bluuebunny/crossref_metadata_2025_split huggingface dataset:
U-Th dating, taphonomy, and taxonomy of shell middens at Klasies River main site indicate stable and systematic coastal exploitation by MIS 5c-d
Authors: Wurz Sarah , Pickering Robyn , Mentzer Susan M. 
Published: November 2022

The archaeological record, particularly of shellfish, from the Klasies River main site (KRM) is important in understanding the fluctuating nature of coastal occupational patterns and changing coastal ecologies. In this paper, we provide new uranium–thorium (U-Th) dates for one of the earlier phases of coastal exploitation at KRM, and the microstratigraphic analyses generate novel information about the taphonomy of shell-bearing deposits from the Later Stone Age (LSA) to the MSA I period that, in turn, provide a broader context for middening at the site. A wide range of syndepositional taphonomic processes related to human activities and post-depositional effects include burning, fragmentation and compaction, chemical alteration, and cementation. Despite such issues influencing recovery, shellfish data are informative and are presented from three layers of the Witness Baulk: Shell Midden One (SMONE), Black Occupational Soils (BOS), and Silty Black Soils (SBLS). These coarse shell midden deposits exhibit visible decalcification coupled with cementation with secondary carbonate formation in association with conditions of high moisture and soft sedimentation deformation of the underlying sediments of SBLS. This stratigraphy section is chronologically anchored for the first time using U-Th dating of speleothems associated with a hiatus after the deposition of BOS. The three ages, 110,060 ± 1,100, 109,800 ± 970, and 106,000 ± 2,100 years, place the BOS layer as the base of the SASL sub-member at over 110 ka, making the underlying middens from the LBS member even older. The zooarchaeological analyses of the three layers indicate coastal ecological changes from more sheltered conditions prior to the hiatus, with the exploitation of alikreukel and brown mussels predominating. Before 110 ka, in BOS and SBLS, more exposed coastal conditions occurred, and the diversity of exploited shellfish increased. SMONE and BOS are associated with MSA II/Mossel Bay lower lithic technology and SBLS with MSA I technology, indicating asynchronous coastal ecological and technological changes. The MIS 5c-d evidence for early coastal occupation at KRM provides details on the period during which coastal occupation became stable and systematic on the South African coast and puts the KRM amongst the handful of sites with shell-bearing deposits, occurring prior to 110 ka in South Africa.
The effect of different administrations of testosterone therapy on adverse prostate events: A Bayesian network meta-analysis
Authors: Zeng Bin , Qiu Shi , Xiong Xingyu , Su Xingyang , Zhang Zilong , Wei Qiang , Yang Lu 
Published: November 2022

BackgroundHypogonadism has become a major cause endangering men’s health and quality of life all over the world. Testosterone Therapy (TT) is a widely accepted treatment for relieving hypogonadal symptoms. However, the effect of different administrations of TT on prostate safety is still unclear.MethodsWe did a thorough search of PubMed, Embase and Cochrane Library to identify eligible studies up to January 2022. Randomized controlled trials (RCTs) and Cohort studies evaluating the impacts of using different formulations of TT on prostate parameters were included. Changes of prostate-specific antigen (PSA) level and prostate cancer (Pca) cases were used as the primary outcomes. Quality of individual studies was estimated by RoB2 (Cochrane tool for assessing the risk of bias in randomized trials) and the Newcastle-Ottawa scale (Tool for assessing non-RCTs). Certainty of evidence for each study was evaluated according to the evidence assessment criteria of the Oxford Evidence-based Medicine Center. Random-effect network meta-analysis(NMA)was performed based on the Bayesian model.ResultsThirty-five studies (30 RCTs and 5 Cohort studies) with 7,740 participants were included. TT administration led to fewer Pca patients (RR=0.62, 95%CI [0.39,0.99], I2=0%), while little decreasing in PSA level (MD=-0.05, 95%CI [-0.08, -0.02], I2=0%). The NMA revealed that compared with other formulations, the intramuscular injection was the most likely to rank first in decreasing Pca cases. The TT also resulted in more biopsy cases (RR=2.38, 95%CI [1.01,5.60], I2=0%). As for NMA, intramuscular injection also performed relatively better in fewer prostate biopsy cases compared with transdermal group.ConclusionTT does not lead to abnormal PSA changes and increased risk of Pca in patients with hypogonadism or low testosterone level. Compared with other preparations of TT, intramuscular injection proved better in minimizing Pca cases and was more likely to result in fewer prostate biopsy cases.
Insulin resistance in school-aged girls with overweight and obesity is strongly associated with elevated white blood cell count and absolute neutrophil count
Authors: He Hong-Mei , Zhang Lu , Qiu Na , Zhou Ze-Tao , Zhang Ka , Li Yan , Chen Hao-Bo , Xu Jia-Ning 
Published: November 2022

