bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptomics reveal different metabolic strategies for acid resistance and gamma-aminobutyric acid (GABA) production in select Levilactobacillus brevis strains
Authors: Banerjee Sagarika , Poore Matthew , Gerdes Svetlana , Nedveck Derek , Lauridsen Lene , Kristensen Heidi Thomsen , Jensen Henrik Max , Byrd Phillip M. , Ouwehand Arthur C. , Patterson Elaine , Morovic Wesley 
Published: September 2021

Abstract
Background
Of the many neurotransmitters in humans, gamma-aminobutyric acid (GABA) shows potential for improving several mental health indications such as stress and anxiety. The microbiota-gut-brain axis is an important pathway for GABAergic effects, as microbially-secreted GABA within the gut can affect host mental health outcomes. Understanding the molecular characteristics of GABA production by microbes within the gut can offer insight to novel therapies for mental health.

Results
Three strains of Levilactobacillus brevis with syntenous glutamate decarboxylase (GAD) operons were evaluated for overall growth, glutamate utilization, and GABA production in typical synthetic growth media supplemented with monosodium glutamate (MSG). Levilactobacillus brevis Lbr-6108™ (Lbr-6108), formerly known as L. brevis DPC 6108, and Levilactobacillus brevis Lbr-35 ™ (Lbr-35) had similar growth profiles but differed significantly in GABA secretion and acid resistance. Lbr-6108 produced GABA early within the growth phase and produced significantly more GABA than Lbr-35 and the type strain Levilactobacillus brevis ATCC 14869 after the stationary phase. The global gene expression during GABA production at several timepoints was determined by RNA sequencing. The GAD operon, responsible for GABA production and secretion, activated in Lbr-6108 after only 6 h of fermentation and continued throughout the stationary phase. Furthermore, Lbr-6108 activated many different acid resistance mechanisms concurrently, which contribute to acid tolerance and energy production. In contrast, Lbr-35, which has a genetically similar GAD operon, including two copies of the GAD gene, showed no upregulation of the GAD operon, even when cultured with MSG.

Conclusions
This study is the first to evaluate whole transcriptome changes in Levilactobacillus brevis during GABA production in different growth phases. The concurrent expression of multiple acid-resistance mechanisms reveals niche-specific metabolic functionality between common human commensals and highlights the complex regulation of GABA metabolism in this important microbial species. Furthermore, the increased and rapid GABA production of Lbr-6108 highlights the strain’s potential as a therapeutic and the overall value of screening microbes for effector molecule output.
Diagnostic value comparison of CellDetect, fluorescent in situ hybridization (FISH), and cytology in urothelial carcinoma
Authors: Shang Donghao , Liu Yuting , Xu Xiuhong , Chen Zhenghao , Wang Daye 
Published: September 2021

Abstract
Background
To evaluate the clinical effectiveness of a novel CellDetect staining technique, compared with fluorescent in situ hybridization (FISH), and urine cytology, in the diagnosis of urothelial carcinoma (UC).

Methods
A total of 264 patients with suspicious UC were enrolled in this study. All tissue specimens were collected by biopsy or surgery. Urine specimen was obtained for examinations prior to the surgical procedure. CellDetect staining was carried out with CellDetect kit, and FISH was performed with UroVysion detection kit, according to the manufacturer’s instructions. For urine cytology, all specimens were centrifuged using the cytospin method, and the slides were stained by standard Papanicolaou stain.

Results
In this study, there were 128 cases of UC and 136 cases of non-UC, with no significant difference in gender and age between the two groups. Results for sensitivity of CellDetect, FISH, and urine cytology were 82.8%, 83.6%, and 39.8%, respectively. The specificity of the three techniques were 88.2%, 90.4%, and 86.0%, respectively. The sensitivity of CellDetect and FISH are significantly superior compared to the conventional urine cytology; however, there was no significant difference in specificity among three staining techniques. In addition, the sensitivity of CellDetect in lower urinary tract UC, upper urinary tract UC, non-muscle-invasive bladder cancer (NMIBC), and muscle-invasive bladder cancer (MIBC) were 83.3%, 81.8%, 83.5%, and 72.0%, respectively. The screening ability of CellDetect has no correlation with tumor location and the tumor stage. The sensitivity of CellDetect in low-grade UC and high-grade UC were 51.6 and 92.8%. Thus, screening ability of CellDetect in high-grade UC is significantly superior compared to that in low-grade UC.

