bluuebunny/crossref_metadata_2025 huggingface dataset:
A chromosome-level reference genome assembly and a full-length transcriptome assembly of the giant freshwater prawn (Macrobrachium rosenbergii)
Authors: Pootakham Wirulda , Sittikankaew Kanchana , Sonthirod Chutima , Naktang Chaiwat , Uengwetwanit Tanaporn , Kongkachana Wasitthee , Ampolsak Kongphop , Karoonuthaisiri Nitsara
Published: July 2024

The giant freshwater prawn (Macrobrachium rosenbergii) is a key species in the aquaculture industry in several Asian, African, and South American countries. Despite a considerable growth in its production worldwide, the genetic complexities of M. rosenbergii various morphotypes pose challenges in cultivation. This study reports the first chromosome-scale reference genome and a high-quality full-length transcriptome assembly for M. rosenbergii. We employed the PacBio High Fidelity (HiFi) sequencing to obtain an initial draft assembly and further scaffolded it with the chromatin contact mapping (Hi-C) technique to achieve a final assembly of 3.73-Gb with an N50 scaffold length of 33.6 Mb. Repetitive elements constituted nearly 60% of the genome assembly, with simple sequence repeats and retrotransposons being the most abundant. The availability of both the chromosome-scale assembly and the full-length transcriptome assembly enabled us to thoroughly probe alternative splicing events in M. rosenbergii. Among the 2,041 events investigated, exon skipping represented the most prevalent class, followed by intron retention. Interestingly, specific isoforms were observed across multiple tissues. Additionally, within a single tissue type, transcripts could undergo alternative splicing, yielding multiple isoforms. We believe that the availability of a chromosome-level reference genome for M. rosenbergii, along with its full-length transcriptome, will be instrumental in advancing our understanding of the giant freshwater prawn biology and enhancing its molecular breeding programs, paving the way for the development of M. rosenbergii with valuable traits in commercial aquaculture.
Optimal allocation method of shared energy storage in multienergy coupled microgrid with carbon emission constraint considering dual uncertainty of source and load
Authors: Li Manshu , Cui Xiaobo , Ma Lei , Tang Liang , Wang Gang , Rao Yao
Published: July 2024

In order to realize the stable operation of the multienergy coupled microgrid under the low-carbon constraint, a carbon emission constrained multienergy coupled microgrid shared energy storage optimization configuration method considering the dual uncertainty of source and load is proposed. This method constructs a source load double uncertainty and carbon emission model, and it analyzes the output characteristics and load demand characteristics of multiple coupled energy sources and the carbon emission results under these characteristics. According to the analysis results, the multienergy coupling microgrid shared energy storage optimization configuration model is constructed, and after the optimization configuration objective function and constraint conditions are determined, the bat algorithm is used to solve it, and the microgrid shared energy storage optimization configuration scheme that meets the objective function and constraint conditions is obtained. The test results show that after the method is applied, the utilization rate of multi-energy sources reaches 90.6%, and the expected carbon emissions are lower than 2.04 × 104kg. The microgrid fluctuation suppression rate reached 92.7%, and the net load fluctuation range was significantly reduced. Thus, it ensures reliable power supply of the microgrid and has good applicability.
Research on power battery recycling mode selection considering dual behavioral preferences under different government subsidies
Authors: Liu Juanjuan , Zhu Liangliang
Published: July 2024

Efficient and stable recycling of power batteries requires the construction of a perfect and reasonable recycling system; the current research however fails to take into account the comprehensive influence of government policies outside the supply chain and internal members’ behavioral preferences at the same time, hence fail to reflect the whole and true recycling reality. This paper studies how different battery recycling subsidy policies and relevant players’ behavioral preferences affect decision-making along the supply chain and tries to work out the optimal power battery recycling model. The results show that (1) Which recycling subsidy policy is better at promoting battery recycling is related to the size of battery capacity; (2) Behavioral preferences of key players, i.e. the risk aversion of the battery manufacturer and the fairness concern preference of the vehicle manufacturer, can be irrelevant or have a negative impact on power battery recycling; (3) The preferred recycling models vary among key stakeholders in the recycling ecosystem. The government encourages battery producers to lead the recycling operation, consumers and battery producers check the risk sensitivity, and vehicle manufacturers prefer to recycle batteries alone.
The effects of β-mannanase supplementation on growth performance, digestive enzyme activity, cecal microbial communities, and short-chain fatty acid production in broiler chickens fed diets with different metabolizable energy levels
Authors: Zhang Lin , Huan Hailin , Zhang Kai , Tu Yuanlu , Yan Junshu , Zhang Hao , Xi Yumeng
Published: July 2024

