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Serological and plasmablast responses and plasmablast-derived IgG monoclonal antibodies (MAbs) have been analysed in three COVID-19 patients with different clinical severities. Potent humoral responses were detected within 3 weeks of onset of illness in all patients and the serological titre was elicited soon after or concomitantly with peripheral plasmablast response. An average of 13.7% and 3.5% of plasmablast-derived MAbs were reactive with virus spike glycoprotein or nucleocapsid, respectively. A subset of anti-spike (10 of 32) antibodies cross-reacted with other betacoronaviruses tested and harboured extensive somatic mutations, indicative of an expansion of memory B cells upon SARS-CoV-2 infection. Fourteen of 32 anti-spike MAbs, including five anti-receptor-binding domain (RBD), three anti-non-RBD S1 and six anti-S2, neutralised wild-type SARS-CoV-2 in independent assays. Anti-RBD MAbs were further grouped into four cross-inhibiting clusters, of which six antibodies from three separate clusters blocked the binding of RBD to ACE2 and five were neutralising. All ACE2-blocking anti-RBD antibodies were isolated from two recovered patients with prolonged fever, which is compatible with substantial ACE2-blocking response in their sera. Finally, the identification of non-competing pairs of neutralising antibodies would offer potential templates for the development of prophylactic and therapeutic agents against SARS-CoV-2.

Conflicting data exists regarding the baseline determinants of virological nonsuppression outcomes in treatment-experienced people living with human immunodeficiency virus (PWH) switching to antiretroviral treatment (ART) with bictegravir/emtricitabine/tenofovir alafenamide fumarate (BIC/FTC/TAF) or dolutegravir/lamivudine (DTG/3TC) in Asia. This retrospective observational study, conducted at a designated HIV-care hospital from October 2019 to January 2023, aimed to address this gap. We assessed the odds of virological nonsuppression (VNS) at weeks 48 using logistic regression. A total of 988 patients were included, 35 patients (3.5%) with VNS at week 48. Pre-existing primary resistance-associated mutations (RAM) to nucleoside reverse transcriptase inhibitor (NRTI) and non-nucleoside reverse transcriptase inhibitor (NNRTI) were identified in 11.0% (51/465) and 14.4% (67/465), respectively. The identified risk factor was a record of virological failure ≥2 times (AOR 5.32, 95% CI 2.04–13.85), while an HIV viral load <50 copies/mL within the past three months before switch (AOR: 0.27, 95% CI 0.11–0.72) was identified as a protective factor. No cases of acquired drug resistance-associated mutations were detected at week 48. Additionally, DTG/3TC was noninferior to BIC/FTC/TAF in achieving or maintaining HIV RNA levels of <50 copies/mL, within a -10% noninferiority margin in the per-protocol analysis (responder proportion: 98.2% vs. 95.0%, respectively; adjusted treatment difference [95% CI], 3.2% [0.7% to 5.3%]). In conclusion, DTG/3TC and BIC/FTC/TAF demonstrated good effectiveness in a real-world cohort, but frequent virological failure before the switch might impact the benefits of these regimens in the short term of follow-up.

Few studies have demonstrated the interplay between human immunodeficiency virus (HIV), anal human papillomavirus (HPV), and anal microbiota, especially in persons living with HIV who are men who have sex with men. We, therefore, explored these interrelationships in a cohort of persons living with HIV, mainly comprising men who have sex with men. HPV genotyping using a commercial genotyping kit and ThinPrep cytology interpreted by Bethesda systems was performed on samples from 291 patients. Samples were characterized by high-throughput sequencing of dual-index barcoded 16s rRNA (V3–4). Bacterial diversity was diminished in individuals living with HIV with CD4+ T cells <500 cells/μL and anal cytology yielding atypical squamous cells of undetermined significance or higher grades (ASCUS+) with detectable HPV 16/18 compared with those with CD4+ T cells ≥500 cells/μL with ASCUS+ and HPV 16/18 and those with normal anal cytology or inflammation without HPV 16/18. Enterobacteriaceae, Ruminococcus , and Bacilli were significantly abundant in persons living with HIV with CD4+ T cells <500 cells/μL with ASCUS+ and HPV 16/18. Bacterial diversity, composition, and homogeneity of dispersion were different in individuals living with HIV with low CD4+ T cells with ASCUS+ and HPV 16/18, and understanding the interaction among immunocompromised hosts, oncogenic HPVs, and microbiota is essential, and the contribution of these factors to anal precancerous lesions needs more in-depth exploration.

