bluuebunny/crossref_metadata_2025 huggingface dataset:
Instagram as a health education tool: Evaluating the efficacy and quality of medical content on Instagram in Azerbaijan
Authors: Graefen Bahar , Hasanli Shams , Jabrayilov Araz , Alakbarova Gulgaz , Tahmazi Khayala , Gurbanova Jamila , Fazal Nadeem
Published: December 2023

Background

In recent years, Instagram has become the most popular tool among professional doctors in Azerbaijan for educating their patients. The use of the Instagram application aims to raise patients’ awareness of the importance of taking care of their health and to increase their knowledge about their health conditions using modern services. In this article, the authors examine the quality of Instagram content for health education among the population.

Methods

We conducted a survey to collect anonymous data from more than 205 respondents and summarized the following points.

Results

65% of the respondents were already obtaining health information from Instagram before to participating in the study. 15.1 % of them frequently visit Instagram for health information while 5% had found the health information accessed there harmful. 71% of respondents think accessing health information in this way is beneficial but that the quality and usefulness of the content is average. 95% of respondents reported that the health information they obtained from the identical platform was not causing them any harm

Conclusion

The medical information shared on Instagram is generally considered useful and beneficial by the population, but it is desirable to improve the quality of the content.
On the dependence of the critical success index (CSI) on prevalence
Authors: Mbizvo Gashirai K. , Larner Andrew J.
Published: December 2023

Recently the critical success index (CSI) has been increasingly discussed and advocated as a unitary outcome measure in various clinical situations where large numbers of true negatives may influence the interpretation of other more traditional outcome measures such as sensitivity and specificity, or when unified interpretation of positive predictive value (PPV) and sensitivity (Sens) is needed. The derivation of CSI from measures including PPV has prompted questions as to whether and how CSI values may vary with disease prevalence (P), just as PPV estimates are dependent on P, and hence whether CSI values are generalizable between studies with differing prevalences. As no detailed study of the relation of CSI to prevalence has been undertaken hitherto, the dataset of a previously published test accuracy study of a cognitive screening instrument was reinterrogated to address this question. Three different methods were used to examine the change in CSI across a range of prevalences, using both Bayes formula and equations directly relating CSI to Sens, PPV, P, and to test threshold (Q). These approaches showed that, as expected, CSI does vary with prevalence, but the dependence differs according to the method of calculation adopted. Bayesian rescaling both Sens and PPV generates a concave curve, suggesting that CSI will be maximal at a particular prevalence which may vary according to the particular dataset.
Imaging neuronal voltage beyond the scattering limit
Authors: Chen Tsai-Wen , Huang Xian-Bin , Plutkis Sarah E. , Holland Katie L. , Lavis Luke D. , Lin Bei-Jung
Published: December 2023

Voltage imaging is a promising technique for high-speed recording of neuronal population activity. However, tissue scattering severely limits its application in dense neuronal populations. Here, we adopted the principle of localization microscopy, a technique that enables super-resolution imaging of single-molecules, to resolve dense neuronal activitiesin vivo. Leveraging the sparse activation of neurons during action potentials (APs), we precisely localize the fluorescence change associated with each AP, creating a super-resolution image of neuronal activities. This approach, termedActivityLocalizationImaging (ALI), identifies overlapping neurons and separates their activities with over 10-fold greater precision than what tissue scattering permits. Using ALI, we simultaneously recorded over a hundred densely-labeled CA1 neurons, creating a map of hippocampal theta oscillation at single-cell and single-cycle resolution.
Whole-genome sequences reveal zygotic composition in chimeric twins
Authors: Yoon Christopher J. , Nam Chang Hyun , Kim Taewoo , Lee Jeong Seok , Kim Ryul , Yi Kijong , Koh June-Young , Kim Jiye , Won Hyein , Oh Ji Won , Griffith Obi L. , Griffith Malachi , Sung Joohon , Kim Tae Yeul , Cho Duck , Choi Ji Seon , Ju Young Seok
Published: December 2023

The monochorionic placenta in dizygotic twins allowsin uteroexchange of embryonic cells, resulting in chimerism in the twins. In practice, this chimerism is incidentally identified on mixed ABO blood types or in the presence of cells with a discordant sex chromosome. Here, we applied whole-genome sequencing to one triplet and one twin families to precisely understand their zygotic compositions, using millions of genomic variants as barcodes of zygotic origins. Peripheral blood showed asymmetrical contributions from two sister zygotes, where one of the zygotes was the major clone in both twins. Single-cell RNA sequencing of peripheral blood tissues further showed differential contributions from the two sister zygotes across blood cell types. In contrast, buccal tissues were pure in genetic composition, suggesting thatin uterocellular exchanges were confined to the blood tissues. Our study illustrates the cellular history of twinning during human development, which is critical for managing the health of chimeric individuals in the era of genomic medicine.
Integration of multi-source gene interaction networks and omics data with graph attention networks to identify novel disease genes
Authors: Yang Kaiyuan , Cheng Jiabei , Cao Shenghao , Pan Xiaoyong , Shen Hong-Bin , Jin Cheng , Yuan Ye
Published: December 2023

