Dual-targeting anti-angiogenic cyclic peptides as potential drug leads for cancer therapy

Peptide analogues derived from bioactive hormones such as somatostatin or certain growth factors have great potential as angiogenesis inhibitors for cancer applications. In an attempt to combat emerging drug resistance many FDA-approved anti-angiogenesis therapies are co-administered with cytotoxic drugs as a combination therapy to target multiple signaling pathways of cancers. However, cancer therapies often encounter limiting factors such as high toxicities and side effects. Here, we combined two anti-angiogenic epitopes that act on different pathways of angiogenesis into a single non-toxic cyclic peptide framework, namely MCoTI-II (Momordica cochinchinensis trypsin inhibitor-II), and subsequently assessed the anti-angiogenic activity of the novel compound. We hypothesized that the combination of these two epitopes would elicit a synergistic effect by targeting different angiogenesis pathways and result in improved potency, compared to that of a single epitope. This novel approach has resulted in the development of a potent, non-toxic, stable and cyclic analogue with nanomolar potency inhibition in in vitro endothelial cell migration and in vivo chorioallantoic membrane angiogenesis assays. This is the first report to use the MCoTI-II framework to develop a 2-in-1 anti-angiogenic peptide, which has the potential to be used as a form of combination therapy for targeting a wide range of cancers

A Note on Optimal Portfolio Selection and Diversification Benefits with a Short Sale Restriction on Real Estate Assets

This paper develops an optimal portfolio selection technique when short sales on real estate assets are restricted. Using the well-known mean-variance efficient concept, we are able to derive the optimal weights for portfolios consisting of both financial assets and real estate assets. Our paper provides a simple but powerful tool for portfolio managers to correctly construct mean-variance portfolios under short sale constraints.

Discovery, isolation and structural characterization of cyclotides from Viola sumatrana miq

Cyclotides are cyclic peptides from plants in the Violaceae, Rubiaceae, Fabaceae, Cucurbitaceae, and Solanaceae families. They are sparsely distributed in most of these families, but appear to be ubiquitous in the Violaceae, having been found in every plant so far screened from this family. However, not all geographic regions have been examined and here we report the discovery of cyclotides from a Viola species from South-East Asia. Two novel cyclotides (Visu 1 and Visu 2) and two known cyclotides (kalata S and kalata B1) were identified in V. sumatrana. NMR studies revealed that kalata S and kalata B1 had similar secondary structures. Their biological activities were determined in cytotoxicity assays; both had similar cytotoxic activity and were more toxic to U87 cells compared with other cell lines. Overall, the study strongly supports the ubiquity of cyclotides in the Violaceae and adds to our understanding of their distribution and cytotoxic activity

Elevated Perioperative Transaminase Level Predicts Intrahepatic Recurrence in Hepatitis B-related Hepatocellular Carcinoma After Curative Hepatectomy

OBJECTIVEWe aimed to evaluate the role of elevated perioperative alanine aminotransferase (ALT) as a surrogate marker of hepatitis activity in determining the risk of recurrence and survival in hepatitis B-related hepatocellular carcinoma (HCC) after curative hepatectomy.METHODSA retrospective review of the hepatectomy database was performed and 142 patients were found who had hepatitis B-related HCC from January 2001 to March 2006. Their ALT levels preoperatively and 1 month, 3 months, and 6 months postoperatively were recorded. The risk factors for recurrence and prognostic factors of survival were analysed.RESULTSAn elevated perioperative ALT level (p = 0.021), multiple tumour nodules in the resected specimen (p < 0.001), and a tumour size greater than 5 cm (p = 0.001) were significant independent risk factors for tumour recurrence. The latter two factors were also independent prognostic factors for overall survival and disease-free survival. An elevated ALT level was an independent prognostic factor for disease-free survival (p = 0.025).CONCLUSIONAn elevated perioperative ALT level, which reflects increased hepatitis activity, is an independent risk factor for intrahepatic recurrence of hepatitis B-related HCC. It is also associated with a poorer disease-free survival rate

