The role of polymorphic cytochrome P450 gene (CYP2B6) in B-chronic lymphocytic leukemia (B-CLL) incidence and outcome among Egyptian patients.

Cytochromes P450 (CYPs) play a prominent role in catalyzing phase I xenobiotic biotransformation and account for about 75% of the total metabolism of commercially available drugs, including chemotherapeutics. The gene expression and enzyme activity of CYPs are variable between individuals, which subsequently leads to different patterns of susceptibility to carcinogenesis by genotoxic xenobiotics, as well as differences in the efficacy and toxicity of clinically used drugs. This research aimed to examine the presence of the CYP2B6*9 polymorphism and its possible association with the incidence of B-CLL in Egyptian patients, as well as the clinical outcome after receiving cyclophosphamide chemotherapy. DNA was isolated from whole blood samples of 100 de novo B-CLL cases and also from 100 sex- and age-matched healthy individuals. The presence of the CYP2B6*9 (G516T) polymorphism was examined by PCR-based allele specific amplification (ASA). Patients were further indicated for receiving chemotherapy, and then they were followed up. The CYP2B6*9 variant indicated a statistically significant higher risk of B-CLL under different genetic models, comprising allelic (T-allele vs. G-allele, OR = 4.8, p < 0.001) and dominant (GT + TT vs. GG, OR = 5.4, p < 0.001) models. Following cyclophosphamide chemotherapy, we found that the patients with variant genotypes (GT + TT) were less likely to achieve remission compared to those with the wild-type genotype (GG), with a response percentage of (37.5% vs. 83%, respectively). In conclusion, our findings showed that the CYP2B6*9 (G516T) polymorphism is associated with B-CLL susceptibility among Egyptian patients. This variant greatly affected the clinical outcome and can serve as a good therapeutic marker in predicting response to cyclophosphamide treatment.

The HLA region in ANCA-associated vasculitis: characterisation of genetic associations in a Scandinavian patient population.

OBJECTIVE: The antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are inflammatory disorders with ANCA autoantibodies recognising either proteinase 3 (PR3-AAV) or myeloperoxidase (MPO-AAV). PR3-AAV and MPO-AAV have been associated with distinct loci in the human leucocyte antigen (HLA) region. While the association between MPO-AAV and HLA has been well characterised in East Asian populations where MPO-AAV is more common, studies in populations of European descent are limited. The aim of this study was to thoroughly characterise associations to the HLA region in Scandinavian patients with PR3-AAV as well as MPO-AAV. METHODS: Genotypes of single-nucleotide polymorphisms (SNPs) located in the HLA region were extracted from a targeted exome-sequencing dataset comprising Scandinavian AAV cases and controls. Classical HLA alleles were called using xHLA. After quality control, association analyses were performed of a joint SNP/classical HLA allele dataset for cases with PR3-AAV (n=411) and MPO-AAV (n=162) versus controls (n=1595). Disease-associated genetic variants were analysed for association with organ involvement, age at diagnosis and relapse, respectively. RESULTS: PR3-AAV was significantly associated with both HLA-DPB1*04:01 and rs1042335 at the HLA-DPB1 locus, also after stepwise conditional analysis. MPO-AAV was significantly associated with HLA-DRB1*04:04. Neither carriage of HLA-DPB1*04:01 alleles in PR3-AAV nor of HLA-DRB1*04:04 alleles in MPO-AAV were associated with organ involvement, age at diagnosis or relapse. CONCLUSIONS: The association to the HLA region was distinct in Scandinavian cases with MPO-AAV compared with cases of East Asian descent. In PR3-AAV, the two separate signals of association to the HLD-DPB1 region mediate potentially different functional effects.

The association of FSCN1 (rs852479, rs1640233) and HOTAIR (rs920778) polymorphisms with the risk of breast cancer in Egyptian women.