This study assessed the effects of β-mannanase (BM) supplementation on growth performance, digestive enzyme activity, cecal microbial communities, and short-chain fatty acid (SCFA) production in broiler chickens fed diets with different metabolizable energy (ME) levels. A total of 1,296 male 1-d-old Cobb 500 broilers were randomly distributed in a 3 × 2 factorial arrangement (3 ME levels × 0 or 200 g/ton BM), with 6 replicates per treatment combination. The 3 ME levels were 3,000 (ME1), 2,930 (ME2), and 2,860 (ME3) kcal/kg, respectively, during the 0 to 3 wk-old stages and 3,150 (ME1), 3,080 (ME2), and 3,010 (ME3) kcal/kg, respectively, during the 3 to 6 wk-old stages. Reducing ME levels increased broiler feed intake (P = 0.036) and decreased average daily gain (ADG, P = 0.002) during the entire period. While BM supplementation increased ADG (P = 0.002) and improved the feed conversion ratio (P = 0.001) during the 0 to 3 wk-old stages, with no effect during the 3 to 6 wk-old stages. Overall, reducing ME levels increased pancreatic lipase (P = 0.045) and amylase (P = 0.013) activity and duodenal amylase activity (P = 0.047). Notably, BM supplementation significantly increased pancreatic lipase activity (P = 0.015) and increased lipase (P = 0.029) and amylase (P = 0.025) activities in the jejunal chyme. Although diet or enzyme supplementation did not affect microbial diversity, significant differences in microbial communities were observed. At the genus level, decreasing ME levels significantly affected the average abundances of Tyzzerella (P = 0.028), Candidatus_Bacilloplasma (P = 0.001), Vibrio (P = 0.005), and Anaerotruncus (P = 0.026) among groups, whereas BM supplementation reduced the average abundances of Escherichia-Shigella (P = 0.048) and increased the average abundances of Barnesiella (P = 0.047), Ruminococcus (P = 0.020), Alistipes (P = 0.050), and Lachnospiraceae_unclassified (P = 0.009). SCFA concentrations strongly depended on bacterial community composition, and BM supplementation increased acetic acid (P = 0.004), propionic acid (P = 0.016), and total SCFA concentrations. In conclusion, BM supplementation improved the performance of younger broilers, and both enzyme supplementation and reduced ME levels positively affected digestive enzyme activity and intestinal microflora.
Tracking procedural justice in stop and search pedestrian encounters with police body-camera records
Authors: Barber Mark , Tankebe Justice
Published: July 2024

Procedural justice has emerged as a crucial dimension of fairness in policing. It encompasses the extent to which police officers listen to citizens, show care for the well-being of citizens, act with neutrality, and show respect to them. These matters arise during police-citizen interactions, such as police stop and search of citizens. In this study, we draw on a random sample of 150 stop-and-search encounters recorded on police body-worn cameras in a police force in England (UK) to assess police adherence to procedural justice principles. The analysis shows high ratings on voice, neutrality, and respect but relatively low score  on trustworthy motives. We found evidence of procedural justice variability across police jurisdictions. However, there was no evidence of an association between procedural justice and outcomes of stop-and-search interactions. The implications of the findings are discussed.
Move a little closer? Information sharing and the spatial clustering of bank branches
Authors: Qi Shusen , De Haas Ralph , Ongena Steven , Straetmans Stefan , Vadasz Tamas
Published: July 2024

We present a model of credit market competition to derive key hypotheses about how information sharing between banks influences the spatial clustering of their branches. We then test these hypotheses using data on 56,555 branches owned by 614 banks across 19 countries. We find that information sharing incentivizes banks to establish branches in localities that are new to them but that are already served by other banks. The resultant branch clustering is associated with reduced spatial credit rationing, as information sharing enables firms to access credit from more distant banks. These findings underscore how information sharing makes it more important for banks to move closer to each other rather than closer to their borrowers.
Dual-specificity phosphatases 13 and 27 as key switches in muscle stem cell transition from proliferation to differentiation
Authors: Hayashi Takuto , Sadaki Shunya , Tsuji Ryosuke , Okada Risa , Fuseya Sayaka , Kanai Maho , Nakamura Ayano , Okamura Yui , Muratani Masafumi , Wenchao Gu , Sugasawa Takehito , Mizuno Seiya , Warabi Eiji , Kudo Takashi , Takahashi Satoru , Fujita Ryo
Published: July 2024

Muscle regeneration depends on muscle stem cell (MuSC) activity. Myogenic regulatory factors, including myoblast determination protein 1 (MyoD), regulate the fate transition of MuSCs. However, the direct target of MYOD in the process is not completely clear. Using previously established MyoD knock-in (MyoD-KI) mice, we revealed that MyoD targets dual-specificity phosphatase (Dusp) 13 and Dusp27. In Dusp13:Dusp27 double knock-out mice, the ability for muscle regeneration after injury was reduced. Moreover, single-cell RNA sequencing of MyoD-high expressing MuSCs from MyoD-KI mice revealed that Dusp13 and Dusp27 are expressed only in specific populations within MyoD-high MuSCs, which also express Myogenin. Overexpressing Dusp13 in MuSCs causes premature muscle differentiation. Thus, we propose a model where DUSP13 and DUSP27 contribute to the fate transition of MuSCs from proliferation to differentiation during myogenesis.
Comparative Transcriptomic Analysis of Soybean Cyst Nematode Inbred Populations Non-adapted or Adapted on Soybean rhg1-a/Rhg4-Mediated Resistance
Authors: Kwon Khee Man , Masonbrink Rick E. , Maier Thomas R. , Gardner Michael N. , Severin Andrew J. , Baum Thomas J. , Mitchum Melissa G.
Published: July 2024

Soybean cyst nematode (SCN, Heterodera glycines) is most effectively managed through planting resistant soybean cultivars, but the repeated use of the same resistance sources has led to a widespread emergence of virulent SCN populations that can overcome soybean resistance. Resistance to SCN HG type 0 (Race 3) in soybean cultivar Forrest is mediated by an epistatic interaction between the soybean resistance genes rhg1-a and Rhg4. We previously developed two SCN inbred populations by mass-selecting SCN HG type 0 (Race 3) on susceptible and resistant recombinant inbred lines, derived from a cross between Forrest and the SCN-susceptible cultivar Essex, which differ for Rhg4. To identify SCN genes potentially involved in overcoming rhg1-a/ Rhg4-mediated resistance, we conducted RNA sequencing on early parasitic juveniles of these two SCN inbred populations infecting their respective hosts, only to discover a handful of differentially expressed genes (DEGs). However, in a comparison with early parasitic juveniles of an avirulent SCN inbred population infecting a resistant host, we discovered 59 and 171 DEGs uniquely up- or downregulated in virulent parasitic juveniles adapted on the resistant host. Interestingly, the proteins coded by these 59 DEGs included vitamin B-associated proteins (reduced folate carrier, biotin synthase, and thiamine transporter) and nematode effectors known to play roles in plant defense suppression, suggesting that virulent SCN may exert a heightened transcriptional response to cope with enhanced plant defenses and an altered nutritional status of a resistant soybean host.

[Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Neonatal Diazepam Exposure Decreases Dendritic Arborization and Spine Density of Cortical Pyramidal Neurons in Rats
Authors: Wadhwa Meetu , Sall Jeffrey W. , Chinn Gregory A.
Published: July 2024

Objective:

Benzodiazepines are extensively utilized in pediatric anesthesia and critical care for their anxiolytic and sedative properties. However, preclinical studies indicate that neonatal exposure to GABAergic drugs, including benzodiazepines, leads to long-term cognitive deficits, potentially mediated by altered GABAergic signaling during brain development. This preclinical study investigated the impact of early-life diazepam exposure on cortical neuronal morphology, specifically exploring dendritic arborization and spine density, crucial factors in synaptogenesis.

Methods:

Male and female Sprague Dawley rat pups were exposed to a single neonatal dose of diazepam (30 mg/kg) or vehicle on postnatal day (PND) 7. Golgi-Cox staining was used to assess cortical pyramidal neuron development at 4 developmental stages: neonatal (PND8), infantile (PND15), juvenile (PND30), and adolescence (PND42). Animals were randomized equally to 4 groups: male-vehicle, male-diazepam, female-vehicle, and female-diazepam. Neuronal morphology was evaluated after reconstruction in neurolucida, and dendritic spine density was analyzed through high-power photomicrographs using ImageJ.

Results:

Diazepam exposure resulted in decreased dendritic complexity in both sexes, with reduced arborization and spine density observed in cortical pyramidal neurons. Significant differences were found at each developmental stage, indicating a persistent impact. Dendritic length increased with age but was attenuated by diazepam exposure. Branching length analysis revealed decreased complexity after diazepam treatment. Spine density at PND42 was significantly reduced in both apical and basal dendrites after diazepam exposure.

Conclusions:

Neonatal diazepam exposure adversely affected cortical pyramidal neuron development, leading to persistent alterations in dendritic arborization and spine density. These structural changes suggest potential risks associated with early-life diazepam exposure. Further research is needed to unravel the functional consequences of these anatomic alterations.
Increased risk of subsequent primary lung cancer among female hormone-related cancer patients: A meta-analysis based on over four million cases
Authors: Wang Yan , Song Wenpeng , Wang Haoyu , Zhu Guonian , Li Yangqian , Wang Zhoufeng , Li Weimin , Che Guowei
Published: July 2024

Background:

The incidence rate of lung cancer in women has significantly increased over the past decade, and previous evidence has indicated a significant relationship between the elevated levels of sex hormones and the risk of lung cancer. Therefore, we hypothesized that female hormone-related cancer (FHRC) patients, including breast, endometrial, cervical, and ovarian cancer patients, may experience a higher risk of developing subsequent lung cancer. This meta-analysis aimed to identify the risk of lung cancer among FHRC patients compared to the general population.

Methods:

The PubMed, Web of Science, EMBASE, Cochrane Library, and CNKI databases were searched up to May 11, 2022. Standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) were used to identify the risk of subsequent lung cancer after FHRC. Subgroup analyses based on the follow-up time and tumor type were also conducted.

Results:

A total of 58 retrospective cohort studies involving 4,360,723 FHRC participants were included. The pooled results demonstrated that FHRC patients had a significantly increased risk of developing subsequent primary lung cancer (SIR = 1.61, 95% CI: 1.48–1.76,P<0.001). Subgroup analysis revealed an obvious trend of increasing lung cancer risk over time (SIRs for <5 years, ≥5 years, ≥10 years, ≥20 years, and ≥30 years after FHRC: 1.32, 1.59, 1.57, 1.68, and 1.95, respectively). In addition, subgroup analysis stratified by tumor type indicated an increased risk of developing subsequent lung cancer after breast (SIR = 1.25,P<0.001), endometrial (SIR = 1.40,P= 0.019), cervical (SIR = 2.56,P<0.001), and ovarian cancer (SIR = 1.50,P= 0.010).

Conclusion:

FHRC patients are more likely to develop lung cancer than the general population. Furthermore, the increased risk of subsequent primary lung cancer is more obvious with a longer survival time and is observed in all types of hormone-related cancer.

Registration:

International Platform of Registered Systematic Review and Meta-analysis Protocols: No. INPLASY202270044; https://inplasy.com/
Trends of diabetes in Beijing, China
Authors: Ma Aijuan , Lyu Jun , Dong Zhong , Nie Li , Xie Chen , Jiang Bo , Han Xueyu , Dong Jing , Zhao Yue , Li Liming
Published: July 2024

Background:

The global rise in diabetes prevalence is a pressing concern. Despite initiatives like “The Healthy Beijing Action 2020–2030” advocating for increased awareness, treatment, and control, the specific situation in Beijing remains unexplored. This study aimed to analyze the trends in diabetes prevalence, awareness, treatment, and control among Beijing adults.