Conclusions
CellDetect and FISH show equal value in diagnosing UC, both are superior to conventional urine cytology. Compared to FISH, CellDetect is cost effective, easy to operate, with extensive clinical application value to monitor recurrence of UC, and to screen indetectable UC.
Impact of long-term exposure to PM2.5 and temperature on coronavirus disease mortality: observed trends in France
Authors: Tchicaya Anastase , Lorentz Nathalie , Omrani Hichem , de Lanchy Gaetan , Leduc Kristell 
Published: September 2021

Abstract
Background
The outbreak of coronavirus disease (COVID-19) began in Wuhan, China in December 2019 and was declared a global pandemic on 11 March 2020. This study aimed to assess the effects of temperature and long-term exposure to air pollution on the COVID-19 mortality rate at the sub-national level in France.

Methods
This cross-sectional study considered different periods of the COVID-19 pandemic from May to December 2020. It included 96 departments (or NUTS 3) in mainland France. Data on long-term exposure to particulate matter (PM2.5), annual mean temperature, health services, health risk, and socio-spatial factors were used as covariates in negative binomial regression analysis to assess their influence on the COVID-19 mortality rate. All data were obtained from open-access sources.

Results
The cumulative COVID-19 mortality rate by department increased during the study period in metropolitan France—from 19.8/100,000 inhabitants (standard deviation (SD): 20.1) on 1 May 2020, to 65.4/100,000 inhabitants (SD: 39.4) on 31 December 2020. The rate was the highest in the departments where the annual average of long-term exposure to PM2.5 was high. The negative binomial regression models showed that a 1 μg/m3 increase in the annual average PM2.5 concentration was associated with a statistically significant increase in the COVID-19 mortality rate, corresponding to 24.4%, 25.8%, 26.4%, 26.7%, 27.1%, 25.8%, and 15.1% in May, June, July, August, September, October, and November, respectively. This association was no longer significant on 1 and 31 December 2020. The association between temperature and the COVID-19 mortality rate was only significant on 1 November, 1 December, and 31 December 2020. An increase of 1 °C in the average temperature was associated with a decrease in the COVID-19-mortality rate, corresponding to 9.7%, 13.3%, and 14.5% on 1 November, 1 December, and 31 December 2020, respectively.

Conclusion
This study found significant associations between the COVID-19 mortality rate and long-term exposure to air pollution and temperature. However, these associations tended to decrease with the persistence of the pandemic and massive spread of the disease across the entire country.
Triglyceride glucose-body mass index and the risk of diabetes: a general population-based cohort study
Authors: Wang Xiaoyu , Liu Jingdong , Cheng Zongyou , Zhong Yanjia , Chen Xiaohua , Song Wei 
Published: September 2021

Abstract
Background
Triglyceride glucose-body mass index (TyG-BMI) has been proven to be a reliable substitute for insulin resistance. However, whether a causal association exists between TyG-BMI and new-onset diabetes remains uncertain. The purpose of this study was to investigate the causal association and predictive performance between TyG-BMI and diabetes.

Methods
A total of 116,661 subjects who underwent a physical examination were included in this study. The subjects were divided into five equal points according to the quintile of TyG-BMI, and the outcome of interest was the occurrence of diabetic events. TyG-BMI = ln [fasting plasma glucose (mg/dL) × fasting triglycerides (mg/dL)/2] × BMI.

Results
During the average follow-up period of 3.1 (0.95) years, 1888 men (1.61 %) and 793 women (0.68 %) were newly diagnosed with diabetes. Multivariate Cox regression analysis showed that TyG-BMI was an independent predictor of new-onset diabetes (HR 1.50 per SD increase, 95 %CI: 1.40 to 1.60, P-trend < 0.00001), and the best TyG-BMI cutoff value for predicting new-onset diabetes was 213.2966 (area under the curve 0.7741, sensitivity 72.51 %, specificity 69.54 %). Additionally, the results of subgroup analysis suggested that the risk of TyG-BMI-related diabetes in young and middle-aged people was significantly higher than that in middle-aged and elderly people, and the risk of TyG-BMI-related diabetes in non-obese people was significantly higher than that in overweight and obese people (P for interaction < 0.05).

Conclusions
This cohort study of the Chinese population shows that after excluding other confounding factors, there is a causal association of TyG-BMI with diabetes, and this independent association is more obvious in young, middle-aged and non-obese people.
Prussian blue-based theranostics for ameliorating acute kidney injury
Authors: Zhang Dong-Yang , Liu Hengke , Zhu Kathy S. , He Ting , Younis Muhammad Rizwan , Yang Chen , Lei Shan , Wu Jiayingzi , Lin Jing , Qu Junle , Huang Peng 
Published: September 2021

Abstract
Background
Acute kidney injury (AKI) with high mortality rates is associated with an excess of reactive oxygen/nitrogen species (RONS) within kidney tissues. Recently, nanomedicine antioxidant therapy has been used to alleviate AKI. Herein, we synthesized ultrasmall Prussian blue nanozymes (PB NZs, 4.5 nm) as theranostic agents for magnetic resonance (MR)/photoacoustic (PA) dual-modal imaging guided AKI treatment.

