bluuebunny/crossref_metadata_2025_split huggingface dataset:
Viral dissemination and immune activation modulate antiretroviral drug levels in lymph nodes of SIV-infected rhesus macaques
Authors: Srinivasula Sharat , Degrange Paula , Perazzolo Simone , Bonvillain Andrew , Tobery Amanda , Kaplan Jacob , Jang Hyukjin , Turnier Refika , Davies Michael , Cottrell Mackenzie , Ho Rodney J. Y. , Di Mascio Michele 
Published: September 2023

Introduction and methodsTo understand the relationship between immunovirological factors and antiretroviral (ARV) drug levels in lymph nodes (LN) in HIV therapy, we analyzed drug levels in twenty-one SIV-infected rhesus macaques subcutaneously treated with daily tenofovir (TFV) and emtricitabine (FTC) for three months.ResultsThe intracellular active drug-metabolite (IADM) levels (TFV-dp and FTC-tp) in lymph node mononuclear cells (LNMC) were significantly lower than in peripheral blood mononuclear cells (PBMC) (P≤0.005). Between Month 1 and Month 3, IADM levels increased in both LNMC (P≤0.001) and PBMC (P≤0.01), with a steeper increase in LNMC (P≤0.01). The viral dissemination in plasma, LN, and rectal tissue at ART initiation correlated negatively with IADM levels at Month 1. Physiologically-based pharmacokinetic model simulations suggest that, following subcutaneous ARV administration, ART-induced reduction of immune activation improves the formation of active drug-metabolites through modulation of kinase activity and/or through improved parent drug accessibility to LN cellular compartments.ConclusionThese observations have broad implications for drugs that need to phosphorylate to exert their pharmacological activity, especially in the settings of the pre-/post-exposure prophylaxis and efficacy of antiviral therapies targeting pathogenic viruses such as HIV or SARS-CoV-2 replicating in highly inflammatory anatomic compartments.
Soluble biomarkers of HIV-1-related systemic immune activation are associated with high plasma levels of growth factors implicated in the pathogenesis of Kaposi sarcoma in adults
Authors: Nana Benderli Christine , Esemu Livo Forgu , Besong Michael Ebangha , Atchombat Derrick Hyacinthe Nyasse , Ogai Kazuhiro , Sobgui Thérèse M. Patricia , Nana Chris Marco Mbianda , Seumko’o Reine Medouen Ndeumou , Awanakan Honoré , Ekali Gabriel Loni , Leke Rose Gana Fomban , Okamoto Shigefumi , Ndhlovu Lishomwa C. , Megnekou Rosette 
Published: September 2023

