Miracle-dz/UniFAR-FTUs huggingface dataset:
Association of Measures of Glucose Metabolism with Colorectal Cancer Risk in Older Chinese: A 13-Year Follow-up of the Guangzhou Biobank Cohort Study-Cardiovascular Disease Substudy and Meta-Analysis

Background Abnormal glucose metabolism is a risk factor for colorectal cancer (CRC). However, association of glycosylated hemoglobin (HbA1c) with CRC risk remains under-reported. We examined the association between glycemic indicators (HbA1c, fasting plasma glucose, fasting insulin, 2-hour glucose, 2-hour insulin, and homeostasis model of risk assessment-insulin resistance index) and CRC risk using prospective analysis and meta-analysis. Methods Participants (n=1,915) from the Guangzhou Biobank Cohort Study-Cardiovascular Disease Substudy were included. CRC events were identified through record linkage. Cox regression was used to assess the associations of glycemic indicators with CRC risk. A meta-analysis was performed to investigate the association between HbA1c and CRC risk. Results During an average of 12.9 years follow-up (standard deviation, 2.8), 42 incident CRC cases occurred. After adjusting for potential confounders, the hazard ratio (95% confidence interval [CI]) of CRC for per % increment in HbA1c was 1.28 (95% CI, 1.01 to 1.63) in overall population, 1.51 (95% CI, 1.13 to 2.02) in women and 1.06 (95% CI, 0.68 to 1.68) in men. No significant association of other measures of glycemic indicators and baseline diabetes with CRC risk was found. Meta-analyses of 523,857 participants including our results showed that per % increment of HbA1c was associated with 13% higher risk of CRC, with the pooled risk ratio being 1.13 (95% CI, 1.01 to 1.27). Subgroupanalyses found stronger associations in women, colon cancer, Asians, and case-control studies. Conclusion Higher HbA1c was a significant predictor of CRC in the general population. Our findings shed light on the pathology of glucose metabolism and CRC, which warrants more in-depth investigation.
Identify gestational diabetes mellitus by deep learning model from cell-free DNA at the early gestation stage

Abstract Gestational diabetes mellitus (GDM) is a common complication of pregnancy, which has significant adverse effects on both the mother and fetus. The incidence of GDM is increasing globally, and early diagnosis is critical for timely treatment and reducing the risk of poor pregnancy outcomes. GDM is usually diagnosed and detected after 24 weeks of gestation, while complications due to GDM can occur much earlier. Copy number variations (CNVs) can be a possible biomarker for GDM diagnosis and screening in the early gestation stage. In this study, we proposed a machine-learning method to screen GDM in the early stage of gestation using cell-free DNA (cfDNA) sequencing data from maternal plasma. Five thousand and eighty-five patients from north regions of Mainland China, including 1942 GDM, were recruited. A non-overlapping sliding window method was applied for CNV coverage screening on low-coverage (~0.2×) sequencing data. The CNV coverage was fed to a convolutional neural network with attention architecture for the binary classification. The model achieved a classification accuracy of 88.14%, precision of 84.07%, recall of 93.04%, F1-score of 88.33% and AUC of 96.49%. The model identified 2190 genes associated with GDM, including DEFA1, DEFA3 and DEFB1. The enriched gene ontology (GO) terms and KEGG pathways showed that many identified genes are associated with diabetes-related pathways. Our study demonstrates the feasibility of using cfDNA sequencing data and machine-learning methods for early diagnosis of GDM, which may aid in early intervention and prevention of adverse pregnancy outcomes.
Invasive meningococcal disease in South-Eastern European countries: Do we need to revise vaccination strategies?