Results
PB NZs exhibited multi-enzyme mimetic abilities, promoting the effective elimination of RONS both in vitro and in vivo. Moreover, benefiting from their imaging contrast properties, the rapid renal accumulation of PB NZs was verified by in vivo PA/MR dual-modal imaging. Due to their excellent enrichment in the kidney and unique multi-enzyme mimetic abilities, ultrasmall PB NZs displayed superior AKI treatment efficacy compared with that of amifostine in two clinically relevant types of AKI induced murine models (either by rhabdomyolysis or cisplatin).

Conclusion
Our findings suggested ultrasmall PB NZs, as nanozyme theranostics, have great potential for AKI management.

Graphic abstract
Synergy of nanodiamond–doxorubicin conjugates and PD-L1 blockade effectively turns tumor-associated macrophages against tumor cells
Authors: Xu Hua-Zhen , Li Tong-Fei , Wang Chao , Ma Yan , Liu Yan , Zheng Mei-Yan , Liu Zhang-Jun-Yan , Chen Jin-Bo , Li Ke , Sun Shi-Kuan , Komatsu Naoki , Xu Yong-Hong , Zhao Li , Chen Xiao 
Published: September 2021

Abstract
Background
Tumor-associated macrophages (TAMs) are the most abundant stromal cells in the tumor microenvironment. Turning the TAMs against their host tumor cells is an intriguing therapeutic strategy particularly attractive for patients with immunologically “cold” tumors. This concept was mechanistically demonstrated on in vitro human and murine lung cancer cells and their corresponding TAM models through combinatorial use of nanodiamond-doxorubicin conjugates (Nano-DOX) and a PD-L1 blocking agent BMS-1. Nano-DOX are an agent previously proved to be able to stimulate tumor cells’ immunogenicity and thereby reactivate the TAMs into the anti-tumor M1 phenotype.

Results
Nano-DOX were first shown to stimulate the tumor cells and the TAMs to release the cytokine HMGB1 which, regardless of its source, acted through the RAGE/NF-κB pathway to induce PD-L1 in the tumor cells and PD-L1/PD-1 in the TAMs. Interestingly, Nano-DOX also induced NF-κB-dependent RAGE expression in the tumor cells and thus reinforced HMGB1’s action thereon. Then, BMS-1 was shown to enhance Nano-DOX-stimulated M1-type activation of TAMs both by blocking Nano-DOX-induced PD-L1 in the TAMs and by blocking tumor cell PD-L1 ligation with TAM PD-1. The TAMs with enhanced M1-type repolarization both killed the tumor cells and suppressed their growth. BMS-1 could also potentiate Nano-DOX’s action to suppress tumor cell growth via blocking of Nano-DOX-induced PD-L1 therein. Finally, Nano-DOX and BMS-1 achieved synergistic therapeutic efficacy against in vivo tumor grafts in a TAM-dependent manner.

Conclusions
PD-L1/PD-1 upregulation mediated by autocrine and paracrine activation of the HMGB1/RAGE/NF-κB signaling is a key response of lung cancer cells and their TAMs to stress, which can be induced by Nano-DOX. Blockade of Nano-DOX-induced PD-L1, both in the cancer cells and the TAMs, achieves enhanced activation of TAM-mediated anti-tumor response.

Graphic abstract
Covid-19 lockdown: Ethnic differences in children’s self-reported physical activity and the importance of leaving the home environment; a longitudinal and cross-sectional study from the Born in Bradford birth cohort study
Authors: Bingham Daniel D. , Daly-Smith Andy , Hall Jennifer , Seims Amanda , Dogra Sufyan A. , Fairclough Stuart J. , Ajebon Mildred , Kelly Brian , Hou Bo , Shire Katy A. , Crossley Kirsty L. , Mon-Williams Mark , Wright John , Pickett Kate , McEachan Rosemary , Dickerson Josie , Barber Sally E. ,   the Bradford Institute for Health Research COVID-19 Scientific Advisory Group
Published: September 2021

Abstract
Background
In England, the onset of COVID-19 and a rapidly increasing infection rate resulted in a lockdown (March-June 2020) which placed strict restrictions on movement of the public, including children. Using data collected from children living in a multi-ethnic city with high levels of deprivation, this study aimed to: (1) report children’s self-reported physical activity (PA) during the first COVID-19 UK lockdown and identify associated factors; (2) examine changes of children’s self-reported PA prior to and during the first UK lockdown.