The pathogenesis of diseases is closely associated with genes, and the discovery of disease genes holds significant importance for understanding disease mechanisms and designing targeted therapeutics. However, biological validation of all genes for diseases is expensive and challenging. In this study, we propose DGP-AMIO, a computational method based on graph attention networks, to rank all unknown genes and identify potential novel disease genes by integrating multi-omics and gene interaction networks from multiple data sources. DGP-AMIO outperforms other methods significantly on 20 disease datasets, with an average AUROC and AUPR exceeding 0.9. The superior performance of DGP-AMIO is attributed to the integration of multiomics and gene interaction networks from multiple databases, as well as triGAT, a proposed GAT-based method that enables precise identification of disease genes in directed gene networks. Enrichment analysis conducted on the top 100 genes predicted by DGP-AMIO and literature research revealed that a majority of enriched GO terms, KEGG pathways and top genes were associated with diseases supported by relevant studies. We believe that our method can serve as an effective tool for identifying disease genes and guiding subsequent experimental validation efforts.
Controllable Protein Design by Prefix-Tuning Protein Language Models
Authors: Luo Jiawei , Liu Xianliang , Li Jiahao , Chen Qingcai , Chen Junjie
Published: December 2023

Designing novel proteins tailored for specific purposes (e.g. drug discovery, vaccine design) presents a promising approach to address various biomedical challenges. Due to the similarity between protein sequences and natural languages, motivated by the remarkable success in NLP tasks that pre-trained language models have enabled text generation with human-like capabilities, protein language models (ProtLMs) are constructed to generate protein sequences with a predictable function across large protein families. The text generation can be controllable by constructing prefix-phase as control tags to prompt NLP language models. However, the vocabulary of protein sequences only contains 20 amino acid residues, which is not like natural language vocabulary to make up flexible control tags. In this study, we propose a controllable protein design method, named PrefixProt, which utilizes prefix tuning to learn virtual tokens as control tags, enabling to efficiently prompt the pre-trained ProtLM for protein generation tailored for specific purposes. The virtual tokens can be learned on any protein properties by data-driven and are flexible to be combined for fine-grained control. To demonstrate the effectiveness of PrefixProt, we train three virtual tokens on alpha-helix structure dataset, antimicrobial peptide (AMP) dataset and anticancer peptide (ACP) dataset, respectively. Our results show that prefix virtual tokens are efficient to prompt the pretrained ProtLM by optimizing fewer trainable parameters compared with fine-tuning, especially under low-data settings. When combining the virtual tokens, the proportion of generated proteins with multiple properties are significantly improved. Therefore, PrefixProt offers a flexible and controllable protein design solution. We anticipate that PrefixProt will contribute to drug discovery and biomedical advancement.

Availability and implementation

The models and associated code are available at:https://github.com/chen-bioinfo/PrefixProt
DNA origami assembled spheroid for evaluating cytotoxicity and infiltration of chimeric antigen receptor macrophage (CAR-M)
Authors: Liu Junhua , He Xiaofang , Zhu Qingyao , Wang Heming , Shan Xiaojiao , Zhao Yicheng , Zhang Luo , Song Guangqi , Yin Xiushan
Published: December 2023

Chimeric antigen receptor (CAR) T-cell therapies have shown remarkable results in patients with hematological malignancies. However, their success in treating solid tumors has been limited. As an alternative candidate for the CAR approach, CAR-macrophages (CAR-M) have demonstrated activation and phagocytosis directed by tumor antigens, showing promise in the treatment of solid tumors. Nevertheless, the mechanisms by which CARs direct tumor chemotaxis and invasion of CAR-M remain poorly understood. In this study, we aim to investigate the role of CARs in CAR-M attachment and infiltration using 3D tumor micro-spheroids, which were created by utilizing a novel nucleic acid nanostructures decorated living cells (NACs) based origami assembly technique. First, the effectiveness of phagocytosis and killing conducted by CAR-M was validated in the conventional 2D well/plate-surface culture models. Then,peripheral blood mononuclear cell (PBMC) invasion assay confirmed that the 3D tumor micro-spheroids were feasible for cell invasion. Finally, our results demonstrated that CAR-M exhibited higher invasion and killing capacity in 3D tumor micro-spheroids. In summary, the 3D NACs-origami assembled tumor spheroid model provides a suitable platform for target screening and pharmacodynamic evaluation of CAR-M.
gNOMO2: a comprehensive and modular pipeline for integrated multi-omics analyses of microbiomes
Authors: Arıkan Muzaffer , Muth Thilo
Published: December 2023

Background

Over the past few years, the rise of omics technologies has offered an exceptional chance to gain a deeper insight into the structural and functional characteristics of microbial communities. As a result, there is a growing demand for user friendly, reproducible, and versatile bioinformatic tools that can effectively harness multi-omics data to offer a holistic understanding of microbiomes. Previously, we introduced gNOMO, a bioinformatic pipeline specifically tailored to analyze microbiome multi-omics data in an integrative manner. In response to the evolving demands within the microbiome field and the growing necessity for integrated multi-omics data analysis, we have implemented substantial enhancements to the gNOMO pipeline.

Results

Here, we present gNOMO2, a comprehensive and modular pipeline that can seamlessly manage various omics combinations, ranging from two to four distinct omics data types including 16S rRNA gene amplicon sequencing, metagenomics, metatranscriptomics, and metaproteomics. Furthermore, gNOMO2 features a specialized module for processing 16S rRNA gene amplicon sequencing data to create a protein database suitable for metaproteomics investigations. Moreover, it incorporates new differential abundance, integration and visualization approaches, all aimed at providing a more comprehensive toolkit and insightful analysis of microbiomes. The functionality of these new features is showcased through the use of four microbiome multi-omics datasets encompassing various ecosystems and omics combinations. gNOMO2 not only replicated most of the primary findings from these studies but also offered further valuable perspectives.