BACKGROUND: Breast cancer (BC) is one of the most prevalent cancers that contribute to mortality among women worldwide. Despite contradictory findings, considerable evidence suggests that single nucleotide polymorphisms (SNPs) in the FSCN1 and HOTAIR genes may have a causative impact on the development of BC. This case-control study was conducted to evaluate the association of genotype frequency in FSCN1 rs852479, rs1640233, and HOTAIR rs920778 with susceptibility and prognosis of BC, as well as the impact of clinical stages and hormonal features. METHODS AND RESULTS: FSCN1 (rs852479, rs1640233) and HOTAIR (rs920778) were genotyped using TaqMan real-time PCR assay in 200 BC patients and 200 cancer-free controls, all representing Egyptian women. Genotypic analyses in association with clinicopathological factors and disease risk were assessed. As a result, a significant association with BC risk was observed for CC genotype frequency of FSCN1 rs852479 A > C (OR = 0.395, 95% CI 0.204-0.76, p-value = 0.005). However, no significant correlation was detected between the FSCN1 rs1640233 C > T and HOTAIR rs920778 C > T polymorphic variants and susceptibility to BC. Interestingly, CC genotype of FSCN1 rs1640233 was more likely to progress tumor size and lymph node invasion in BC cases (p-value = 0.04 and 0.02, respectively). Moreover, it was revealed that there was a non-significant correlation between the haplotype distributions of FSCN1 rs852479 and rs1640233 and the probability of BC. CONCLUSIONS: Based on the sample size and genetic characteristics of the subjects involved in the present study, our findings indicated that FSCN1 rs852479 may contribute to BC susceptibility in a sample of the Egyptian population.

Association of CCND1 rs9344 polymorphism with lung cancer susceptibility and clinical outcomes: a case-control study.

BACKGROUND: Cyclin D1 (CCND1) plays a pivotal role in cancer susceptibility and the platinum-based chemotherapy response. This study aims to assess the relationship between a common polymorphism (rs9344 G > A) in CCND1 gene with cancer susceptibility, platinum-based chemotherapy response, toxicities and prognosis of patients with lung cancer. METHODS: This study involved 498 lung cancer patients and 213 healthy controls. Among them, 467 patients received at least two cycles of platinum-based chemotherapy. Unconditional logistical regression analysis and meta-analysis were performed to evaluate the associations. RESULTS: The lung adenocarcinoma risk was significantly higher in patients with AA than GG + GA genotype (adjusted OR = 1.755, 95%CI = 1.057-2.912, P = 0.030). CCND1 rs9344 was significantly correlated with platinum-based therapy response in patients receiving PP regimen (additive model: adjusted OR = 1.926, 95%CI = 1.029-3.605, P = 0.040; recessive model: adjusted OR = 11.340, 95%CI = 1.428-90.100, P = 0.022) and in the ADC subgroups (recessive model: adjusted OR = 3.345, 95%CI = 1.276-8.765, P = 0.014). Furthermore, an increased risk of overall toxicity was found in NSCLC patients (additive model: adjusted OR = 1.395, 95%CI = 1.025-1.897, P = 0.034; recessive model: adjusted OR = 1.852, 95%CI = 1.088-3.152, P = 0.023), especially ADC subgroups (additive model: adjusted OR = 1.547, 95%CI = 1.015-2.359, P = 0.043; recessive model: adjusted OR = 2.030, 95%CI = 1.017-4.052, P = 0.045). Additionally, CCND1 rs9344 was associated with an increased risk of gastrointestinal toxicity in non-smokers (recessive model: adjusted OR = 2.620, 95%CI = 1.083-6.336, P = 0.035). Non-significant differences were observed in the 5-year overall survival rate between CCND1 rs9344 genotypes. A meta-analysis of 5432 cases and 6452 control samples did not find a significant association between lung cancer risk and CCND1 rs9344 polymorphism. CONCLUSION: This study suggests that in the Chinese population, CCND1 rs9344 could potentially serve as a candidate biomarker for cancer susceptibility and treatment outcomes in specific subgroups of patients.

Echinococcus granulosus ubiquitin-conjugating enzymes (E2D2 and E2N) promote the formation of liver fibrosis in TGFß1-induced LX-2 cells.