ABSTRACT Invasive meningococcal disease (IMD) is an acute life-threatening infection caused by the gram-negative bacterium, Neisseria meningitidis. Globally, there are approximately half a million cases of IMD each year, with incidence varying across geographical regions. Vaccination has proven to be successful against IMD, as part of controlling outbreaks, and when incorporated into national immunization programs. The South-Eastern Europe Meningococcal Advocacy Group (including representatives from Croatia, the Czech Republic, Greece, Hungary, Poland, Romania, Serbia, Slovenia and Ukraine) was formed in order to discuss the potential challenges of IMD faced in the region. The incidence of IMD across Europe has been relatively low over the past decade; of the countries that came together for the South-Eastern Meningococcal Advocacy Group, the notification rates were lower than the European average for some country. The age distribution of IMD cases was highest in infants and children, and most countries also had a further peak in adolescents and young adults. Across the nine included countries between 2010 and 2020, the largest contributors to IMD were serogroups B and C; however, each individual country had distinct patterns for serogroup distribution. Along with the variations in epidemiology of IMD between the included countries, vaccination policies also differ.
TLR2 regulates Moraxella catarrhalis adhesion to and invasion into alveolar epithelial cells and mediates inflammatory responses

ABSTRACT Moraxella catarrhalis is a major cause of chronic obstructive pulmonary disease. Toll-like receptor 2 (TLR2) plays an important role in the inflammatory response in host respiratory epithelial cells. M. catarrhalis induces an inflammatory immune response in respiratory epithelial cells that is mostly dependent on TLR2. However, the mechanisms by which this pathogen adheres to and invades the respiratory epithelium are not well understood. The present study aimed to reveal the role of TLR2 in M. catarrhalis adhesion to and invasion into alveolar epithelial cells, using molecular techniques. Pretreatment with the TLR2 inhibitor TLR2-IN-C29 enhanced M. catarrhalis adhesion to A549 cells but reduced its invasion, whereas the agonist Pam3CSK4 reduced both M. catarrhalis adhesion and invasion into A549 cells. Similarly, M. catarrhalis 73-OR strain adhesion and invasion were significantly reduced in TLR2−/− A549 cells. Moreover, the lung clearance rate of the 73-OR strain was significantly higher in TLR2−/− C57/BL6J mice than in wild-type (WT) mice. Histological analysis showed that inflammatory responses were milder in TLR2−/− C57/BL6J mice than in WT mice, which was confirmed by a decrease in cytokine levels in TLR2−/− C57/BL6J mice. Overall, these results indicate that TLR2 promoted M. catarrhalis adhesion and invasion of A549 cells and lung tissues and mediated inflammatory responses in infected lungs. This study provides important insights into the development of potential therapeutic strategies against M. catarrhalis and TLR2-induced inflammatory responses.
The Transient Response of the Southern Ocean to Stratospheric Ozone Depletion

AbstractRecent studies have suggested that the response of the Southern Ocean to stratospheric ozone depletion is nonmonotonic in time; consisting of an initial cooling followed by a long-term warming. This result may be significant for the attribution of observed Southern Ocean temperature and sea ice trends, but the time scale and magnitude of the response is poorly constrained, with a wide spread among climate models. Furthermore, a long-lived initial cooling period has only been observed in a model with idealized geometry and lacking an explicit representation of ozone. Here the authors calculate the transient response of the Southern Ocean to a step-change in ozone in a comprehensive coupled climate model, GFDL-ESM2Mc. The Southern Ocean responds to ozone depletion with an initial cooling, lasting 25 yr, followed by a warming. The authors extend previous studies to investigate the dependence of the response on the ozone forcing as well as the regional pattern of this response. The response of the Sou.
First detection of Omicron variant BA.4.1 lineage in dogs, Chile