BackgroundHuman Herpesvirus-8 (HHV-8) is the etiologic agent of Kaposi’s sarcoma (KS), a multicentric angio-proliferative cancer commonly associated with Human Immunodeficiency Virus (HIV) infection. KS pathogenesis is a multifactorial condition hinged on immune dysfunction yet the mechanisms underlying the risk of developing KS in HHV-8 seropositive adults remains unclear. Here we explored whether soluble markers of HIV-1-related systemic immune activation (SIA) and angiogenesis (VEGF and FGF acidic) are involved in the pathogenesis of KS in adults with HHV8.MethodologyBlood samples from 99 HIV-1 infected and 60 HIV-1 uninfected adults were collected in Yaoundé, Cameroon. CD3+/CD4+ T cell counts and HIV-1 plasma viral load were determined using the Pima Analyzer and the RT-PCR technique, respectively. Plasma levels of SIA biomarkers (sCD163, sCD25/IL-2Rα, and sCD40/TNFRSF5) and biomarkers of progression to KS (VEGF and FGF acidic) were measured using the Luminex assay. Seropositivity (IgG) for HHV-8 was determined using the ELISA method.ResultsOverall, 20.2% (20/99) of HIV-1 infected and 20% (12/60) of HIV-1 uninfected participants were seropositive for HHV8. Levels of sCD163, sCD25/IL-2Rα, sCD40/TNFRSF5, and FGF acidic were higher in the HIV-1 and HHV8 co-infection groups compared to the HIV-1 and HHV8 uninfected groups (all P &lt;0.05). In addition, Higher plasma levels of VEGF correlated with sCD163 (rs = 0.58, P =0.0067) and sCD40/TNFRSF5 (rs = 0.59, P = 0.0064), while FGF acidic levels correlated with sCD40/TNFRSF5 (rs = 0.51, P = 0.022) in co-infected. In HIV-1 mono-infected donors, VEGF and FGF acidic levels correlated with sCD163 (rs =0.25, P = 0.03 and rs = 0.30, P = 0.006 respectively), sCD25/IL-2Rα (rs = 0.5, P &lt;0.0001 and rs = 0.55, P &lt;0.0001 respectively) and sCD40/TNFRSF5 (rs = 0.7, P &lt;0.0001 and rs = 0.59, P &lt;0.0001 respectively) and even in patients that were virally suppressed sCD25/IL-2Rα (rs = 0.39, P = 0.012 and rs = 0.53, P = 0.0004 respectively) and sCD40/TNFRSF5 (rs = 0.81, P &lt;0.0001 and rs = 0.44, P = 0.0045 respectively).ConclusionOur findings suggest that although the development of KS in PLWH is multifactorial, HIV-associated SIA might be among the key drivers in coinfections with HHV8 and is independent of the patients’ viremic status.
Novel quantitative immunohistochemical analysis for evaluating PD-L1 expression with phosphor-integrated dots for predicting the efficacy of patients with cancer treated with immune checkpoint inhibitors
Authors: Ohkuma Ryotaro , Miura Sakiko , Muto Satoshi , Toyomasu Yoshitaka , Fujimoto Yuki , Ieguchi Katsuaki , Onishi Nobuyuki , Shimizu Takashi , Watanabe Makoto , Takayanagi Daisuke , Goshima Tsubasa , Horiike Atsushi , Hamada Kazuyuki , Ariizumi Hirotsugu , Shimokawa Masahiro , Hirasawa Yuya , Ishiguro Tomoyuki , Suzuki Risako , Iriguchi Nana , Tsurui Toshiaki , Mura Emiko , Takenoshita Sachiko , Numajiri Kazuki , Okabe Naoyuki , Yoshimura Kiyoshi , Tsuji Mayumi , Kiuchi Yuji , Yajima Toshiki , Ishida Hideyuki , Suzuki Hiroyuki , Yamochi Toshiko , Kobayashi Shinichi , Tsunoda Takuya , Wada Satoshi 
Published: September 2023

IntroductionProgrammed cell death ligand 1 (PD-L1) expression in tumor tissues is measured as a predictor of the therapeutic efficacy of immune checkpoint inhibitors (ICIs) in many cancer types. PD-L1 expression is evaluated by immunohistochemical staining using 3,3´-diaminobenzidine (DAB) chronogenesis (IHC-DAB); however, quantitative and reproducibility issues remain. We focused on a highly sensitive quantitative immunohistochemical method using phosphor-integrated dots (PIDs), which are fluorescent nanoparticles, and evaluated PD-L1 expression between the PID method and conventional DAB method.MethodsIn total, 155 patients with metastatic or recurrent cancer treated with ICIs were enrolled from four university hospitals. Tumor tissue specimens collected before treatment were subjected to immunohistochemical staining with both the PID and conventional DAB methods to evaluate PD-L1 protein expression.ResultsPD-L1 expression assessed using the PID and DAB methods was positively correlated. We quantified PD-L1 expression using the PID method and calculated PD-L1 PID scores. The PID score was significantly higher in the responder group than in the non-responder group. Survival analysis demonstrated that PD-L1 expression evaluated using the IHC-DAB method was not associated with progression-free survival (PFS) or overall survival (OS). Yet, PFS and OS were strikingly prolonged in the high PD-L1 PID score group.ConclusionQuantification of PD-L1 expression as a PID score was more effective in predicting the treatment efficacy and prognosis of patients with cancer treated with ICIs. The quantitative evaluation of PD-L1 expression using the PID method is a novel strategy for protein detection. It is highly significant that the PID method was able to identify a group of patients with a favorable prognosis who could not be identified by the conventional DAB method.
Zhishi Daozhi decoction alleviates constipation induced by a high-fat and high-protein diet via regulating intestinal mucosal microbiota and oxidative stress
Authors: Peng Xinxin , Yi Xin , Deng Na , Liu Jing , Tan Zhoujin , Cai Ying 
Published: September 2023