Methods:

Through a stratified multistage probability cluster sampling method, a series of representative cross-sectional surveys were conducted in Beijing from 2005 to 2022, targeting adults aged 18–79 years. A face-to-face questionnaire, along with body measurements and laboratory tests, were administered to 111,943 participants. Data from all survey were age- and/or gender-standardized based on the 2020 Beijing census population. Annual percentage rate change (APC) or average annual percentage rate change (AAPC) was calculated to determine prevalence trends over time. Complex sampling logistic regression models were employed to explore the relationship between various characteristics and diabetes.

Results:

From 2005 to 2022, the total prevalence of diabetes among Beijing adults aged 18–79 years increased from 9.6% (95% CI: 8.8–10.4%) to 13.9% (95% CI: 13.1–14.7%), with an APC/AAPC of 2.1% (95% CI: 1.1–3.2%, P <0.05). Significant increases were observed among adults aged 18–39 years and rural residents. Undiagnosed diabetes rose from 3.5% (95% CI: 3.2–4.0%) to 7.2% (95% CI: 6.6–7.9%) with an APC/AAPC of 4.1% (95% CI: 0.5–7.3%, P <0.05). However, diabetes awareness and treatment rates showed annual declines of 1.4% (95% CI: −3.0% to −0.2%, P <0.05) and 1.3% (95% CI: −2.6% to −0.2%, P <0.05), respectively. The diabetes control rate decreased from 21.5% to 19.1%, although not statistically significant (APC/AAPC = −1.5%, 95% CI: −5.6% to 1.9%). Overweight and obesity were identified as risk factors for diabetes, with ORs of 1.65 (95% CI: 1.38–1.98) and 2.48 (95% CI: 2.07–2.99), respectively.

Conclusions:

The prevalence of diabetes in Beijing has significantly increased between 2005 and 2022, particularly among young adults and rural residents. Meanwhile, there has been a concerning decrease in diabetes awareness and treatment rates, while control rates have remained stagnant. Regular blood glucose testing, especially among adults aged 18–59 years, should be warranted. Furthermore, being male, elderly, overweight, or obese was associated with higher diabetes risk, suggesting the needs for targeted management strategies.
Tumor suppressive role of the antimicrobial lectin REG3A targeting the O-GlcNAc glycosylation pathway
Authors: Moniaux Nicolas , Geoffre Nicolas , Deshayes Alice , Dos Santos Alexandre , Job Sylvie , Lacoste Claire , Nguyen Tung-Son , Darnaud Marion , Friedel-Arboleas Mélanie , Guettier Catherine , Purhonen Janne , Kallijärvi Jukka , Amouyal Gilles , Amouyal Paul , Bréchot Christian , R. Vivès Romain , Buendia Marie Annick , Issad Tarik , Faivre Jamila
Published: July 2024

Background and Aims:

Antimicrobial proteins of the regenerating family member 3 alpha (REG3A) family provide a first line of protection against infections and transformed cells. Their expression is inducible by inflammation, which makes their role in cancer biology less clear since an immune-inflammatory context may preexist or coexist with cancer, as occurs in HCC. The aim of this study is to clarify the role of REG3A in liver carcinogenesis and to determine whether its carbohydrate-binding functions are involved.

Approach and Results:

This study provides evidence for a suppressive role of REG3A in HCC by reducing O-GlcNAcylation in 2 mouse models of HCC, in vitro cell studies, and clinical samples. REG3A expression in hepatocytes significantly reduced global O-GlcNAcylation and O-GlcNAcylation of c-MYC in preneoplastic and tumor livers and markedly inhibited HCC development in REG3A-c-MYC double transgenic mice and mice exposed to diethylnitrosamine. REG3A modified O-GlcNAcylation without altering the expression or activity of O-linked N-acetylglucosaminyltransferase, O-linked N-acetylglucosaminyl hydrolase, or glutamine fructose-6-phosphate amidotransferase. Reduced O-GlcNAcylation was consistent with decreased levels of UDP-GlcNAc in precancerous and cancerous livers. This effect was linked to the ability of REG3A to bind glucose and glucose-6 phosphate, suggested by a REG3A mutant unable to bind glucose and glucose-6 phosphate and alter O-GlcNAcylation. Importantly, patients with cirrhosis with high hepatic REG3A expression had lower levels of O-GlcNAcylation and longer cancer-free survival than REG3A-negative cirrhotic livers.

Conclusions:

REG3A helps fight liver cancer by reducing O-GlcNAcylation. This study suggests a new paradigm for the regulation of O-GlcNAc signaling in cancer-related pathways through interactions with the carbohydrate-binding function of REG3A.
Use of fixed-dose combinations for cardiovascular indications from 2018 to 2023: a nationwide population-based study
Authors: Götzinger Felix , Kieble Marita , Daudí Andrea Espinosa , Kunz Michael , Lauder Lucas , Böhm Michael , Laufs Ulrich , Mahfoud Felix , Schulz Martin
Published: July 2024

Aims:

Clinical guidelines support the use of fixed-dose combinations (FDC) for prevention of cardiovascular disease. Implementation of FDC into clinical care remains challenging, and current population-based data are scarce.

