bluuebunny/crossref_metadata_2025_split huggingface dataset:
Win-paired cues modulate the effect of dopamine neuron sensitization on decision making and cocaine self-administration: divergent effects across sex
Authors: Hynes Tristan J. , Chernoff Chloe S. , Hrelja Kelly M. , Tse Maric T.L. , Avramidis Dimitrios , Lysenko-Martin Melanie R. , Calderhead Lucas , Kaur Sukhbir , Floresco Stan B. , Winstanley Catharine A. 
Published: May 2023

AbstractPsychostimulant use and engagement with probabilistic schedules of reward both sensitize the mesocorticolimbic dopamine system. Such behaviours may act synergistically to explain the high comorbidity between stimulant use and gambling disorder. The salient audiovisual stimuli of modern electronic gambling may exacerbate the situation. To probe these interactions, we sensitized ventral tegmental area (VTA) dopamine neurons via chronic chemogenetic stimulation while rats learned the rat gambling task in the presence or absence of casino-like cues. The same rats then learned to self-administer cocaine. In a separate cohort, we confirmed that our chemogenetic methods sensitized the locomotor response to cocaine, and potentiated phasic excitability of VTA dopamine neurons through in vivo electrophysiological recordings. In the absence of cues, sensitization promoted risk-taking in both sexes. When rewards were cued, sensitization expedited the development of a risk-preferring phenotype in males, while attenuating cue-induced risk-taking in females. While these results provide further confirmation that VTA dopamine neurons critically modulate risky decision making, they also reveal stark sex differences in the decisional impact which dopaminergic signals exert when winning outcomes are cued. As previously observed, risky decision-making on the cued rGT increased as both males and females learned to self-administer cocaine. The combination of dopamine sensitization and win-paired cues while gambling lead to significantly greater cocaine-taking, but these rats did not show any increase in risky choice as a result. Cocaine and heavily-cued gambles may therefore partially substitute for each other once the dopamine system is rendered labile through sensitization, compounding addiction risk across modalities.
Periaqueductal gray activates antipredatory neural responses in the amygdala of foraging rats
Authors: Kim Eun Joo , Kong Mi-Seon , Park Sanggeon , Cho Jeiwon , Kim Jeansok J. 
Published: May 2023

AbstractPavlovian fear conditioning research suggests that the interaction between the dorsal periaqueductal gray (dPAG) and basolateral amygdala (BLA) acts as a prediction error mechanism in the formation of associative fear memories. However, their roles in responding to naturalistic predatory threats, characterized by less explicit cues and the absence of reiterative trial-and-error learning events, remain unexplored. In this study, we conducted single-unit recordings in rats during an ‘approach food-avoid predator’ task, focusing on the responsiveness of dPAG and BLA neurons to a rapidly approaching robot predator. Optogenetic stimulation of the dPAG triggered fleeing behaviors and increased BLA activity in naive rats. Notably, BLA neurons activated by dPAG stimulation displayed immediate responses to the robot, demonstrating heightened synchronous activity compared to BLA neurons that did not respond to dPAG stimulation. Additionally, the use of anterograde and retrograde tracer injections into the dPAG and BLA, respectively, coupled with c-Fos activation in response to predatory threats, indicates that the midline thalamus may play an intermediary role in innate antipredatory defensive functioning.
Thermal adaptation of soil microbial growth traits in response to chronic warming
Authors: Eng Ashley Y. , Narayanan Achala , Alster Charlotte J. , DeAngelis Kristen M. 
Published: May 2023