Conclusions

gNOMO2 enables the thorough integration of taxonomic and functional analyses in microbiome multi-omics data, opening up avenues for novel insights in the field of both host associated and free-living microbiome research. gNOMO2 is available freely athttps://github.com/muzafferarikan/gNOMO2.
The effects of alternative rabbit control methods on feral cat activity in an open, semi-arid landscape
Authors: Jansen Jeroen , Comte Sebastien , Dean Abbey T , Axford Geoff , Moseby Katherine E , Peacock David E , Brandle Robert , Jones Menna E
Published: December 2023

The availability of invasive prey often plays an important role in regulating cointroduced invasive predator populations. As predators have been shown to respond rapidly to declines in prey populations, our objective was to experimentally test how local population reduction of an invasive prey species, the European rabbit (Oryctolagus cuniculus), affects the activity of an introduced predator, the feral cat (Felis catus). To test the effectiveness of three different rabbit control methods, activity levels of cats were surveyed with remote infrared wildlife cameras in three treatment and four control sites. The rabbit control treatments were implemented in extensive open landscapes in the semi-arid zone of South Australia, and consisted of shooting of rabbits, destruction of rabbit warrens, and the targeted delivery of baits treated with RHDV. The results indicate that only the destruction of rabbit warrens has observable effects on the number of cat detections on cameras. Cat detections decreased in the areas where rabbit warrens were destroyed and increased in adjacent areas where rabbits were still abundant. This suggests that cats vacated the treated area and moved into surrounding areas of abundant introduced prey.
Landscape and functional repertoires of long noncoding RNAs in the pan-cancer tumor microenvironment using single-nucleus total RNA sequencing
Authors: Fan Tongqiang , Ni Shengyu , Chen Haide , Xu Ziye , Fan Longjiang , Wang Yongcheng
Published: December 2023

Intratumor heterogeneity (ITH) plays crucial roles in tumor progression. However, the atlas of long noncoding RNAs (lncRNAs) in the context of ITH across multiple cancer types remains largely unexplored. Here, we analyze over 800,000 cells from ten different cancer types generated from the random-primed single-nucleus total RNA sequencing and provide a systematic landscape of lncRNAs in tumor microenvironment (TME) and malignant programs. Our study employe a robust cell annotation pipeline called scAnnotation, which allows us to identify 39 distinct cell types within the pan-cancer TME. By applying stringent criteria, we identify thousands of reliable marker genes, including both mRNAs and lncRNAs. Next, we identify sets of cell type-specific lncRNA-mRNA pairs by our LncPairs algorithm. Moreover, we identify nine expression meta-programs (MPs) associated with diverse biological processes in malignant cells across multiple cancer types. MP-specific lncRNA-transcription factor (TF) regulatory networks are further constructed and key lncRNAs and regulons that exert control over MP-specific gene expression are identified. The comprehensive atlas of lncRNAs in the pan-cancer context, coupled with the bioinformatics tools tailored for the random-primed datasets, is expected to accelerate advancements in the field of lncRNA research at the single-cell resolution.
Effects of greening-induced warming and cooling on tree phenology in temperate and boreal forests
Authors: Guo Jing , Wang Jinmei , Qiao Yuxin , Smith Nicholas G. , Liu Zhiyong , Zhang Rui , Chen Xiuzhi , Wu Chaoyang , Chen Lei
Published: December 2023

Tree phenology, periodic biological events in trees, is highly sensitive to climate change. It has been reported that forest greening can influence the local climate by altering the seasonal surface energy budget. However, tree phenological responses to forest greening remains poorly understood at large spatial scales. Combining remote-sensing derived phenological and leaf area indices since 2001, herein we show that forest greening led to earlier spring (−1.05 ± 0.17 d) and autumn phenology (−1.95 ± 0.14 d) in temperate and boreal forests. Our results show that forest greening in winter and spring decreased surface albedo and thus resulted in biophysical warming that caused earlier spring leaf phenology. In contrast, forest greening in summer and autumn triggered biophysical cooling by enhancing evapotranspiration, which led to earlier autumn leaf phenology. These findings suggest that forest greening could significantly alter tree phenology through seasonal biophysical impacts. Therefore, it is essential to incorporate these complicated biophysical impacts of greening into tree phenology models to accurately predict future shifts in tree phenology under future climate change.
Seabird traits and seasonality modulate nutrient dynamics of terrestrial and marine habitats on atolls
Authors: Appoo Jennifer , Bunbury Nancy , Letori Jake , Hector Aurelie , Gendron Annie , Graham Nicholas A.J. , Rocamora Gerard , Corre Matthieu Le , Jaquemet Sébastien
Published: December 2023

