Dataset from a proteomics analysis of tumor antigens shared between an allogenic tumor cell lysate vaccine and pancreatic tumor tissue.

The data described was acquired as part of a clinical study with the aim to investigate the potential of tumor-reactive T-cell response as response to vaccination of pancreatic cancer patients with an allogenic tumor cell lysate vaccine (Lau et al., 2022). Proteomics analysis was carried out to identify tumor antigens that are shared between the allogeneic tumor cell lysate used for the vaccine and pancreatic ductal adenocarcinoma (PDAC) tissue samples. To this objective, cell lysates of the vaccine and of nine tissue samples were enzymatically digested and isotopically labeled with tandem mass tags (TMT) in a so-called six-plex manner (Thermo Fisher Scientific). Three pools were prepared by mixing the samples according to their TMT-labels. Subsequently, the three sample pools were fractionated into 24 fractions with high-pH reversed phase chromatography. These fractions were first analyzed on a nano-liquid chromatography (LC) system online coupled to a high-resolution Eclipse Orbitrap mass spectrometer (MS) equipped with a high-field asymmetric-waveform ion-mobility spectrometry (FAIMS) source using a data-dependent MS2 shotgun method. Overall, 126,618 unique peptide sequences, on basis of 768,638 peptide spectra matches and corresponding to 7,597 protein groups, were identified in the total sample set including 61 tumor antigens (Supplement Table S2 in Lau et al. 2022) that were prioritized by Cheever and co-workers as vaccine target antigens on basis of a series of objective criteria (Cheever et al., 2009). In the second phase of the experiment, this set of tumor antigens was targeted using a serial precursor selection (SPS) MS3 method. From this data, ion trap MS2 and Orbitrap MS3 fragment spectra were extracted for peptide identification (protein sequence database-dependent search) and relative quantification using the TMT labels, respectively. The dataset ultimately allowed the identification and quantification of 51 proteins and 163 related peptide precursors with the TMT labels (see Fig. 2B and Supplemental Fig. 8, Lau et al. 2022).

Autologous dendritic cells pulsed with allogeneic tumour cell lysate induce tumour-reactive T-cell responses in patients with pancreatic cancer: A phase I study.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is notorious for its poor prognosis even after curative resection. Responses to immunotherapy are rare and related to inadequate T-cell priming. We previously demonstrated the potency of allogeneic lysate-dendritic cell (DC) vaccination in a preclinical model. Here we translate this concept to patients. METHODS: In this phase I study, patients with resected PDAC were included when they demonstrated no radiologic signs of recurrence after standard-of-care treatment. Allogeneic tumour lysate-loaded autologous monocyte-derived DCs were injected at weeks 0, 2, 4 and at months 3 and 6. Objectives are feasibility, safety and immunogenicity of allogeneic tumour-DCs. The presence of tumour antigens shared between the vaccine and patient tumours was investigated. Immunological analyses were performed on peripheral blood, skin and tumour. RESULTS: Ten patients were included. DC production and administration were successful. All patients experienced a grade 1 injection-site and infusion-related reaction. Two patients experienced a grade 2 fever and 1 patient experienced a grade 3 dyspnoea. No vaccine-related serious adverse events were observed. Shared tumour antigens were found between the vaccine and patient tumours. All evaluated patients displayed a vaccine-induced response indicated by increased frequencies of Ki67+ and activated PD-1+ circulating T-cells. In addition, treatment-induced T-cell reactivity to autologous tumour of study patients was detected. Seven out of ten patients have not experienced disease recurrence or progression at a median follow-up of 25 months (15-32 months). CONCLUSION: Allogeneic tumour lysate-DC treatment is feasible, safe and induces immune reactivity to PDAC expressed antigens.

Multi-disciplinary Psychiatric Case Management Model in Hong Kong: Service Coverage and Risk Stratification.

INTRODUCTION: Community mental health services in Hong Kong follow a multi-disciplinary case management model. We investigated whether at-risk patients received higher intensity care and whether risk stratification concorded between personalised care programmes and integrated community centres of mental wellness. METHODS: Records of all patients in North Lantau and Mongkok districts who received case management services (from personalised care programmes and/or integrated community centres of mental wellness) between 1 April 2014 and 30 June 2015 were reviewed. Patients' levels of risk, demographic data, and clinical characteristics were analysed. RESULTS: Identified at-risk patients received high-intensity care from personalised care programmes and integrated community centres of mental wellness. Case management was coordinated between the Hospital Authority and non-government organisations. However, risk stratification did not correlate with assessment rating scores of psychopathology or psychosocial functioning. Assessment rating scales appear unsuitable to provide any optimal cut-off scores for risk stratification. CONCLUSIONS: Risk stratification should be a structured clinical judgement based on comprehensive and accurate information of protective and risk factors, rather than relying on cut-off scores of assessment rating scales.