BackgroundThe primary objective of the study was to discuss the sex differences in insulin resistance-induced changes in metabolic and inflammatory markers in school-aged children with overweight and obesity.MethodsA cross-sectional study of 800 children aged seven and twelve years was performed. Questionnaires, anthropometric data and fasting blood samples were collected.ResultsChildren with overweight and obesity showed statistically significant differences in multiple metabolic and inflammatory markers compared with children with normal BMI. The correlation coefficient (r) between white blood cell count, absolute neutrophil count, fasting plasma insulin, HOMA-IR, HOMA-β, triglyceride, HDL-C, triglyceride/HDL ratio, alanine transaminase, serum uric acid, systolic blood pressure and BMI were higher in all children, but the linear relationships between white blood cell count, absolute neutrophil count and BMI were stronger in girls with overweight and obesity than in boys with overweight and obesity. Subsequently, HOMA-IR was shown to be more strongly associated with increased white blood cell count and absolute neutrophil count in school-aged girls with overweight and obesity by partial correlation analysis and the multiple linear regression analysis.ConclusionsElevated white blood cell count and absolute neutrophil count in children with overweight and obesity, especially girls, can serve as markers of insulin resistance.
Mitochondrial genomic integrity and the nuclear epigenome in health and disease
Authors: Morin Amanda L. , Win Phyo W. , Lin Angela Z. , Castellani Christina A. 
Published: November 2022

Bidirectional crosstalk between the nuclear and mitochondrial genomes is essential for proper cell functioning. Mitochondrial DNA copy number (mtDNA-CN) and heteroplasmy influence mitochondrial function, which can influence the nuclear genome and contribute to health and disease.Evidence shows that mtDNA-CN and heteroplasmic variation are associated with aging, complex disease, and all-cause mortality. Further, the nuclear epigenome may mediate the effects of mtDNA variation on disease. In this way, mitochondria act as an environmental biosensor translating vital information about the state of the cell to the nuclear genome.Cellular communication between mtDNA variation and the nuclear epigenome can be achieved by modification of metabolites and intermediates of the citric acid cycle and oxidative phosphorylation. These essential molecules (e.g. ATP, acetyl-CoA, ɑ-ketoglutarate and S-adenosylmethionine) act as substrates and cofactors for enzymes involved in epigenetic modifications.The role of mitochondria as an environmental biosensor is emerging as a critical modifier of disease states. Uncovering the mechanisms of these dynamics in disease processes is expected to lead to earlier and improved treatment for a variety of diseases. However, the influence of mtDNA-CN and heteroplasmy variation on mitochondrially-derived epigenome-modifying metabolites and intermediates is poorly understood. This perspective will focus on the relationship between mtDNA-CN, heteroplasmy, and epigenome modifying cofactors and substrates, and the influence of their dynamics on the nuclear epigenome in health and disease.
Phytoextraction of lead (Pb) contaminated soil by switchgrass (Panicum virgatum L): Impact of BAP and NTA applications
Authors: Hart Genna , Gilly Austin , Koether Marina , McElroy Thomas , Greipsson Sigurdur 
Published: November 2022

