HBV reactivation (HBVr) can occur in hepatitis B surface antigen (HBsAg)-positive and negative patients. Here, we determined the incidence of HBVr and its related hepatitis in patients with systemic ...lupus erythematosus (SLE). From 2000 to 2017, 3307 SLE cases were retrospectively reviewed for episodes of hepatitis. The incidence, long-term outcomes and risk factors associated with HBVr, including HBsAg reverse seroconversion (RS) were analyzed. Among them, 607 had available HBsAg status. Fifty-five (9.1%) patients were positive for HBsAg and 63 (11.4%) were HBsAg-negative/antibody to hepatitis B core antigen (anti-HBc)-positive (resolved hepatitis B infection, RHB). None of them received antiviral prophylaxis before immunosuppressive treatment. During a mean 15.4 years of follow-up, 30 (54.5%) HBsAg-positive patients developed HBVr and seven (23.3%) died of liver failure, whereas only two (3.2%) RHB cases experienced HBsAg reverse seroconversion (RS). Multivariate logistic regression analysis showed that age ≥ 40 years at diagnosis of SLE (HR 5.30, p < 0.001), receiving glucocorticoid-containing immunosuppressive therapy (HR 4.78, p = 0.003), and receiving glucocorticoid ≥ 10 mg prednisolone equivalents (HR 3.68, p = 0.003) were independent risk factors for HBVr in HBsAg-positive patients. Peak level of total bilirubin ≥ 5 mg/dL during HBVr was an independent factor of mortality (p = 0.002). In conclusion, the risk of HBVr was associated with glucocorticoid daily dose. Antiviral prophylaxis is mandatory for SLE patients diagnosed at age of ≥40 years who receive ≥ 10 mg daily dose of oral prednisone or equivalent.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The human body is colonized by a wide range of microorganisms. The field of viromics has expanded since the first reports on the detection of viruses via metagenomic sequencing in 2002. With the ...continued development of reference materials and databases, viral metagenomic approaches have been used to explore known components of the virome and discover new viruses from various types of samples. The virome has attracted substantial interest since the outbreak of the coronavirus disease 2019 (COVID-19) pandemic. Increasing numbers of studies and review articles have documented the diverse virome in various sites in the human body, as well as interactions between the human host and the virome with regard to health and disease. However, there have been few studies of direct causal relationships. Viral metagenomic analyses often lack standard references and are potentially subject to bias. Moreover, most virome-related review articles have focused on the gut virome and did not investigate the roles of the virome in other sites of the body in human disease. This review presents an overview of viral metagenomics, with updates regarding the relations between alterations in the human virome and the pathogenesis of human diseases, recent findings related to COVID-19, and therapeutic applications related to the human virome.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background and Aim
It is not clear whether prophylactic clipping after endoscopic mucosal resection (EMR) of large nonpedunculated colorectal lesions (LNPCLs) prevents delayed bleeding (DB). We aimed ...to conduct a meta‐analysis to clarify the efficacy of prophylactic clipping in prevention of DB following EMR of LNPCLs.
Methods
We searched PubMed, EMBASE, Web of Science, ScienceDirect, Cochrane Library databases, and ClinicalTrials.gov for studies that compared clipping versus (vs) nonclipping in prevention of DB following EMR of LNPCLs. Pooled odds ratio (OR) was determined using a random effects model. The pooled ORs of DB, perforation, and post‐polypectomy syndrome in the clipping group compared with the nonclipping group comprised the outcomes. Subgroup analyses based on study design, polyp location, and completeness of wound closure were performed.
Results
Five studies with a total of 3112 LNPCLs were extracted. Prophylactic clipping reduced the risk of DB compared with nonclipping (3.3% vs 6.2%, OR: 0.494, P = 0.002) following EMR of LNPCLs. In subgroup analysis, prophylactic clipping reduced DB of LNPCLs at proximal location (3.8% vs 9.8%, P = 0.029), but not of them at distal location (P = 0.830). Complete wound closure showed superior efficacy to prevent DB compared with partial closure (2.0% vs 5.4%, P = 0.004). No benefit of clipping for preventing perforation or post‐polypectomy syndrome was observed (P = 0.301 and 0.988, respectively).