BACKGROUND: Cystic echinococcosis (CE) is a widespread zoonosis caused by the infection with Echinococcus granulosus sensu lato (E. granulosus s.l.). CE cysts mainly develop in the liver of intermediate hosts, characterized by the fibrotic tissue that separates host organ from parasite. However, precise mechanism underlying the formation of fibrotic tissue in CE remains unclear. METHODS: To investigate the potential impact of ubiquitin-conjugating enzymes on liver fibrosis formation in CE, two members of ubiquitin-conjugating (UBC) enzyme of Echinococcus granulosus (EgE2D2 and EgE2N) were recombinantly expressed in Escherichia coli and analyzed for bioinformatics, immunogenicity, localization, and enzyme activity. In addition, the secretory pathway and their effects on the formation of liver fibrosis were also explored. RESULTS: Both rEgE2D2 and rEgE2N possess intact UBC domains and active sites, exhibiting classical ubiquitin binding activity and strong immunoreactivity. Additionally, EgE2D2 and EgE2N were widely distributed in protoscoleces and germinal layer, with differences observed in their distribution in 25-day strobilated worms. Further, these two enzymes were secreted to the hydatid fluid and CE-infected sheep liver tissues via a non-classical secretory pathway. Notably, TGFß1-induced LX-2 cells exposed to rEgE2D2 and rEgE2N resulted in increasing expression of fibrosis-related genes, enhancing cell proliferation, and facilitating cell migration. CONCLUSIONS: Our findings suggest that EgE2D2 and EgE2N could secrete into the liver and may interact with hepatic stellate cells, thereby promoting the formation of liver fibrosis.

[Research progress in genetics of noise-induced hearing loss].

Noise-induced hearing loss（NIHL） is an acquired sensorineural hearing loss induced by long-term noise exposure. The susceptibility of exposed people may vary even in the same noise environment. With the development of sequencing techniques, genes related to oxidative stress, immunoinflammatory, ion homeostasis, energy metabolism, DNA damage repair and other mechanisms in NIHL have been reported continuously. And some genes may interact with noise exposure indexes. In this article, population studies on NIHL-related gene polymorphisms and gene-environment interactions in the past 20 years are reviewed, aimed to providing evidence for the construction of NIHL-related risk prediction models and the formulation of individualized interventions.

Dual toeholds regulated CRISPR-Cas12a sensing platform for ApoE single nucleotide polymorphisms genotyping.

Single nucleotide polymorphisms (SNPs) are closely associated with many biological processes, including genetic disease, tumorigenesis, and drug metabolism. Accurate and efficient SNP determination has been proved pivotal in pharmacogenomics and diagnostics. Herein, a universal and high-fidelity genotyping platform is established based on the dual toeholds regulated Cas12a sensing methodology. Different from the conventional single stranded or double stranded activation mode, the dual toeholds regulated mode overcomes protospacer adjacent motif (PAM) limitation via cascade toehold mediated strand displacement reaction, which is highly universal and ultra-specific. To enhance the sensitivity for biological samples analysis, a modified isothermal recombinant polymerase amplification (RPA) strategy is developed via utilizing deoxythymidine substituted primer and uracil-DNA glycosylase (UDG) treatment, designated as RPA-UDG. The dsDNA products containing single stranded toehold domain generated in the RPA-UDG allow further incorporation with dual toeholds regulated Cas12a platform for high-fidelity human sample genotyping. We discriminate all the single-nucleotide polymorphisms of ApoE gene at rs429358 and rs7412 loci with human buccal swab samples with 100% accuracy. Furthermore, we engineer visual readout of genotyping results by exploiting commercial lateral flow strips, which opens new possibilities for field deployable implementation.

High burden of human papillomavirus infection among men in Guangzhou, South China: Implications for HPV vaccination strategies.