Abstract SARS-CoV-2’s rapid global spread caused the declaration of COVID-19 as a pandemic in March 2020. Alongside humans, domestic dogs and cats are also susceptible to infection. However, limited reports on pet infections in Chile prompted a comprehensive study to address this knowledge gap. Between March 2021 and March 2023, the study assessed 65 pets (26 dogs and 39 cats) from 33 COVID-19+ households alongside 700 nasal swabs from animals in households with unknown COVID-19 status. Using RT-PCR, nasal, fecal, and environmental samples were analyzed for the virus. In COVID-19+ households, 6.06% tested positive for SARS-CoV-2, belonging to 3 dogs, indicating human-to-pet transmission. Pets from households with unknown COVID-19 status tested negative for the virus. We obtained 2 SARS-CoV-2 genomes from animals, that belonged to Omicron BA.4. 1 variant, marking the first report of pets infected with this lineage globally. Phylogenetic analysis showed these sequences clustered with human sequences collected in Chile during the same period when the BA.4. 1 variant was prevalent in the country. The prevalence of SARS-CoV-2 in Chilean pets was relatively low, likely due to the country’s high human vaccination rate. Our study highlights the importance of upholding and strengthening human vaccination strategies to mitigate the risk of interspecies transmission. It underscores the critical role of the One Health approach in addressing emerging zoonotic diseases, calling for further research on infection dynamics and risk factors for a comprehensive understanding.
Baroreflex sensitivity is blunted in hypoxia independently of changes in inspired carbon dioxide pressure in prematurely born male adults

Premature birth may result in specific cardiovascular responses to hypoxia and hypercapnia, that might hamper high‐altitude acclimatization. This study investigated the consequences of premature birth on baroreflex sensitivity (BRS) under hypoxic, hypobaric and hypercapnic conditions. Seventeen preterm born males (gestational age, 29 ± 1 weeks), and 17 age‐matched term born adults (40 ± 0 weeks) underwent consecutive 6‐min stages breathing different oxygen and carbon dioxide concentrations at both sea‐level and high‐altitude (3375 m). Continuous blood pressure and ventilatory parameters were recorded in normobaric normoxia (NNx), normobaric normoxic hypercapnia (NNx + CO2), hypobaric hypoxia (HHx), hypobaric normoxia (HNx), hypobaric normoxia hypercapnia (HNx + CO2), and hypobaric hypoxia with end‐tidal CO2 clamped at NNx value (HHx + clamp). BRS was assessed using the sequence method. Across all conditions, BRS was lower in term born compared to preterm (13.0 ± 7.5 vs. 21.2 ± 8.8 ms⋅mmHg−1, main group effect: p < 0.01) participants. BRS was lower in HHx compared to NNx in term born (10.5 ± 4.9 vs. 16.0 ± 6.0 ms⋅mmHg−1, p = 0.05), but not in preterm (27.3 ± 15.7 vs. 17.6 ± 8.3 ms⋅mmHg−1, p = 0.43) participants, leading to a lower BRS in HHx in term born compared to preterm (p < 0.01). In conclusion, this study reports a blunted response of BRS during acute high‐altitude exposure without any influence of changes in inspired CO2 in healthy prematurely born adults.
Assessment of quality of life for frail, elderly patients post-ICU discharge: a protocol for a scoping review

Introduction Rises in average life expectancy, increased comorbidities and frailty among older patients lead to higher admission rates to intensive care units (ICU). During an ICU stay, loss of physical and cognitive functions may occur, causing prolonged rehabilitation. Some functions may be lost permanently, affecting quality of life (QoL). There is a lack of understanding regarding how many variables are relevant to health-related outcomes and which outcomes are significant for the QoL of frail, elderly patients following discharge from the ICU. Therefore, this scoping review aims to identify reported variables for health-related outcomes and explore perspectives regarding QoL for this patient group. Methods and analysis The Joanna Briggs Institute guidelines for scoping reviews will be employed and original, peer-reviewed studies in English and Scandinavian languages published from 2013 to 2023 will be included. The search will be conducted from July 2023 to December 2023, according to the inclusion criteria in Embase, MEDLINE, PsycINFO and CINAHL. References to identified studies will be hand-searched, along with backward and forward citation searching for systematic reviews. A librarian will support and qualify the search strategy. Two reviewers will independently screen eligible studies and perform data extraction according to predefined headings. In the event of disagreements, a third reviewer will adjudicate until consensus is achieved. Results will be presented narratively and in table form and discussed in relation to relevant literature. Ethics and dissemination Ethical approval is unnecessary, as the review synthesises existing research. The results will be disseminated through a peer-reviewed publication in a scientific journal.
Do Land Use Regulations Matter? Why and How?