AbstractAdaptation of soil microbes due to warming from climate change has been observed, but it remains unknown what microbial growth traits are adaptive to warming. We studied bacterial isolates from the Harvard Forest Long-Term Ecological Research site, where field soils have been experimentally heated to 5°C above ambient temperature with unheated controls for thirty years. We hypothesized that Alphaproteobacteria from warmed plots have (1) less temperature sensitive growth rates; (2) higher optimum growth temperatures; and (3) higher maximum growth temperatures compared to isolates from control plots. We made high-throughput measurements of bacterial growth in liquid cultures over time and across temperatures from 22-37°C in 2-3°C increments. We estimated growth rates by fitting Gompertz models to the growth data. Temperature sensitivity of growth rate, optimum growth temperature, and maximum growth temperature were estimated by the Ratkowsky 1983 model and a modified Macromolecular Rate Theory (MMRT) model. To determine evidence of adaptation, we ran phylogenetic generalized least squares tests on isolates from warmed and control soils. Our results showed evidence of adaptation of higher optimum growth temperature of bacterial isolates from heated soils. However, we observed no evidence of adaptation of temperature sensitivity of growth and maximum growth temperature. Our project begins to capture the shape of the temperature response curves, but illustrates that the relationship between growth and temperature is complex and cannot be limited to a single point in the biokinetic range.ImportanceSoils are the largest terrestrial carbon sink and the foundation of our food, fiber, and fuel systems. Healthy soils are carbon sinks, storing more carbon than they release. This reduces the amount of carbon dioxide released to the atmosphere and buffers against climate change. Soil microbes drive biogeochemical cycling and contribute to soil health through organic matter breakdown, plant growth promotion, and nutrient distribution. In this study, we determined how soil microbial growth traits respond to long-term soil warming. We found that bacterial isolates from warmed plots showed evidence of adaptation of increased optimum growth temperature. This suggests that increased microbial biomass and growth relative to respiration in a warming world should result in greater carbon storage. As temperatures increase, greater microbial activity may help reduce the soil carbon feedback loop. Our results provide insight on how atmospheric carbon cycling and soil health may respond in a warming world.
Immune checkpoint inhibitors combined with antiangiogenic drugs in the treatment of unresectable locally advanced / distant metastatic esophageal squamous cell carcinoma: a systematic review protocol
Authors: Lu Juanjuan , Li Honglin , Chang Sisi , YahuiZhu  , Gao Fuyan , Shao Shuai , Ma Chunzheng 
Published: May 2023

AbstractBackground and purposeEsophageal cancer has the seventh highest incidence and sixth highest fatality rate of all malignant tumors. It’s a type of cancer that has a greater fatality rate than morbidity. In the treatment of advanced esophageal and squamous cell carcinoma, targeted and immune checkpoint inhibitors have showed promising outcomes in recent years. The aim of this research was to examine the effectiveness and safety of immune checkpoint inhibitors in combination with antiangiogenic medicines in the treatment of unresectable patients with locally progressed / distant metastatic esophageal squamous cell carcinoma.MethodsBefore April 15, 2022, randomized controlled trials of immune checkpoint inhibitors combined with anti-angiogenic drugs in the treatment of esophageal cancer will be searched on PubMed, Cochrane Library, EMBASE, WebofScience, China Knowledge Network, Wanfang Data Knowledge Service Platform, and VIP. The two authors independently extracted the data, checked the data, and used the “bias risk” tool in the Cochrane intervention system evaluation manual to independently evaluate the bias included in the study. When the extracted data were similar enough, the Revman5.4 software was used for meta analysis. If the summary data could not be collected for meta analysis, the results would be summarized in a narrative way.DiscussionThis paper introduces in detail the systematic review and design method of immune checkpoint inhibitors mixture with antiangiogenic drugs in the treatment of unresectable locally advanced / distant metastatic esophageal squamous cell carcinoma.Systematic review registrationThe review protocol has been registered in PROSPERO CRD42022324666
Chemoenzymatic syntheses of fluorine-18-labeled disaccharides from [18F]FDG yield potent sensors of living bacteriain vivo
Authors: Sorlin Alexandre M. , López-Álvarez Marina , Rabbitt Sarah J. , Alanizi Aryn A. , Shuere Rebecca , Bobba Kondapa Naidu , Blecha Joseph , Sakhamuri Sasank , Evans Michael J. , Bayles Kenneth W. , Flavell Robert R. , Rosenberg Oren S. , Sriram Renuka , Desmet Tom , Nidetzky Bernd , Engel Joanne , Ohliger Michael A. , Fraser James S. , Wilson David M. 
Published: May 2023