The epidemiological and clinical aspects of Human Papillomavirus (HPV) infection in women have been extensively studied. However, there is a lack of information regarding HPV characteristics in males. In this study, we conducted a retrospective and observational study of 3737 consecutive male individuals attending outpatient clinics of Guangdong Women and Children Hospital from 2012 to 2023 in Guangzhou, South China, to determine the age- and genotype-specific prevalence of HPV in men. The results showed the overall prevalence of HPV among men was 42.15% (1575/3737), with variations ranging from 29.55% to 81.31% across distinct diagnostic populations. Low-risk HPV6 (15.47%), HPV11 (8.94%), and high-risk HPV52 (5.51%) were the most common types. The annual HPV prevalence decreased significantly (Z = -3.882, p < .001), ranging from 31.44% to 52.90%. 28.77% (1075/3737) of men manifested infection with a singular HPV type, predominantly identified as a low-risk type. The age-specific distribution of HPV infections revealed distinctive peaks in the < 25 y age group (47.60%, 208/437) and the 40-44 y age group (44.51%, 154/346). Notably, the positive rate of Chlamydia trachomatis was significantly higher among HPV-positive individuals in comparison to HPV-negatives (16.14% vs. 11.25%, p < .05). Our findings reveal a substantial prevalence of HPV infection among outpatient men in Guangzhou, South China. It is recommended to consider the inclusion of HPV vaccination for adolescent males in national immunization schedules, once an adequate supply of vaccines is accessible.

Association between novel genetic variants of Notch signaling pathway genes and survival of hepatitis B virus-related hepatocellular carcinoma.

BACKGROUND: Although the Notch pathway plays an important role in formation and progression of hepatocellular carcinoma (HCC), few studies have reported the associations between functional genetic variants and the survival of hepatitis B virus (HBV)-related HCC. METHODS: In the present study, we performed multivariable Cox proportional hazard regression analysis to evaluate associations between 36,101 SNPs in 264 Notch pathway-related genes and overall survival (OS) of 866 patients with HBV-related HCC. RESULTS: It was found that three independent SNPs (NEURL1B rs4868192, CNTN1 rs444927 and FCER2 rs1990975) were significantly associated with the HBV-related HCC OS. The number of protective genotypes (NPGs) were significantly associated with better survival in a dose-response manner (ptrend <0.001). Compared with the model with sole clinical factors, the addition of protective genotypes to the predict models significantly increased the AUC, i.e., from 72.72% to 75.13% (p = 0.002) and from 72.04% to 74.76 (p = 0.004) for 3-year and 5-year OS, respectively. The expression quantitative trait loci (eQTL) analysis further revealed that the rs4868192 C allele was associated with lower mRNA expression levels of NEURL1B in the whole blood (p = 1.71 × 10-3), while the rs1990975 T allele was correlated with higher mRNA expression levels of FCER2 in the whole blood and normal liver tissues (p = 3.51 × 10-5 and 0.033, respectively). CONCLUSIONS: Three potentially functional SNPs of NEURL1B, CNTN1 and FCER2 may serve as potential prognostic biomarkers for HBV-related HCC.

[Genetic analysis of two patients with a rare Ael subtype].

OBJECTIVE: To analyze the genetic sequences of two patients with a rare Ael blood subgroup. METHODS: Two female patients undergoing treatment respectively for adenomyoma of the uterus and gastritis at the Second Affiliated Hospital, Yuying Children's Hospital of Wenzhou Medical University in June 2019 and September 2020 were selected as the study subjects. Their Ael subtypes were identified with a saline tube agglutination assay and absorption-emission assay. Sequence of the ABO gene Ael subtypes was determined by the Sanger method. The impact of genetic variants on the structural stability of N-acetylgalactosaminyl transferase (GTA) was analyzed with PyMOL software by constructing a structure predicted model. RESULTS: Both patients were determined as Ael blood subgroup. Sequencing result of patient 1 was ABO*O.01.02/ABO*O.01.02, which has resulted in a p.Thr88Profs*31 amino acid substitution. The sequencing result of patient 2 was ABO*Ael.06/ABO*O.01.02, in which c.425C>T and c.467C>T variants in exon 7 have led to p.Met142Thr and p.Pro156Leu substitutions. Prediction of the protein model speculated that the p.Met142Thr not only can change the binding of GTA protein with water molecules, but also the local hydrogen bond network of GTA, which may lead to decreased enzymatic activity. By contrast, the p.Pro156Leu variant has trivial effect on the structural stability of GTA. CONCLUSION: The molecular structure of Ael subtypes can be diverse. The genotypes of the two patients have been respectively determined as ABO*O.01.02/ABO*O.01.02 with a G261 deletion and ABO*Ael.06/ABO*O.01.02.