Marine nutrients underpin productivity and functioning of oceanic island ecosystems. Seabirds represent a primary source of marine nutrients. In tropical regions, some of the largest seabird populations nest on atolls, yet there is limited information available on seabird contributions to atoll ecosystem nutrient dynamics. To investigate the spatial and seasonal dynamics of seabird contributions, we assessed seabird colonies of different taxa, including red-footed boobies and terns, nesting on separate islands of Farquhar Atoll, Seychelles. We assessed nutrient concentrations of guano, soil, coastal plants and nearby seagrass in seabird colonies and at a control island with no seabirds, during the wet and dry seasons. Sooty terns contributed the highest quantities of nutrients, estimated at 71.2 N tonne.yr-1and 52.2 P tonne.yr-1. Seabird-derived nutrient transfer occurred year-round from seabird colonies to soil, coastal plants and seagrass. Soil macro- and inorganic nutrients were higher in the high-density, ground-nesting tern colony and during the dry season, coinciding with the breeding period of sooty terns. Both red-footed booby and tern colonies maintained high nitrogen levels (%N) in coastal plants year-round, while phosphorus levels (%P) did not differ between islands or seasons. Seabird-derived nitrogen reversed nitrogen limitation (log C:N) of seagrass during the dry season. We provide the first insights into seabird nutrient contributions to atoll ecosystems in Seychelles, with recommendations for seabird conservation to boost and support atoll and island ecosystem resilience. Our results from a relatively undisturbed atoll serve as a baseline with which more impacted atolls and future changes can be assessed.
Overcoming Observation Bias for Cancer Progression Modeling
Authors: Schill Rudolf , Klever Maren , Lösch Andreas , Hu Y. Linda , Vocht Stefan , Rupp Kevin , Grasedyck Lars , Spang Rainer , Beerenwinkel Niko
Published: December 2023

Cancers evolve by accumulating genetic alterations, such as mutations and copy number changes. The chronological order of these events is important for understanding the disease, but not directly observable from cross-sectional genomic data. Cancer progression models (CPMs), such as Mutual Hazard Networks (MHNs), reconstruct the progression dynamics of tumors by learning a network of causal interactions between genetic events from their co-occurrence patterns. However, current CPMs fail to include effects of genetic events on the observation of the tumor itself and assume that observation occurs independently of all genetic events. Since a dataset contains by definition only tumors at their moment of observation, neglecting any causal effects on this event leads to the “conditioning on a collider” bias: Events that make the tumor more likely to be observed appear anti-correlated, which results in spurious suppressive effects or masks promoting effects among genetic events. Here, we extend MHNs by modeling effects from genetic progression events on the observation event, thereby correcting for the collider bias. We derive an efficient tensor formula for the likelihood function and learn two models on somatic mutation datasets from the MSK-IMPACT study. In colon adenocarcinoma, we find a strong effect on observation by mutations in TP53, and in lung adenocarcinoma by mutations in EGFR. Compared to classical MHNs, this explains away many spurious suppressive interactions and uncovers several promoting effects.

The data, code, and results are available athttps://github.com/cbg-ethz/ObservationMHN.
Limitation of switching sensory information flow in flexible perceptual decision making
Authors: Luo Tianlin , Xu Mengya , Zheng Zhihao , Okazawa Gouki
Published: December 2023

Humans can flexibly change rules to categorize sensory stimuli, but their performance degrades immediately after a task switch. This switch cost is believed to reflect a limitation in cognitive control, although the bottlenecks responsible for this remain controversial. Here, we show that humans exhibit a brief reduction in the efficiency of converting sensory inputs into decision evidence immediately after changing rules in perceptual tasks. Participants performed a flexible face categorization task in which they classified parametrically generated face stimuli based on one of two rules, switching every few trials. Although participants were always informed of a rule switch by a context cue, they showed a specific pattern of increase in reaction times, regardless of the time they were given to prepare for the switch. Psychophysical reverse correlation and computational modeling revealed a reduction in sensory weighting immediately after a rule switch, which recovered within a few hundred milliseconds after stimulus presentation. Furthermore, this cost depends on the sensory features being switched, suggesting a major bottleneck at the stage of adjusting the sensory information flow. We propose that decision-making circuits cannot fully adjust their sensory readout based on an abstract context cue alone, but rather require the presence of an actual stimulus to tune it, leading to a limitation in flexible perceptual decision making.
A Data Science Pipeline Applied to Australia’s 2022 COVID-19 Omicron Waves
Authors: Trauer James M , Hughes Angus E , Shipman David S , Meehan Michael T , Henderson Alec S , McBryde Emma S , Ragonnet Romain
Published: December 2023

The field of software engineering is advancing at astonishing speed, with packages now available to support many stages of data science pipelines. These packages can support infectious disease modelling to be more robust, efficient and transparent, which has been particularly important during the COVID-19 pandemic. We developed a package for the construction of infectious disease models, integrated this with several open-source libraries and applied this pipeline to multiple data sources that provided insights into Australia’s 2022 COVID-19 epidemic. We aimed to identify the key processes relevant to COVID-19 transmission dynamics and thereby develop a model that could quantify relevant epidemiological parameters. Extending the base model to include mobility effects slightly improved model fit to data, but including the effect of 2022 vaccination programs on transmission did not. Our simulations suggested that one in every two to six COVID-19 episodes were detected, subsequently emerging Omicron subvariants escaped 30 to 60% of recently acquired natural immunity and that natural immunity lasted only one to eight months. We documented our analyses algorithmically and present our methods in conjunction with interactive online notebooks.
Metabolic variation reflects dietary intake in a multi-ethnic Asian population
Authors: Low Dorrain Yanwen , Mina Theresia Handayani , Sadhu Nilanjana , Wong Kari E , Jain Pritesh Rajesh , Dalan Rinkoo , Ng Hong Kiat , Xie Wubin , Lam Benjamin , Tay Darwin , Wang Xiaoyan , Yew Yik Weng , Best James , Sarangarajan Rangaprasad , Elliott Paul , Riboli Elio , Lee Jimmy , Lee Eng Sing , Ngeow Joanne , Sheridan Patricia A , Michelotti Gregory A , Loh Marie , Chambers John
Published: December 2023

