Extramammary Paget's Disease: 20 Years of Experience in Chinese Population

Background. To examine the results of treatment of Extramammary Paget's disease (EMPD) in ethnic Chinese. Method. Between 1990 and 2010, patients treated for EMPD were reviewed. Data were analyzed retrospectively. Results. Forty-eight patients were treated by surgical resection. Local recurrence rate was 14.6%. The postresection defects were repaired by primary closure (8.3%), partial thickness skin graft (72.9%), or local/regional flaps (18.8%). Dermal invasion was found in 9 patients (18.8%). Seven patients (14.6%) developed regional lymph node metastasis (concurrent with surgery, n = 1; subsequent to surgery, n = 6), and 3 patients (6.3%) had systemic metastasis after surgery. The presence of dermal invasion was associated with significantly higher incidence of regional lymph nodes and systemic metastasis. The incidence of associated internal malignancy was 8.3%. Conclusion. The mainstay of treatment for EMPD is surgery. Pathological dermal invasion increases the chance of regional lymph node as well as systemic metastasis. The association with internal malignancy warrants preoperative endoscopic examination in all patients

A systematic review and meta-analysis of the effects of long-term antibiotic use on cognitive outcomes

Antibiotics are indispensable to infection management. However, use of antibiotics can cause gut microbiota dysbiosis, which has been linked to cognitive impairment by disrupting communication between the gut microbiota and the brain. We conducted a systematic review and meta-analysis on the effects of long-term antibiotic use on cognitive outcomes. We have searched PubMed, Web of Science, Embase, Cochrane Library and Scopus for English publications before March 2023 following the PRISMA guidelines. Screening, data extraction, and quality assessment were performed in duplicate. 960 articles were screened and 16 studies which evaluated the effect of any antibiotic compared to no antibiotics or placebo were included. Case-reports, in vitro and animal studies were excluded. We found that antibiotic use was associated with worse cognitive outcomes with a pooled effect estimate of - 0.11 (95% CI - 0.15, - 0.07, Z = 5.45; P &lt; 0.00001). Subgroup analyses performed on adult vs pediatric patients showed a similar association of antibiotic on cognition in both subgroups. Antibiotic treatment was not associated with worse cognition on subjects with existing cognitive impairment. On the other hand, antibiotic treatment on subjects with no prior cognitive impairment was associated with worse cognitive performance later in life. This calls for future well-designed and well-powered studies to investigate the impact of antibiotics on cognitive performance.</p

A systematic review and meta-analysis of the effects of long-term antibiotic use on cognitive outcomes

Antibiotics are indispensable to infection management. However, use of antibiotics can cause gut microbiota dysbiosis, which has been linked to cognitive impairment by disrupting communication between the gut microbiota and the brain. We conducted a systematic review and meta-analysis on the effects of long-term antibiotic use on cognitive outcomes. We have searched PubMed, Web of Science, Embase, Cochrane Library and Scopus for English publications before March 2023 following the PRISMA guidelines. Screening, data extraction, and quality assessment were performed in duplicate. 960 articles were screened and 16 studies which evaluated the effect of any antibiotic compared to no antibiotics or placebo were included. Case-reports, in vitro and animal studies were excluded. We found that antibiotic use was associated with worse cognitive outcomes with a pooled effect estimate of - 0.11 (95% CI - 0.15, - 0.07, Z = 5.45; P &lt; 0.00001). Subgroup analyses performed on adult vs pediatric patients showed a similar association of antibiotic on cognition in both subgroups. Antibiotic treatment was not associated with worse cognition on subjects with existing cognitive impairment. On the other hand, antibiotic treatment on subjects with no prior cognitive impairment was associated with worse cognitive performance later in life. This calls for future well-designed and well-powered studies to investigate the impact of antibiotics on cognitive performance.</p

Unveiling falling urban trees before and during Typhoon Higos (2020): empirical case study of potential structural failure using tilt sensor