Conclusions
Prophylactic clipping can reduce DB following EMR of LNPCLs at proximal location. Besides, complete wound closure showed superior efficacy to prevent DB compared with partial closure. Further cost analyses should be conducted to implement the most cost‐effective strategies.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The genome of the multihost bacteriophage ΦK64-1, capable of infecting
capsular types K1, K11, K21, K25, K30, K35, K64, and K69, as well as new capsular types KN4 and KN5, was analyzed and revealed ...that 11 genes (
,
,
,
,
,
,
,
,
,
, and
) encode proteins with amino acid sequence similarity to tail fibers/spikes or lyases.
previously was shown to encode a K64 capsule depolymerase (K64dep). Specific capsule-degrading activities of an additional eight putative capsule depolymerases (S2-4 against K1, S1-1 against K11, S1-3 against K21, S2-2 against K25, S2-6 against K30/K69, S2-3 against K35, S1-2 against KN4, and S2-1 against KN5) was demonstrated by expression and purification of the recombinant proteins. Consistent with the capsular type-specific depolymerization activity of these gene products, phage mutants of
,
,
, or
lost infectivity for KN4, K25, K35, or K30/K69, respectively, indicating that capsule depolymerase is crucial for infecting specific hosts. In conclusion, we identified nine functional capsule depolymerase-encoding genes in a bacteriophage and correlated activities of the gene products to all ten hosts of this phage, providing an example of type-specific host infection mechanisms in a multihost bacteriophage.
We currently identified eight novel capsule depolymerases in a multihost
bacteriophage and correlated the activities of the gene products to all hosts of this phage, providing an example of carriage of multiple depolymerases in a phage with a wide capsular type host spectrum. Moreover, we also established a recombineering system for modification of
bacteriophage genomes and demonstrated the importance of capsule depolymerase for infecting specific hosts. Based on the powerful tool for modification of phage genome, further studies can be conducted to improve the understanding of mechanistic details of
phage infection. Furthermore, the newly identified capsule depolymerases will be of great value for applications in capsular typing.
Lenvatinib, a multi-tyrosine kinase inhibitor that inhibits vascular endothelial growth factor and fibroblast growth factor receptors pathway, activated the immune response in tumor microenvironment. ...However, the combination of lenvatinib and anti-PD-1 has been reported in early phase studies. Hence, this study aims to explore the efficacy and toxicity of lenvatinib combined with nivolumab in the real-world setting. Advanced HCC patients who underwent lenvatinib combined with nivolumab (L + N group) treatment at Taipei Veterans General Hospital (Taipei, Taiwan) were reviewed between January 2016 and December 2020. Treatment response and outcomes were collected and analyzed. A control group with lenvatinib (L group) was also included for comparison. Forty patients were included in L + N group and 47 in L group. The L + N group demonstrated a higher objective response rate than L group (45.0% vs. 23.4%,
p
= 0.03). The L + N group also achieved longer PFS (7.5 vs. 4.8 months,
p
= 0.05) and OS (22.9 vs. 10.3 months,
p
= 0.01) than L group. Patients with HBV infection and REFLECT criteria fit demonstrated a trend of better prognosis. The PFS for those with PR, SD and PD groups were 11.2, 6.4, and 2.2 months and OS were non-reached, 14.6 and 4.7 months, respectively. Portal vein thrombosis (HR 4.3, 95% C.I. 1.5–12.8) and AFP > 400 ng/mL (HR 3.3, 95% C.I. 1.1–9.3) were poor prognostic factors and nivolumab used remained a protective factor (HR 0.2, 95% C.I. 0.1–0.7). Dermatitis (35.0%), pruritis (27.5%), and hypothyroidism (27.5%) were the common toxicities. Few patients developed grade 3/4 toxicities, including dermatitis (15%), gastrointestinal bleeding (7.5%), hypertension (5.0%), pneumonitis (2.5%) and stomatitis (2.5%). This is the first real-world data reporting the promising efficacy and tolerable toxicities of lenvatinib combined with nivolumab in advanced HCC. Further randomized trials are prompted.