[Molecular study of an individual with Bel subtype due to a novel c.620T>C variant].

OBJECTIVE: To explore the molecular basis for an individual with Bel subtype of the ABO blood type due to a novel c.620T>C variant gene, and assess its impact on the structure of GTB transferase. METHODS: An individual who had visited the First Affiliated Hospital of Zhengzhou University on February 11, 2023 was selected as the study subject. ABO phenotyping was initially conducted with serological methods, which was followed by direct sequencing of 7 exons of the ABO gene. Subsequently, single-strand sequencing was carried out by using allele-specific primers, and the variant in the B transferase was homology-modeled using the Modeller software. The impact of the variant on the transferase's spatial structure was analyzed with the PyMOL software. RESULTS: The serological phenotype of the patient was identified as the Bel subtype. Direct sequencing revealed that she has harbored a novel c.620T>C variant, resulting in a p.Leu207Pro substitution in the polypeptide chain. Combined with single-strand sequencing, her genotype was ultimately determined as ABO*BELnew/ABO*O.01.02. Three-dimensional protein structure modeling showed that, compared with the wild type, the distance of one hydrogen bond between Proline and Glycine at position 272 has increased, along with disappearance of another hydrogen bond. CONCLUSION: The novel c.620T>C (p.Leu207Pro) variant of B allele may affect the structural stability of the glycosyltransferase. The weakened enzyme activity in turn may lead to reduced B antigen expression, manifesting as the Bel subtype by serological analysis.

Effects of VDR and CYP24A1 gene polymorphisms on the outcome of supraglottic larynx cancer.

OBJECTIVE: Vitamin D has been demonstrated to play a protective role in carcinogenesis. Polymorphisms of the vitamin D receptor (VDR) genes and 24-α-hydroxylase (encoded by CYP24A1) may affect the outcome of some cancers. This study examines the effects of the VDR gene and CYP24A1 single nucleotide polymorphisms on the outcome of supraglottic larynx cancer. PATIENTS AND METHODS: Patients diagnosed with supraglottic larynx cancer between 2017 and 2022 were enrolled. Single nucleotide polymorphisms of the VDR gene (rs2228570, rs731236, rs7975232, rs11574113, rs11168267 and rs11168266) and CYP24A1 gene (rs4809960, rs6022999, rs6068816, rs2259735 and rs2296241) were investigated. All patients were followed up for any evidence of local recurrence, regional recurrence, distant metastasis, and second primary tumor development. Cox regression analysis was performed to evaluate the prognostic value of single-nucleotide polymorphisms (SNPs). Kaplan-Meier method was used for survival analysis. RESULTS: 87 patients were included. The mean follow-up time was 45.02±24.47 months. Cox regression analysis for locoregional recurrence revealed that the hazard ratio of rs731236 GG was 2.098 (95% CI, range: 1.047-4.202, p=0.037). Locoregional recurrence for rs731236 AA, AG, and GG were 38.6%, 23.1%, and 53.3%, respectively. In the presence of rs731236 GG polymorphism, disease-specific survival was significantly shorter (47.63±7.48 months, p=0.015), and disease-free survival (45.71±6.3 months) was significantly shorter (p=0.040). Rates of metastases and second primary tumors were not significantly different between SNPs. CONCLUSIONS: This study has demonstrated the possible effects of VDR rs731236 SNP on the locoregional recurrence and prognosis of supraglottic larynx cancer.

Impact of toll-like receptor 4 variations on nasopharyngeal carcinoma risk and survival in tunisian population.