Origin of Enriched Regulatory T Cells in Patients Receiving Combined Kidney-Bone Marrow Transplantation to Induce Transplantation Tolerance.

We examined tolerance mechanisms in patients receiving HLA-mismatched combined kidney-bone marrow transplantation (CKBMT) that led to transient chimerism under a previously published nonmyeloablative conditioning regimen (Immune Tolerance Network study 036). Polychromatic flow cytometry and high-throughput sequencing of T cell receptor-ß hypervariable regions of DNA from peripheral blood regulatory T cells (Tregs) and CD4 non-Tregs revealed marked early enrichment of Tregs (CD3+ CD4+ CD25high CD127low Foxp3+ ) in blood that resulted from peripheral proliferation (Ki67+ ), possibly new thymic emigration (CD31+ ), and, in one tolerant subject, conversion from non-Tregs. Among recovering conventional T cells, central memory CD4+ and CD8+ cells predominated. A large proportion of the T cell clones detected in posttransplantation biopsy specimens by T cell receptor sequencing were detected in the peripheral blood and were not donor-reactive. Our results suggest that enrichment of Tregs by new thymic emigration and lymphopenia-driven peripheral proliferation in the early posttransplantation period may contribute to tolerance after CKBMT. Further, most conventional T cell clones detected in immunologically quiescent posttransplantation biopsy specimens appear to be circulating cells in the microvasculature rather than infiltrating T cells.

Anatomical study of the dorsal cutaneous branch of the ulnar nerve (DCBUN) and its clinical relevance in TFCC repair.

The aim of this study was to define a detailed description of the dorsal cutaneous branch of the ulnar nerve (DCBUN) in particular in relevance to triangular fibrocartilage complex (TFCC) repairs. In 20 formalin-embalmed arms, the DCBUN was dissected, and the course in each arm was mapped and categorized. Furthermore, the point of origin of the DCBUN, that is, from the ulnar nerve in association with the ulnar styloid process, was defined. Finally, the distance between the ulnar styloid process and the branching of the radial-ulnar communicating branch (RUCB) and the first branch of DCBUN was measured. The distance between the origin of the DCBUN in relation to the ulnar styloid process ranges from 55 to 111 mm (mean 87 mm; STD 14 mm). The distance between the ulnar styloid process and the RUCB ranges from 1 to 54 mm (mean 19 mm; STD 12 mm). Finally, the distance between the ulnar styloid process and the lateral distal branch shows a range of -6 to 28 mm (mean 10 mm; STD 9 mm). In general, three dorsal digital nerves (medial, intermediate, and lateral branch), run at the dorsal ulnar aspect of the hand. The RUCB is often less abundant and shows a large amount of variation. No complete safe zone could be identified; the course of the DCBUN suggests a longitudinal incision for the 6R portal. In fact, a more dorsal incision also prevents damage to the main branches of the DCBUN.

Macrochimerism in Intestinal Transplantation: Association With Lower Rejection Rates and Multivisceral Transplants, Without GVHD.

Blood chimerism has been reported sporadically among visceral transplant recipients, mostly in association with graft-vs-host disease (GVHD). We hypothesized that a higher degree of mixed chimerism would be observed in multivisceral (MVTx) than in isolated intestinal (iITx) and isolated liver transplant (iLTx) recipients, regardless of GVHD. We performed a longitudinal prospective study investigating multilineage blood chimerism with flow cytometry in 5 iITx and 4 MVTx recipients up to one year posttransplant. Although only one iITx patient experienced GVHD, T cell mixed chimerism was detected in 8 out of 9 iITx/MVTx recipients. Chimerism was significantly lower in the four subjects who displayed early moderate to severe rejection. Pre-formed high-titer donor-specific antibodies, bound in vivo to the circulating donor cells, were associated with an accelerated decline in chimerism. Blood chimerism was also studied in 10 iLTx controls. Among nonsensitized patients, MVTx recipients exhibited greater T and B cell chimerism than either iITx or iLTx recipients. Myeloid lineage chimerism was present exclusively among iLTx and MVTx (6/13) recipients, suggesting that its presence required the hepatic allograft. Our study demonstrates, for the first time, frequent T cell chimerism without GVHD following visceral transplantation and a possible relationship with reduced rejection rate in MVTx recipients.

Flexographic printing-assisted fabrication of ZnO nanowire devices.

