Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with gastric cancer.

The European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with gastric cancer (GC), published in late 2022 and the updated ESMO Gastric Cancer Living Guideline published in July 2023, were adapted in August 2023, according to previously established standard methodology, to produce the Pan-Asian adapted (PAGA) ESMO consensus guidelines for the management of Asian patients with GC. The adapted guidelines presented in this manuscript represent the consensus opinions reached by a panel of Asian experts in the treatment of patients with GC representing the oncological societies of China (CSCO), Indonesia (ISHMO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO), coordinated by ESMO and the Japanese Society of Medical Oncology (JSMO). The voting was based on scientific evidence and was independent of the current treatment practices, drug access restrictions and reimbursement decisions in the different Asian regions represented by the 10 oncological societies. The latter are discussed separately in the manuscript. The aim is to provide guidance for the optimisation and harmonisation of the management of patients with GC across the different regions of Asia, drawing on the evidence provided by both Western and Asian trials, whilst respecting the differences in screening practices, molecular profiling and age and stage at presentation. Attention is drawn to the disparity in the drug approvals and reimbursement strategies, between the different regions of Asia.

Cell types and structures involved in tench, Tinca tinca (L.), defence mechanisms against a systemic digenean infection.

Histopathological and ultrastructural investigations were conducted on 36 tench, Tinca tinca (L.), from Lake Trasimeno (Italy). The gills, intestine, liver, spleen, kidney and heart of 21 individuals were found to harbour an extensive infection of larvae of an unidentified digenean trematode. The eyes, gonads, swim bladder and muscles were uninfected. The parasites in each tissue type were embedded in a granulomatous proliferation of tissue, forming a reactive fibroconnective capsule around each larva. Most of the encysted larvae were metacercariae, in a degenerative state, but on occasion some cercariae were found. Many of the granulomas were either necrotic or had a calcified core. Within the granuloma of each, the occurrence of granulocytes, macrophages, rodlet cells and pigment-bearing macrophage aggregates was observed. Hearts bore the highest parasitic infection. Whilst the presence of metacercariae within the intestine was found positioned between the submucosa and muscle layers, metacercariae in the liver were commonly found encysted on its surface where the hepatocytes in close contact with the granuloma were observed to have electron-lucent vesicles within their cytoplasm. Metacercariae encysting adjacent to the cartilaginous rods of gill filaments were seen to elicit a proliferation of the cartilage from the perichondrium. Rodlet cells, neutrophils and mast cells were frequently observed in close proximity to, and within, infected gill capillaries. Given the degenerated state of most granulomas, a morphology-based identification of the enclosed digeneans was not possible.

Innate immune defence mechanisms of tench, Tinca tinca (L.), naturally infected with the tapeworm Monobothrium wageneri.

A histochemical and ultrastructural investigation of the cellular inflammatory response within the intestines of tench Tinca tinca L. naturally infected with the caryophyllidean cestode Monobothrium wageneri was conducted and the data obtained compared to those in uninfected counterparts. Cestode infections within the intestines were evident through the appearance of raised inflammatory swellings induced by the deep penetration of their scolices into the intestinal wall. Cestodes typically attached in tight clusters, inducing a massive hyperplastic granulocyte response of mast cells and neutrophils, which were significantly more numerous (P < 0·01) in the intestines of infected (n = 14) than of uninfected (n = 9) tench. Neutrophils were more abundant than mast cells (P < 0·01) in host tissues in close proximity to the parasite tegument. In transmission electron microscopy sections, mast cells and neutrophils were frequently observed in contact with or inside capillaries, and in close proximity to the cestode. Degranulation of both cell types was seen in the submucosa and lamina muscularis, notably in the immediate tissues surrounding the scolex of M. wageneri. No tegumental secretions were seen at the host-parasite interface. Occasional rodlet cells were encountered in the submucosa of infected fish.

Confirmation of the hosts involved in the life cycle of an acanthocephalan parasite of Anguilla anguilla (L.) from Lake Piediluco and its effect on the reproductive potential of its amphipod intermediate host.