ABSTRACTChemoenzymatic techniques have been applied extensively to pharmaceutical development, most effectively when routine synthetic methods fail. The regioselective and stereoselective construction of structurally complex glycans is an elegant application of this approach, that is seldom applied to positron emission tomography (PET) tracers. We sought a method to dimerize 2-deoxy-[18F]-fluoro-D-glucose ([18F]FDG), the most common tracer used in clinical imaging, to form [18F]-labeled disaccharides for detecting microorganismsin vivobased on their bacteria-specific glycan incorporation. When [18F]FDG was reacted with β-D-glucose-1-phosphate in the presence of maltose phosphorylase, both the α-1,4 and α-1,3-linked products 2-deoxy-[18F]-fluoro-maltose ([18F]FDM) and 2-deoxy-2-[18F]-fluoro-sakebiose ([18F]FSK) were obtained. This method was further extended with the use of trehalose (α,α-1,1), laminaribiose (β-1,3), and cellobiose (β-1,4) phosphorylases to synthesize 2-deoxy-2-[18F]fluoro-trehalose ([18F]FDT), 2-deoxy-2-[18F]fluoro-laminaribiose ([18F]FDL), and 2-deoxy-2-[18F]fluoro-cellobiose ([18F]FDC). We subsequently tested [18F]FDM and [18F]FSKin vitro,showing accumulation by several clinically relevant pathogens includingStaphylococcus aureusandAcinetobacter baumannii,and demonstrated their specific uptakein vivo.The lead sakebiose-derived tracer [18F]FSK was stable in human serum and showed high uptake in preclinical models of myositis and vertebral discitis-osteomyelitis. Both the synthetic ease, and high sensitivity of [18F]FSK toS. aureusincluding methicillin-resistant (MRSA) strains strongly justify clinical translation of this tracer to infected patients. Furthermore, this work suggests that chemoenzymatic radiosyntheses of complex [18F]FDG-derived oligomers will afford a wide array of PET radiotracers for infectious and oncologic applications.
Investigating antibody reactivity to the intestinal microbiome in severe myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)
Authors: Seton Katharine A. , Defernez Marianne , Telatin Andrea , Tiwari Sumeet K. , Savva George M. , Hayhoe Antonietta , Noble Alistair , Carvalho Ana , James Steve , Bansal Amolak , Wileman Thomas , Carding Simon R. 
Published: May 2023

AbstractMyalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multisystemic disease of unknown aetiology that is characterised by disabling chronic fatigue and involves both the immune and gastrointestinal (GI) systems. Patients display alterations in GI microbiome with a significant proportion experiencing GI discomfort and pain and elevated blood biomarkers for altered intestinal permeability compared with healthy individuals. To investigate a possible GI origin of ME/CFS we designed a feasibility study to test the hypothesis that ME/CFS pathogenesis is a consequence of increased intestinal permeability that results in microbial translocation and a breakdown in immune tolerance leading to generation of antibodies reactive to indigenous intestinal microbes. Secretory IgA and serum IgG levels and reactivity to intestinal microbes were assessed in five pairs of severe ME/CFS patients and matched same-household healthy controls. For profiling serum IgG we developed IgG-Seq which combines flow-cytometry based bacterial cell sorting and metagenomics to detect mucosal IgG reactivity to the microbiome. We uncovered evidence for immune dysfunction in severe ME/CFS patients that was characterised by reduced capacity and reactivity of serum IgG to stool microbes, irrespective of their source. This study provides the rationale for additional studies in larger cohorts of ME/CFS patients to further explore immune-microbiome interactions.
Effects of enriched biochar treatments on CO2release, soil nitrate and ammonium, and wheat growth parameters in saline soils
Authors: Moradi Salahedin , Rasouli-Sadaghiani Mirhassan , Sepehr Ebrahim , Khodaverdiloo Habib , Barin Mohsen , Vetukuri Ramesh Raju 
Published: May 2023

AbstractThe effects of treatment with simple and enriched biochar on microbial respiration, nitrate and ammonium concentrations, and wheat growth parameters in saline soils were investigated using a completely randomized factorial experimental design with three replications, three soil salinity levels (1.5, 4.5 and 9 dS.m-1), and five biochar treatments including control, 2% simple (SB) or enriched biochar (EB) amendment, and 4% SB or EB amendment. The basal respiration rate and the concentrations of ammonium, and nitrate were measured at multiple time points. Additionally, total soil nitrogen, organic carbon, and microbial biomass carbon, microbial biomass nitrogen, and microbial biomass phosphorus were measured together with the height and fresh and dry weight of wheat after a 100-day growth period and at the end of the experiment. Salinity significantly affected basal respiration, nitrate and ammonium concentrations, plant height, and wet and dry weight. Biochar amendment significantly affected pH, basal respiration, nitrate and ammonium concentrations, total soil nitrogen, soil organic carbon, microbial biomass carbon, microbial biomass nitrogen, and microbial biomass phosphorus in both rhizosphere and non-rhizosphere soil, as well as wheat height, and wet and dry weight. The interaction between salinity and biochar significantly affected nitrate and ammonium concentrations and also plant height and fresh and dry weight. Finally, the effects of different biochar amendments and salinity levels on the basal respiration rate and the concentrations of nitrate and ammonium varied significantly over time. Overall, the results obtained show that biochar amendment can significantly moderate the adverse effects of soil salinity, especially if enriched biochar is used.
Exploring Urban Street Green Perception from the Perspective of Combining GVI and NDVI: A Case Study of Zhongshan City, Guangdong Province
Authors: Su Lei , Chen Weifeng , Zhou Yan , Fan Lei , Li Junying 
Published: May 2023