Urban trees in a densely populated environment may pose risks to the public’s safety in terms of the potential danger of injuries and fatalities, loss of property, impacts on traffic, etc. The biological and mechanical features of urban trees may change over time, thereby affecting the stability of the tree structure. This can be a gradual process but can also be drastic, especially after typhoons or heavy rainstorms. Trees may fall at any time with no discernible signs of failure being exhibited or detected. It is always a challenge in urban tree management to develop a preventive alert system to detect the potential failure of hazardous urban trees and hence be able to have an action plan to handle potential tree tilting or tree collapse. Few studies have considered the comparison of tree morphology to the tilt response relative to uprooting failure in urban cities. New methods involving numerical modeling and sensing technologies provide tools for an effective and deeper understanding of the interaction of root-plate movement and windstorm with the application of the tailor-made sensor. In this study, root-plate tilt variations of 889 trees with sensors installed during Typhoon Higos (2020) are investigated, especially the tilting pattern of the two trees that failed in the event. The correlation of tree response during the typhoon among all trees with tilt measurements was also evaluated. The results from two alarm levels developed in the study, i.e., Increasing Trend Alarm and Sudden Increase Alarm indicated that significant root-plate movement to wind response is species-dependent. These systems could help inform decision making to identify the problematic trees in the early stage. Through the use of smart sensors, the data collected by the alert system provides a very useful analysis of the stability of tree structure and tree health in urban tree management

Jerantinine A induces tumor-specific cell death through modulation of splicing factor 3b subunit 1 (SF3B1)

Precursor mRNA (pre-mRNA) splicing is catalyzed by a large ribonucleoprotein complex known as the spliceosome. Numerous studies have indicated that aberrant splicing patterns or mutations in spliceosome components, including the splicing factor 3b subunit 1 (SF3B1), are associated with hallmark cancer phenotypes. This has led to the identification and development of small molecules with spliceosome-modulating activity as potential anticancer agents. Jerantinine A (JA) is a novel indole alkaloid which displays potent anti-proliferative activities against human cancer cell lines by inhibiting tubulin polymerization and inducing G2/M cell cycle arrest. Using a combined pooled-genome wide shRNA library screen and global proteomic profiling, we showed that JA targets the spliceosome by up-regulating SF3B1 and SF3B3 protein in breast cancer cells. Notably, JA induced significant tumor-specific cell death and a significant increase in unspliced pre-mRNAs. In contrast, depletion of endogenous SF3B1 abrogated the apoptotic effects, but not the G2/M cell cycle arrest induced by JA. Further analyses showed that JA stabilizes endogenous SF3B1 protein in breast cancer cells and induced dissociation of the protein from the nucleosome complex. Together, these results demonstrate that JA exerts its antitumor activity by targeting SF3B1 and SF3B3 in addition to its reported targeting of tubulin polymerization

Immunoregulatory Protein Profiles of Necrotizing Enterocolitis versus Spontaneous Intestinal Perforation in Preterm Infants

Necrotizing enterocolitis (NEC) and spontaneous intestinal perforation (SIP) are the most common acute surgical emergencies associated with high morbidity and mortality in preterm infants. We aimed to compare the profiles of immunoregulatory proteins and identify novel mediators in plasma of NEC and SIP infants. We also investigated the expression of target genes in resected intestinal tissues and an enterocyte cell line. Using Cytokine Antibody Array assay, we reported the first comparative profiles of immunoregulatory proteins in plasma of NEC and SIP infants, and showed that dysregulated proteins belonged to functionally diversified categories, including pro- and anti-inflammation, angiogenesis, cell growth, wound healing, anti-apoptosis, cell adhesion and extracellular matrix reorganization. Validation by ELISA confirmed significantly higher concentrations of interleukin (IL)-6, angiopoietin (Ang)-2, soluble type II interleukin-1 receptor (sIL-1RII), and soluble urokinase-type plasminogen activator receptor (suPAR) in NEC infants compared with gestational age-matched control, and a lower level of an epidermal growth factor receptor, secreted form of receptor tyrosine-protein kinase ErbB3 (sErbB3), compared with SIP infants. mRNA expressions of IL1-RII and uPAR were up-regulated in resected bowel tissues from NEC infants, indicating that immunoregulation also occurred at the cellular level. In FHs-74 Int cells, Ang-2, IL1-RII and uPAR mRNA expressions were significantly induced by the combined treatment with lipopolysaccharide (LPS) and platelet activating factor (PAF). Our study provided plasmatic signatures of immunoregulatory proteins in NEC and SIP infants, and demonstrated involvement of multiple functional pathways. The magnitude of changes in these proteins was significantly more extensive in NEC infants, reflecting the different nature of injury and/or severity of inflammation. We speculate that dysregulation of IL-6, Ang-2, IL-1RII and uPAR occurred at both systemic and cellular levels, and probably mediated via LPS and endogeneous PAF signals. Such exaggerated immunologic responses may account for the high morbidity and mortality in NEC compared with SIP patients