INTRODUCTION: The Toll-like receptor 4 (TLR4), an important member of the host's innate immune response, is coded by a polymorphic gene. This polymorphism could be a predisposing factor for NasoPharyngeal Carcinoma (NPC). AIM: To determine the association between TLR4 gene polymorphisms and the susceptibility to NPC in a cohort of Tunisian affected patients. METHODS: Genomic DNAs from 245 unrelated patients affected by undifferentiated carcinoma type (UCNT) and 264 unrelated healthy controls were genotyped for the five single nucleotides polymorphisms (SNPs) of TLR4 locus (4434 A>G (rs1927914),7263 G>C (rs10759932), 6134 A>G(rs4986790), 8851C>T (rs 4986791), 5272 T>C(rs11536889), +8469 T>C (rs11536891)) by Taqman® 5'-nuclease assay. RESULTS: Among all polymorphisms studied, only the rs4986790 G and rs4986791 T alleles were significantly more prevalent in patients' group than controls (45% vs. 38%; p=0.03; pc=0.06) and increased the risk of the NPC (OR=1.3, 95% CI=1.01-1.69). Also, we found that the frequency of the rs4986790 AA and rs4986791 TT genotypes was significantly higher in controls than in patients (25.7% vs 37%; p=0.006, pc=0.02) and conferred a protector factor in NPC (OR= 0.59, 95% CI= 0.39-0.87). Further, based on the Kaplan-Meier survival curve we observed also the positive effect ofrs1927914 AA genotype on a prognostic of NPC (p=0.006; pc=0.01). CONCLUSION: Our study demonstrated that impaired production of TLR4 seems to be a risk factor of NPC development but functional studies are needed to confirm these findings. As to rs1927914 AA appears to be a good biomarker for better survival in a patient with NPC.

Characterization of human papillomavirus genotypes and their coverage in vaccine delivered to Ethiopian women.

Cervical cancer is a significant public health concern in Ethiopia. It is mainly caused by persistent infection with the human papillomaviruses. The aim of this study was to assess the relationship between carcinogenic risk of probable, possible and low risk HPV infection and those of cervical intraepithelial neoplasia (CIN) and cervical cancer. A cross sectional study nested from prospective cohort study was conducted in Bahir Dar, northwest Ethiopia. Statistical analyses were performed using SPSSversion 26.0. HPV-16 was associated with a relatively higher risk of CIN II+, (AOR = 15.42; 95% CI 6.81-34.91). In addition, HPV-52, -18, -53 and -58, were significantly associated with an increased risk of CIN II+, (AOR = 7.38 (1.73-31.54), 5.42 (1.61-18.31), 4.08 (1.53-10.87), and 3.17 (1.00-10.03)), respectively. The current study shows high rate of HPV with predominance of HPV-16, -53, -58, -18, -35, and -52. The quadrivalent and nonavalent vaccine had only covered 27.1% and 45% of the circulating HPV genotypes. Ethiopia may need to consider introduction of nonavalent vaccine into the national public health strategy. Polyvalent vaccine which includes the genotypes not covered by existing approved vaccines should be considered.

CYP2C8 rs11572080 and CYP3A4 rs2740574 risk genotypes in paclitaxel-treated premenopausal breast cancer patients.

Breast cancer (BC) is the most prevalent malignancy in women globally. At time of diagnosis, premenopausal BC is considered more aggressive and harder to treat than postmenopausal cases. Cytochrome P450 (CYP) enzymes are responsible for phase I of estrogen metabolism and thus, they are prominently involved in the pathogenesis of BC. Moreover, CYP subfamily 2C and 3A play a pivotal role in the metabolism of taxane anticancer agents. To understand genetic risk factors that may have a role in pre-menopausal BC we studied the genotypic variants of CYP2C8, rs11572080 and CYP3A4, rs2740574 in female BC patients on taxane-based therapy and their association with menopausal status. Our study comprised 105 female patients with histologically proven BC on paclitaxel-therapy. They were stratified into pre-menopausal (n = 52, 49.5%) and post-menopausal (n = 53, 50.5%) groups. Genotyping was done using TaqMan assays and employed on Quantstudio 12 K flex real-time platform. Significant increased frequencies of rs11572080 heterozygous CT genotype and variant T allele were established in pre-menopausal group compared to post-menopausal group (p = 0.023, 0.01, respectively). Moreover, logistic regression analysis revealed a significant association between rs11572080 CT genotype and premenopausal BC. However, regarding rs2740574, no significant differences in genotypes and allele frequencies between both groups were detected. We reported a significant association between CYP2C8 genotypic variants and premenopausal BC risk in Egyptian females. Further studies on larger sample sizes are still needed to evaluate its importance in early prediction of BC in young women and its effect on treatment outcome.