Methods and results:

Claims data on dispensed drugs in an outpatient care setting of approximately 87% of the German population were analysed regarding the use of FDC according to time, age of the insured persons, and active ingredients. The overarching trend for all FDC revealed a decrease from 77.3 defined daily doses per 1000 statutory health-insured (SHI) persons per day (DID) in the second half-year of 2018 (2018HY02) to 60.8 DID in the first half-year of 2023 (2023HY01) (Spearman ρ = -0.988; P < 0.001). The total DID for all antihypertensives (AHT) increased from 590.6 in 2018HY02 to 624.8 in 2023HY01 (ρ = 0.855; P = 0.002), but the DID for fixed-dose AHT (AHT-FDC) declined from 74.1 in 2018HY02 to 55.0 in 2023HY01 (ρ = -0.988; P < 0.001). Conversely, the use of all lipid-lowering agents (LLA) and LLA-FDC continuously increased: The total DID of all LLA rose from 92.5 in 2018HY02 to 134.4 in 2023HY01 (ρ = 1.000; P = 0.000), and for LLA-FDC from 3.1 in 2018HY02 to 5.5 DID in 2023HY01 (ρ = 0.915; P < 0.001). AHT-FDC and LLA-FDC were less frequently dispensed to patients at least 80 years than to patients less than 80 years. Dispensing of multiple purpose FDC increased from 2018HY02 to 2023HY01 from 0.11 DID to 0.26 DID (ρ = 1.000; P = 0.000) but remained negligible.

Conclusion:

Use of AHT-FDC in Germany is declining. In contrast, FDC containing LLA are increasingly prescribed. Dispensing of multiple purpose FDC is very low. Strategies are needed to facilitate the use of FDC as recommended by current guidelines.
Head Contact and Suspected Concussion Rates in Youth Basketball: Time to Target Head Contact Penalties for Prevention
Authors: Fehr Christy J. , West Stephen W. , Hagel Brent E. , Goulet Claude , Emery Carolyn A.
Published: July 2024

Objective:

To compare game events, head contact (HC) rates, and suspected concussion incidence rates (IRs) in boys' and girls' youth basketball.

Design:

Cross-sectional.

Setting:

Canadian club basketball teams (U16-U18).

Participants:

Players from 24 boys' and 24 girls' Canadian club basketball teams during the 2022 season.

Assessment of Risk Factors:

Recorded games were analyzed using Dartfish video analysis software to compare sexes.

Main Outcome Measures:

Poisson regression analyses were used to estimate HCs [direct (HC1) and indirect (HC2)], suspected concussion IRs, and IR ratios (IRRs). Game event, court location, and HC1 fouls were reported.

Results:

Division 1 HC rates did not differ between boys (n = 238; IR = 0.50/10 player-minutes; 95% confidence interval [CI], 0.43-0.56) and girls (n = 220; IR = 0.46/10 player-minutes; 95% CI, 0.40-0.52). Division 2 boys experienced 252 HCs (IR = 0.53/10 player-minutes; 95% CI, 0.46-0.59); girls experienced 192 HCs (IR = 0.40/10 player-minutes; 95% CI, 0.35-0.46). Division 2 boys sustained higher HC1 IRs compared with Division 2 girls (IRR = 1.42; 95% CI, 1.15-1.74). Head contacts, rates did not differ between boys and girls in either Division. Suspected concussion IRs were not significantly different for boys and girls in each Division. Head contacts occurred mostly in the key for boys and girls in each Division. Despite illegality, HC1 penalization ranged from 3.9% to 19.7%. Head contact mechanisms varied across Divisions and sexes.

Conclusions:

Despite current safety measures, both HCs and suspected concussions occur in boys' and girls' basketball. Despite the illegality and potential danger associated with HC, only a small proportion of direct HCs were penalized and therefore targeting greater enforcement of these contacts may be a promising prevention target.
Assessment of the clinical value of five noninvasive predictors of metabolic dysfunction–associated steatotic liver disease in Han Chinese adults
Authors: Ma Xiaopu , Zou Haoxuan , Zhan Junyi , Gao Junzhu , Xie Yan
Published: July 2024

Background:

Fatty Liver Index (FLI), Triglyceride–Glucose Index (TyG), Lipid Accumulation Product (LAP), Zhejiang University Index (ZJU), and Visceral Adiposity Index (VAI) are five classical predictive models for fatty liver disease. Our cross-sectional study aimed to identify the optimal predictors by comparing the predictive value of five models for metabolic dysfunction–associated steatotic liver disease (MASLD) risk.

Methods

Data on 2687 participants were collected from West China Hospital of Sichuan University. Controlled attenuation parameters assessed by transient elastography were used to effectively diagnose MASLD. Logistic regression analysis was used to estimate the odd ratios and 95% confidence intervals between indices and MASLD risk. Receiver operating characteristic curves were plotted to evaluate the predictive value of indices.

Results

This study included 1337 normal and 1350 MASLD samples. The average age of MASLD patients is 47 years old, and the prevalence was higher in males (39.3%) than in females (10.9%). Five indices were positively correlated with MASLD risk, with the strongest correlation for TyG. Overall, the area under the curve of the indicators was: ZJU 0.988, FLI 0.987, LAP 0.982, TyG 0.942, and VAI 0.941. In the gender stratification, ZJU (0.989) performed best in males. FLI (0.988) and ZJU (0.987) had similar predictive ability in females. In the age stratification, FLI performed better in predicting the middle-aged group aged 30–40 years (0.991).

Conclusion

For Chinese Han adults, ZJU is the best predictive index for initial screening of MASLD. FLI can serve as an alternative tool for ZJU to predict females.
Evaluation of online chat-based artificial intelligence responses about inflammatory bowel disease and diet
Authors: Naqvi Haider A. , Delungahawatta Thilini , Atarere Joseph O. , Bandaru Sumanth Kumar , Barrow Jasmine B. , Mattar Mark C.
Published: July 2024

Introduction

The USA has the highest age-standardized prevalence of inflammatory bowel disease (IBD). Both genetic and environmental factors have been implicated in IBD flares and multiple strategies are centered around avoiding dietary triggers to maintain remission. Chat-based artificial intelligence (CB-AI) has shown great potential in enhancing patient education in medicine. We evaluate the role of CB-AI in patient education on dietary management of IBD.