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CEKLJ, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Photocatalytic hydrogen evolution from natural seawater faces the severe challenges of abundant salts, which adsorb on the active sites and result in undesirable side reactions and photocatalyst ...poisoning. Herein, a series of main‐chain‐engineered discontinuously conjugated polymer (DCP) photocatalysts is presented with bifunctional crown ether (CE) structures for hydrogen evolution from seawater. The hydrophilic CE can significantly inhibit the aggregation of DCPs induced by salts. Meanwhile, cyclic CE can effectively adsorb cations to uncover the active sites to increase their interaction with protons, which can increase the hydrogen evolution rates and significantly reduce the efficiency roll‐off in natural seawater. Through atomistic studies, the formation of hydrogen bonds with bifunctional CE is elucidated and further analysis of the microscale mechanisms is also conducted using molecular dynamics and ab initio techniques. This work suggests that CE‐based polymer has the potential to enhance its ability to produce hydrogen through photocatalysis using seawater.
The first example of incorporating crown ether structure into polymer photocatalysts is demonstrated via a main‐chain‐engineering strategy. The innovative approach significantly reduces ion adsorption on the active sites, resulting in less hydrogen evolution reaction (HER) roll‐off in natural seawater. P‐8CE, in particaular, shows remarkable results with 200% and 258% higher HER than the model photocatalyst, PCzDBTO, in pure water and natural seawater, respectively.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Conjugated polymers (CPs) have recently gained increasing attention as photocatalysts for sunlight-driven hydrogen evolution. However, they suffer from insufficient electron output sites and poor ...solubility in organic solvents, severely limiting their photocatalytic performance and applicability. Herein, solution-processable all-acceptor (A
-A
)-type CPs based on sulfide-oxidized ladder-type heteroarene are synthesized. A
-A
-type CPs showed upsurging efficiency improvements by two to three orders of magnitude, compared to their donor-acceptor -type CP counterparts. Furthermore, by seawater splitting, PBDTTTSOS exhibited an apparent quantum yield of 18.9% to 14.8% at 500 to 550 nm. More importantly, PBDTTTSOS achieved an excellent hydrogen evolution rate of 35.7 mmol h
g
and 150.7 mmol h
m
in the thin-film state, which is among the highest efficiencies in thin film polymer photocatalysts to date. This work provides a novel strategy for designing polymer photocatalysts with high efficiency and broad applicability.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Summary
Background
Chronic hepatitis B virus (HBV) infection is a great health burden with geographical variations.
Aims
To explore genetic variants associated with chronic HBV infection.
Methods
The ...study included 15 352 participants seropositive for HBV core antibodies in Taiwan Biobank. Among them, 2591 (16.9%) seropositive for HBV surface antigen (HBsAg) were defined as having chronic HBV infection. All participants were examined for whole‐genome genotyping by Axiom‐Taiwan Biobank Array. The human leucocyte antigen (HLA) imputation was performed after identification of the variants within the region. Logistic regressions were used to estimate odds ratios (ORs) with 95% confidence intervals. Correlations of different HLA allele frequencies with HBsAg seroprevalence were evaluated across worldwide populations by Pearson correlation coefficients. Epitope prediction was performed for HLA alleles using NetMHCIIpan method.
Results
Located within a cluster of 450 single nucleotide polymorphisms in HLA class II, rs7770370 (P = 2.73 × 10−35) was significantly associated with HBV chronicity (Pcorrected < 8.6 × 10−8). Imputation analyses showed that HLA‐DPA1*02:02 and HLA‐DPB1*05:01 were associated with chronic HBV, with adjusted ORs of 1.43 (1.09‐1.89) and 1.61 (1.29‐2.01). These allele frequencies were positively correlated with global HBsAg seroprevalence, with R of 0.75 and 0.62 respectively (P < 0.05). HLA‐DRB1*13:02, HLA‐DQA1* 01:02 and HLA‐DQB1*06:09 associated with HBV chronicity negatively, with adjusted ORs of 0.31 (0.17‐0.58), 0.70 (0.56‐0.87) and 0.33 (0.18‐0.63). These HLA alleles had various binding affinities to the predicted epitopes derived from HBV nucleocapsid protein.