Prevalence, genotypes, and infection risk factors of psittacine beak and feather disease virus and budgerigar fledgling disease virus in captive birds in Hong Kong.

Psittacine beak and feather disease virus (PBFDV) and budgerigar fledgling disease virus (BFDV) are significant avian pathogens that threaten both captive and wild birds, particularly parrots, which are common hosts. This study involved sampling and testing of 516 captive birds from households, pet shops, and an animal clinic in Hong Kong for PBFDV and BFDV. The results showed that PBFDV and BFDV were present in 7.17% and 0.58% of the samples, respectively. These rates were lower than those reported in most parts of Asia. Notably, the infection rates of PBFDV in pet shops were significantly higher compared to other sources, while no BFDV-positive samples were found in pet shops. Most of the positive samples came from parrots, but PBFDV was also detected in two non-parrot species, including Swinhoe's white-eyes (Zosterops simplex), which had not been reported previously. The ability of PBFDV to infect both psittacine and passerine birds is concerning, especially in densely populated urban areas such as Hong Kong, where captive flocks come into close contact with wildlife. Phylogenetic analysis of the Cap and Rep genes of PBFDV revealed that the strains found in Hong Kong were closely related to those in Europe and other parts of Asia, including mainland China, Thailand, Taiwan, and Saudi Arabia. These findings indicate the presence of both viruses among captive birds in Hong Kong. We recommend implementing regular surveillance for both viruses and adopting measures to prevent contact between captive and wild birds, thereby reducing the transmission of introduced diseases to native species.

Effects of Glutathione S-Transferases (GSTM1, GSTT1 and GSTP1) gene variants in combination with smoking or drinking on cancers: A meta-analysis.

BACKGROUND: This meta-analysis aimed to systematically summarize the association between cancer risks and glutathione s-transferases (GSTs) among smokers and drinkers. METHODS: Literature was searched through PubMed, Web of Science, CNKI, and WANFANG published from 2001 to 2022. Stata was used with fixed-effect model or random-effect model to calculate pooled odds ratios (ORs) and the 95% confidence interval (95% CI). Sensitivity and heterogeneity calculations were performed, and publication bias was analyzed by Begg and Egger's test. Regression analysis was performed on the correlated variables about heterogeneity, and the false-positive report probabilities (FPRP) and the Bayesian False Discovery Probability (BFDP) were calculated to assess the confidence of a statistically significant association. RESULTS: A total of 85 studies were eligible for GSTs and cancer with smoking status (19,604 cases and 23,710 controls), including 14 articles referring to drinking status (4409 cases and 5645 controls). GSTM1-null had significant associations with cancer risks (for smokers: OR = 1.347, 95% CI: 1.196-1.516, P < .001; for nonsmokers: OR = 1.423, 95% CI: 1.270-1.594, P < .001; for drinkers: OR = 1.748, 95% CI: 1.093-2.797, P = .02). GSTT1-null had significant associations with cancer risks (for smokers: OR = 1.356, 95% CI: 1.114-1.651, P = .002; for nonsmokers: OR = 1.103, 95% CI: 1.011-1.204, P = .028; for drinkers: OR = 1.423, 95% CI: 1.042-1.942, P = .026; for nondrinkers: OR = 1.458, 95% CI: 1.014-2.098, P = .042). Negative associations were found between GSTP1rs1695(AG + GG/AA) and cancer risks among nondrinkers (OR = 0.840, 95% CI: 0.711-0.985, P = .032). CONCLUSIONS: GSTM1-null and GSTT1-null might be related cancers in combination with smoking or drinking, and GSTP1rs1695 might be associated with cancers among drinkers.