Methods

Six questions evaluating important concepts about the dietary management of IBD which then were posed to three CB-AI models – ChatGPT, BingChat, and YouChat three different times. All responses were graded for appropriateness and reliability by two physicians using dietary information from the Crohn’s and Colitis Foundation. The responses were graded as reliably appropriate, reliably inappropriate, and unreliable. The expert assessment of the reviewing physicians was validated by the joint probability of agreement for two raters.

Results

ChatGPT provided reliably appropriate responses to questions on dietary management of IBD more often than BingChat and YouChat. There were two questions that more than one CB-AI provided unreliable responses to. Each CB-AI provided examples within their responses, but the examples were not always appropriate. Whether the response was appropriate or not, CB-AIs mentioned consulting with an expert in the field. The inter-rater reliability was 88.9%.

Discussion

CB-AIs have the potential to improve patient education and outcomes but studies evaluating their appropriateness for various health conditions are sparse. Our study showed that CB-AIs have the ability to provide appropriate answers to most questions regarding the dietary management of IBD.
Real-life experiences of switching from intravenous to subcutaneous vedolizumab maintenance therapy in patients with inflammatory bowel disease
Authors: Kolehmainen Sara , Rautakorpi Jaakko , Löyttyniemi Eliisa , af Björkesten Clas-Göran , Arkkila Perttu , Salminen Kimmo , Sipponen Taina
Published: July 2024

Background

A few prospective cohort studies support the safety of switching from intravenous to subcutaneous administration of vedolizumab during maintenance therapy in patients with inflammatory bowel disease. Real-life data on switching after intravenous induction therapy are lacking.

Objective

The aim was to obtain real-world data on subcutaneous vedolizumab treatment in patients with inflammatory bowel disease after switching from intravenous vedolizumab induction or maintenance therapy, and to evaluate treatment persistence, safety, and changes in disease activity and serum vedolizumab concentrations.

Methods

We performed a retrospective registry-based study of inflammatory bowel disease patients who received subcutaneous vedolizumab therapy in two tertiary centres.

Results

Altogether, 103 patients (26 Crohn’s disease and 77 ulcerative colitis) switching from intravenous maintenance therapy (group 1) and 44 patients (14 and 30, respectively) switching from intravenous induction therapy (group 2) were included. At 6 months from baseline, 90.3% of the patients in group 1 and 90.9% of the patients in group 2 continued on subcutaneous vedolizumab. After the switch in group 1, disease activity remained stable. In group 2, clinical disease activity decreased significantly in ulcerative colitis patients (P = 0.002). The median serum vedolizumab concentration was 34.00 µg/ml during subcutaneous maintenance therapy in group 1, which was significantly higher than the median concentration during intravenous therapy (17.00 µg/ml, P < 0.001), but remained unchanged in group 2 after the switch (31.50 µg/ml).

Conclusion

Based on these data, subcutaneous vedolizumab treatment is well-tolerated and the treatment persistence remains high after switching from intravenous to subcutaneous vedolizumab therapy.
Neuroprotection of the P2X7 receptor antagonist A740003 on retinal ganglion cells in experimental glaucoma
Authors: Zhu Yan , Li Shu-Ying , Zhang Lu-Jia , Lei Bo , Wang Yong-Chen , Wang Zhongfeng
Published: July 2024

The aim of this study was to explore the neuroprotective effects of the P2X7 receptor antagonist A740003 on retinal ganglion cells (RGCs) in chronic intraocular hypertension (COH) experimental glaucoma mouse model. Bioinformatics was used to analyze the glaucoma-related genes. Western blot, real-time fluorescence quantitative PCR, and immunofluorescence staining techniques were employed to explore the mechanisms underlying the neuroprotective effects of A740003 on RGCs in COH retinas. Bioinformatic analysis revealed that oxidative stress, neuroinflammation, and cell apoptosis were highly related to the pathogenesis of glaucoma. In COH retinas, intraocular pressure elevation significantly increased the levels of translocator protein, a marker of microglial activation, which could be reversed by intravitreal preinjection of A740003. A740003 also suppressed the increased mRNA levels of proinflammatory cytokines interleukin (IL) 1β and tumor necrosis factor α in COH retinas. In addition, although the mRNA levels of anti-inflammatory cytokine IL-4 and IL-10 were kept unchanged in COH retinas, administration of A740003 could increase their levels. The mRNA and protein levels of Bax and cleaved caspase-3 were increased in COH retinas, which could be partially reversed by A740003, while the levels of Bcl-2 kept unchanged in COH retinas with or without the injections of A740003. Furthermore, A740003 partially attenuated the reduction in the numbers of Brn-3a-positive RGCs in COH mice. A740003 could provide neuroprotective roles on RGCs by inhibiting the microglia activation, attenuating the retinal inflammatory response, reducing the apoptosis of RGCs, and enhancing the survival of RGCs in COH experimental glaucoma.
Evidence for low affinity of GABA at the vesicular monoamine transporter VMAT2 – implications for transmitter co-release from dopamine neurons
Authors: Limani Fabian , Srinivasan Sivakumar , Hanzlova Michaela , La Batide-Alanore Ségolène , Klotz Sigrid , Hnaskoxs Thomas S. , Steinkellner Thomas
Published: July 2024

Background and Purpose

Midbrain dopamine (DA) neurons comprise a heterogeneous population of cells. For instance, some DA neurons express the vesicular glutamate transporter VGLUT2 allowing these cells to co-release DA and glutamate. Additionally, GABA may be co-released from DA neurons. However, most cells do not express the canonical machinery to synthesize GABA or the vesicular GABA transporter VGAT. Instead, GABA seems to be taken up into DA neurons by a plasmalemmal GABA transporter (GAT1) and stored in synaptic vesicles via the vesicular monoamine transporter VMAT2. Yet, it remains unclear whether GABA indeed interacts with VMAT2, or whether another transmitter could be responsible for the observed inhibitory effects attributed to GABA.