Methods
This study is part of the Born in Bradford (BiB) COVID-19 Research Study. PA (amended Youth Activity Profile), sleep, sedentary behaviours, daily frequency/time/destination/activity when leaving the home, were self-reported by 949 children (9–13 years). A sub-sample (n = 634) also self-reported PA (Physical Activity Questionnaire for Children) pre-pandemic (2017-February 2020). Univariate analysis assessed differences in PA between sex and ethnicity groups; multivariable logistic regression identified factors associated with children’s PA. Differences in children's levels of being sufficiently active prior to and during the lockdown were examined using the McNemar test; and multivariable logistic regression was used to identify factors explaining change.

Results
During the pandemic, White British (WB) children were more sufficiently active (34.1%) compared to Pakistani Heritage children (PH) (22.8%) or ‘Other’ ethnicity children (O) (22.8%). WB children reported leaving the home more frequently and for longer periods than PH and O children. Modifiable variables related to being sufficiently active were frequency, duration, type of activity, and destination away from the home environment. There was a large reduction in children being sufficiently active during the first COVID-19 lockdown (28.9%) compared to pre-pandemic (69.4%).

Conclusions
Promoting safe extended periods of PA everyday outdoors is important for all children, in particular for children from ethnic minority groups. Children’s PA during the first COVID-19 UK lockdown has drastically reduced from before. Policy and decision makers, and practitioners should consider the findings in order to begin to understand the impact and consequences that COVID-19 has had upon children’s PA which is a key and vital behaviour for health and development.
Biologic medicine inclusion in 138 national essential medicines lists
Authors: Kraus Raphaël , Yeung Rae S. M. , Persaud Nav 
Published: September 2021

AbstractBackgroundEssential medicines lists (EMLs) are intended to reflect the priority health care needs of populations. We hypothesized that biologic disease-modifying antirheumatic drugs (DMARDs) are underrepresented relative to conventional DMARDs in existing national EMLs. We aimed to survey the extent to which biologic DMARDs are included in EMLs, to determine country characteristics contributing to their inclusion or absence, and to contrast this with conventional DMARD therapies.MethodsWe searched 138 national EMLs for 10 conventional and 14 biologic DMARDs used in the treatment of childhood rheumatologic diseases. Via regression modelling, we determined country characteristics accounting for differences in medicine inclusion between national EMLs.ResultsEleven countries (7.97%) included all 10 conventional DMARDs, 115 (83.33%) ≥5, and all countries listed at least one. Gross domestic product (GDP) per capita was associated with the total number of conventional DMARDs included (β11.02 [95% CI 0.39, 1.66];P = 0.00279). Among biologic DMARDs, 3 countries (2.2%) listed ≥10, 15 (10.9%) listed ≥5, and 47 (34.1%) listed at least one. Ninety-one (65.9%) of countries listed no biologic DMARDs. European region (β11.30 [95% CI 0.08, 2.52];P = 0.0367), life expectancy (β1–0.70 [95% CI -1.22, − 0.18];P = 0.0085), health expenditure per capita (β11.83 [95% CI 1.24, 2.42];P < 0.001), and conventional DMARDs listed (β10.70 [95% CI 0.33, 1.07];P < 0.001) were associated with the total number of biologic DMARDs included.ConclusionBiologic DMARDs are excluded from most national EMLs. By comparison, conventional DMARDs are widely included. Countries with higher health spending and longer life expectancy are more likely to list biologics.
Sex differences and similarities in the neuroimmune response to central administration of poly I:C
Authors: Posillico Caitlin K. , Garcia-Hernandez Rosa E. , Tronson Natalie C. 
Published: September 2021

Abstract
Background
The neuroimmune system is required for normal neural processes, including modulation of cognition, emotion, and adaptive behaviors. Aberrant neuroimmune activation is associated with dysregulation of memory and emotion, though the precise mechanisms at play are complex and highly context dependent. Sex differences in neuroimmune activation and function further complicate our understanding of its roles in cognitive and affective regulation.

Methods
Here, we characterized the physiological sickness and inflammatory response of the hippocampus following intracerebroventricular (ICV) administration of a synthetic viral mimic, polyinosinic:polycytidylic acid (poly I:C), in both male and female C57Bl/6N mice.

