Miracle-dz/UniFAR-FTUs huggingface dataset:
SIRT3 Expression Predicts Overall Survival and Neoadjuvant Chemosensitivity in Triple-Negative Breast Cancer

Background The Sirtuin (SIRT) family consists of seven evolutionary conserved NAD-dependent deacetylases that play important roles in various cancers, including breast cancer (BC). SIRTs expression has been reported to have prognostic value in BC, but these studies used limited sample size and yielded inconsistent conclusions. This study evaluated the association of SIRT3 and other SIRT family members with survival and neoadjuvant chemotherapy outcomes. Methods BC patients’ data was obtained from the TCGA-BRCA, METABRIC and GEO databases, comprising 4336 samples. SIRTs expression and overall survival (OS) were analyzed using Kaplan-Meier analysis and Cox proportional hazards regression. SIRT3 expression levels were compared between pathologic complete response (pCR) and non-pCR groups after neoadjuvant chemotherapy in triple-negative breast cancer (TNBC). Protein-protein interaction networks were constructed using the STRING database. Gene set enrichment analysis (GSEA) was performed to explore potential functions of SIRT3. Results Through systematic analysis of SIRTs expression and OS of BC using three independent cohorts: TCGA-BRCA, METABRIC and GSE16446, we found that high SIRT3 expression was significantly associated with worse OS in TNBC in the TCGA-BRCA cohort, which was validated in the METABRIC and GSE16446 cohorts. SIRT3 expression was correlated with BC subtypes and American Joint Committee on Cancer (AJCC) T stage, but not with age-at-diagnosis, race, or tumor stage. Moreover, TNBC patients with higher SIRT3 expression had lower pCR rates after neoadjuvant chemotherapy (p = 6.40e-03) and SIRT3 expression was significantly lower in the pCR group than in the non-pCR group in TNBC (p = 4.2e-03). GSEA indicated that SIRT3 was involved in drug-related pathways such as oxidative phosphorylation, metabolism of xenobiotics by cytochrome P450, and drug metabolism. Conclusion Our study suggests that SIRT3 is a potential biomarker for both OS and neoadjuvant chemosensitivity in TNBC. It may also assist in selecting suitable candidates and treatment options for TNBC patients.
Reproducing Long‐Range Correlations in Global Mean Temperatures in Simple Energy Balance Models

We study global mean surface temperature records since 1850 and their potential forcings. We find long range correlations by the method of detrended fluctuation analysis in most data sets, in agreement with previous studies. As a predictive model, we employ a zero‐dimensional energy balance model without memory that reproduces temperature data on the timescale of years. Even when driven with white noise, this model generates data that reproduce the observed long‐range correlations. We are able to explain this with theoretical results for the AR(1) process, which demonstrates that even processes with exponentially decaying correlations yield nontrivial detrended fluctuation analysis results if the available data set is too short. This article gives new support to the scepticism about long memory in global mean temperatures and discusses further implications of our findings.
Effects of short‐ and long‐term plant functional group loss on alpine meadow community structure and soil nutrients

Abstract The rapid loss of global biodiversity can greatly affect the normal functioning of ecosystems. However, how biodiversity losses affect plant community structure and soil nutrients is unclear. We conducted a field experiment to examine the short‐ and long‐term effects of removing plant functional groups (Gramineae, Cyperaceae, legumes, and forbs) on the interrelationships among the species diversity, productivity, community structure, and soil nutrients in an alpine meadow ecosystem at Menyuan County, Qinghai Province. The variations in the species richness, above‐ and belowground biomass of the community gradually decreased over time. Species richness and productivity were positively correlated, and this correlation tended to be increasingly significant over time. Removal of the Cyperaceae, legumes, and other forbs resulted in fewer Gramineae species in the community. Soil total nitrogen, phosphorus, organic matter, and moisture contents increased significantly in the legume removal treatment. The removal of other forbs led to the lowest negative cohesion values, suggesting that this community may have difficulty recovering its previous equilibrium state within a short time. The effects of species removal on the ecosystem were likely influenced by the species structure and composition within the community. Changes in the number of Gramineae species indicated that they were more sensitive and less resistant to plant functional group removal. Legume removal may also indirectly cause distinct community responses through starvation and compensation effects. In summary, species loss at the community level led to extensive species niche shifts, which caused community resource redistribution and significant changes in community structure.
Evolutionary change in flight-to-light response in urban moths comes with changes in wing morphology

