%–27% for Intel x86 and 11%–34% for IBM POWER10 architectures. The total convolution speedup for model inference is 13%–28% on Intel x86 and 23%–39% on IBM POWER10. SConv also outperforms BLAS GEMM, when computing pointwise convolutions in more than 82% of the 219 tested instances.
Polypharmacy and Deprescribing in Older Adults
Authors: Thompson Wade , McDonald Emily G.
Published: September 2023

Older adults commonly end up on many medications. Deprescribing is an important part of individualizing care for older adults. It is an opportunity to discuss treatment options and revisit medications that may not have been reassessed in many years. A large evidence base exists in the field, suggesting that deprescribing is feasible and safe, though questions remain about the potential clinical benefits. Deprescribing research faces a myriad of challenges, such as identifying and employing the optimal outcome measures. Further, there is uncertainty about which deprescribing approaches are likely to be most effective and in what contexts. Evidence on barriers and facilitators to deprescribing has underscored how deprescribing in routine clinical practice can be complex and challenging. Thus, finding practical, sustainable ways to implement deprescribing is a priority for future research in the field.
Molecular Characterization of Plastic Waste Using Standoff Photothermal Spectroscopy
Authors: Zhao Yaoli , Chakraborty Patatri , Meng Zixia , Nair Asalatha , Goyal Amit , Thundat Thomas
Published: September 2023

An accurate molecular identification of plastic waste is important in increasing the efficacy of automatic plastic sorting in recycling. However, identification of real-world plastic waste, according to their resin identification code, remains challenging due to the lack of techniques that can provide high molecular selectivity. In this study, a standoff photothermal spectroscopy technique, utilizing a microcantilever, was used for acquiring mid-infrared spectra of real-world plastic waste, including those with additives, surface contaminants, and mixed plastics. Analysis of the standoff spectral data, using Convolutional Neural Network (CNN), showed 100% accuracy in selectively identifying real-world plastic waste according to their respective resin identification codes. Standoff photothermal spectroscopy, together with CNN analysis, offers a promising approach for the selective characterization of waste plastics in Material Recovery Facilities (MRFs).
Promising Markers in the Context of Mesenchymal Stem/Stromal Cells Subpopulations with Unique Properties
Authors: Smolinska Agnieszka , Bzinkowska Aleksandra , Rybkowska Paulina , Chodkowska Magdalena , Sarnowska Anna
Published: September 2023

The heterogeneity of the mesenchymal stem/stromal cells (MSCs) population poses a challenge to researchers and clinicians, especially those observed at the population level. What is more, the lack of precise evidences regarding MSCs developmental origin even further complicate this issue. As the available evidences indicate several possible pathways of MSCs formation, this diverse origin may be reflected in the unique subsets of cells found within the MSCs population. Such populations differ in specialization degree, proliferation, and immunomodulatory properties or exhibit other additional properties such as increased angiogenesis capacity. In this review article, we attempted to identify such outstanding populations according to the specific surface antigens or intracellular markers. Described groups were characterized depending on their specialization and potential therapeutic application. The reports presented here cover a wide variety of properties found in the recent literature, which is quite scarce for many candidates mentioned in this article. Even though the collected information would allow for better targeting of specific subpopulations in regenerative medicine to increase the effectiveness of MSC-based therapies.
Ethnomedicinal Knowledge of Plants Used in Nonconventional Medicine in the Management of Diabetes Mellitus in Kinshasa (Democratic Republic of the Congo)
Authors: Chiribagula Valentin Bashige , Ndjolo Philippe Okusa , Mboni Henry Manya , Mushagalusa Kasali Félicien
Published: September 2023