BackgroundA growing body of evidence has demonstrated that a high-fat and high-protein diet (HFHPD) causes constipation. This study focuses on understanding how the use of Zhishi Daozhi decoction (ZDD) affects the intricate balance of intestinal microorganisms. The insights gained from this investigation hold the potential to offer practical clinical approaches to mitigate the constipation-related issues associated with HFHPD.Materials and methodsMice were randomly divided into five groups: the normal (MN) group, the natural recovery (MR) group, the low-dose ZDD (MLD) group, the medium-dose ZDD (MMD) group, and the high-dose ZDD (MHD) group. After the constipation model was established by HFHPD combined with loperamide hydrochloride (LOP), different doses of ZDD were used for intervention. Subsequently, the contents of cholecystokinin (CCK) and calcitonin gene-related peptide (CGRP) in serum, superoxide dismutase (SOD), and malondialdehyde (MDA) in the liver were determined. The DNA of intestinal mucosa was extracted, and 16S rRNA amplicon sequencing was used to analyze the changes in intestinal mucosal microbiota.ResultsAfter ZDD treatment, CCK content in MR group decreased and CGRP content increased, but the changes were not significant. In addition, the SOD content in MR group was significantly lower than in MLD, MMD, and MHD groups, and the MDA content in MR group was significantly higher than in MN, MLD, and MHD groups. Constipation modeling and the intervention of ZDD changed the structure of the intestinal mucosal microbiota. In the constipation induced by HFHPD, the relative abundance of pathogenic bacteria such as Aerococcus, Staphylococcus, Corynebacterium, Desulfovibrio, Clostridium, and Prevotella increased. After the intervention of ZDD, the relative abundance of these pathogenic bacteria decreased, and the relative abundance of Candidatus Arthromitus and the abundance of Tropane, piperidine, and pyridine alkaloid biosynthesis pathways increased in MHD group.ConclusionConstipation induced by HFHPD can increase pathogenic bacteria in the intestinal mucosa, while ZDD can effectively relieve constipation, reduce the relative abundance of pathogenic bacteria, and alleviate oxidative stress injury. In addition, high-dose ZDD can increase the abundance of beneficial bacteria, which is more conducive to the treatment of constipation.
Dissecting the association between gut microbiota and liver cancer in European and East Asian populations using Mendelian randomization analysis
Authors: Jiang Hua , Song Tianjun , Li Zhongyi , An Lingxuan , He Chiyi , Zheng Kai 
Published: September 2023

BackgroundAmple evidence suggests an important role of the gut microbiome in liver cancer, but the causal relationship between gut microbiome and liver cancer is unclear. This study employed Mendelian randomization (MR) analysis to examine the causal relationship between the gut microbiome and liver cancer in European and East Asian populations.MethodsWe sourced genetic variants linked to gut microbiota from the MiBioGen consortium meta-analysis, and procured liver cancer genome-wide association study (GWAS) summary data from the FinnGen consortium and Biobank Japan. We employed the inverse variance weighted method for primary statistical analysis, fortified by several sensitivity analyses such as MR-PRESSO, MR-Egger regression, weighted median, weighted mode, and maximum likelihood methods for rigorous results. We also evaluated heterogeneity and horizontal pleiotropy.ResultsThe study examined an extensive set of gut microbiota, including 131 genera, 35 families, 20 orders, 16 classes, and 9 phyla. In Europeans, ten gut microbiota types displayed a suggestive association with liver cancer (p &lt; 0.05). Notably, Oscillospira and Mollicutes RF9 exhibited a statistically significant positive association with liver cancer risk, with odds ratios (OR) of 2.59 (95% CI 1.36–4.95) and 2.03 (95% CI 1.21–3.40), respectively, after adjusting for multiple testing. In East Asians, while six microbial types demonstrated suggestive associations with liver cancer, only Oscillibacter displayed a statistically significant positive association (OR = 1.56, 95% CI 1.11–2.19) with an FDR &lt; 0.05. Sensitivity analyses reinforced these findings despite variations in p-values.ConclusionThis study provides evidence for a causal relationship between specific gut microbiota and liver cancer, enhancing the understanding of the role of the gut microbiome in liver cancer and may offer new avenues for preventive and therapeutic strategies.
Development and characterization of rice bran-gum Arabic based encapsulated biofertilizer for enhanced shelf life and controlled bacterial release
Authors: Kaur Rajinder , Kaur Sukhminderjit , Dwibedi Vagish , Kaur Charanjit , Akhtar Nadeem , Alzahrani Abdulhakeem 
Published: September 2023