The accumulation of Pb deposits in soil is a growing global concern. Soil remediation options include phytoextraction that involves the use of plants and associated soil microorganism. Switchgrass (Panicum virgatum L.), a second-generation bioenergy crop was used in this study due to its ability to produce high biomass and grow in metal polluted soils. Plants were grown in Pb-contaminated soil (5,802.5 mg kg−1) in an environmentally controlled greenhouse. Plants were treated with exogenous application of the plant growth regulator (PGR) benzylaminopurine (BAP) or complete foliar nutrient solution (Triple-12®) twice a week until harvested. Plants also received the soil fungicide propiconazole (Infuse™) that was followed by the soil chelate nitrilotriacetic acid (NTA). Two concentrations of NTA were compared (5 mM and 10 mM) and combined application of NTA (10 mM) + APG (alkyl polyglucoside). Soil fungicide (propiconazole) was used to arrest arbuscular mycorrhizal fungi (AMF) activities in the roots of switchgrass in order to enhance Pb-phytoextraction. Lead (Pb) was measured in dry plant materials using an ICP-OES. Phytoextraction by switchgrass was significantly improved by dual soil applications of 10 mM NTA, APG and foliar applications of BAP which resulted in the greatestaverage Pb concentration of 5,942 mg kg−1. The average dry mass of plants and the average value for total phytoextracted Pb (mg) per pot were significantly greatestfor plants treated with 10 mM NTA, APG and BAP. Also, plants treated with NTA and BAP showed average bioconcentration factor of 1.02. The results suggested that chemically enhanced phytoextraction significantly improved biomass production of switchgrass and at the same time increased phytoextracted Pb which is important for phytoremediation and bioenergy industry.
Effects of litter chemical traits and species richness on soil carbon cycling changed over time
Authors: Yang Hongling , Li Yulin , Zhan Jin , Bao Chelmeg , Luo Yongqing 
Published: November 2022

Litter decomposition is the main driver of nutrient cycling process in terrestrial ecosystems. Afforestation completely altered vegetation composition and litter species, disrupting the long-term carbon balance in grassland ecosystem. However, there is a lack of understanding of how litter mixing effect (LME) affects soil carbon cycling in afforested ecosystem. Here, we investigated the effects of litter richness and quality of tree, shrub, and grass species and their litter mixture on soil CO2 fluxes. The results showed that cumulative soil CO2 flux in the early stage (1–28 days) was 1.75 times higher than that in the late stage (29–113 days), indicating litter decomposition was intensive at first and then decreased with time. Soil carbon flux changed with decomposition stages. In the early-stage of decomposition, soil CO2 flux increased with the concentrations of litter carbon, nitrogen and condense tannin. In the late phase of decomposition, all litter chemical traits were negatively related to the soil carbon flux. Additionally, plant litter richness was negatively correlated to early-stage soil CO2 flux, whereas it was positively related to late-stage soil carbon flux. Our results provide evidence that long-term carbon balance in grassland ecosystems was interrupted by afforestation, and the dominant litter chemical traits that controlling soil carbon cycling changed over time.
TLR3 serves as a novel diagnostic and prognostic biomarker and is closely correlated with immune microenvironment in three types of cancer
Authors: Zou Xiong , Guo Yi , Mo Zengnan 
Published: November 2022

Background: Toll-like receptor 3 (TLR3) plays an important role in both innate and adaptive immunity, but the prognostic value of TLR3 in heterogeneous tumors and the correlations between TLR3 expression and immune infiltration of heterogeneous tumors remain unclear.Methods: We investigated the expression of TLR3 in a variety of tumors and focused on the diagnostic and prognostic values of TLR3 in kidney renal clear cell carcinoma (KIRC), pancreatic adenocarcinoma (PAAD) and brain lower grade glioma (LGG) by GEPIA, DriverDBv3, UALCAN, TIMER, LinkedOmics, STRING, GeneMANIA and FunRich, as well as the possible mechanisms of TLR3 affecting tumor prognosis were discussed. Additionally, real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) was used to validate TLR3 expression in early KIRC. We also compared the expression of TLR3 in the plasma of early KIRC patients and normal controls by enzyme linked immunosorbent assay (ELISA).Results: TLR3 expression was significantly different in multiple tumors compared with paracancerous nontumor tissues. Elevated expression of TLR3 contributed to the prolonged survival outcome in KIRC patients. Suppressed expression of TLR3 contributed to the prolonged survival outcome in LGG and PAAD patients. Moreover, TLR3 was significantly elevated in stage1, grade1 and N0 of KIRC. The expression and function of TLR3 in KIRC, LGG and PAAD were closely related to tumor immune microenvironment. TRAF6 was a key gene in the interactions between TLR3 and its interacting genes. Finally, the results of RT-qPCR and ELISA indicated that TLR3 expression levels were significantly raised in renal tissue and plasma of early KIRC patients.Conclusion: TLR3 has the potential to be a diagnostic biomarker of KIRC, LGG and PAAD as well as a biomarker for evaluating the prognosis of KIRC, LGG and PAAD, particularly for the early diagnosis of KIRC. TLR3 affects tumors mainly by acting on the immune microenvironment of KIRC, LGG and PAAD. These findings could lead to new insights into the immunotherapeutic targets for KIRC, LGG, and PAAD.
Individual and combined effects of the GSTM1, GSTT1, and GSTP1 polymorphisms on type 2 diabetes mellitus risk: A systematic review and meta-analysis
Authors: Liu Liang-shu , Wang Di , Tang Ru , Wang Qi , Zheng Lu , Wei Jian , Li Yan , He Xiao-feng 
Published: November 2022