Background. People with diabetes, herbalists, and traditional medicine practitioners (TMPs) from Kinshasa use plants to treat diabetes, but no study has inventoried the plants used by these populations. The present study was conducted to identify the plants used in Kinshasa to treat diabetes mellitus. Methods. The survey conducted in the form of a semistructured interview between March 2005 and August 2006 made it possible to collect ethnobotanical information from people with diabetes (n = 126), herbalists (n = 80), and TMPs (n = 120). Results. The 326 subjects consulted (sex ratio M/F = 0.6, age 51 ± 7 years, and experience: 17 ± 5 years) provided information on 71 plants, most of which are trees (35%), belonging to 38 families dominated by Fabaceae (19.7%) and indicated in 51 other cases of consultation dominated by malaria (12%). From these 71 plants derived, 86 antidiabetic recipes were administered orally, where the leaf is the most used part (>50%) and the decoction (>46%) is the most common mode of preparation. This study reports for the first time the antidiabetic use of 11 species, among which Tephrosia vogeliiX (0.08), Chromolaena corymbosaX (0.06), and Baphia capparidifoliaX (0.06) present the highest consensus indexes (CI) and Marsdenia latifoliaW (UVp = 0.08) and Rauvolfia manniiX (UVp = 0.06) present the highest UVs. Conclusion. The results show that Kinshasa people treat diabetes using several plants. Some are specific to the ecological environment; others are used in other regions. Pharmacological studies are underway to assess the therapeutic efficacy of these plants.
Effect on Satisfactory Seizure Control and Heart Rate Variability of Thread-Embedding Acupuncture for Drug-Resistant Epilepsy: A Patient-Assessor Blinded, Randomized Controlled Trial
Authors: Nguyen Van-Dan , Pham Duc-Thang , Le Minh-An Thuy , Shen Guo-Ming
Published: September 2023

This randomized controlled trial investigates the efficacy of thread-embedding acupuncture (TEA) compared to sham TEA in treating drug-resistant epilepsy (DRE). Fifty-four DRE outpatients were randomly divided into two groups: TEA (27 patients) and sham TEA (27 patients). Both groups received four sessions of TEA or sham TEA, spaced four weeks apart, targeting GV20, GV14, BL15, BL18, ST40, and GB34 acupoints. Antiseizure medications were maintained at consistent doses throughout the study. Outcome measures included satisfactory seizure control, seizure freedom, and heart rate (HR) and heart rate variability (HRV) measurements. TEA demonstrated a significantly higher rate of satisfactory seizure control at follow-up compared to the sham TEA group (37% vs. 3.7%,

p
=
0.003

). While no significant intergroup differences were observed in HR, HRV, and HRV components at each stage, the TEA group experienced a significant decrease in HR and a significant increase in HRV posttreatment. This study demonstrates TEA’s effectiveness in managing DRE and suggests its impact may relate to heightened parasympathetic nerve activity. Further research with extended follow-up periods is necessary to validate these findings.
Strength and Microscopic Characteristics of Slag-Based Geopolymer-Solidified Sludge after Dry–Wet Cycling with Chloride Salt Solutions
Authors: Yu Kai , Deng Yunsheng , Jiang Shaowu , Qiu Chang
Published: September 2023

As a new type of green soil-curing agent, geopolymers have the advantages of high strength, good durability, and low carbon emissions, and slag is widely used as a common geopolymer precursor in geopolymer production. Therefore, it is important to investigate the strength and durability of slag-based polymer-solidified sludge under the action of dry–wet cycling with chloride salt solutions. After curing the slag-based polymer-solidified sludge with NaOH (NO), Na2SiO3 (NS), and calcium carbide slag (CS) as alkali excitants to different curing ages (7, 14, 28 days), experiments involving different numbers of dry–wet cycles (0, 5, 10, 20, 30) with NaCl solutions of different concentrations (0%, 5%, 10%) were performed to investigate the unconfined compressive strength and micromorphology of the solidified sludge after undergoing dry–wet cycling. The test results showed that the strength of sludge cured with NO for 7 and 14 days showed a trend of increasing and then decreasing with an increasing number of dry–wet cycles, and the strength of sludge cured with NO for 28 days showed a trend of gradually decreasing with an increasing number of dry–wet cycles. The order of the resistance of sludge cured with the three excitants to the effect of the dry–wet cycles of chlorine salt was CS > NO > NS. After the dry–wet cycling, small cracks appeared on the surface of the NS-cured soil, the surface of the NO-cured soil was intact, and a small amount of surface peeling was observed for the CS-cured soil. Scanning electron microscopy test results showed that the chloride salt dry–wet cycles caused the formation of pores and cracks in the soil, and NaCl crystallization and Friedel’s salt production were observed in the soil, thus reducing the strength of the solidified sludge.
Mulberry Juice-Derived Carbon Quantum Dots as a Cu2+ Ion Sensor: Investigating the Influence of Fruit Ripeness on the Optical Properties
Authors: Salih Ajaj Chiayee , Sadiq Diyar
Published: September 2023