Dietary biomarkers reflecting habitual diet are explored largely in European and American populations. However, the “food metabolome” is highly complex, with its composition varying to region and culture. Here, by assessing 1,055 plasma metabolites and 169 foods/beverages in 8,391 comprehensively phenotyped individuals from the multi-ethnic Asian HELIOS cohort (69% Chinese, 12% Malay, 19% South Asian), we report novel observations for ethnic-relevant and common foods. Using machine-learning feature selection approach, we developed dietary multi-biomarker panels (3-39 metabolites each) for key foods and beverages in respective training sets. These panels comprised distinct and shared metabolite networks, and captured variances in intake prediction models in test sets better than single biomarkers. Composite metabolite scores, derived from the biomarker panels, associated significantly and more strongly with clinical phenotypes (HOMA-IR, type 2 diabetes, BMI, fat mass index, carotid intima-media thickness and hypertension), compared to self-reported intakes. Lastly, in 235 individuals that returned for a repeat visit (averaged 322 days apart), diet-metabolite relationships were robust over time, with predicted intakes, derived from biomarker panels and metabolite scores, showing better reproducibility than self-reported intakes. Altogether, our findings show new insights into multi-ethnic diet-related metabolic variations and new opportunity to link exposure to health outcomes in Asian populations.
Comparison of Clinical Outcomes in Acute Coronary Syndrome Patients Who Undergo Percutaneous Coronary Intervention Using Different P2Y12 Inhibitors: A SMS Hospital Based Observational Study
Authors: Swami Raghuraj , Kumar Sharma Sohan , Meena Pradeep
Published: December 2023

Background

To compare the safety, and efficacy of contemporary P2Y12 inhibitors, prescription rates, drug defaulter and switch over rates in acute coronary syndrome (ACS) patients following percutaneous coronary intervention (PCI).

Methods

in this prospective observational study we studied 195 ACS patients who underwent PCI in SMS Hospital, Jaipur. We compared prescription rates, bleeding, and major adverse cardiac events (MACEs: cardiac death, nonfatal myocardial infarction, or stroke) according to ticagrelor, prasugrel, or clopidogrel use.

Results

The prescription rates of ticagrelor, prasugrel, and clopidogrel were 29.5%, 4.3%, and 66.2% respectively. Bleeding occurred in total 6 patients (2.9%) out of which 3 patients (2.2%) in clopidogrel group, 1 patient (11.1%) in prasugrel group and 2 patients (3.2%) in ticagrelor group (p=0.29)), respectively, with higher incidence in ticagrelor and prasugrel users than in clopidogrel users but statistically not significant. After six month follow up, all-cause mortality was total 5 cases (2.4%) out of which 4 death (2.9%) occurred in clopidogrel group while 1 death (1.6%) occurred in ticagrelor group(p=0.76). no mortality was recorded in prasugrel group. Repeat myocardial infarction (Re MI) occurred in total 4 patients (1.9%) with 2 patients in clopidogrel and ticagrelor group each. A total 5 patients (2.4%) switch over to another p2y12 inhibitor, mostly from ticagrelor group(p=0.045). During this follow up period, a total of 4 patients (1.9%) were drug defaulter (0.622).

Conclusions

As clopidogrel based DAPT was prescribed more in our centre because of free institutional supply and found no significant difference in clinical outcomes, although slight increase in bleeding risk in ticagrelor or prasugrel based DAPT, demonstrate clopidogrel based DAPT regime can be preferably prescribed safely in our population. Drug defaulter rates in first six month following PCI are low in all groups but more switch over from ticagrelor group to other groups significantly shows importance of low cost and free institutional supply in drug adherence.
The Tumor-Associated Calcium Signal Transducer 2 (TACSTD2) oncogene is upregulated in pre-cystic epithelial cells revealing a new target for polycystic kidney disease
Authors: Smith Abigail O. , Frantz William Tyler , Preval Kenley M. , Edwards Yvonne J.K. , Ceol Craig J. , Jonassen Julie A. , Pazour Gregory J.
Published: December 2023

Polycystic kidney disease (PKD) is an important cause of end stage renal disease, but treatment options are limited. While later stages of the disease have been extensively studied, mechanisms driving the initial conversion of renal tubules into cysts are not understood. To identify factors that promote the initiation of cysts we deleted polycystin-2 (Pkd2) in mice and surveyed transcriptional changes before and immediately after cysts developed. We identified 74 genes which we term cyst initiation candidates (CICs). To identify conserved changes with relevance to human disease we compared these murine CICs to single cell transcriptomic data derived from patients with PKD and from healthy controls. Tumor-associated calcium signal transducer 2 (Tacstd2) stood out as an epithelial-expressed gene whose levels were elevated prior to cystic transformation and further increased with disease progression. Human tissue biopsies and organoids show that TACSTD2 protein is low in normal kidney cells but is elevated in cyst lining cells. While TACSTD2 has not been studied in PKD, it has been studied in cancer where it is highly expressed in solid tumors while showing minimal expression in normal tissue. This property is being exploited by antibody drug conjugates that target TACSTD2 for the delivery of cytotoxic drugs. Our finding that Tacstd2 is highly expressed in cysts, but not normal tissue, suggests that it should be explored as a candidate for drug development in PKD. More immediately, our work suggests that PKD patients undergoing TACSTD2 treatment for cancer should be monitored for kidney effects.