Moths and other insects are attracted by artificial light sources. This flight-to-light behaviour disrupts their general activity focused on finding resources, such as mating partners, and increases predation risk. It thus has substantial fitness costs. In illuminated urban areas, spindle ermine moths Yponomeuta cagnagella were reported to have evolved a reduced flight-to-light response. Yet, the specific mechanism remained unknown, and was hypothesized to involve either changes in visual perception or general flight ability or overall mobility traits. Here, we test whether spindle ermine moths from urban and rural populations—with known differences in flight-to-light responses—differ in flight-related morphological traits. Urban individuals were found to have on average smaller wings than rural moths, which in turn correlated with a lower probability of being attracted to an artificial light source. Our finding supports the reduced mobility hypothesis, which states that reduced mobility in urban areas is associated with specific morphological changes in the flight apparatus.
Factors associated with consuming unhealthy food in school children: A population‐based study from Hong Kong

Abstract Background and Aims Unhealthy diets were found to be the main contributor to the overweight problem among adolescents. In this study, we aim to identify the factors causing unhealthy eating habits in adolescents. Methods School‐aged children and adolescents participated in this cross‐sectional observational study with additional school and parental consent. A self‐administered survey was conducted by 30 primary schools and 25 secondary schools. Participants were asked about the frequency of consuming unhealthy food and the types of unhealthy food consumed. A descriptive analysis was performed to demonstrate the proportions of characteristics. The prevalence of the outcome among participants of various factors was also analyzed using separate binary regression models. Results A total of 4884 responses were collected. Among primary school students (grade 4, mean age: 10.06), people who (1) were actively gaining weight (aOR: 1.651, 95% CI 1.006–2.708, p = 0.047), (2) went to bed after 11 p.m. (aOR: 1.652, 95% CI 1.065–2.563, p = 0.025), (3) had more than 2 h of gaming (aOR: 2.833, 95% CI 1.913–4.195, p < 0.001), (4) suffered from self‐report depressive symptoms (aOR: 1.753, 95% CI 1.233–2.493, p = 0.002) was more likely to consume unhealthy food. As for secondary school students (grade 3, mean age: 15.28), (1) males (aOR: 1.266, 95% CI 1.0004–1.601, p = 0.0496), (2) average‐to‐high socioeconomic status (Average: aOR: 1.471, 95% CI 1.115–1.941, p = 0.006; High: aOR: 2.253, 95% CI 1.585–3.202. p < 0.001), (3) having more than 2 h of gaming (aOR: 1.342, 95% CI 1.069–1.685, p = 0.011), (4) suffering from psychological distress (aOR: 1.395, 95% CI 1.051–1.852, p = 0.021) were associated with the increased odds of consuming unhealthy food. Conclusion Several lifestyle and health factors were significantly associated with unhealthy eating behaviors in school‐aged children and adolescents in Hong Kong, sharing similarities with many other countries. In conjunction with implementing a policy that addresses factors for unhealthy eating habits, further research should investigate potential interventions targeting these factors to ultimately tackle the overweight and obesity concern for children and adolescents in Hong Kong.
Comprehensive Nomograms Using Routine Biomarkers Beyond Eosinophil Levels: Enhancing Predictability of Corticosteroid Treatment Outcomes in AECOPD