Conclusions
HLA class II variants are relevant for chronicity after HBV acquisition.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Gastric cancer is one of the global health concerns. A series of studies on the stomach have confirmed the role of the microbiome in shaping gastrointestinal diseases. Delineation of microbiome ...signatures to distinguish chronic gastritis from gastric cancer will provide a non-invasive preventative and treatment strategy. In this study, we performed whole metagenome shotgun sequencing of fecal samples to enhance the detection of rare bacterial species and increase genome sequence coverage. Additionally, we employed multiple bioinformatics approaches to investigate the potential targets of the microbiome as an indicator of differentiating gastric cancer from chronic gastritis.
A total of 65 patients were enrolled, comprising 33 individuals with chronic gastritis and 32 with gastric cancer. Within each group, the chronic gastritis group was sub-grouped into intestinal metaplasia (n = 15) and non-intestinal metaplasia (n = 18); the gastric cancer group, early stage (stages 1 and 2, n = 13) and late stage (stages 3 and 4, n = 19) cancer. No significant differences in alpha and beta diversities were detected among the patient groups. However, in a two-group univariate comparison, higher Fusobacteria abundance was identified in phylum; Fusobacteria presented higher abundance in gastric cancer (LDA scored 4.27, q = 0.041 in LEfSe). Age and sex-adjusted MaAsLin and Random Forest variable of importance (VIMP) analysis in species provided meaningful features; Bacteria_caccae was the most contributing species toward gastric cancer and late-stage cancer (beta:2.43, se:0.891, p:0.008, VIMP score:2.543). In contrast, Bifidobacterium_longum significantly contributed to chronic gastritis (beta:-1.8, se:0.699, p:0.009, VIMP score:1.988). Age, sex, and BMI-adjusted MasAsLin on metabolic pathway analysis showed that GLCMANNANAUT-PWY degradation was higher in gastric cancer and one of the contributing species was Fusobacterium_varium.
Microbiomes belonging to the pathogenic phylum Fusobacteria and species Bacteroides_caccae and Streptococcus_anginosus can be significant targets for monitoring the progression of gastric cancer. Whereas Bifidobacterium_longum and Lachnospiraceae_bacterium_5_1_63FAA might be protection biomarkers against gastric cancer.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Scope
Pathological bacterial translocation from the disrupted intestinal barrier leads to substantial complications and mortality in liver cirrhosis. Vitamin D is reported as beneficial to gut ...barriers in some animal models. However, its effect on cirrhotic bacterial translocation is unknown. The authors aim to investigate the effects of calcitriol on bacterial translocation in cirrhotic rats.
Methods and Results
Cirrhotic rats are administrated with a 2‐week course of active vitamin D3 (calcitriol, 0.1 μg kg−1 per day) or vehicle by oral gavage after thioacetamide (TAA) injection for 16 weeks. Bacterial translocation, gut permeability, gut microbiota, and associated mechanisms are investigated. Calcitriol treatment significantly attenuates bacterial translocation and reduces intestinal permeability in TAA‐induced cirrhotic rats. It upregulates the expressions of occludin in the small intestine and claudin‐1 in the colon of cirrhotic rats directly independent of intrahepatic status. Even when a short period of calcitriol treatment do not reduce intestinal bacterial overgrowth, it induces a remarkable change of bacterial diversities and enrichment of Muribaculaceae, Bacteroidales, Allobaculum, Anaerovorax, and Ruminococcaceae.
Conclusion
Calcitriol treatment attenuates intestinal permeability, reduces bacterial translocation, and enriches potentially beneficial gut microbiota in cirrhotic rats that may enable it as a potential therapeutic agent to prevent cirrhotic complications.
Calcitriol treatment attenuates intestinal permeability and bacterial translocation in cirrhotic rats with upregulated expressions of tight junction proteins. Calcitriol treatment enriches potentially beneficial taxa of gut microbiota in cirrhotic rats. Calcitriol may have therapeutic potential to reduce cirrhotic infectious complications.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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