AbstractUrban street greening has a positive impact on the health of citizens and the urban environment. This study takes the representative streets in the main urban area of Zhongshan City, Guangdong Province as an example to explore urban street greening perception from the perspective of combining Green visual index (GVI) and Normalized difference vegetation index (NDVI). This study uses a deep learning based image semantic segmentation method to analyze Baidu Street View to calculate the GVI of the street, and uses GF-1 satellite data to calculate NDVI to compare and analyze the characteristics and correlation of GVI and NDVI of urban streets. The results show that: 1. The GVI of streets in the central urban area of Zhongshan varies from 8.06% to 36.00%, with Xingzhong Road in Shiqi District Street having the highest GVI; 2. The mean value of NDVI of each street shows different changes with the increase of buffer scale, and the mean value of NDVI has a strong scale sensitivity; 3. The highest Pearson correlation coefficient between GVI and 25m DNVI mean value was 0.862; 4. The GVI prediction model based on NDVI is: y=0.8249x+0.0181, R2=0.7433. On this basis, the shortcomings of street landscape are analyzed and optimization suggestions are given, providing reference for urban street landscape evaluation, spatial optimization, and landscape improvement.
Expression, activity, and consequences of biochemical inhibition of α- and β-glucosidases in different life stages ofCulex quinquefasciatus
Authors: Burgess Edwin R. , Sanscrainte Neil D. , Taylor Caitlin E. , Buss Lyle J. , Estep Alden S. 
Published: May 2023

AbstractMosquitoes utilize a plethora of digestive enzymes to meet the challenge of both requisite blood and sugar meals that enable them to survive and reproduce. Sugar meals, typically derived from plant sources, are critical to maintain energy in both male and female mosquitoes, whereas blood meals are taken only by females to complete oogenesis. Enzymes involved in sugar digestion have been the subject of study for decades but have been limited to a relatively narrow range of mosquito species. The southern house mosquito,Culex quinquefasciatus, is of public health importance and seldom considered in these types of studies outside of topics related toBacillus sphaericus, a biocontrol agent that requires interaction with a specific gut-associated α-glucosidase. Here we sought to describe the nature of α-glucosidases and the unexplored β-glucosidases that may aidCx. quinquefasciatuslarvae in acquiring nutrients from cellulosic sources in their aquatic environments. Consistent with our hypothesis, we found both α- and β-glucosidase activity in larvae. Interestingly, β-glucosidase activity all but disappeared at the pupal stage and remained low in adults, while α-glucosidase activity remained in the pupal stage and then exceeded larval activity by approximately 1.5-fold. Expression of the putative α- and β-glucosidase genes chosen did not generally follow the trends seen in enzyme activities. When the α-glucosidase inhibitor acarbose was administered to adults, mortality was seen especially in males but also in females after two days of exposure and key energetic storage molecules, glycogen and lipids, were significantly lower than controls. In contrast, administering the β-glucosidase inhibitor conduritol β-epoxide to larvae did not produce mortality even at the highest soluble concentration. Here we provide insights into the importance of α- and β-glucosidases on the survival ofCx. quinquefasciatusin their three mobile life stages.
Large-language-model-based 10-year risk prediction of cardiovascular disease: insight from the UK biobank data
Authors: Han Changho , Kim Dong Won , Kim Songsoo , You Seng Chan , Bae SungA , Yoon Dukyong 
Published: May 2023