A total of 37 European eels, Anguilla anguilla, collected from Lake Piediluco, Central Italy, and measuring 35 to 75.5 cm in total length (mean±1 SD, 56.41 ± 10.89 cm) were examined, and their acanthocephalan infections assessed. Thirty-two (86.49%) eels were infected with Acanthocephalus rhinensis (mean±1 SD, 67.38 ± 65.16; range, 1-350), a species that, purportedly, can be discriminated on the basis of a characteristic band of orange-brown pigmentation encircling the anterior end of the trunk. This feature, however, was not seen on any of the A. rhinensis specimens that were removed, either attached to the gut wall or free within the gut lumen, from infected eels. Approximately 40% of the eels were coinfected with the dracunculid swimbladder nematode Anguillicoloides crassus, while a single eel was also coinfected with eight specimens of a second acanthocephalan, Dentitruncus truttae. From the stomachs of two eels, 109 intact and partially digested specimens of amphipod Echinogammarus tibaldii (Pinkster & Stock 1970) were recovered, 16 (14.6%) of these were infected with one to two cystacanths of A. rhinensis per host. From a sample of 850 E. tibaldii taken from the peripheral lakeside vegetation, 102 (12%; sex ratio, 1:1) gammarids were infected with one to two A. rhinensis cystacanths. Unparasitised ovigerous female E. tibaldii specimens had significantly higher numbers of eggs in their brood pouches compared with their infected counterparts (t-test, P < 0.01).

Does Loosening the Inclusion Criteria of the CROSS Trial Impact Outcomes in the Curative-Intent Trimodality Treatment of Oesophageal and Gastroesophageal Cancer Patients?

AIM: To determine the efficacy of preoperative chemoradiotherapy as per the CROSS protocol for oesophageal/gastroesophageal junction cancer (OEGEJC), when expanded to patients outside of the inclusion/exclusion criteria defined in the original clinical trial. MATERIALS AND METHODS: Data were collected retrospectively on 229 OEGEJC patients referred for curative-intent preoperative chemoradiotherapy. Outcomes including pathological complete response (pCR), overall survival (OS), cancer-specific survival and recurrence-free survival (RFS) of patients who met CROSS inclusion criteria (MIC) versus those who failed to meet criteria (FMIC) were determined. RESULTS: In total, 42.8% of patients MIC, whereas 57.2% FMIC; 16.6% of patients did not complete definitive surgery. The MIC cohort had higher rates of pCR, when compared with the FMIC cohort (33.3% versus 20.6%, P = 0.039). The MIC cohort had a better RFS, cancer-specific survival and OS compared with the FMIC cohort (P = 0.006, P = 0.004 and P = 0.009, respectively). Age >75 years and pretreatment weight loss >10% were not associated with a poorer RFS (P = 0.541 and 0.458, respectively). Compared with stage I-III patients, stage IVa was associated with a poorer RFS (hazard ratio (HR) = 2.158; 95% confidence interval (CI) = 1.339-3.480, P = 0.001). Tumours >8 cm in length or >5 cm in width had a trend towards worse RFS (HR = 2.060; 95% CI = 0.993-4.274, P = 0.052). CONCLUSION: Our study showed that the robust requirements of the CROSS trial may limit treatment for patients with potentially curable OEGEJC and can be adapted to include patients with a good performance status who are older than 75 years or have >10% pretreatment weight loss. However, the inclusion of patients with celiac nodal metastases or tumours >8 cm in length or >5 cm in width may be associated with poor outcomes.

Depth measurements of etch-pits in GaN with shape reconstruction from SEM images.

The method, which allows shape reconstruction by reading the intensity from the scanning electron microscopy image, is presented and discussed in details. The method is applied to read the morphology of etch-pits, which were formed on the GaN surface by etching in molten KOH-NaOH eutectic mixture to delineate dislocations. The etch-pit depth distributions are obtained and used to determine densities of pits related to screw, mixed or edge-type dislocations. The results are compared with atomic force microscopy.