Purpose Patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) exhibit heterogeneous responses to corticosteroid treatment. We aimed to determine whether combining eosinophil levels with other routine clinical indicators can enhance the predictability of corticosteroid treatment outcomes and to come up with a scoring system. Patients and Methods Consecutive patients admitted with AECOPD receiving corticosteroid treatment between July 2013 and March 2022 at Beijing Chao-Yang Hospital were retrospectively analyzed. Data on patients’ demographics, smoking status, hospitalization for AECOPD in the previous year, comorbidities, blood laboratory tests, in-hospital treatment and clinical outcomes were collected. Least absolute shrinkage and selection operator (LASSO) regression and backward logistic regression were used for predictor selection, and predictive nomograms were developed. The discrimination and calibration of the nomograms were assessed using the area under the receiver operating curve (AUC) and calibration plots. Internal validation was performed using the 500-bootstrap method, and clinical utility was evaluated using decision curve analysis (DCA). Results Among the 3254 patients included, 804 (24.7%) had treatment failure. A nomogram of eosinophils, platelets, C-reactive protein (CRP), low density lipoprotein cholesterol, prognostic nutritional index (PNI), hospitalization for AECOPD in the previous year, ischemic heart diseases and chronic hepatic disease was developed to predict treatment failure for patients with a smoking history. For patients without a smoking history, a nomogram of CRP, PNI, ischemic heart diseases and chronic hepatic disease was developed. Although the AUCs of these two nomograms were only 0.644 and 0.647 respectively, they were significantly superior to predictions based solely on blood eosinophil levels. Conclusion We developed easy-to-use comprehensive nomograms utilizing readily available clinical biomarkers related to inflammation, nutrition and immunity, offering modestly enhanced predictive value for treatment outcomes in corticosteroid-treated patients with AECOPD. Further investigations into novel biomarkers and additional patient data are imperative to optimize the predictive performance.
The Effect of the Nature of Messages Conveyed Between the Extension Officers and Farmers on the Adoption of Irish Potato Farming in Meru County

This study was an investigation of the effect of the nature of messages conveyed between extension officers and farmers on the adoption of Irish potato farming. The problem of this study was that past studies had limited focus on the nature of extension messages conveyed between extension officers and farmers on adoption of Irish potato farming, hence a gap that demands specific studies to be carried out in order to fill it. The study’s general objective was to determine the effect of the nature of messages conveyed between extension officers and farmers on the adoption of Irish potato farming. The target population for this descriptive study comprised farmers from four sub-locations (Kimbo, Gathuine, Kiamiogo, Mburugiti) of Kibirichia Ward in Meru County and all the three extension officers involved in the production of Irish potato crop. From the sampling frame, respondents were selected using purposive sampling. Farmers who took part in focus group discussions were selected using homogeneous sampling. Total population sampling method was used to take the total population of the three extension officers that train Irish potato farmers in the four sub-locations in Kibirichia Ward. One focus group discussion and one in-depth interview were conducted from each sub-location in Kibirichia Ward. Using qualitative methods in data analysis, focus group and interview data was transcribed, coded and categorized into relevant themes and sub-themes and possible and plausible explanations of the findings drawn. Findings of this study revealed extension messages contained information, ideas and technologies on soil testing, seed varieties, spacing, weeding, earthingup, pesticides, fertilizer and manure application, crop rotations, diseases and harvesting. Farmers’ comprehension of most extension messages led to the high adoption of Irish potato farming in Kibirichia Ward. The researcher recommended that there is need to find the effect of the nature of messages conveyed between extension officers and farmers on the rate of adoption on Irish potato farming.
Octavius: Mitigating Task Interference in MLLMs via LoRA-MoE