American cities face tremendous challenges including housing affordability, rising economic inequality, and climate change. Land use regulatory reform can play an important role in addressing these issues. But, the evolution, determinants, and effects of land use regulations remain unclear. I use Los Angeles as a case study to answer important questions about why and how land use regulations matter. I organize the dissertation as three related but independent papers. The first paper characterizes how land use regulations change. In Los Angeles, zoning designations were largely static between 2002 and 2014; the city rezoned only about two percent of its parcel land area during this period. While rezonings were uncommon, the city adopted new land use regulations or expanded existing regulations, including several transit-oriented development plans, a density bonus ordinance, an adaptive reuse ordinance, and the expansion of historic preservation overlays. In general, this illustrates a bifurcated evolution of regulations. Single-family neighborhoods remain protected, while significant changes occur in downtown Los Angeles and some high-density neighborhoods near transit. The second paper examines why zoning is changed. I use logistic regression models to analyze the relationship between parcel-scale “upzoning” and housing demand factors, supply constraints, the influence of interest groups, and municipal policy drivers. I find that upzoning in Los Angeles follows the path of biggest opportunity and least political resistance. My research supports the “homevoter hypothesis,” meaning that concentrations of homeowners deter zoning changes to allow higher densities. The third paper explains how regulations matter for housing production. Using negative binomial regression models, I find strong associations between high-density zoning and multifamily housing production across Los Angeles. In the city’s oldest transit-oriented development (TOD) plan area, the average multifamily development was built at 132% of the baseline allowable residential density, 107% of the allowable floor area ratio, and 102% of the allowable height. The regression results and the TOD analysis provide evidence that developers would build more densely, in neighborhoods with housing demand, if land use regulations were more permissive.
Evaluating outcome associations with race after mechanical thrombectomy: an analysis of the NVQI-QOD acute ischemic stroke registry

Background Mechanical thrombectomy has become the standard of care for acute ischemic stroke due to large vessel occlusions. Racial differences in outcomes after mechanical thrombectomy for acute ischemic stroke have not been extensively studied. We evaluate the real-world evidence for differences between races in the outcomes of thrombectomy for large vessel occlusions using the NeuroVascular Quality Initiative-Quality Outcomes Database (NVQI-QOD). Methods Data from the NVQI-QOD acute ischemic stroke registry were analyzed and compared for racial differences in outcomes after mechanical thrombectomy in 4507 patients from 28 US centers (17 states) between January 2014 and April 2021. Race was dichotomized into non-Hispanic White (NHW, n=3649) and non-Hispanic Black (NHB, n=858). We performed 1:1 propensity score matching resulting in a subsample of matched groups (n=761 each for NHB and NHW) to compare study endpoints using Welch’s two-sided t-tests and Χ2 test for continuous and categorical outcomes, respectively. Results Prior to matching, NHW and NHB patients significantly differed in age, comorbidities, medication use, smoking status, and presenting stroke severity. No significant difference in functional outcomes or mortality, at discharge or follow-up, were revealed. NHB patients had higher average postprocedure length of stay than NHW patients, which persisted following matching (11.2 vs 9.1 days, P=0.004). Conclusion Evidence from the NVQI-QOD acute ischemic stroke registry showed that outcome metrics, such as modified Rankin Scale score and mortality, did not differ significantly between racial groups; however, disparity between NHW and NHB patients in postprocedure length of stay following mechanical thrombectomy was revealed.
Obesity-related Plasma CXCL10 Drives CX3CR1-dependent Monocytic Secretion of Macrophage Migration Inhibitory Factor