COVID-19 Vaccination Preferences of University Students and Staff in Hong Kong

IMPORTANCE: COVID-19 has required universities to rapidly develop vaccination policies for students and staff, yet little is known about the preferences of these individuals toward vaccination. OBJECTIVE: To quantify student and staff preferences for COVID-19 vaccination at a university in Hong Kong. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional online survey study was conducted from July 20 to September 21, 2021, before the announcement of a campus-wide vaccine mandate. A survey of 42 451 eligible university students and staff used discrete-choice experiment methods to quantify 7 attributes of COVID-19 vaccination: risk of a mild or moderate adverse event after vaccination, risk of a severe adverse event after vaccination, efficacy against COVID-19 infection, efficacy against severe manifestation of COVID-19 infection, duration of protection after vaccination, incentive for completing vaccination, and out-of-pocket costs. MAIN OUTCOMES AND MEASURES: A mixed logit regression model was used to estimate the preferences of attributes for COVID-19 vaccines and marginal willingness to pay (mWTP) adjusted for background characteristics, role, vaccination, and COVID-19 infection status of family or friends, adverse event status after vaccination among family and friends of participants, and scenario block. RESULTS: Among 42 451 eligible university students and staff invited, 3423 individuals completed the survey (mean [SD] age, 27.1 [9.9] years; 2053 [60.0%] women). Participants included 2506 students (73.2%) and 917 staff (26.8%), with a response rate of 8.1%. Quarantine-free travel was preferred (β = 0.86; 95% CI, 0.72-0.99; mWTP: $235.9; 95$190.3-$294.2), followed by efficacy against any COVID-19 infection (β = 0.30; 95$84.1; 95% CI, $71.8-$100.8), against severe manifestation of COVID-19 infection (β = 0.25; 95% CI, 0.24-0.27; mWTP: $69.7; 95$465-$653), and risk of severe adverse events following vaccination (β = −0.24; 95$66.8; 95% CI, −$81.5 to −$55.3). Participants were less concerned about protection duration (β = 0.17; 95% CI, 0.15-0.18; mWTP: $46.0; 95$38.6-$56.2) and risk of mild to moderate adverse events (β = −0.12; 95$32.7; 95% CI, −$41.2 to −$26.4). CONCLUSIONS AND RELEVANCE: Preference of all attributes were significant and were considered important by the participants for vaccine decision-making. Insights drawn could assist policy makers in future vaccination decisions, such as campus vaccine mandate and requirement of a third dose

Wideband Endfire Antenna Array for 5G mmWave Mobile Terminals

In this paper, a compact endfire antenna array with low-profile, small clearance, and wideband operation is proposed for millimeter-wave (mmWave) fifth-generation (5G) mobile terminals. The wideband operation is achieved by exciting two identical bow-tie dipoles inserted on both sides of a multilayer substrate fed by an asymmetric open-end stripline to slotline transition. The antenna performance is significantly improved by introducing a set of vertical metallic vias. The proposed antenna element can achieve 29 % from 24.2 GHz to 32.4 GHz with a peak realized gain that varies from 3.5 dBi to 4.5 dBi. A linear 4-element antenna array is arranged and fabricated to verify the proposed antenna beamforming capabilities. The simulated and measured bandwidth achieves a wide range of 34.4 % (24-34 GHz) to support 26, 28, and 30 GHz 5G mmWave bands with an isolation level better than 20 dB and a peak realized gain over the interested bands ranging from 7.56 to 8.14 dBi. The simulated array scanning angle is ± 68 • at 28 GHz within 3-dB gain deterioration. Furthermore, the simulated spherical coverage has met the requirements of 3GPP standards which make the proposed antenna array a promising candidate to be integrated within mmWave 5G mobile devices. INDEX TERMS 5G, antenna array, beamforming, endfire, mmWave bands, mobile terminal, wideband

Safety of BNT162b2 or CoronaVac COVID-19 vaccines in patients with heart failure: A self-controlled case series study

BACKGROUND: COVID-19 vaccines are important for patients with heart failure (HF) to prevent severe outcomes but the safety concerns could lead to vaccine hesitancy. This study aimed to investigate the safety of two COVID-19 vaccines, BNT162b2 and CoronaVac, in patients with HF. METHODS: We conducted a self-controlled case series analysis using the data from the Hong Kong Hospital Authority and the Department of Health. The primary outcome was hospitalization for HF and the secondary outcomes were major adverse cardiovascular events (MACE) and all hospitalization. We identified patients with a history of HF before February 23, 2021 and developed the outcome event between February 23, 2021 and March 31, 2022 in Hong Kong. Incidence rate ratios (IRR) were estimated using conditional Poisson regression to evaluate the risks following the first three doses of BNT162b2 or CoronaVac. FINDINGS: We identified 32,490 patients with HF, of which 3035 were vaccinated and had a hospitalization for HF during the observation period (BNT162b2 = 755; CoronaVac = 2280). There were no increased risks during the 0–13 days (IRR 0.64 [95% confidence interval 0.33–1.26]; 0.94 [0.50–1.78]; 0.82 [0.17–3.98]) and 14–27 days (0.73 [0.35–1.52]; 0.95 [0.49–1.84]; 0.60 [0.06–5.76]) after the first, second and third doses of BNT162b2. No increased risks were observed for CoronaVac during the 0–13 days (IRR 0.60 [0.41–0.88]; 0.71 [0.45–1.12]; 1.64 [0.40–6.77]) and 14–27 days (0.91 [0.63–1.32]; 0.79 [0.46–1.35]; 1.71 [0.44–6.62]) after the first, second and third doses. We also found no increased risk of MACE or all hospitalization after vaccination. INTERPRETATION: Our results showed no increased risk of hospitalization for HF, MACE or all hospitalization after receiving BNT162b2 or CoronaVac vaccines in patients with HF. FUNDING: The project was funded by a Research Grant from the Food and Health Bureau, The Government of the Hong Kong Special Administrative Region (Ref. No. COVID19F01). F.T.T.L. (Francisco T.T. Lai) and I.C.K.W. (Ian C.K. Wong)'s posts were partly funded by the D24H; hence this work was partly supported by AIR@InnoHK administered by Innovation and Technology Commission