GWAS determined genetic loci associated with callus induction in oil palm tissue culture.

KEY MESSAGE: GWAS identified six loci at 25 kb downstream of WAK2, a crucial gene for cell wall and callus formation, enabling development of a SNP marker for enhanced callus induction potential. Efficient callus induction is vital for successful oil palm tissue culture, yet identifying genomic loci and markers for early detection of genotypes with high potential of callus induction remains unclear. In this study, immature male inflorescences from 198 oil palm accessions (dura, tenera and pisifera) were used as explants for tissue culture. Callus induction rates were collected at one-, two- and three-months after inoculation (C1, C2 and C3) as phenotypes. Resequencing generated 11,475,258 high quality single nucleotide polymorphisms (SNPs) as genotypes. GWAS was then performed, and correlation analysis revealed a positive association of C1 with both C2 (R = 0.81) and C3 (R = 0.50), indicating that C1 could be used as the major phenotype for callus induction rate. Therefore, only significant SNPs (P ≤ 0.05) in C1 were identified to develop markers for screening individuals with high potential of callus induction. Among 21 significant SNPs in C1, LD block analysis revealed six SNPs on chromosome 12 (Chr12) potentially linked to callus formation. Subsequently, 13 SNP markers were identified from these loci and electrophoresis results showed that marker C-12 at locus Chr12_12704856 can be used effectively to distinguish the GG allele, which showed the highest probability (69%) of callus induction. Furthermore, a rapid SNP variant detection method without electrophoresis was established via qPCR-based melting curve analysis. Our findings facilitated marker-assisted selection for specific palms with high potential of callus induction using immature male inflorescence as explant, aiding ortet palm selection in oil palm tissue culture.

Genomic characterization of human respiratory syncytial virus circulating in Islamabad, Pakistan, during an outbreak in 2022-2023.

In this study, conducted at the National Institute of Health, Islamabad, during an outbreak of human respiratory syncytial virus (hRSV) from December 2022 to January 2023, the first whole-genome sequences of hRSV isolates from Islamabad, Pakistan, were determined. Out of 10 positive samples, five were sequenced, revealing the presence of two genotypes: RSV-A (GA2.3.5, ON1 strain) and RSV-B (GB5.0.5.a, BA-10 strain). A rare non-synonymous substitution (E232G) in G the protein and N276S in the F protein were found in RSV-A. In RSV-B, the unique mutations K191R, Q209R, and I206M were found in the F protein. These mutations could potentially influence vaccine efficacy and viral pathogenicity. This research underscores the importance of genomic surveillance for understanding RSV diversity and guiding public health responses in Pakistan.

Predictors for survival in patients with Alzheimer's disease: a large comprehensive meta-analysis.

The prevalence of Alzheimer's disease (AD) is increasing as the population ages, and patients with AD have a poor prognosis. However, knowledge on factors for predicting the survival of AD remains sparse. Here, we aimed to systematically explore predictors of AD survival. We searched the PubMed, Embase and Cochrane databases for relevant literature from inception to December 2022. Cohort and case-control studies were selected, and multivariable adjusted relative risks (RRs) were pooled by random-effects models. A total of 40,784 reports were identified, among which 64 studies involving 297,279 AD patients were included in the meta-analysis after filtering based on predetermined criteria. Four aspects, including demographic features (n = 7), clinical features or comorbidities (n = 13), rating scales (n = 3) and biomarkers (n = 3), were explored and 26 probable prognostic factors were finally investigated for AD survival. We observed that AD patients who had hyperlipidaemia (RR: 0.69) were at a lower risk of death. In contrast, male sex (RR: 1.53), movement disorders (including extrapyramidal signs) (RR: 1.60) and cancer (RR: 2.07) were detrimental to AD patient survival. However, our results did not support the involvement of education, hypertension, APOE genotype, Aß42 and t-tau in AD survival. Our study comprehensively summarized risk factors affecting survival in patients with AD, provided a better understanding on the role of different factors in the survival of AD from four dimensions, and paved the way for further research.