IntroductionCurrently, microbe-based approaches are being tested to address nutrient deficiencies and enhance nutrient use efficiency in crops. However, these bioinoculants have been unsuccessful at the commercial level due to differences in field andin-vivoconditions. Thus, to enhance bacterial stability, microbial formulations are considered, which will provide an appropriate microenvironment and protection to the bacteria ensuring better rhizospheric-colonization.MethodsThe present study aimed to develop a phosphobacterium-based encapsulated biofertilizer using the ion-chelation method, wherein a bacterial strain,Myroid gitamensiswas mixed with a composite solution containing rice bran (RB), gum Arabic (GA), tricalcium phosphate, and alginate to develop low-cost and slow-release microbeads. The developed microbead was studied for encapsulation efficiency, shape, size, external morphology, shelf-life, soil release behavior, and biodegradability and characterized using SEM, FTIR, and XRD. Further, the wheat growth-promoting potential of microbeads was studied.ResultsThe developed microbeads showed an encapsulation efficiency of 94.11%. The air-dried beads stored at 4°C were favorable for bacterial survival for upto 6 months. Microbeads showed 99.75% degradation within 110 days of incubation showing the bio-sustainable nature of the beads. The application of dried formulations to the pot-grown wheat seedlings resulted in a higher germination rate, shoot length, root length, fresh weight, dry weight of the seedlings, and higher potassium and phosphorus uptake in wheat.DiscussionThis study, for the first time, provides evidence that compared to liquid biofertilizers, the RB-GA encapsulated bacteria have better potential of enhancing wheat growth and can be foreseen as a future fertilizer option for wheat.
Association of age-related hearing loss with cognitive impairment and dementia: an umbrella review
Authors: Ying Guo , Zhao Guangran , Xu Xianpeng , Su Su , Xie Xin 
Published: September 2023

BackgroundHearing loss, cognitive impairment and dementia have become common problems for older adults. Currently, systematic reviews and meta-analyses of the association between age-related hearing loss (ARHL) with cognitive impairment and dementia may have inconsistent results. To explore and validate the association between ARHL with cognitive impairment and dementia through summarizing and evaluating existing evidence.MethodsFrom inception to February 01, 2023, PubMed, Web of Science, Embase, and Cochrane Library databases were systematically searched. AMSTAR 2 was used to evaluate methodological quality and GRADE system was used to evaluate evidence quality. We summarized the basic characteristics of the included studies and extracted effect data for ARHL with cognitive impairment and dementia. Forest plots were used to describe the relative risk associated with ARHL and cognitive impairment, and the relative risk associated with ARHL and dementia, respectively.ResultsA total of 11 systematic reviews and meta-analyses met the inclusion criteria. Overall, the methodological quality of the included SRs/MAs was moderate and the quality of the evidence was low. The combined results found that the pooled risk ratio of ARHL and cognitive impairment was 1.30 (random-effects; 95% CI 1.16 to 1.45), and the pooled risk ratio of ARHL and dementia was 1.59 (random-effects; 95% CI 1.34 to 1.90).ConclusionBased on the evidence reported in this umbrella review, age-related hearing loss is significantly associated with cognitive impairment and dementia. Hearing loss may be a high risk factor for cognitive impairment and dementia in older adults.
Efficacy of a strength-based exercise program in patients with chronic tension type headache: a randomized controlled trial
Authors: Martín-Vera Daniel , Sánchez-Sierra Alberto , González-de-la-Flor Ángel , García-Pérez-de-Sevilla Guillermo , Domínguez-Balmaseda Diego , del-Blanco-Muñiz Jose Ángel 
Published: September 2023