Intestinal inflammatory response of powan Coregonus lavaretus (Pisces) to the presence of acanthocephalan infections.

Immunopathological and ultrastructural studies were carried out on the gut of 30 specimens of powan Coregonus lavaretus (L.) from Lake Piediluco, Italy. The digestive tracts of 10 (33.3%) of the powan were found to harbour an acanthocephalan Dentitruncus truttae (Sinzar 1955). The numerous trunk spines of D. truttae reduced the number of mucosal folds near the parasite site of infection. The acanthocephalan induced hyperplasia and hypertrophy of the intestinal mucous cells and many worms were surrounded with an adherent mucous gel. Near the site of acanthocephalan attachment, the number of mucous cells was significantly higher (P<0.01) in comparison to those found in uninfected intestines. Rodlet cells (RCs) were present in the epithelial layer in both infected and uninfected fish, with no significant difference in the numbers observed (P>0.05). In infected intestine, mast cells were more abundant than in uninfected gut (P<0.01). Migration of the mast cells and their intense degranulation at the site of infection were suggested. Immunohistochemical tests applied to sections of intestinal tissue of both infected and uninfected powan revealed that the parasitized C. lavaretus had a larger number of mast cells positive for met-enkephalin and serotonin antisera.

Imaging global auroras in space.

China's initial participation in the global monitoring of auroras for scientific and space weather investigations has been enabled by the successful launch of the Chinese Fengyun-3D satellite, which carries a wide-field auroral imager.

Laboratory tumor lysis syndrome complicating LBH589 therapy in a patient with acute myeloid leukaemia.

LBH589 is a novel cinnamic hydroxamic acid analog (HAA) pan-histone deacetylase inhibitor (HDACi) currently in early phase clinical development.

Socioeconomic status influences bystander CPR and survival rates for out-of-hospital cardiac arrest victims.

OBJECTIVES: While lower socioeconomic status is associated with lower level of education and increased incidence of cardiovascular diseases, the impact of socioeconomic status on out-of-hospital cardiac arrest outcomes is unclear. We used residential property values as a proxy for socioeconomic status to determine if there was an association with: (1) bystander CPR rates and (2) survival to hospital discharge for out-of-hospital cardiac arrest. METHODS: We performed a secondary data analysis of cardiac arrest cases prospectively collected as part of the Ontario Prehospital Advanced Life Support study, conducted in 20 cities with ALS and BLS-D paramedics. We measured patient and system characteristics for cardiac arrests of cardiac origin, not witnessed by EMS, occurring in a single residential dwelling. We obtained property values from the Municipal Property Assessment Corporation. Analyses included descriptive statistics with 95% CIs and stepwise logistic regression. RESULTS: Three thousand six hundred cardiac arrest cases met our inclusion criteria between 1 January 1995 and 31 December 1999. Patient characteristics were: mean age 69.2, male 67.8%, witnessed 44.7%, bystander CPR 13.2%, VF/VT 33.8%, time to vehicle stop 5:36min:s, return of spontaneous circulation 12.7%, and survival 2.7%. Median property value was $184,000 (range $25,500-2,494,000). For each $100,000 increment in property value, the likelihood of receiving bystander CPR increased (OR=1.07; 95% CI 1.01-1.14; p=0.03) and survival decreased (OR=0.77; 95% CI 0.61-0.97; p=0.03). CONCLUSIONS: This is the largest study showing an association between socioeconomic status and survival, and the first study showing an association with bystander CPR. Our findings suggest targeting CPR training among lower socioeconomic groups.

Effect of Acanthocephala infection on the reproductive potential of crustacean intermediate hosts.