Abstract Obesity is characterized by excessive body fat accumulation and comorbidities such as diabetes mellitus, cardiovascular disease, and obstructive sleep apnea syndrome (OSAS). Both obesity and OSAS are associated with immune disturbance, alterations of systemic inflammatory mediators, and immune cell recruitment to metabolic tissues. Chemokine CXCL10 is an important regulator of proinflammatory immune responses and is significantly increased in patients with severe obesity. This research project aims to investigate the impact of CXCL10 on human monocytes in patients with obesity. We studied the distribution of the CD14/CD16 monocyte subsets as well as their CX3CR1 expression patterns in whole-blood measurements from 92 patients with obesity and/or OSAS with regard to plasma CXCL10 values and individual clinical parameters. Furthermore, cytokine secretion by THP-1 monocytes in response to CXCL10 was analyzed. Data revealed significantly elevated plasma CXCL10 in patients with obesity with an additive effect of OSAS. CXCL10 was found to drive monocytic secretion of macrophage migration inhibitory factor via receptor protein CX3CR1, which significantly correlated with the individual body mass index. Our data show, for the first time, to our knowledge, that CX3CR1 is involved in alternative CXCL10 signaling in human monocytes in obesity-related inflammation. Obesity is a multifactorial disease, and further investigations regarding the complex interplay between obesity-related inflammatory mediators and systemic immune balances will help to better understand and improve the individual situation of our patients.
Irrigation increases carbon in agricultural soils

Irrigated agriculture sequesters significant amounts of organic C. Irrigation may also sequester significant amounts of inorganic C. Inorganic C reactions are important chemical reactions in irrigated soils and may contribute to the total amount of C sequestered. Calcium content of arid and semi-arid soils tends to be higher than rainfed temperate soils due to calcium rich parent material and low rainfall. Carbonate formation is usually controlled by carbonate equilibrium reactions in the solid and g as phase CO2 . Respiration in plant roots and soil microorganisms continually produce CO, increasing its concentration in the soil atmosphere, modifying carbonate solubility. Since irrigation water flows through a series of canals, where smaller amounts of water are directly exposed to incoming radiation, irrigation water usually has higher temperatures than stream or ground water. Carbon dioxide dissolves in water to form both CO2 as a gas and H2CO3 in solution. Warmer water increases reaction time and, in favourable conditions, precipitates CaCO3 . We measured organic and inorganic C stored in southern Idaho soils having long term land use histories that supported native sagebrush vegetation (NSB), irrigated mouldboard ploughed crops (IMP), irrigated conservation - chisel- tilled crops (ICT) and irrigated pasture systems (IP). Inorganic C and total C (inorganic + organic C) in soil decreased in the order IMP>ICT>IP>NSB. We use our findings to estimate the amount of possible organic, inorganic and total C sequestration if irrigated agriculture were expanded by 10%. If irrigated agricultural land were expanded by 10% worldwide and NSB were converted to IMP, a possible 1.90 x 10' Mg total (organic +inorganic) C (2.72 % of the total C emitted in the next 30 yr) could be sequestered in soil. If irrigated agricultural lands were expanded by 10% worldwide and NSB were converted to ICT, a possible 1.30 x 10' Mg total C (2.24 % of the total C emitted in the next 30 yr) could be sequestered in soil. If irrigated agricultural land were expanded worldwide and NSB were converted to IP a possible gain of 1.7 x 10 8 Mg total C (1.174 % of the total C emitted in the next 30 yr) could be sequestered in soils. Altering land use to produce crops on high output irrigated agriculture, while selected less-productive rainfed agricultural land were returned to temperate forest or native grassland. there could be meaningful reductions in atmospheric CO 2 .
Developing outdoor map design guidelines using a real-world wayfinding task

This exploratory study aims to elucidate the mental processes of wayfinding in an outdoor area and the effects of map contour representations, map color, individual differences of users (gender, brain dominance, experience level, and cultural differences), and environmental cues using a field study in an established trail network in Jefferson National Forest. Six maps with three different contour representations (contour lines, shaded relief, and schematic) and two color codes (color and black-and-white) were tested for wayfinding performance. Thirty-six participants of different nationalities (Locals versus Internationals), experience in map usage (experienced versus novice), handedness, and gender took part in the study. Three out of ten junctions on the test route had directional signs while the rest had no sign. The participants performed wayfinding tasks in a national forest trail park, using the think aloud and retrospective protocols to obtain the information processes used by the participants during wayfinding. Subjective feedback was also obtained to find out users’ map preferences and opinions on their experience during the