Results
We observed that poly I:C induced weight loss, fever, and elevations of cytokine and chemokines in the hippocampus of both sexes. Specifically, we found transient increases in gene expression and protein levels of IL-1α, IL-1β, IL-4, IL-6, TNFα, CCL2, and CXCL10, where males showed a greater magnitude of response compared with females. Only males showed increased IFNα and IFNγ in response to poly I:C, whereas both males and females exhibited elevations of IFNβ, demonstrating a specific sex difference in the anti-viral response in the hippocampus.

Conclusion
Our data suggest that type I interferons are one potential node mediating sex-specific cytokine responses and neuroimmune effects on cognition. Together, these findings highlight the importance of using both males and females and analyzing a broad set of inflammatory markers in order to identify the precise, sex-specific roles for neuroimmune dysregulation in neurological diseases and disorders.
Transmitted drug resistance and transmission clusters among HIV-1 treatment-naïve patients in Guangdong, China: a cross-sectional study
Authors: Lan Yun , Li Linghua , He Xiang , Hu Fengyu , Deng Xizi , Cai Weiping , Li Junbin , Ling Xuemei , Fan Qinghong , Cai Xiaoli , Li Liya , Li Feng , Tang Xiaoping 
Published: September 2021

Abstract
Background
Transmitted drug resistance (TDR) that affects the effectiveness of the first-line antiretroviral therapy (ART) regimen is becoming prevalent worldwide. However, its prevalence and transmission among HIV-1 treatment-naïve patients in Guangdong, China are rarely reported. We aimed to comprehensively analyze the prevalence of TDR and the transmission clusters of HIV-1 infected persons before ART in Guangdong.

Methods
The HIV-1 treatment-naïve patients were recruited between January 2018 and December 2018. The HIV-1 pol region was amplified by reverse transcriptional PCR and sequenced by sanger sequencing. Genotypes, surveillance drug resistance mutations (SDRMs) and TDR were analyzed. Genetic transmission clusters among patients were identified by pairwise Tamura-Nei 93 genetic distance, with a threshold of 0.015.

Results
A total of 2368 (97.17%) HIV-1 pol sequences were successfully amplified and sequenced from the enrolled 2437 patients. CRF07_BC (35.90%, 850/2368), CRF01_AE (35.56%, 842/2368) and CRF55_01B (10.30%, 244/2368) were the main HIV-1 genotypes circulating in Guangdong. Twenty-one SDRMs were identified among fifty-two drug-resistant sequences. The overall prevalence of TDR was 2.20% (52/2368). Among the 2368 patients who underwent sequencing, 8 (0.34%) had TDR to protease inhibitors (PIs), 22 (0.93%) to nucleoside reverse transcriptase inhibitors (NRTIs), and 23 (0.97%) to non-nucleoside reverse transcriptase inhibitors (NNRTIs). Two (0.08%) sequences showed dual-class resistance to both NRTIs and NNRTIs, and no sequences showed triple-class resistance. A total of 1066 (45.02%) sequences were segregated into 194 clusters, ranging from 2 to 414 sequences. In total, 15 (28.85%) of patients with TDR were included in 9 clusters; one cluster contained two TDR sequences with the K103N mutation was observed.

Conclusions
There is high HIV-1 genetic heterogeneity among patients in Guangdong. Although the overall prevalence of TDR is low, it is still necessary to remain vigilant regarding some important SDRMs.
The relationship between test anxiety and emotion regulation: the mediating effect of psychological resilience
Authors: Liu Yuguo , Pan Haiyan , Yang Runhuang , Wang Xingjie , Rao Jiawei , Zhang Xingshan , Pan Congcong 
Published: September 2021

Abstract
Background
Test anxiety has been widely found in medical students. Emotion regulation and psychological resilience have been identified as key factors contributing to anxiety. However, studies on relationships were limited. This study investigated the links between psychological resilience, emotion regulation, and test anxiety in addition to exploring the differences about socio-demographic factors.

Methods
A sample of 1266 medical students was selected through cross-sectional survey from a medical university in China during 2019. Data were obtained by network technique using designed questionnaire, which assesses the level of test anxiety, emotion regulation and psychological resilience, respectively.

Results
Medical students experienced test anxiety at different levels, 33.7% of these were seriously. It revealed significant effects of the gender and academic performance on test anxiety. Results of logistic regression indicated that test anxiety was significantly associated with emotion regulation and psychological resilience (p < 0.01). Psychological resilience played a mediating role on the relationship between emotion regulation and test anxiety.

Conclusions
These findings highlight the importance of psychological resilience and emotion regulation in understanding how psychological resilience relates to test anxiety in medical students. Resilience-training intervention may be developed to support students encountering anxiety during the exam.