Backgrounds: Compared with previously published meta-analyses, this is the first study to investigate the combined effects of glutathione-S-transferase polymorphisms (GSTM1, GSTT1 and GSTP1 IIe105Val) and type 2 diabetes mellitus (T2DM) risk; moreover, the credibility of statistically significant associations was assessed; furthermore, many new original studies were published.Objectives: To determine the relationship between GSTM1, GSTT1, and GSTP1 polymorphisms with T2DM risk.Methods: PubMed, Embase, Wanfang, and China National Knowledge Infrastructure Databases were searched. We quantify the relationship using crude odds ratios and their 95% confidence intervals Moreover, the Venice criteria, false-positive report probability (FPRP), and Bayesian false discovery probability (BFDP) were used to validate the significance of the results.Results: Overall, significantly increased T2DM risk was found between individual and combined effects of GSTM1, GSTT1, and GSTP1 polymorphisms on T2DM risk, but, combined effects of the GSTT1 and GSTP1 polymorphisms was not statistically significant. GSTT1 gene polymorphism significantly increases the risk of T2DM complications, while GSTM1 and GSTP1 polymorphisms had no statistical significance. The GSTM1 null genotype was linked to a particularly increased risk of T2DM in Caucasians; the GSTT1 null genotype was connected to a significantly higher risk of T2DM in Asians and Indians; and the GSTP1 IIe105Val polymorphism was related to a substantially increased T2DM risk in Indians. Moreover, the GSTM1 and GSTT1 double null genotype was associated with substantially increased T2DM risk in Caucasians and Indians; the combined effects of GSTM1 and GSTP1 polymorphisms was associated with higher T2DM risk in Caucasians. However, all significant results were false when the Venice criteria, FPRP, and BFDP test were used (any FPRP &gt;0.2 and BFDP value &gt;0.8).Conclusion: The current analysis strongly suggests that the individual and combined effects of GSTM1, GSTT1 and GSTP1 polymorphisms might not be connected with elevated T2DM risk.
Tertiary lymphoid structure patterns aid in identification of tumor microenvironment infiltration and selection of therapeutic agents in bladder cancer
Authors: An Ye , Sun Jian-Xuan , Xu Meng-Yao , Xu Jin-Zhou , Ma Si-Yang , Liu Chen-Qian , Liu Zheng , Wang Shao-Gang , Xia Qi-Dong 
Published: November 2022

BackgroundTertiary lymphoid structures (TLSs) are emerging as a potential predictor of prognosis and response to immunotherapy in some solid tumors. However, the comprehensive role of TLSs in bladder cancer remains unclear.MethodsEighteen bladder cancer (BCa) datasets were downloaded from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), ArratyExpress and IMvigor210. Based on 39 validated TLS signature genes (TSGs), we evaluated the TLS patterns in all patients, and correlated the TLS patterns with prognosis and tumor microenvironment (TME) cell-infiltrating characteristics. The cox regression model and principal component analysis (PCA) algorithms were used to construct the TLS score, which helps to quantify the TLS pattern in individuals.ResultsThe landscape of 39 validated TSGs in BCa was assessed first. Five distinct TLS patterns and four gene clusters were determined. TLS cluster C2 and gene cluster A were thought to be characterized by mature TLSs and showed better prognosis and higher immune cells infiltration than other clusters. The TLS score was discovered to be tightly correlated with the infiltration level of immune cells, and could predict the maturation status of TLSs to some extent. We found TLS score was an excellent predictor for prognosis in patients with BCa independent of tumor mutation burden (TMB), and low TLS score was related to better prognosis than high TLS score. Besides, low TLS score was correlated with a better response to immune checkpoint blockade (ICB) immunotherapy and commonly used chemotherapy drugs.ConclusionsOur work demonstrated the characteristics of TLSs in BCa. By using the TLS score, we could evaluate the TLS pattern in individuals. Better understanding of TLS pattern and the usage of TLS score could help instruct clinical strategy and precision medicine for BCa.
A two-year longitudinal study of retinal vascular impairment in patients with amnestic mild cognitive impairment
Authors: Criscuolo Chiara , Cennamo Gilda , Montorio Daniela , Carotenuto Antonio , Migliaccio Miriana , Moccia Marcello , Salvatore Elena , Lanzillo Roberta , Costagliola Ciro , Morra Vincenzo Brescia 
Published: November 2022