Background Early diagnosis and treatment of patients with sepsis reduce mortality significantly. In terms of exploring new diagnostic tools of sepsis, monocyte distribution width (MDW), as part of the white blood cell (WBC) differential count, was first reported in 2017. MDW greater than 20 and abnormal WBC count together provided a satisfactory accuracy and was proposed as a novel diagnostic tool of sepsis. This study aimed to compare MDW and procalcitonin (PCT)’s diagnostic accuracy on sepsis in the emergency department. Methods This was a single-center prospective cohort study. Laboratory examinations including complete blood cell and differentiation count (CBC/DC), MDW, PCT were obtained while arriving at the ED. We divided patients into non-infection, infection without systemic inflammatory response syndrome (SIRS), infection with SIRS, and sepsis-3 groups. This study’s primary outcome is the sensitivity and specificity of MDW, PCT, and MDW + WBC in differentiating septic and non-septic patients. In addition, the cut-off value for MDW was established to maximize sensitivity at an optimal level of specificity. Results From May 2019 to September 2020, 402 patients were enrolled for data analysis. Patient number in each group was: non-infection 64 (15.9%), infection without SIRS 82 (20.4%), infection with SIRS 202 (50.2%), sepsis-3 15 (7.6%). The AUC of MDW, PCT, and MDW + WBC to predict infection with SIRS was 0.753, 0.704, and 0.784, respectively (p < 0.01). The sensitivity, specificity, PPV, and NPV of MDW using 20 as the cutoff were 86.4%, 54.2%, 76.4%, and 70%, compared to 32.9%, 88%, 82.5%, and 43.4% using 0.5 ng/mL as the PCT cutoff value. On combing MDW and WBC count, the sensitivity and NPV further increased to 93.4% and 80.3%, respectively. In terms of predicting sepsis-3, the AUC of MDW, PCT, and MDW + WBC was 0.72, 0.73, and 0.70, respectively. MDW, using 20 as cutoff, exhibited sensitivity, specificity, PPV, and NPV of 90.6%, 37.1%, 18.7%, and 96.1%, respectively, compared to 49.1%, 78.6%, 26.8%, and 90.6% when 0.5 ng/mL PCT was used as cutoff. Conclusions In conclusion, MDW is a more sensitive biomarker than PCT in predicting infection-related SIRS and sepsis-3 in the ED. MDW < 20 shows a higher NPV to exclude sepsis-3. Combining MDW and WBC count further improves the accuracy in predicting infection with SIRS but not sepsis-3. Trial registration The study was retrospectively registered to the ClinicalTrial.gov (NCT04322942) on March 26th, 2020.

In this study, we evaluated the efficacy of hydroxychloroquine (HCQ) against coronavirus disease 2019 (COVID-19) via a randomized controlled trial (RCT) and a retrospective study. Subjects admitted to 11 designated public hospitals in Taiwan between April 1 and May 31, 2020, with COVID-19 diagnosis confirmed by pharyngeal real-time RT-PCR for SARS-CoV-2, were randomized at a 2:1 ratio and stratified by mild or moderate illness. HCQ (400 mg twice for 1 d or HCQ 200 mg twice daily for 6 days) was administered. Both the study and control group received standard of care (SOC). Pharyngeal swabs and sputum were collected every other day. The proportion and time to negative viral PCR were assessed on day 14. In the retrospective study, medical records were reviewed for patients admitted before March 31, 2020. There were 33 and 37 cases in the RCT and retrospective study, respectively. In the RCT, the median times to negative rRT-PCR from randomization to hospital day 14 were 5 days (95% CI; 1, 9 days) and 10 days (95% CI; 2, 12 days) for the HCQ and SOC groups, respectively (p = 0.40). On day 14, 81.0% (17/21) and 75.0% (9/12) of the subjects in the HCQ and SOC groups, respectively, had undetected virus (p = 0.36). In the retrospective study, 12 (42.9%) in the HCQ group and 5 (55.6%) in the control group had negative rRT-PCR results on hospital day 14 (p = 0.70). Neither study demonstrated that HCQ shortened viral shedding in mild to moderate COVID-19 subjects.