In this study, the use of flexographic printing was investigated for low cost, high volume production of devices incorporating nanowires through the printing of zinc acetate precursors on a substrate used to form zinc oxide (ZnO) seeds for the growth of nanowires using a hydrothermal growth technique. The printing of precursors allows the selective area growth of ZnO nanowires, which has implications in high-yield production of devices incorporating ZnO nanowires. The work presented here achieved printed line widths of <60 µm with low edge distortion (<3 µm) using a printing plate with a line width of 50 µm. The hydrothermally grown ZnO nanowires show uniform density of growth over the printed area with nanowire diameters between 40 and 60 nm on both silicon and polyimide substrates. Energy-dispersive x-ray spectra showed contamination-free crystals with a 1:1 (zinc to oxygen) stoichiometry. Crystal orientation is along the c-axis with high quality crystalline structure shown using x-ray diffraction spectroscopy and high resolution transmission electron microscopy. A ZnO nanowire gas sensor, fabricated using the flexographic printing technique, is demonstrated. Such a printing-assisted fabrication offers low cost, high volume production of devices incorporating ZnO nanowires, ranging from gas sensors to field emission devices.

Ultraviolet electroluminescence from randomly assembled n-SnO(2) nanowiresp-GaN:Mg heterojunction.

Electroluminescence characteristics of a heterojunction light-emitting diode, which was fabricated by depositing a layer of randomly assembled n-SnO(2) nanowires on p-GaN:Mg/sapphire substrate via vapor transport method, were investigated at room temperature. Peak wavelength emission at around 388 nm was observed for the diode under forward bias. This is mainly related to the radiative recombination of weakly bounded excitons at the shallow-trapped states of SnO(2) nanowires, Under reverse bias, near bandedge emission from the p-GaN:Mg/sapphire leads to the observation of emission peak at around 370 nm.

Surface plasmonic lasing via the amplification of coupled surface plasmon waves inside dielectric-metal-dielectric waveguides.

Coupling of surface plasmon (SP) waves between two metal-dielectric interfaces of a dielectric-metal-dielectric (DMD) waveguide, in which one of the dielectric layers is incorporated with optical gain, is proposed to realize plasmonic lasing. The propagation characteristics of the SP waves supported inside the DMD waveguides are studied by finite-difference time-domain method. It is found that there are optimized thicknesses for the metal film and gain region to obtain minimum propagation loss. Furthermore, a coupled-mode model is developed to analyze the lasing characteristics of the DMD waveguides with coherent optical feedback. The conditions to achieve single-longitudinal-mode lasing from the DMD waveguides are also investigated.

Near-field focusing properties of zone plates in visible regime--new insights.

Near-field focusing properties of zone plates are investigated in the visible regime by a 3-dimensional finite-difference time-domain method. It is shown that Frensel zone plates (FZPs) with metallic coatings can achieve subwavelength focusing in the visible wavelength. The characteristics of subwavelength focusing are found to be independent of the type of metal coatings used. All the FZPs exhibit similar shift in focal length and depth of focus when compared with classical calculations. These results indicate that plasmonic waves do not contribute to subwavelength focusing. Instead the subwavelength focusing characteristic is attributed to the interference of diffracted evanescent waves from a large numerical aperture. It is found that the near-field focusing of FZPs suppresses higher order foci such that the corresponding diffraction efficiency is improved. The use of phase zone plate structured on glass without opaque coating is proposed to improve the diffraction efficiency of subwavelength focusing.

Local measurement of secondary electron emission from ZnO-coated carbon nanotubes.

The secondary electron emission (SEE) of ZnO-coated carbon nanotubes (CNTs) was measured using a biasing technique in a scanning electron microscope. The SEE yield of the ZnO-coated CNTs is higher than that of the ZnO film deposited on Si substrates. Direct observation of the variation in SEE from tip-end and non-CNT positions was demonstrated. Local measurement reveals that the SEE yield at the tip-end of the ZnO-coated CNTs is much higher than that of non-CNT positions. The enhancement of SEE is attributed to the strong local field generated at the tip of the CNTs.

Stable superhydrophobic surface via carbon nanotubes coated with a ZnO thin film.

We report the formation of a stable superhydrophobic surface via aligned carbon nanotubes (CNTs) coated with a zinc oxide (ZnO) thin film. The CNT template was synthesized by chemical vapor deposition on an Fe-N catalyst layer. The ZnO film, with a low surface energy, was deposited on the CNT template by the filtered cathodic vacuum arc technique. Contact angle measurement reveals that the surface of the ZnO-coated CNTs is superhydrophobic with water contact angle of 159 degrees . Unlike the uncoated CNTs surface, the ZnO-coated CNTs surface shows no sign of water seepage even after a prolonged period of time. The wettability of the surface can be reversibly changed from superhydrophobicity to hydrophilicity by alternation of ultraviolet (UV) irradiation and dark storage.