This study synthesized carbon quantum dots (CQDs) with green photoluminescence through a hydrothermal method that utilized mulberry juice as the carbon source. The influence of fruit ripeness on the physical and chemical properties, focusing on the fluorescence spectra, has been explored. Fourier-transform infrared spectroscopy (FT-IR) and energy dispersive X-ray analysis (EDX) showed that there were oxygen-containing groups, and X-ray diffraction (XRD) showed that the carbon quantum dots (CQDs) were graphitic. The results revealed that the CQDs had an average size of around 7.4 nm and 9.7 nm for unripe and ripe mulberry juice, respectively. These CQDs emitted green light at 500 nm and 510 nm in unripe and ripe mulberry juice, respectively, when excited at a wavelength of 400 nm. The prepared CQDs exhibited excitation-dependent photoluminescence (PL) emission behavior, demonstrating their dependence on the excitation light. The impact of fruit ripeness on optical properties was explored by examining fluorescent spectra from different fruits (including tomato and blackberry), demonstrating comparable behaviors observed in mulberry fruit. In addition, the prepared CQDs were utilized as a fluorescent sensor with high specificity to detect Cu2+ ions. The detection limit (DL) for this sensor was determined to be 0.2687 µM, and the limit of qualification (LOQ) is 0.814 µM. The linear range for detection lies between 0.1 and 1 µM. The selectivity of the CQDs towards Cu2+ ions was confirmed by recording the PL response for Cu2+ ions compared to the weak response of other metal ions. According to these results, the CQDs can be applied in various cellular imaging and biology applications, bio-sensing, optoelectronics, and sensors.
Fatty Acid Oxidation Mediated by Malonyl-CoA Decarboxylase Represses Renal Cell Carcinoma Progression
Authors: Zhou Lijie , Luo Yongbo , Liu Yuenan , Zeng Youmiao , Tong Junwei , Li Mengting , Hou Yaxin , Du Kaixuan , Qi Yabin , Pan Wenbang , Liu Yuanhao , Wang Rongli , Tian Fengyan , Gu Chaohui , Chen Ke
Published: September 2023

Fatty acid metabolism reprogramming is a prominent feature of clear cell renal cell carcinoma (ccRCC). Increased lipid storage supports ccRCC progression, highlighting the importance of understanding the molecular mechanisms driving altered fatty acid synthesis in tumors. Here, we identified that malonyl-CoA decarboxylase (MLYCD), a key regulator of fatty acid anabolism, was downregulated in ccRCC, and low expression correlated with poor prognosis in patients. Restoring MLYCD expression in ccRCC cells decreased the content of malonyl CoA, which blocked de novo fatty acid synthesis and promoted fatty acid translocation into mitochondria for oxidation. Inhibition of lipid droplet accumulation induced by MLYCD-mediated fatty acid oxidation disrupted endoplasmic reticulum and mitochondrial homeostasis, increased reactive oxygen species levels, and induced ferroptosis. Moreover, overexpressing MLYCD reduced tumor growth and reversed resistance to sunitinib in vitro and in vivo. Mechanistically, HIF2α inhibited MLYCD translation by upregulating expression of eIF4G3 microexons. Together, this study demonstrates that fatty acid catabolism mediated by MLYCD disrupts lipid homeostasis to repress ccRCC progression. Activating MLYCD-mediated fatty acid metabolism could be a promising therapeutic strategy for treating ccRCC.

Significance:

MLYCD deficiency facilitates fatty acid synthesis and lipid droplet accumulation to drive progression of renal cell carcinoma, indicating inducing MYLCD as a potential approach to reprogram fatty acid metabolism in kidney cancer.
Genome-Wide CRISPR Screens Identify Multiple Synthetic Lethal Targets That Enhance KRASG12C Inhibitor Efficacy
Authors: Mukhopadhyay Suman , Huang Hsin-Yi , Lin Ziyan , Ranieri Michela , Li Shuai , Sahu Soumyadip , Liu Yingzhuo , Ban Yi , Guidry Kayla , Hu Hai , Lopez Alfonso , Sherman Fiona , Tan Yi Jer , Lee Yeuan Ting , Armstrong Amanda P. , Dolgalev Igor , Sahu Priyanka , Zhang Tinghu , Lu Wenchao , Gray Nathanael S. , Christensen James G. , Tang Tracy T. , Velcheti Vamsidhar , Khodadadi-Jamayran Alireza , Wong Kwok-Kin , Neel Benjamin G.
Published: September 2023