ObjectiveTo evaluate the relation between retinal vascular impairment and cognitive decline in patients with amnestic mild cognitive impairment (aMCI) over time.MethodsSpectral domain-optical coherence tomography (SD-OCT) and OCT angiography study was performed in aMCI patients over 2 years follow-up and compared to baseline.ResultsThirty-eight eyes from 19 aMCI patients were evaluated. Structural and vascular OCT measures were reduced at follow-up except for vessel density (VD) of the choriocapillaris, unchanged, and foveal avascular zone, which was increased; no changes in any parameter were found in 18 age-matched healthy controls. Overall, these findings were confirmed when patients were evaluated separately according to progression to dementia. Only non-converters to dementia showed significant VD reduction in the deep capillary plexuses (coeff. β = −4.20; p &lt; 0.001), may be for an initial massive VD depletion becoming less evident with progression of the disease. MMSE reduction was associated with a higher ganglion cell complex reduction (coeff. β = 0.10; p = 0.04) and a higher VD reduction in the radial peripapillary capillary (RPC) plexus (coeff. β = 0.14; p = 0.02) in the whole patient group, while it was associated with a higher VD reduction only in RPC plexus in converters (coeff. β = 0.21; p &lt; 0.001).ConclusionOur data shows vascular impairment progression in the inner retina of aMCI patients and support the hypothesis that vascular changes may contribute to the onset and progression of Alzheimer’s disease. Other follow-up studies, with a larger number of patients, are needed to better define VD as a potential biomarker.
Waist-to-height ratio is a simple and practical alternative to waist circumference to diagnose metabolic syndrome in type 2 diabetes
Authors: Ma Yi-Lin , Jin Chun-Hua , Zhao Cui-Chun , Ke Jiang-Feng , Wang Jun-Wei , Wang Yu-Jie , Lu Jun-Xi , Huang Gao-Zhong , Li Lian-Xi 
Published: November 2022

BackgroundAs an indicator of abdominal obesity, waist circumference (WC) varied with race and gender in diagnosing metabolic syndrome (MetS). Therefore, it is clinically important to find an alternative indicator of abdominal obesity independent of these factors to diagnose MetS. Our aims were to evaluate the association between waist-to-height ratio (WHtR) and MetS and further determine whether WHtR could be used as a simple and practical alternative to WC to diagnose MetS in patients with type 2 diabetes mellitus (T2DM).MethodsThis cross-sectional, real-world study recruited 8488 hospitalized T2DM patients including 3719 women (43.8%) aged from 18 to 94 years and 4769 men (56.2%) aged from 18 to 91 years. A WHtR cut-off of 0.52 was used to diagnose MetS in both men and women T2DM patients based on our previous study. The association of WHtR with MetS in T2DM patients was analyzed by binary logistic regression. The consistency of two diagnostic criteria for MetS according to WC and WHtR was determined by Kappa test.ResultsThe prevalence of MetS according to WHtR was 79.4% in women and 68.6% in men T2DM patients, which was very close to the prevalence of MetS according to WC in both women (82.6%) and men (68.3%). The prevalence of MetS diagnosed by WC in both men and women with WHtR ≥ 0.52 was significantly higher than in those with WHtR &lt; 0.52 after adjustment for age and duration of diabetes (89.2 vs. 38.7% for men; 92.8 vs. 57.4% for women; respectively, all p &lt; 0.001). Binary logistic regression analysis displayed that after adjusting for confounding factors, WHtR was significantly associated with the presence of MetS in both men and women (men: OR = 4.821, 95% CI: 3.949–5.885; women: OR = 3.096, 95% CI: 2.484–3.860; respectively, all p &lt; 0.001). Kappa test revealed that there was an excellent consistency between the diagnosis of MetS based on WC and on WHtR in T2DM patients (men: kappa value = 0.929, 95% CI: 0.918–0.940; women: kappa value = 0.874, 95% CI: 0.854–0.894; total: kappa value = 0.911, 95% CI: 0.901–0.921; respectively, all p &lt; 0.001).ConclusionWHtR is independently associated with the presence of MetS and can be used as a simple and practical alternative to WC to diagnose MetS regardless of gender in T2DM patients.