Differentiation between extrahepatic and intrahepatic cholestasis by discriminant analysis.

Discriminant analysis was used to differentiate between extrahepatic biliary atresia and intrahepatic cholestasis. Among the ten laboratory variables tested, three (gamma-glutamyl transpeptidase, alkaline phosphatase and total serum bilirubin) were useful in the differential diagnosis. gamma-Glutamyl transpeptidase contributed most to the discrimination (85%). From a population study of 28 babies with extrahepatic biliary atresia and 24 infants with intrahepatic cholestasis, the procedure achieved a diagnostic accuracy and specificity of 92.9% and an efficiency of 92.3%. The jackknife procedure has also confirmed that the mathematical model was robust for discriminant analysis and therefore it may be valid for screening infants with cholestasis for early surgical intervention. Discriminant analysis is a useful adjunct for differentiation between intrahepatic cholestasis and extrahepatic biliary atresia.

Effects of overweight on lung function.

Spirometric data from 1586 healthy children, who did not smoke, were analysed to examine the effects of overweight as measured by the body mass index (weight/height2) on lung function. Overweight (72 boys, 88 girls) was defined as on or above the 90th percentile weight for height. After having controlled for the confounding variables of height and age, there were positive partial correlations between body mass index and lung function in girls whose weight was normal, in overweight girls, and in boys whose weight was normal, but not in overweight boys. In contrast to adults, body mass index has a positive effect on lung function in girls, whatever their weight. No such correlation between body mass index and lung function was seen in overweight boys. The observations may be accounted for by distinct sex dependent patterns of fat distribution in children.

Properties and clinical implications of body mass indices.

The properties of body mass indices were evaluated in a cross sectional study of the weights and heights of 5016 Chinese boys and girls aged between 3 and 18 years. Of the indices examined (weight/height (W/H), weight/height2 (W/H2), weight/height3 (W/H3) and weight/heightp (W/Hp], W/Hp was the only one that consistently showed least correlation with height, and so could be regarded as the optimal body mass index by the criterion of independence of the index from height. The exponent 'p' of W/Hp is, however, highly dependent on age; the value increases steadily between the age of 3 and 7-9 years, and then varies considerably around puberty. Only the age specific exponent ensures a lack of correlation between body mass index (W/Hp) and height. Age specific W/Hp should therefore be used in intrapopulation studies of weight or problems associated with obesity in children. Interpopulation comparison of weight and adiposity by W/H, W/H2, or W/H3 may give misleading results because of their dependence on height. Our results also suggest that the conventional weight for height charts may not be accurate enough for clinical use.

Ethnic determinants of perinatal statistics of Chinese: demography of China, Hong Kong and Singapore.

Despite limited health resources, the Chinese have achieved reasonably good perinatal and neonatal mortality rates comparable to those of many developed countries. China, Hong Kong and Singapore, areas with different socioeconomic structures, have shared the same favourable ethnic determinants of perinatal mortality. The Chinese have much lower incidence of very low birthweight babies (less than 1000 g) and lethal congenital anomalies. The former is probably related to the rarity of teenage pregnancy, maternal smoking and alcohol consumption. Asphyxia remains a major contributor to perinatal deaths. The perinatal mortality rate in mainland China has remained relatively unchanged in contrast to the dramatic falling trend in Hong Kong and Singapore in the past two decades. This may be accounted for by differences in socioeconomic conditions despite their identical ethnic origin. Studying the Chinese sociocultural pattern may have a great impact on perinatal mortality by preventing low birthweight babies.

A new method of expired gas collection for the measurement of breath hydrogen (H2) in infants and small children.

The measurement of hydrogen (H2) in breath is becoming increasingly useful as a diagnostic and research tool, but there is still no satisfactory method of sampling expired air in infants and small children. We tested a modified open-flow hood method where the child's head is put in a perspex box and expired air is collected by sucking air from the box by means of an air pump. Comparison of this method with end-expiratory sampling by a modified Haldane-Priestly and nasopharyngeal catheter gave a correlation coefficient of 0.83 and 0.65, respectively. We conclude that expired air sampling in children with this method is a more satisfactory and as reliable a method as any available at present, and has the added advantage of being quantitative.

Cortical blindness in toxaemia of pregnancy: findings on computed tomography.

Two patients with toxaemia of pregnancy presented with cortical blindness. Immediate cranial computed tomography (CT) demonstrated bilateral hypodense areas in the occipital lobes. Both patients underwent Caesarean section for delivery. There was gradual and complete recovery of vision, together with CT documentation of resolution of the cerebral changes, indicative of the reversible nature of the ischaemic lesion.