AbstractObjectiveTo evaluate the effects of four drug (quadruple) versus three drug (triple) combination antiretroviral therapies in treatment naive people with HIV, and explore the implications of existing trials for clinical practice and research.DesignSystematic review and meta-analysis of randomised controlled trials.Data sourcesPubMed, EMBASE, CENTRAL, Web of Science, and the Cumulative Index to Nursing and Allied Health Literature from March 2001 to December 2016 (updated search in PubMed and EMBASE up to June 2018); and reference lists of eligible studies and related reviews.Study selectionRandomised controlled trials comparing quadruple with triple combination antiretroviral therapies in treatment naive people with HIV and evaluating at least one effectiveness or safety outcome.Review methodsOutcomes of interest included undetectable HIV-1 RNA, CD4 T cell count, virological failure, new AIDS defining events, death, and severe adverse effects. Random effects meta-analyses were conducted.ResultsTwelve trials (including 4251 people with HIV) were eligible. Quadruple and triple combination antiretroviral therapies had similar effects on all relevant effectiveness and safety outcomes, with no point estimates favouring quadruple therapy. With the triple therapy as the reference group, the risk ratio was 0.99 (95% confidence interval 0.93 to 1.05) for undetectable HIV-1 RNA, 1.00 (0.90 to 1.11) for virological failure, 1.17 (0.84 to 1.63) for new AIDS defining events, 1.23 (0.74 to 2.05) for death, and 1.09 (0.89 to 1.33) for severe adverse effects. The mean difference in CD4 T cell count increase between the two groups was −19.55 cells/μL (−43.02 to 3.92). In general, the results were similar, regardless of the specific regimens of combination antiretroviral therapies, and were robust in all subgroup and sensitivity analyses.ConclusionIn this study, effects of quadruple combination antiretroviral therapy were not better than triple combination antiretroviral therapy in treatment naive people with HIV. This finding lends support to current guidelines recommending the triple regimen as first line treatment. Further trials on this topic should be conducted only when new research is justified by adequate systematic reviews of the existing evidence. However, this study cannot exclude the possibility that quadruple cART would be better than triple cART when new classes of antiretroviral drugs are made available.

Glucocorticoid (GC)-exacerbated hyperglycemia is prevalent in hospitalized patients with diabetes mellitus (DM) but evidence-based insulin guidelines in inpatient settings are lacking. Retrospective cohort study with capillary blood glucose (CBG) readings and insulin use, dosed with 50% basal (glargine)-50% bolus (lispro) insulin, analyzed in hospitalized patients with insulin-treated DM given GC and matched controls without GC (n = 131 pairs). GC group (median daily prednisone-equivalent dose: 53.36 mg (IQR 30.00, 80.04)) had greatest CBG differences compared to controls at dinner (254±69 vs. 184±63 mg/dL, P<0.001) and bedtime (260±72 vs. 182±55 mg/dL, P<0.001). In GC group, dinner CBG was 30% higher than lunch (254±69 vs. 199±77 mg/dL, P<0.001) when similar lispro to controls given at lunch. Bedtime CBG not different from dinner when 20% more lispro given at dinner (0.12 units/kg (IQR 0.08, 0.17) vs. 0.10 units/kg (0.06, 0.14), P<0.01). Despite receiving more lispro, bedtime hypoglycemic events were lower in GC group (0.0% vs. 5.9%, P = 0.03). Since equal bolus doses inadequately treat large dinner and bedtime GC-exacerbated glycemic excursions, initiating higher bolus insulin at lunch and dinner with additional enhanced GC-specific insulin supplemental scale may be needed as initial insulin doses in setting of high-dose GC.