Patterning of L10 FePt Nanoparticles with Ultra-High Coercivity for Bit-Patterned Media

L1(0)-ordered FePt nanoparticles (NPs) with ultra-high coercivity were directly prepared from a new metallopolyyne using a one-step pyrolysis method. The chemical ordering, morphology and magnetic properties of the as-synthesized FePt NPs have been studied. Magnetic measurements show the coercivity of these FePt NPs is as high as 3.6 T. Comparison of NPs synthesized under the Ar and Ar/H-2 atmospheres shows that the presence of H-2 in the annealing environment influences the nucleation and promotes the growth of L1(0)-FePt NPs. Application of this metallopolymer for bit-patterned media was also demonstrated using nanoimprint lithography.Department of Applied PhysicsDepartment of Applied Biology and Chemical Technolog

Effectiveness of BNT162b2 and CoronaVac vaccinations against mortality and severe complications after SARS-CoV-2 Omicron BA.2 infection: a case–control study

Data regarding protection against mortality and severe complications after Omicron BA.2 infection with CoronaVac and BNT162b2 vaccines remains limited. We conducted a case–control study to evaluate the risk of severe complications and mortality following 1–3 doses of CoronaVac and BNT162b2 using electronic health records database. Cases were adults with their first COVID-19-related mortality or severe complications between 1 January and 31 March 2022, matched with up-to 10 controls by age, sex, index date, and Charlson Comorbidity Index. Vaccine effectiveness against COVID-19-related mortality and severe complications by type and number of doses was estimated using conditional logistic regression adjusted for comorbidities and medications. Vaccine effectiveness (95% CI) against COVID-19-related mortality after two doses of BNT162b2 and CoronaVac were 90.7% (88.6–92.3) and 74.8% (72.5–76.9) in those aged ≥65, 87.6% (81.4–91.8) and 80.7% (72.8–86.3) in those aged 50–64, 86.6% (71.0–93.8) and 82.7% (56.5–93.1) in those aged 18–50. Vaccine effectiveness against severe complications after two doses of BNT162b2 and CoronaVac were 82.1% (74.6–87.3) and 58.9% (50.3–66.1) in those aged ≥65, 83.0% (69.6–90.5) and 67.1% (47.1–79.6) in those aged 50–64, 78.3% (60.8–88.0) and 77.8% (49.6–90.2) in those aged 18–50. Further risk reduction with the third dose was observed especially in those aged ≥65 years, with vaccine effectiveness of 98.0% (96.5–98.9) for BNT162b2 and 95.5% (93.7–96.8) for CoronaVac against mortality, 90.8% (83.4–94.9) and 88.0% (80.8–92.5) against severe complications. Both CoronaVac and BNT162b2 vaccination were effective against COVID-19-related mortality and severe complications amidst the Omicron BA.2 pandemic, and risks decreased further with the third dose

Laboratory Diagnosis of SARS

The virologic test results of 415 patients with severe acute respiratory syndrome (SARS) were examined. The peak detection rate for SARS-associated coronavirus occurred at week 2 after illness onset for respiratory specimens, at weeks 2 to 3 for stool or rectal swab specimens, and at week 4 for urine specimens. The latest stool sample that was positive by reverse transcription–polymerase chain reaction (RT-PCR) was collected on day 75 while the patient was receiving intensive care. Tracheal aspirate and stool samples had a higher diagnostic yield (RT-PCR average positive rate for first 2 weeks: 66.7% and 56.5%, respectively). Pooled throat and nasal swabs, rectal swab, nasal swab, throat swab, and nasopharyngeal aspirate specimens provided a moderate yield (29.7%–40.0%), whereas throat washing and urine specimens showed a lower yield (17.3% and 4.5%). The collection procedures for stool and pooled nasal and throat swab specimens were the least likely to transmit infection, and the combination gave the highest yield for coronavirus detection by RT-PCR. Positive virologic test results in patient groups were associated with mechanical ventilation or death (p < 0.001), suggesting a correlation between viral load and disease severity