The effect of a naturally acquired infection by three acanthocephalan parasites Dentitruncus truttae, Echinorhynchus truttae, and Polymorphus minutus on the reproductive potential of their intermediate host, Echinogammarus tibaldii (Amphipoda) from Lake Piediluco (Centre of Italy) was assessed. During May 2007, 1135 amphipods were collected from two different samplings and examined for larval helminths. Forty-five amphipods were infected and of those, 16 were infected with D. truttae (intensity=1-3 larvae), 15 with E. truttae (intensity=1-2 larvae), and 14 with P. minutus (intensity=1 larva). The sex ratio was nearly 1:1 in all examined amphipods. One female infected with D. truttae contained six eggs in the brood pouch and another female infected with E. truttae contained five eggs. However, none of the eight female amphipods harbouring P. minutus larva contained eggs in their brood pouch. Uninfected females of the same size and body length as that of the infected females contained between 20 and 32 eggs. No acanthocephalan species were found to co-occur.

The inflammatory response of fish to helminth parasites.

Fish serve as a good model for studying vertebrate immune systems because they have a relatively simple system. Descriptions of histopathological effects of helminth parasites on fish are few and far between with limited observations made on the identification of the inflammatory cells involved in the host reaction. Recently, two cell types found within teleosts received a great deal of attention, namely mast cells and rodlet cells. Fish most cells also known as eosinophilic granule cells, are morphologically and functionally similar to their mammalian counterparts. Acute tissue damage causes mast cells degranulation and the release of mediators of inflammation, whereas, an increase in the number of these cells is usually found in chronically inflamed tissues. Rodlet cells, however, are exclusive to fish and are characterized by a distinct cell cortex and conspicuous inclusions, called rodlets, which accounts for their name. Piscidin has also been encountered within rodlet cells. As important cell types within the immune system of fish, both mast cells and rodlet cells have been seen to increase in number in infected fish, notably at the sites of pathogen attachment or infection. The present survey will provide data from studies with the light microscope on the response of mast cells and rodlet cells in a range of fish species (Anguilla anguilla, Oncorhynchus mykiss, Salmo trutta, Coregonus lavoretus) infected with a range of different parasite genera including representatives from the Digenea, Cestoda, Nematoda and Acanthocephala.

Frozen-in condition for ions and electrons: implication on magnetic flux transport by dipolarizing flux bundles.

The ability of dipolarizing flux bundles (DFBs) in transporting magnetic flux from the mid-tail reconnection site for near-Earth dipolarization is evaluated by two methods: the generalized Ohm's law and the concept of flux preserving and line preserving. From the generalized Ohm's law, the breakdown of the frozen-in condition (FIC) for ions is shown to be intimately related to that for electrons. When FIC is not satisfied for the ion fluid associated with energy conversion, it also implies the same for the electron fluid. When FIC holds, the plasma has the flux preserving property. It further guarantees that charged particles on a given magnetic field line will stay together on a magnetic field line at later times, i.e., line preserving. Conversely, when line preserving does not hold, flux preserving does not hold also. Previous detailed examination on the FIC for DFBs revealed that the majority of DFBs associated with energy conversion violate the FIC for the ion fluid. This implies that FIC does not hold for the electron fluid also. Furthermore, plasmas in substorm injections come from vastly different locations, violating the line preserving property and implying that FIC is broken for the magnetic flux tubes associated with substorm injection and dipolarization. These observations indicate that DFBs are not an effective agent to transport magnetic flux within the magnetosphere and further imply that mid-tail magnetic reconnection is rather ineffective in transporting magnetic flux for near-Earth dipolarization.

Plasma content of B6 vitamers and its relationship to hepatic vitamin B6 metabolism.