Recent studies have demonstrated Large Language Models (LLMs) can extend their zero-shot generalization capabilities to multimodal learning through instruction tuning. As more modalities and downstream tasks are introduced, negative conflicts and interference may have a worse impact on performance. While this phenomenon has been overlooked in previous work, we propose a novel and extensible framework, called Octavius, for comprehensive studies and experimentation on multimodal learning with Multimodal Large Language Models (MLLMs). Specifically, we combine the well-known Mixture-of-Experts (MoE) and one of the representative PEFT techniques, i.e., LoRA, designing a novel LLM-based decoder, called LoRA-MoE, for multimodal learning. To the best of our knowledge, we are one of the pioneering efforts to introduce MoE into MLLMs to address this problem. The experimental results (about 20% improvement) have shown the effectiveness and versatility of our design in various 2D and 3D downstream tasks. Code and datasets are available at https://openlamm.github. io/paper_list/Octavius.
Evaluating and improving the usability of a mHealth platform to assess postoperative dental pain

Abstract Objectives The use of interactive mobile health (mHealth) applications to monitor patient-reported postoperative pain outcomes is an emerging area in dentistry that requires further exploration. This study aimed to evaluate and improve the usability of an existing mHealth application. Materials and methods The usability of the application was assessed iteratively using a 3-phase approach, including a rapid cognitive walkthrough (Phase I), lab-based usability testing (Phase II), and in situ pilot testing (Phase III). The study team conducted Phase I, while providers and patients participated in Phase II and III. Results The rapid cognitive walkthrough identified 23 potential issues that could negatively impact user experience, with the majority classified as system issues. The lab-based usability testing yielded 141 usability issues. ; 43% encountered by patients and 57% by dentists. Usability problems encountered during pilot testing included undelivered messages due to mobile phone carrier and service-related issues, errors in patients’ phone number data entry, and problems in provider training. Discussion Through collaborative and iterative work with the vendor, usability issues were addressed before launching a trial to assess its efficacy. Conclusion The usability of the mHealth application for postoperative dental pain was remarkably improved by the iterative analysis and interdisciplinary collaboration.
MSC-Derived Exosomes Mitigate Myocardial Ischemia/Reperfusion Injury by Reducing Neutrophil Infiltration and the Formation of Neutrophil Extracellular Traps

Introduction Acute inflammatory storm is a major cause of myocardial ischemia/reperfusion (I/R) injury, with no effective treatment currently available. The excessive aggregation of neutrophils is correlated with an unfavorable prognosis in acute myocardial infarction (AMI) patients. Exosomes derived from mesenchymal stromal cells (MSC-Exo) have certain immunomodulatory potential and might be a therapeutic application. Therefore, we investigated the protective role of MSC-Exo in modulating neutrophil infiltration and formation of neutrophil extracellular traps (NETs) following myocardial I/R injury. Methods Exosomes were isolated from the supernatant of MSCs using a gradient centrifugation method. We used flow cytometry, histochemistry, and immunofluorescence to detect the changes of neutrophils post-intravenous MSC-Exo injection. Additionally, cardiac magnetic resonance (CMR) and thioflavin S experiments were applied to detect microvascular obstruction (MVO). The NLR family pyrin domain containing 3 (NLRP3) inflammasome was examined for mechanism exploration. Primary neutrophils were extracted for in vitro experiment. Antibody of Ly6G was given to depleting the neutrophils in mice for verification the effect of MSC-Exo. Finally, we analyzed the MiRNA sequence of MSC-Exo and verified it in vitro. Results MSC-Exo administration reduced neutrophil infiltration and NETs formation after myocardial I/R. MSC-Exo treatment also could attenuate the activation of NLRP3 inflammasome both in vivo and in vitro. At the same time, the infarction size and MVO following I/R injury were reduced by MSC-Exo. Moreover, systemic depletion of neutrophils partly negated the therapeutic effects of MSC-Exo. Up-regulation of miR-199 in neutrophils has been shown to decrease the expression of NETs formation after stimulation. Discussion Our results demonstrated that MSC-Exo mitigated myocardial I/R injury in mice by modulating neutrophil infiltration and NETs formation. This study provides novel insights into the potential therapeutic application of MSC-Exo for myocardial ischemia/reperfusion injury.
TREX reveals proteins that bind to specific RNA regions in living cells