This prospective study investigated whether integrating the Clinical Frailty Scale (CFS) with a triage system would improve triage for older adult emergency department (ED) patients. We enrolled ED patients aged 65 years or older at 5 study sites in Taiwan between December 2020 and April 2021. All eligible patients were assigned a triage level by using the Taiwan Triage and Acuity Scale (TTAS) in accordance with usual practice. A CFS score was collected from them. The primary outcome was critical events, defined as ICU admission or in-hospital mortality. The secondary outcomes were ED medical expenditures, number of orders in the ED, and length of hospital stay (LOS). We applied a reclassification concept and integrated the CFS and TTAS to create the Triage Frailty Acuity Scale (TFAS). We compared the outcomes achieved between the TTAS and TFAS. Of 1023 screened ED patients, 890 were enrolled. The majority were assigned to TTAS level 3 (73.26%) and had CFS scores of 4 to 9 (55.96%). The primary outcomes were better predicted by the TFAS than the TTAS (area under the curve [AUC] 0.82 vs. 064). Using multivariable approach, TTAS level 1 (odds ratio [OR], 4.8; 95% confidence interval [CI], 1.7–13.4) and CFS score (OR, 5.8; 95% CI, 1.9–17.2) were significantly associated with the primary outcomes. For older adults at the highest triage level, the TFAS was not associated with an increase in the primary outcomes compared with the TTAS; however, the TFAS was associated with a significant decrease in the number of older ED patients assigned to triage levels 3 to 5. In addition, TFAS had a longer average LOS but did not have a higher average number of orders or ED medical expenditures compared to TTAS. The TFAS identified more older ED patients who had been triaged as less emergent but proceeded to need ICU admission or in-hospital death. Incorporating the CFS into triage may reduce the under-triage of older adults in the ED.

Scientific literacy is considered a crucial part of learners’ basic capacities. In primary schools, scientific literacy is generally cultivated through the implementation of a natural science curriculum, in which botany is an essential course. To enhance learning effectiveness, learning activities that involve observing specific plants and carried out in outdoor learning environments have been widely adopted in instructional design. Augmented reality (AR) technology can provide views of the real-world environment simulated by a computer in connection with a target learning object. Hence, AR-based learning material was employed in this study to provide multifaceted views of plants being studied, thereby enhancing the learning experience. To validate the effectiveness of this approach, 54 third-grade students were recruited as participants in a plant observation activity that involved various learning materials. Their learning outcomes when using AR were measured according to Bloom’s cognitive levels, showing the degree of learning achievement for different stages. According to the results, students in the experimental group observing the plants through AR had significantly greater comprehension compared with those in the control group, with respect to conceptual analysis and identification of leaf arrangement. The findings suggest that compared with the traditional learning approach involving plant observation, AR-based learning material could significantly enhance students’ higher-level cognitive capabilities, enabling them to more effectively scaffold knowledge about target plants in the observational learning activity.

Infection with hepatitis C virus (HCV) does not induce protective immunity, and re-exposure to HCV can reinfect the population engaging in high-risk behavior. An increasing incidence of acute hepatitis C infection in people living with HIV (PLWH) has been described in recent years. This retrospective cohort study was conducted in PLWH who completed HCV therapy between June 2009 and June 2020 at an HIV care hospital, to analyze their basic characteristics and risky behavior. Of 2419 patients, 639 were diagnosed with HCV infection and 516 completed the HCV therapy with a sustained virologic response. In total, 59 patients (11.4%) were reinfected with acute hepatitis C, and the median time to reinfection was 85.3 weeks (IQR: 57–150). The incidence of reinfection was 6.7 cases/100 person-years. The factors associated with reinfection were being male (AHR, 8.02; 95% CI 1.08–59.49), DAA (direct-acting antiviral) treatment (AHR, 2.23; 95% CI 1.04–4.79), liver cirrhosis (AHR, 3.94; 95% CI 1.09–14.22), heroin dependency (AHR: 7.41; 95% CI 3.37–14.3), and HIV viral loads <50 copies/mL at the follow-up (AHR: 0.47, 95% CI 0.24–0.93) in the subgroup of people who inject drugs (PWID). Amphetamine abuse (AHR: 20.17; 95% CI 2.36–172.52) was the dominant factor in the subgroup of men who have sex with men (MSM). Our study suggests that education and behavioral interventions are needed in this population to prevent reinfection.