BackgroundStrength-based exercise is widely used to treat tension-type headache, but the evidence of its benefit is unclear. This study aims to analyze the efficacy of a strength-based exercise program in patients with chronic tension-type headaches.MethodsA randomized controlled trial with a 12-week strength-based exercise program, with chronic tension-type headache. The headache characteristics (which were the primary outcomes: frequency, duration, and intensity), cervical muscle thickness at rest or contraction of multifidus and longus-colli muscle, cervical range of motion, pain pressure threshold of temporalis, upper trapezius, masseter, tibialis muscle and median nerve, and cervical craniocervical flexion test were assessed at baseline and 12-weeks of follow-up in the intervention group (n = 20) and the control group (n = 20) was performed on 40 patients (85% women, aged 37.0 ± 13.3 years).ResultsBetween baseline and week-12 of follow-up the intervention group showed statistically significant differences compared to control group in the following primary outcomes: duration and intensity of headaches. In addition, the intervention group improved the thickness of deep cervical muscles, reduced the peripheral sensitization, and improved the strength of deep cervical flexors.ConclusionA 12-week strength training of neck and shoulder region induced changes in pain intensity and duration, and physical-related factors in patients with TTH. Future interventions are needed to investigate if normalization of pain characteristics and physical factors can lead to an increase of headache-related impact.
Can developmental trajectories in gait variability provide prognostic clues in motor adaptation among children with mild cerebral palsy? A retrospective observational cohort study
Authors: Visscher Rosa M. S. , Gwerder Michelle , Viehweger Elke , Taylor William R. , Brunner Reinald , Singh Navrag B. 
Published: September 2023

AimTo investigate whether multiple domains of gait variability change during motor maturation and if this change over time could differentiate children with a typical development (TDC) from those with cerebral palsy (CwCP).MethodsThis cross-sectional retrospective study included 42 TDC and 129 CwCP, of which 99 and 30 exhibited GMFCS level I and II, respectively. Participants underwent barefoot 3D gait analysis. Age and parameters of gait variability (coefficient of variation of stride-time, stride length, single limb support time, walking speed, and cadence; as well as meanSD for hip flexion, knee flexion, and ankle dorsiflexion) were used to fit linear models, where the slope of the models could differ between groups to test the hypotheses.ResultsMotor-developmental trajectories of gait variability were able to distinguish between TDC and CwCP for all parameters, except the variability of joint angles. CwCP with GMFCS II also showed significantly higher levels of gait variability compared to those with GMFCS I, these levels were maintained across different ages.InterpretationThis study showed the potential of gait variability to identify and detect the motor characteristics of high functioning CwCP. In future, such trajectories could provide functional biomarkers for identifying children with mild movement related disorders and support the management of expectations.
The ameliorative effects of choline on ethanol-induced cell death in the neural tube of susceptible BXD strains of mice
Authors: Xu Fannia , Thomas Jennifer D. , Goldowitz Dan , Hamre Kristin M. 
Published: September 2023

IntroductionFetal alcohol spectrum disorders (FASD) are the leading preventable cause of intellectual disability, providing the impetus for evaluating various potential treatments to ameliorate ethanol’s teratogenic effects, particularly in the nervous system. One treatment is the dietary supplement choline which has been shown to mitigate at least some of ethanol’s teratogenic effects. The present study was designed to investigate the effects of genetics on choline’s efficacy in ameliorating cell death in the developing neural tube. Previously, we examined BXD recombinant inbred mice, and their parental C57BL/6 J (B6) and DBA/2 J strains, and identified strains that were sensitive to ethanol’s teratogenic actions. Thus, we used these strains to identify response to choline treatment.Materials and methodsTimed pregnant mice from 4 strains (B6, BXD51, BXD73, BXD2) were given either ethanol or isocaloric maltose-dextrin (5.8 g/kg in two administrations separated by 2 h) with choline at one of 3 doses: 0, 100 or 250 mg/kg. Subjects were exposed via intragastric gavage on embryonic day 9 and embryos were collected 7 h after the initial ethanol administrations. Cell death was analyzed using TUNEL staining in the developing forebrain and brainstem.ResultsCholine ameliorated the ethanol-induced cell death across all 4 strains without causing enhanced cell death in control mice. Choline was effective in both the developing telencephalon and in the brainstem. Both doses diminished cell death, with some differences across strains and brain regions, although the 100 mg/kg dose was most consistent in mitigating ethanol-related cell death. Comparisons across strains showed that there was an effect of strain, particularly in the forebrain at the higher dose.DiscussionThese results show that choline is effective in ameliorating ethanol-induced cell death at this early stage of nervous system development. However, there were some strain differences in its efficacy, especially at the high dose, providing further evidence of the importance of genetics in influencing the ability of choline to protect against prenatal alcohol exposure.