One Sentence Summary

The oncogene, tumor-associated calcium signal transducer 2 (Tacstd2) mRNA increased in abundance shortly after Pkd2 loss and may be a driver of cyst initiation in polycystic kidney disease.
Interleukin-6 -174 G/C promoter gene polymorphism and polycystic ovary syndrome: A cross sectional investigation in adult women
Authors: Gupta A , Gupta V , Shah K , Gupta V
Published: December 2023

Polycystic ovarian syndrome (PCOS), a metabolic disorder, manifests itself in a variety of ways. In this cross-sectional study, we evaluated the IL-6-174 G/C promoter gene polymorphism in adult PCOS women and its relationship to circulating levels and metabolic risk indicators. A total of 298 women between the ages between 15 and 35 years were chosen, 126 of whom had PCOS, and 172 of whom did not (control group). Both groups were further divided into subgroups of obese and lean women. The lipid profile, serum IL-6 level, and Homeostatic Model Assessment (HOMA) index were all examined. By using PCR-RFLP, the genotype of IL-6-174 G/C was identified. Women in the PCOS and non-PCOS groups showed significant variations in genotype frequencies and metabolic risk indicators. In PCOS compared to non-PCOS, there was a stronger correlation between the mutant ‘C’ allele of IL-6-174 G/C (p<0.0001; OR=1.91; 95% CI=1.38-2.66). Women with PCOS (61.2%) were significantly more associated with both the homozygous CC and heterozygous GC genotypes of IL-6-174 G/C in respect of WHR>0.85 than non-PCOS women (59.2%). In PCOS women, the distribution of the mutant genotypes CC and GC of the IL-6-174 G/C gene was likewise significantly different from GG, with higher WHR (p=0.0191), HOMA index (p=0.031), and serum IL-6 level (p=0.0094). These findings imply that the IL-6-174 G/C promoter mutant CC genotype was substantially related with increased circulating IL-6 levels, and that the presence of IR may be a risk indicator for the development of the metabolic syndrome (MetS) in PCOS women.
Clinical application of ISO and CEN/TS standards for liquid biopsies - information everybody wants but nobody wants to pay for
Authors: Bonstingl Lilli , Skofler Christina , Ulz Christine , Zinnegger Margret , Sallinger Katja , Schönberger Julia , Schuch Katharina , Pankratz Karin , Borrás-Cherrier Anatol , Somodi Visnja , Abuja Peter M. , Oberauner-Wappis Lisa , Bauernhofer Thomas , Kroneis Thomas , El-Heliebi Amin
Published: December 2023

Background

Liquid biopsies are emerging as valuable clinical biomarkers for cancer monitoring. Despite increasing clinical use, standardization remains a challenge. ISO and CEN/TS standardized workflows exist, but their integration into clinical practice is underdeveloped. We aimed to assess the applicability of ISO and CEN/TS liquid biopsy standards in a real-world clinical setting.

Methods

We evaluated 659 peripheral blood samples from advanced prostate cancer patients against ISO and CEN/TS standards and tracked all essential criteria. This included assessing tube filing level, complete timing from blood draw until storage, transport conditions, temperature control, hemolysis score and tube draw order and its effects on hemolysis.

Results

Among 659 samples, 92.4% (609/659) met the essential criteria for ISO and CEN/TS compliance. In total 83.8% (552/659) of blood collection tubes had high fill levels above 80% of nominal filing level. In our advanced prostate cancer cohort, 12.9% (40/311) of the evaluated plasma samples were hemolytic. Within the draw order of five blood collection tubes, hemolysis did not significantly increase from tube one to five. The complete ccfDNA ISO and CTC CEN/TS workflows were completed within an average of 168 (+/- 71 min) and 248 minutes (+/- 76 min), respectively, from blood draw until storage.

Conclusions

Our study demonstrates the feasibility and benefits of adhering to ISO and CEN/T standards in a clinical liquid biopsy study. ISO and CEN/TS standards revealed that hemolysis is a common phenomenon in pre-treated advanced prostate cancer patients, as we eliminated pre-analytical errors as cause.
A computational model for lipid-anchored polysaccharide export by the outer-membrane protein GfcD
Authors: Fruet Cecilia , Martinez-Goikoetxea Mikel , Merino Felipe , Lupas Andrei N.
Published: December 2023

Many bacteria are protected by different types of polysaccharide capsules, structures formed of long repetitive glycan chains that are sometimes free and sometimes anchored to the outer membrane via lipid tails. One type, called group 4 capsule, results from expression of thegfcABCDE-etp-etkoperon inEscherichia coli. Of the proteins encoded in this operon, GfcE is thought to provide the export pore for free polysaccharide chains, but none of the proteins has been implicated in the export of chains carrying a lipid anchor. For this function, GfcD has been a focus of attention as the only outer-membrane β-barrel encoded in the operon. AlphaFold predicts two β-barrel domains in GfcD, a canonical N-terminal one of 12 strands and an unusual C-terminal one of 13 strands, which features a large lateral aperture between strands β1 and β13. This immediately suggests a lateral exit gate for hydrophobic molecules into the membrane, analogous to the one proposed for the lipopolysaccharide export pore LptD. Here, we report an unsteered molecular dynamics study of GfcD embedded in the bacterial outer membrane, with the common polysaccharide anchor, lipid A, inserted in the pore of the C-terminal barrel. Our results show that the lateral aperture does not collapse during simulations, that membrane lipids nevertheless do not penetrate the barrel, but that the lipid chains of the lipid A molecule readily exit into the membrane.