AbstractBackgroundConventional cardiovascular risk prediction models provide insights into population-level risk factors and have been widely adopted in clinical practice. However, these models have limited generalizability and flexibility. Large language models (LLMs) have demonstrated remarkable proficiency for use in various industries.MethodsIn this study, we have investigated the feasibility of Large Language Models (LLMs) such as ChatGPT-3.5, ChatGPT-4, and Bard for predicting 10-year cardiovascular risk of a patient. We used data from the UK Biobank Cohort, a major biomedical database in the UK, and the Korean Genome and Epidemiology Study (KoGES), a large-scale prospective study in Korea, for additional validation and multi-institutional research. These databases provided a wide array of information including age, sex, medical history, lipid profile, blood pressure, and physical measurement. Based on these data, we generated language sentences for individual analysis and input these into the LLM to derive results. The performance of the LLMs was then compared with the Framingham Risk Score (FRS), a conventional risk prediction model, using this real-world data. We confirmed the model performance of both the LLMs and FRS, evaluating their accuracy, sensitivity, specificity, Positive Predictive Value (PPV), Negative Predictive Value (NPV), and F1 score. Their performance in predicting 10-year cardiovascular risk was compared through Kaplan-Meier survival analysis and Cox-hazard ratio analysis.FindingsGPT-4 achieved performance comparable to the FRS in cardiovascular risk prediction in both the UK Biobank {accuracy (0·834 vs· 0·773) and F1 score (0·138 vs· 0·132)} and KoGES {accuracy (0·902 vs· 0·874)}. The Kaplan–Meier survival analysis of GPT-4 demonstrated distinct survival patterns among groups, which revealed a strong association between the GPT risk prediction output and survival outcomes. The additional analysis of limited variables using GPT-3·5 indicated that ChatGPT’s prediction performance was preserved despite the omission of a few variables in the prompt, especially without physical measurement dataInterpretationThis study proposed that ChatGPT can achieve performance comparable to conventional models in predicting cardiovascular risk. Furthermore, ChatGPT exhibits enhanced accessibility, flexibility, and the ability to provide user-friendly outputs. With the evolution of LLMs, such as ChatGPT, studies should focus on applying LLMs to various medical scenarios and subsequently optimizing their performance.
Breast cancer risk based on a deep learning predictor of senescent cells in normal tissue
Authors: Heckenbach Indra , Powell Mark , Fuller Sophia , Henry Jill , Rysdyk Sam , Cui Jenny , Teklu Amanuel Abraha , Verdin Eric , Benz Christopher , Scheibye-Knudsen Morten 
Published: May 2023

SummaryBackgroundThe ability to predict future risk of cancer development in non-malignant biopsies is poor. Cellular senescence has been associated with cancer as either a barrier mechanism restricting autonomous cell proliferation or a tumor-promoting microenvironmental mechanism that secretes pro-inflammatory paracrine factors. With most work done in non-human models and the heterogenous nature of senescence the precise role of senescent cells in the development of cancer in humans is not well understood. Further, more than one million non-malignant breast biopsies are taken every year that could be a major source of risk-stratification for women.MethodsWe applied single cell deep learning senescence predictors based on nuclear morphology to histological images of 4,411 H&E-stained breast biopsies from healthy female donors. Senescence was predicted in the epithelial, stromal, and adipocyte compartments using predictor models trained on cells induced to senescence by ionizing radiation (IR), replicative exhaustion (RS), or antimycin A, Atv/R and doxorubicin (AAD) exposures. To benchmark our senescence-based prediction results we generated 5-year Gail scores, the current clinical gold standard for breast cancer risk prediction.FindingsWe found significant differences in adipocyte-specific IR and AAD senescence prediction for the 86 out of 4,411 healthy women who developed breast cancer an average 4.8 years after study entry. Risk models demonstrated that individuals in the upper median of scores for the adipocyte IR model had a higher risk (OR=1.71 [1.10-2.68], p=0.019), while the adipocyte AAD model revealed a reduced risk (OR=0.57 [0.36-0.88], p=0.013). Individuals with both adipocyte risk factors had an OR of 3.32 ([1.68-7.03], p<0.001). Alone, 5-year Gail scores yielded an OR of 2.70 ([1.22-6.54], p=0.019). When combining Gail scores with our adipocyte AAD risk model, we found that individuals with both of these risk predictors had an OR of 4.70 ([2.29-10.90], p<0.001).InterpretationAssessment of senescence with deep learning allows considerable prediction of future cancer risk from non-malignant breast biopsies, something that was previously impossible to do. Furthermore, our results suggest an important role for microscope image-based deep learning models in predicting future cancer development. Such models could be incorporated into current breast cancer risk assessment and screening protocols.FundingThis study was funded by the Novo Nordisk Foundation (#NNF17OC0027812), and by the National Institutes of Health (NIH) Common Fund SenNet program (U54AG075932).