Wideband Endfire Antenna Array for 5G mmWave Mobile Terminals

In this paper, a compact endfire antenna array with low-profile, small clearance, and wideband operation is proposed for millimeter-wave (mmWave) fifth-generation (5G) mobile terminals. The wideband operation is achieved by exciting two identical bow-tie dipoles inserted on both sides of a multilayer substrate fed by an asymmetric open-end stripline to slotline transition. The antenna performance is significantly improved by introducing a set of vertical metallic vias. The proposed antenna element can achieve 29 % from 24.2 GHz to 32.4 GHz with a peak realized gain that varies from 3.5 dBi to 4.5 dBi. A linear 4-element antenna array is arranged and fabricated to verify the proposed antenna beamforming capabilities. The simulated and measured bandwidth achieves a wide range of 34.4 % (24-34 GHz) to support 26, 28, and 30 GHz 5G mmWave bands with an isolation level better than 20 dB and a peak realized gain over the interested bands ranging from 7.56 to 8.14 dBi. The simulated array scanning angle is ±68° at 28 GHz within 3-dB gain deterioration. Furthermore, the simulated spherical coverage has met the requirements of 3GPP standards which make the proposed antenna array a promising candidate to be integrated within mmWave 5G mobile devices

The psychophysiological effects of Tai-chi and exercise in residential Schizophrenic patients: a 3-arm randomized controlled trial

BACKGROUND: Patients with schizophrenia are characterized by high prevalence rates and chronicity that often leads to long-term institutionalization. Under the traditional medical model, treatment usually emphasizes the management of psychotic symptoms through medication, even though anti-psychotic drugs are associated with severe side effects, which can diminish patients’ physical and psychological well-being. Tai-chi, a mind-body exercise rooted in Eastern health philosophy, emphasizes the motor coordination and relaxation. With these potential benefits, a randomized controlled trial (RCT) is planned to investigate the effects of Tai-chi intervention on the cognitive and motor deficits characteristic of patients with schizophrenia. METHODS/DESIGN: A 3-arm RCT with waitlist control design will be used in this study. One hundred and fifty three participants will be randomized into (i) Tai-chi, (ii) exercise or (iii) waitlist control groups. Participants in both the Tai-chi and exercise groups will receive 12-weeks of specific intervention, in addition to the standard medication and care received by the waitlist control group. The exercise group will serve as a comparison, to delineate any unique benefits of Tai-chi that are independent of moderate aerobic exercise. All three groups will undergo three assessment phases: (i) at baseline, (ii) at 12 weeks (post-intervention), and (iii) at 24 weeks (maintenance). All participants will be assessed in terms of symptom management, motor coordination, memory, daily living function, and stress levels based on self-perceived responses and a physiological marker. DISCUSSION: Based on a promising pilot study conducted prior to this RCT, subjects in the Tai-chi intervention group are expected to be protected against deterioration of motor coordination and interpersonal functioning. They are also expected to have better symptoms management and lower stress level than the other treatment groups. TRIAL REGISTRATION: The trail has been registered in the Clinical Trials Center of the University of Hong Kong (HKCTR-1453)

Investment Case for a Comprehensive Package of Interventions Against Hepatitis B in China: Applied Modeling to Help National Strategy Planning.

BACKGROUND content: In 2016, the first global viral hepatitis elimination targets were endorsed. An estimated one-third of the world's population of individuals with chronic hepatitis B virus (HBV) infection live in China and liver cancer is the sixth leading cause of mortality, but coverage of first-line antiviral treatment was low. In 2015, China was one of the first countries to initiate a consultative process for a renewed approach to viral hepatitis. We present the investment case for the scale-up of a comprehensive package of HBV interventions. METHODS content: A dynamic simulation model of HBV was developed and used to simulate the Chinese HBV epidemic. We evaluated the impact, costs, and return on investment of a comprehensive package of prevention and treatment interventions from a societal perspective, incorporating costs of management of end-stage liver disease and lost productivity costs. RESULTS content: Despite the successes of historical vaccination scale-up since 1992, there will be a projected 60 million people still living with HBV in 2030 and 10 million HBV-related deaths, including 5.7 million HBV-related cancer deaths between 2015 and 2030. This could be reduced by 2.1 million by highly active case-finding and optimal antiviral treatment regimens. The package of interventions is likely to have a positive return on investment to society of US$1.57 per US dollar invested. CONCLUSIONS content: Increases in HBV-related deaths for the next few decades pose a major public health threat in China. Active case-finding and access to optimal antiviral treatment are required to mitigate this risk. This investment case approach provides a real-world example of how applied modeling can support national dialog and inform policy planning