The plasma content of B6 vitamers is governed by, among other factors, dietary supply and metabolic interconversion. This study examines the effect of pyridoxine supplementation on the plasma content of B6 vitamers and pyridoxic acid in man, and the metabolic conversion and release of B6 compounds in isolated rat hepatocytes. Six healthy human subjects were given 100 mg pyridoxine-HCl/d orally for 1--3 wk. Before pyridoxine supplementation, the mean total plasma level of B6 vitamers was 114 +/- 9 nM; and pyridoxal-P, pyridoxamine-P, pyridoxal, pyridoxine, and pyridoxamine accounted for 54, 3, 11, 27, and 5%, respectively. Plasma level of pyridoxic acid was 40 +/- 7 nM. Thus, pyridoxal-P is the principal B6 vitamer in plasma. During pyridoxine supplementation, mean plasma levels of the B6 vitamers and pyridoxic acid increased to 655 +/- 122 and 222 +/- 55 nM, respectively. The plasma content of pyridoxal-P and pyridoxic acid increased 6--7-fold and that of pyridoxal, 12-fold, but the pyridoxine level did not increase. Isolated hepatocytes, 1 g/15 ml, were incubated for 2 h with 3.33 microM [14C]pyridoxine (6 microCi/mumol). At zero time, the cells contained about 35 nmol pyridoxal-P and 25 nmol pyridoxamine-P. After 2 h incubation, the cellular content of pyridoxal-P and pyridoxamine-P did not change significantly, but the medium contained 5.9 nmol pyridoxal-P, 0.3 nmol pyridoxamine-P, 7.2 nmol pyridoxal, 26.6 nmol pyridoxine, 0.3 nmol pyridoxamine, and 7.5 nmol pyridoxic acid. Whereas the specific radioactivity of pyridoxal-P, pyridoxal, and pyridoxic acid in the medium approached that of [14C]pyridoxine, the specific radioactivity of cellular pyridoxal-P and pyridoxamine-P was only 20% of that of pyridoxine. Thus, newly synthesized pyridoxal-P is not freely exchangeable with endogenous pyridoxal-P, but is preferentially released or degraded to pyridoxal and pyridoxic acid. The latter B6 compounds are also released. These results suggest that orally ingested pyridoxine is rapidly metabolized in liver and its products are released into the circulation in the form of pyridoxal-P, pyridoxal, and pyridoxic acid.

The effect of levamisole on cell-mediated immunity and suppressor cell function.

The immunopotentiating drug, levamisole, was found to augment human lymphocyte responses to allogeneic cells and plant mitogens in vitro. The effect was critically dose dependent and, at high doses, suppression rather than augmentation of the immune response was observed. Our hypothesis that augmentation of immune responses by the drug is due to the selective impairment of immunoregulatory suppressor activity was tested in a model using human splenic and thymic suppressor cells. Contrary to expectation, the drug was found to be capable of augmenting suppressor activity rather than abolishing it. It is concluded that levamisole is a nonspecific stimulator of lymphocyte function, irrespective of the role played by these cells in the human response.

Microwave dielectric characterisation of 3D-printed BaTiO3/ABS polymer composites.

3D printing is used extensively in product prototyping and continues to emerge as a viable option for the direct manufacture of final parts. It is known that dielectric materials with relatively high real permittivity-which are required in important technology sectors such as electronics and communications-may be 3D printed using a variety of techniques. Among these, the fused deposition of polymer composites is particularly straightforward but the range of dielectric permittivities available through commercial feedstock materials is limited. Here we report on the fabrication of a series of composites composed of various loadings of BaTiO3 microparticles in the polymer acrylonitrile butadiene styrene (ABS), which may be used with a commercial desktop 3D printer to produce printed parts containing user-defined regions with high permittivity. The microwave dielectric properties of printed parts with BaTiO3 loadings up to 70 wt% were characterised using a 15 GHz split post dielectric resonator and had real relative permittivities in the range 2.6-8.7 and loss tangents in the range 0.005-0.027. Permittivities were reproducible over the entire process, and matched those of bulk unprinted materials, to within ~1%, suggesting that the technique may be employed as a viable manufacturing process for dielectric composites.

Profound inhibition of myogenic tone in rat cardiac allografts is due to eNOS- and iNOS-based nitric oxide and an intrinsic defect in vascular smooth muscle contraction.