Different regions of RNA molecules can often engage in specific interactions with distinct RNA-binding proteins (RBPs), giving rise to diverse modalities of RNA regulation and function. However, there are currently no methods for unbiased identification of RBPs that interact with specific RNA regions in living cells under endogenous settings. Here, we introduce TREX (Targeted RNase H-mediated extraction of crosslinked RBPs), a highly sensitive approach for identifying proteins that directly bind to specific RNA regions in living cells. We demonstrate that TREX outperforms existing methods in identifying known interactors of U1 snRNA, and reveals endogenous region-specific interactors of NORAD lncRNA. Using TREX, we generated a comprehensive region-by-region interactome for 45S rRNA, uncovering both established and novel interactions that regulate ribosome biogenesis. With its applicability to any RNA in any cell-type, TREX is the first RNA-centric tool for unbiased positional mapping of endogenous RNA-protein interactions in living cells.
Landscape of pharmacogenetic variants associated with non-insulin antidiabetic drugs in the Indian population

Introduction Genetic variants contribute to differential responses to non-insulin antidiabetic drugs (NIADs), and consequently to variable plasma glucose control. Optimal control of plasma glucose is paramount to minimizing type 2 diabetes-related long-term complications. India’s distinct genetic architecture and its exploding burden of type 2 diabetes warrants a population-specific survey of NIAD-associated pharmacogenetic (PGx) variants. The recent availability of large-scale whole genomes from the Indian population provides a unique opportunity to generate a population-specific map of NIAD-associated PGx variants. Research design and methods We mined 1029 Indian whole genomes for PGx variants, drug–drug interaction (DDI) and drug–drug–gene interactions (DDGI) associated with 44 NIADs. Population-wise allele frequencies were estimated and compared using Fisher’s exact test. Results Overall, we found 76 known and 52 predicted deleterious common PGx variants associated with response to type 2 diabetes therapy among Indians. We report remarkable interethnic differences in the relative cumulative counts of decreased and increased response-associated alleles across NIAD classes. Indians and South Asians showed a significant excess of decreased metformin response-associated alleles compared with other global populations. Network analysis of shared PGx genes predicts high DDI risk during coadministration of NIADs with other metabolic disease drugs. We also predict an increased CYP2C19-mediated DDGI risk for CYP3A4/3A5-metabolized NIADs, saxagliptin, linagliptin and glyburide when coadministered with proton-pump inhibitors (PPIs). Conclusions Indians and South Asians have a distinct PGx profile for antidiabetes drugs, marked by an excess of poor treatment response-associated alleles for various NIAD classes. This suggests the possibility of a population-specific reduced drug response in atleast some NIADs. In addition, our findings provide an actionable resource for accelerating future diabetes PGx studies in Indians and South Asians and reconsidering NIAD dosing guidelines to ensure maximum efficacy and safety in the population.
Cancer-associated fibroblasts produce matrix-bound vesicles that influence endothelial cell function

Intercellular communication between different cell types in solid tumors contributes to tumor growth and metastatic dissemination. The secretome of cancer-associated fibroblasts (CAFs) plays major roles in these processes. Using human mammary CAFs, we unveil a mechanism of cell-cell communication between CAFs with myofibroblast phenotype and endothelial cells (ECs) based on intercellular protein transfer through extracellular vesicles (EVs). CAFs transfer proteins to ECs, including plasma membrane receptors, which we have identified by using mass spectrometry- based proteomics. Using THY1 as an example of transferred plasma membrane-bound protein, we show that CAF-derived proteins can influence how ECs interact with other cell types. Here, we show that CAFs produce high amounts of matrix-bound EVs that have a key role in protein transfer. Hence, our work paves the way for further studies to understand how CAF-derived matrix-bound EVs influence tumor pathology by regulating functions of neighboring cancer, stromal and immune cells. One sentence summary CAFs with a myofibroblastic-like phenotype transfer proteins to ECs, including plasma membrane receptors, through matrix-bound EVs