Statement of Significance

Despite the essential role polysaccharide capsules play in the resilience of bacteria to hostile environments, many aspects of their biogenesis are still poorly understood. One aspect concerns the export of capsular polysaccharides carrying a lipid anchor, for which even the proteins mediating the process are unknown. Here we propose that one of the largest families of β-barrel proteins in the bacterial outer membrane is a key agent of this process and show by biophysical simulation that it allows the exit of lipid anchors into the membrane through a lateral opening. More generally, our model illuminates the lateral exit mechanisms proposed for the export of hydrophobic macromolecules into the bacterial outer membrane.

Graphical abstract
Membrane to cortex attachment determines different mechanical phenotypes in LGR5+ and LGR5- colorectal cancer cells
Authors: Conti Sefora , Venturini Valeria , Cañellas-Socias Adrià , Cortina Carme , Abenza Juan F. , Attolini Camille Stephan-Otto , Guerra Emily Middendorp , Xu Catherine K , Li Jia Hui , Rossetti Leone , Stassi Giorgio , Roca-Cusachs Pere , Diz-Muñoz Alba , Ruprecht Verena , Guck Jochen , Batlle Eduard , Labernadie Anna , Trepat Xavier
Published: December 2023

Colorectal cancer tumors are composed of heterogeneous and plastic cell populations, including a pool of cancer stem cells that express LGR5. Whether these distinct cell populations display different mechanical properties, and how these properties might contribute to metastasis is unknown. Using CRC patient derived organoids (PDOs), we found that compared to LGR5- cells, LGR5+ cancer stem cells are stiffer, adhere better to the extracellular matrix (ECM), move slower both as single cells and clusters, display higher nuclear YAP, show a higher survival rate in response to mechanical confinement, and form larger transendothelial gaps. These differences are largely explained by the downregulation of the membrane to cortex attachment proteins Ezrin/Radixin/Moesin (ERMs) in the LGR5+ cells. By analyzing scRNA-seq expression patterns from a patient cohort, we show that this downregulation is a robust signature of colorectal tumors. Our results show that LGR5- cells display a mechanically dynamic phenotype suitable for dissemination from the primary tumor whereas LGR5+ cells display a mechanically stable and resilient phenotype suitable for extravasation and metastatic growth.
ISWI catalyzes nucleosome sliding in condensed nucleosome arrays
Authors: Vizjak Petra , Kamp Dieter , Hepp Nicola , Scacchetti Alessandro , Gonzalez Pisfil Mariano , Bartho Joseph , Halic Mario , Becker Peter B. , Smolle Michaela , Stigler Johannes , Mueller-Planitz Felix
Published: December 2023

How chromatin enzymes work in condensed chromatin and how they maintain diffusional mobility inside remains unexplored. We investigated these challenges using theDrosophilaISWI remodeling ATPase, which slides nucleosomes along DNA. Folding of chromatin fibers did not affect slidingin vitro. Catalytic rates were also comparable in- and outside of chromatin condensates. ISWI cross-links and thereby stiffens condensates, except when ATP hydrolysis is possible. Active hydrolysis is also required for ISWI’s mobility in condensates. Energy from ATP hydrolysis therefore fuels ISWI’s diffusion through chromatin and prevents ISWI from cross-linking chromatin. Molecular dynamics simulations of a ‘monkey-bar’ model in which ISWI grabs onto neighboring nucleosomes, then withdraws from one before rebinding another in an ATP hydrolysis-dependent manner qualitatively agree with our data. We speculate that ‘monkey-bar’ mechanisms could be shared with other chromatin factors and that changes in chromatin dynamics caused by mutations in remodelers could contribute to pathologies.
Alternative splicing expands the antiviral IFITM repertoire in Chinese horseshoe bats
Authors: Mak Nelly , Zhang Dan , Li Xiaomeng , Rahman Kazi , Datta Siddhartha A.K. , Taylor Jordan , Liu Jingyan , Shi Zhengli , Temperton Nigel , Irving Aaron T. , Compton Alex A. , Sloan Richard D.
Published: December 2023

The interferon response is shaped by the evolutionary arms race between hosts and the pathogens they carry. The human interferon-induced transmembrane protein (IFITM) family consists of three antiviralIFITMgenes that arose by gene duplication, they restrict virus entry and are key players of the interferon response. Yet, little is known about IFITMs in other mammals. Here, we identified anIFITMgene in Chinese horseshoe bat, a natural host of SARS-coronaviruses, that is alternatively spliced to produce two IFITM isoforms. These bat IFITMs have conserved structures in vitro and differential antiviral activities against influenza A virus and coronaviruses including SARS- and MERS-coronavirus. In parallel with human IFITM1-3, the bat IFITM isoforms localize to distinct cellular compartments. Further analysis of IFITM repertoires in 205 mammals reveals that alternative splicing is a ubiquitous strategy for IFITM diversification, albeit less widely adopted than gene duplication. These findings showcase an example of convergent evolution where species-specific selection pressures led to expansion of the IFITM family through multiple means, underscoring the importance of IFITM diversity as a component of innate immunity.
Neurophysiology of perceptual decision-making and its alterations in attention-deficit hyperactivity disorder (ADHD)
Authors: Biabani Mana , Walsh Kevin , Zhou Shou-Han , Wagner Joseph , Johnstone Alexandra , Paterson Julia , Johnson Beth P. , Loughnane Gerard M. , O’Connell Redmond G. , Bellgrove Mark A.
Published: December 2023