BACKGROUND: The physiological consequences of inducible NO synthase (iNOS) expression were studied in allograft coronary arteries by pressure myography. METHODS AND RESULTS: Septal coronary arteries (diameter, 200.6+/-3.3 microm) were harvested from allograft and isograft hearts, and their myogenic properties were measured before and after iNOS and nonselective NOS inhibition with aminoguanidine (AG, 100 micromol/L) and N(G)-nitro-L-arginine methyl ester (L-NAME) (200 micromol/L). Fura 2 fluorescence microscopy was used to measure [Ca(2+)](i) in isolated endothelial cells. Monoclonal anti-iNOS immunostains demonstrated iNOS protein in day 2, 7, 14, and 28 allograft vessels, but only in day 2 isograft vessels. Myogenic tone was profoundly inhibited in allograft vessels from day 4 onward. In day 4 allograft vessels, these differences were abolished by L-NAME but not AG, suggesting greater basal release of eNOS-based NO from allograft endothelium. Fluorescence measurements confirmed elevation of [Ca(2+)](i) in day 4 allograft endothelium, providing a mechanism for enhanced eNOS activity. For days 7 to 28, AG potentiated myogenic tone in allograft but not isograft vessels, indicating that vasoactive iNOS-based NO was present. In mature vessels, constriction via agonist- and depolarization-mediated mechanisms showed parallel inhibition, suggesting an intrinsic defect in vascular smooth muscle cell contraction. CONCLUSIONS: Our data indicate that the profound inhibition of myogenic tone in allograft arteries involves direct vasodilation by eNOS- and iNOS-based NO, as well as an intrinsic defect in vascular smooth muscle contraction. The hemodynamic profile resulting from these changes in allograft resistance vessel function would favor movement of extracellular fluid from the intravascular space into the myocardial interstitium, resulting in edema, increased ventricular stiffness, and poor ventricular performance.

The influence of pyridoxine in diabetic peripheral neuropathy.

To determine the role of pyridoxine in the treatment of diabetic peripheral neuropathy, 18 symptomatic diabetic patients were treated with vitamin B6 or placebo in a double-blind controlled study. Only one patient had a low plasma pyridoxal phosphate level at the start of the study. After 4 mo of treatment with pyridoxine hydrochloride (50 mg three times daily) 6 of 9 pyridoxine-treated and 4 of 9 placebo-treated patients noted significant relief from their neuropathic symptoms. There was no difference between the two groups with regard to fasting plasma glucose, motor nerve conduction velocity, or ophthalmologic examination at the beginning or at the conclusion of the study. Our results suggest that vitamin B6 deficiency is not a factor in the etiology of diabetic peripheral neuropathy. Furthermore, treating diabetic peripheral neuropathy with high dose vitamin B6 or placebo results in a similar frequency of symptomatic improvement.

Effect of insecticides (Dimiline WP 25, Torak EC 24 and Gamacide 20) on hydra (Hydra vulgaris Pallas).

Investigations showed that the three insecticides used had the most damaging effect upon hydra immediately after treatment. The tentacles and the hypostome are the parts most often damaged. Inse the affected cells, lesions appear in the intracellular membranes, the nucleus shell and the membranes of the mitochondria, Golgi complex and the endoplasmic reticulum, while the cell membrane is preserved. The damaged parts of the body regenerate within three days. Zymogen cells play a significant role in the course of regeneration. They dedifferentiate into gastrodermal interstitial cells and later into other types of cells of the ectoderm and the gastroderm. Apart from their intense participation in regeneration, these totipotent cells also invariably participate in the formation of new hydra buds. It was observed that Dimiline WP 25 and Torak EC 24 in the concentrations used stimulate asexual reproduction of this animal.

Mapping of multi-elements during melting and solidification using synchrotron X-rays and pixel-based spectroscopy.

A new synchrotron-based technique for elemental imaging that combines radiography and fluorescence spectroscopy has been developed and applied to study the spatial distribution of Ag, Zr and Mo in an Al alloy during heating and melting to 700, and then re-soldification. For the first time, multi-element distributions have been mapped independently and simultaneously, showing the dissolution of Ag- and Zr-rich particles during melting and the inter-dendritic segregation of Ag during re-solidification. The new technique is shown to have wide potential for metallurgical and materials science applications where the dynamics of elemental re-distribution and segregation in complex alloys is of importance.