Experimental Approach

We used radiotracer flux measurements in VMAT2 expressing HEK-293 cells and synaptic vesicles from rodents to determine whether GABA qualifies as substrate at VMAT2. mRNAin situhybridization was employed to determine expression of VMAT2 and GAT1 transcripts in DA neurons of mouse and in human midbrains.

Key Results

We found that GABA reduced uptake of VMAT2 substrates in rodent synaptic vesicle preparations from striatum and cerebellum at millimolar concentrations but had no effect in VMAT2-expressing cells indicating that key components are missing in a non-neuronal system. Roughly 60 % of murine and human DA neurons in the substantia nigra express VMAT2 and GAT1 suggesting that many may be capable of co-releasing DA and GABA.

Conclusion and Implication

Our experiments suggest that GABA is a low-affinity substrate at VMAT2 with potential implications for basal ganglia physiology and disease.

Bullet point summary

What is already known

Subpopulations of dopamine neurons co-release glutamate and/or GABA.

While glutamate is loaded into vesicles by VGLUT2, GABA co-release depends on GAT1 and VMAT2.

What this study adds

The relative affinity of GABA at VMAT2 was found to be in the millimolar range.

Human midbrain dopamine neurons express GAT1.

Clinical significance

GABA co-release from midbrain dopamine neurons may also occur in humans.

GABA co-release from dopamine neurons may play a role in neuropsychiatric diseases
A Universal, Single-Component Multilayered Self-Assembling Protein Nanoparticle Vaccine Based on Extracellular Domains of Matrix Protein 2 Against Both Influenza A and B
Authors: Zhang Yi-Nan , Gomes Keegan Braz , Lee Yi-Zong , Ward Garrett , Xie Bomin , Auclair Sarah , He Linling , Zhu Jiang
Published: July 2024

The development of an effective and broadly protective influenza vaccine against circulating and emerging strains remains elusive. In this study, we evaluated single-component self-assembling protein nanoparticles (1c-SApNPs) presenting the conserved matrix protein 2 ectodomain (M2e) from influenza A and B viruses (IAV and IBV, respectively) as a universal influenza vaccine. We previously designed a tandem antigen comprising three IAV M2e domains of human, avian/swine, and human/swine origins (termed M2ex3). The M2ex3-presenting 1c-SApNPs conferred complete protection in mice against sequential lethal challenges with H1N1 and H3N2. To broaden this protection to counter IBVs, we designed a series of antigens incorporating different arrangements of three IAV M2e domains and three copies of IBV M2e. The tandem repeats of IAV and IBV (termed influenza A-B) M2e arrayed on the I3-01v9a 60-mer 1c-SApNP, when formulated with an oil-in-water emulsion adjuvant, generated greater M2e-specifc immunogenicity and protective efficacy than the soluble influenza A-B M2e trimer, as indicated by higher survival rates and lower weight loss post-challenge. Importantly, one of the influenza A-B M2e SApNP constructs elicited 100% protection against a lethal influenza A (H1N1) challenge in mice and 70% protection against a lethal influenza B (Yamagata lineage) challenge, the latter of which has not been reported in the literature to date. Our study thus provides a truly universal single-component M2e-based vaccine candidate against two major types of influenza virus circulating in humans.
In vivo CRISPR base editing for treatment of Huntington’s disease
Authors: Shirguppe Shraddha , Gapinske Michael , Swami Devyani , Gosstola Nicholas , Acharya Pankaj , Miskalis Angelo , Joulani Dana , Szkwarek Maddie G. , Bhattacharjee Abhishek , Elias Gianna , Stilger Michelle , Winter Jackson , Woods Wendy S. , Anand Daphine , Lim Colin K.W. , Gaj Thomas , Perez-Pinera Pablo
Published: July 2024

Huntington’s disease (HD) is an inherited and ultimately fatal neurodegenerative disorder caused by an expanded polyglutamine-encoding CAG repeat within exon 1 of the huntingtin (HTT) gene, which produces a mutant protein that destroys striatal and cortical neurons. Importantly, a critical event in the pathogenesis of HD is the proteolytic cleavage of the mutant HTT protein by caspase-6, which generates fragments of the N-terminal domain of the protein that form highly toxic aggregates. Given the role that proteolysis of the mutant HTT protein plays in HD, strategies for preventing this process hold potential for treating the disorder. By screening 141 CRISPR base editor variants targeting splice elements in the HTT gene, we identified platforms capable of producing HTT protein isoforms resistant to caspase-6-mediated proteolysis via editing of the splice acceptor sequence for exon 13. When delivered to the striatum of a rodent HD model, these base editors induced efficient exon skipping and decreased the formation of the N-terminal fragments, which in turn reduced HTT protein aggregation and attenuated striatal and cortical atrophy. Collectively, these results illustrate the potential for CRISPR base editing to decrease the toxicity of the mutant HTT protein for HD.
Single-cell omics for complex microbial communities
Authors: Lan Xihong , Liang Qiaoxing , Wu Jiayi , He Jinhua , Zhang Xiaoying , Li Fei , Zhao Guoping , Guo Ruidong , Jia Huijue
Published: July 2024