Despite the prevalence of ADHD, efforts to develop a detailed understanding of the neuropsychology of this neurodevelopmental condition are complicated by the diversity of interindividual presentations and the inability of current clinical tests to distinguish between its sensory, attentional, arousal or motoric contributions. Identifying objective methods that can decompose the clinical heterogeneity of ADHD is a long-held goal that is hoped to advance our understanding of etiological processes and potentially aid the development of personalized treatment approaches. Here, we examine key neuropsychological components of ADHD within an electrophysiological (EEG) perceptual decision-making paradigm that is capable of isolating distinct neural signals of several key information processing stages necessary for sensory-guided actions from attentional selection to motor responses. We show that compared to typically developing children, children with ADHD displayed slower and less accurate performance, which was driven by the atypical dynamics of discrete electrophysiological signatures of attentional selection, the accumulation of sensory evidence, and strategic adjustments reflecting urgency of response. These findings offer an integrated account of decision-making in ADHD and establish discrete neural signals that can be used to understand the wide range of neuropsychological performance variations in individuals with ADHD.

Significance Statement

The efficacy of diagnostic and therapeutic pathways in ADHD is limited by our incomplete understanding of its neurological basis. One promising avenue of research is the search for basic neural mechanisms that may contribute to the variety of cognitive challenges associated with ADHD. We developed a mechanistic account of differences in a fundamental cognitive process by integrating across neurocognitive, neurophysiological (i.e., EEG), and computational levels of analysis. We detected distinct neural changes in ADHD that explained altered performance (e.g., slowed and less accurate responses). These included changes in neural patterns of attentional selection, sensory information processing, and response preparation. These findings enhance our understanding of the neurophysiological profile of ADHD and may offer potential targets for more effective, personalized interventions.
Performance of neural networks for prediction of asparagine content in wheat grain from imaging data
Authors: Oddy Joseph
Published: December 2023

Background

The prediction of desirable traits in wheat from imaging data is an area of growing interest thanks to the increasing accessibility of remote sensing technology. However, as the amount of data generated continues to grow, it is important that the most appropriate models are used to make sense of this information. Here, the performance of neural network models in predicting grain asparagine content is assessed against the performance of other models.

Results

Neural networks had greater accuracies than partial least squares regression models and gaussian naïve Bayes models for prediction of grain asparagine content, yield, genotype, and fertiliser treatment. Genotype was also more accurately predicted from seed data than from canopy data.

Conclusion

Using wheat canopy spectral data and combinations of wheat seed morphology and spectral data, neural networks can provide improved accuracies over other models for the prediction of agronomically important traits.
Armillaria korhonenii, the sixteenth biological species ofArmillariafrom China
Authors: Liu Jianwei , Qin Guofu , Chen Jian , Song Jing , Yan Zhuyue , Yang Shimei , Tian Meng-hua , Xu Xin , Zhang Changfei , Luangharn Thatsanee , Bhunjun Chitrabhanu S. , Yu Fuqiang , Yang Zhuliang
Published: December 2023

Armillaria korhonenii, designated as Chinese biological species Q (CBSQ) here, is described as a new species based on phylogenetic and morphological evidence as well as the results of mating tests. This species is the sixteenth biological species ofArmillariareported from China following the discovery of 15 previously known biological species. Phylogenetically,A.korhoneniiis the earliest divergent lineage of the genusArmillariaas inferred from the nucleotide sequences of the Elongation Factor 1-Alpha (EF1a). Morphologically, it is characterized by its ellipsoid to elongate basidiospores, yellowish orange to honey yellow pileus with fibrillose squamules. Mating tests indicated thatA.korhoneniiis a tetrapolar heterogeneous species and is inter-sterile with all the tested species except partial compatibility with CBSH.
Exploring natural genetic variation in photosynthesis-related traits of barley in the field
Authors: Gao Yanrong , Stein Merle , Oshana Lilian , Zhao Wenxia , Matsubara Shizue , Stich Benjamin
Published: December 2023

Optimizing photosynthesis is considered an important strategy for improving crop yields to ensure food security. To evaluate the potential of using photosynthesis-related parameters in crop breeding programs, we measured chlorophyll fluorescence along with growth-related and morphological traits of 23 barley inbreds across different developmental stages in field conditions. The photosynthesis-related parameters were highly variable, changing with light intensity and developmental progression of plants. Yet, the variations in photosystem II (PSII) quantum yield observed among the inbreds in the field largely reflected the variations in CO2assimilation properties in controlled climate chamber conditions, confirming that the chlorophyll fluorescence-based technique can provide proxy parameters of photosynthesis to explore genetic variations under field conditions. Heritability (H2) of the photosynthesis-related parameters in the field ranged from 0.16 for the quantum yield of non-photochemical quenching to 0.78 for the fraction of open PSII center. Two parameters, the maximum PSII efficiency in light-adapted state (H20.58) and the total non-photochemical quenching (H20.53), showed significant positive and negative correlations, respectively, with yield-related traits (dry weight per plant and net straw weight) in the barley inbreds. These results indicate the possibility of improving crop yield through optimizing photosynthetic light use efficiency by conventional breeding programs.