Non–small lung cancers (NSCLC) frequently (∼30%) harbor KRAS driver mutations, half of which are KRASG12C. KRAS-mutant NSCLC with comutated STK11 and/or KEAP1 is particularly refractory to conventional, targeted, and immune therapy. Development of KRASG12C inhibitors (G12Ci) provided a major therapeutic advance, but resistance still limits their efficacy. To identify genes whose deletion augments efficacy of the G12Cis adagrasib (MRTX-849) or adagrasib plus TNO155 (SHP2i), we performed genome-wide CRISPR/Cas9 screens on KRAS/STK11-mutant NSCLC lines. Recurrent, potentially targetable, synthetic lethal (SL) genes were identified, including serine–threonine kinases, tRNA-modifying and proteoglycan synthesis enzymes, and YAP/TAZ/TEAD pathway components. Several SL genes were confirmed by siRNA/shRNA experiments, and the YAP/TAZ/TEAD pathway was extensively validated in vitro and in mice. Mechanistic studies showed that G12Ci treatment induced gene expression of RHO paralogs and activators, increased RHOA activation, and evoked ROCK-dependent nuclear translocation of YAP. Mice and patients with acquired G12Ci- or G12Ci/SHP2i-resistant tumors showed strong overlap with SL pathways, arguing for the relevance of the screen results. These findings provide a landscape of potential targets for future combination strategies, some of which can be tested rapidly in the clinic.

Significance:

Identification of synthetic lethal genes with KRASG12C using genome-wide CRISPR/Cas9 screening and credentialing of the ability of TEAD inhibition to enhance KRASG12C efficacy provides a roadmap for combination strategies.

See related commentary by Johnson and Haigis, p. 4005
Tumor-Infiltrating Normal B Cells Revealed by Immunoglobulin Repertoire Clonotype Analysis Are Highly Prognostic and Crucial for Antitumor Immune Responses in DLBCL
Authors: Xu-Monette Zijun Y. , Li Yong , Snyder Thomas , Yu Tiantian , Lu Tingxun , Tzankov Alexandar , Visco Carlo , Bhagat Govind , Qian Wenbin , Dybkaer Karen , Chiu April , Tam Wayne , Zu Youli , Hsi Eric D. , Hagemeister Fredrick B. , Wang Yingjun , Go Heounjeong , Ponzoni Maurilio , Ferreri Andrés J.M. , Møller Michael B. , Parsons Benjamin M. , Fan Xiangshan , van Krieken J. Han , Piris Miguel A. , Winter Jane N. , Au Qingyan , Kirsch Ilan , Zhang Mingzhi , Shaughnessy John , Xu Bing , Young Ken H.
Published: September 2023

Purpose:

Tumor-infiltrating B lymphocytes (TIL-B) have demonstrated prognostic and predictive significance in solid cancers. In this study, we aimed to distinguish TIL-Bs from malignant B-cells in diffuse large B-cell lymphoma (DLBCL) and determine the clinical and biological significance.

Experimental Design:

A total of 269 patients with de novo DLBCL from the International DLBCL R-CHOP Consortium Program were studied. Ultra-deep sequencing of the immunoglobulin genes was performed to determine B-cell clonotypes. The frequencies and numbers of TIL-B clonotypes in individual repertoires were correlated with patient survival, gene expression profiling (GEP) data, and frequencies of DLBCL-infiltrating immune cells quantified by fluorescent multiplex IHC at single-cell resolution.

Results:

TIL-B abundance, evaluated by frequencies of normal B-cell clonotypes in the immunoglobulin repertoires, remarkably showed positive associations with significantly better survival of patients in our sequenced cohorts. DLBCLs with high versus low TIL-B abundance displayed distinct GEP signatures, increased pre-memory B-cell state and naïve CD4 T-cell state fractions, and higher CD4+ T-cell infiltration. TIL-B frequency, as a new biomarker in DLBCL, outperformed the germinal center (GC) B-cell–like/activated B-cell–like classification and TIL-T frequency. The identified TIL-B–high GEP signature, including genes upregulated during T-dependent B-cell activation and those highly expressed in normal GC B cells and T cells, showed significant favorable prognostic effects in several external validation cohorts.

Conclusions:

TIL-B frequency is a significant prognostic factor in DLBCL and plays a crucial role in antitumor immune responses. This study provides novel insights into the prognostic determinants in DLBCL and TIL-B functions with important therapeutic implications.