Despite over a decade of effort, microbial single-cell genomics and transcriptomics remain a challenge, especially for complex communities such as the human microbiome. Here we report a solution based on the Laser-Induced Forward Transfer (LIFT) technology, which circumvent the need for droplet microfluidics and complex barcoding, and allow selective amplification of the genome and the transcriptome of commensal bacteria from complex samples. We capture the diverse oral microbiome, and elucidate the single-cell transcriptome in sporulation. This single-cell method is both scalable and precise, and enables investigation into tissue samples. The approach shows great promise for elucidating the single-cell fate of microbial populations and the native environment of the host-associated microbiome.
Diffusion Basis Spectrum Imaging of White Matter in Schizophrenia and Bipolar Disorder
Authors: Mamah Daniel , Patel Aakash , Chen ShingShiun , Wang Yong , Wang Qing
Published: July 2024

Background

Multiple studies point to the role of neuroinflammation in the pathophysiology of schizophrenia (SCZ), however, there have been fewin vivotools for imaging brain inflammation. Diffusion basis spectrum imaging (DBSI) is an advanced diffusion-based MRI method developed to quantitatively assess microstructural alternations relating to neuroinflammation, axonal fiber, and other white matter (WM) pathologies.

Methods

We acquired one-hour-long high-directional diffusion MRI data from young control (CON,n=27), schizophrenia (SCZ,n=21), and bipolar disorder (BPD,n=21) participants aged 18-30. We applied Tract-based Spatial Statistics (TBSS) to allow whole-brain WM analyses and compare DBSI-derived isotropic and anisotropic diffusion measures between groups. Clinical relationships of DBSI metrics with clinical symptoms were assessed across SCZ and control participants.

Results

In SCZ participants, we found a generalized increase in DBSI-derived cellularity (a putative marker of neuroinflammation), a decrease in restricted fiber fraction (a putative marker of apparent axonal density), and an increase in extra-axonal water (a putative marker of vasogenic edema) across several WM tracts. There were only minimal WM abnormalities noted in BPD, mainly in regions of the corpus callosum (increase in DTI-derived RD and extra-axonal water). DBSI metrics showed significant partial correlations with psychosis and mood symptoms across groups.

Conclusion

Our findings suggest that SCZ involves generalized white matter neuroinflammation, decreased fiber density, and demyelination, which is not seen in bipolar disorder. Larger studies are needed to identify medication-related effects. DBSI metrics could help identify high-risk groups requiring early interventions to prevent the onset of psychosis and improve outcomes.
Identification of the Risk Factors for Complex-Multiple Long-term Conditions (C-MLTC): A Scoping Review
Authors: Heneghan Carl J. , Brassey Jon , Sheppard James P. , Tsiachristas Apostolos , Bhui Kamaldeep , Perera Rafael , Bennett Derrick , Onakpoya Igho J.
Published: July 2024

Background

Complex multiple long-term conditions (C-MLTC) are commonly defined as the presence of four or more long-term conditions, and their prevalence is projected to increase significantly over the next decade.

Methods

We undertook a scoping review of the literature to identify available evidence on the risk factors for C-MLTC and map out the potential clusters. We focussed on a subset of 18 chronic conditions because they include the most commonly reported and prevalent conditions in the general population. For guidelines we searched NICE Clinical Knowledge Summaries (CKS) and for systematic reviews we searched PubMed, Google Scholar and the TRIP database.

Results

We found 53 risk factors associated with 18 long-term conditions. Sixteen of these are linked to C-MLTC, with 11 being modifiable. Although we reviewed 51 systematic reviews, inconsistent reporting made it difficult to quantify the risk factors and conditions associated with C-MLTC. Diabetes mellitus was a risk factor for most other conditions (10), followed by coronary heart disease, hypertension, and chronic kidney disease (each associated with 8 long-term conditions). Additionally, depression and anxiety are commonly associated with other long-term conditions, with 19 and 20 conditions, respectively.

Conclusion

Several risks and conditions contribute to the development of multimorbidity. Anxiety and depression are nearly associated with all long-term conditions. Reporting problems within the existing evidence and a lack of clear definitions prevent adequate quantification of the risks related to C-MLTC.
Raman Sideband Cooling of Molecules in an Optical Tweezer Array to the 3D Motional Ground State
Authors: Bao Yicheng , Yu Scarlett S. , You Jiaqi , Anderegg Loïc , Chae Eunmi , Ketterle Wolfgang , Ni Kang-Kuen , Doyle John M.
Published: July 2024

Ultracold polar molecules are promising for quantum information processing and searches for physics beyond the standard model. Laser cooling to ultracold temperatures is an established technique for trapped diatomic and triatomic molecules. Further cooling of the molecules to near the motional ground state is crucial for reducing various dephasings in quantum and precision applications. In this work, we demonstrate Raman sideband cooling (RSC) of CaF molecules in optical tweezers to near their motional ground state, with average motional occupation quantum numbers of n¯x=0.16(12), n¯y=0.17(17) (radial directions), and n¯z=0.22(16) (axial direction), and a 3-D motional-ground-state probability of 54±18% of the molecules that survive the RSC. This process paves the way to increase molecular coherence times in optical tweezers for robust quantum computation and simulation applications.

Published by the American Physical Society
2024