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PurposeIn National Wilms Tumor Study 5 (NWTS-5), tumor-specific combined loss of heterozygosity of chromosomes 1p and 16q (LOH1p/16q) was associated with adverse outcomes in patients with favorable histology Wilms tumor. The AREN0533/AREN0532 studies assessed whether augmenting therapy improved event-free survival (EFS) for these patients. Patients with stage I/II disease received regimen DD4A (vincristine, dactinomycin and doxorubicin) but no radiation therapy. Patients with stage III/IV disease received regimen M (vincristine, dactinomycin, and doxorubicin alternating with cyclophosphamide and etoposide) and radiation therapy.MethodsPatients were enrolled through the AREN03B2 Biology study between October 2006 and October 2013; all underwent central review of pathology, surgical reports, and imaging. Tumors were evaluated for LOH1p/16q by microsatellite testing. EFS and overall survival were compared using the log-rank test between NWTS-5 and current studies.ResultsLOH1p/16q was detected in 49 of 1,147 evaluable patients with stage I/II disease (4.27%) enrolled in AREN03B2; 32 enrolled in AREN0532. LOH1p/16q was detected in 82 of 1,364 evaluable patients with stage III/IV disease (6.01%) in AREN03B2; 51 enrolled in AREN0533. Median follow-up for 83 eligible patients enrolled in AREN0532/0533 was 5.73 years (range, 2.84 to 9.63 years). The 4-year EFS for patients with stage I/II and stage III/IV disease with LOH1p/16 was 87.3% (95% CI, 75.1% to 99.5%) and 90.2% (95% CI, 81.8% to 98.6%), respectively. These results are improved compared with the NWTS-5 updated 4-year EFS of 68.8% for patients with stage I/II disease (P = .042), and 61.3% for patients with stage III/IV disease (P = .001), with trends toward improved 4-year overall survival. The most common grade 3 or higher nonhematologic toxicities with regimen M were febrile neutropenia (39.2%) and infections (21.6%).ConclusionAugmentation of therapy improved EFS for patients with favorable histology Wilms tumor and LOH1p/16q compared with the historical NWTS-5 comparison group, with an expected toxicity profile.

The durian (genus Durio) has aroused curiosity among botanists for centuries, and influenced local culture across Southeast Asia for millennia. Of the 30 described species of Durio, about a third produce edible fruits, yet just one (Durio zibethinus) is grown on a commercial scale. Several new species have been described recently, which may be a reservoir of important genetic resources. Meanwhile, unregulated durian cultivation triggered by rapidly growing demand and a high return on investment may pose a threat to natural forests. Here we review recent findings in the genus with a focus on Malaysia and Indonesia. We suggest that further research into obscure wild relatives and local cultivars, will be important in the context of growing international demand for durian, coupled with an increasing reliance on commercial cultivars of this economically and culturally important fruit. Finally we suggest greater attention should be given to the potential threat to biodiversity posed by illegal durian plantations in one of the most biodiverse regions of the planet.

Abstract Background Predominant affective temperament may affect adherence to prescribed pharmacotherapeutic interventions, warranting systematic review and meta-analysis. Methods The Scopus, Web of Science, PubMed, and OVID MedLine databases were inquired since inception up to 31st of March 2022 for records of any study design documenting quantitative evidence about affective temperaments as measured by the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego (TEMPS-A) questionnaire and treatment adherence measured by the means of major rating scales on the matter. People with low vs. high levels of treatment adherence, matched for otherwise clinically relevant variables, were deemed as cases and controls, respectively, using standardized mean differences (SMDs) in pertinent scores under random-effects meta-analysis. Results Nine studies encompassing 1138 subjects pointed towards significantly higher cyclothymic (SMD = −0.872; CI: [−1.51 to −0.24]; p = 0.007), irritable (SMD = −0.773; CI: [−1.17 to −0.37]; p

Abstract Background The preventive and curative strategies of malaria are based on promoting the use of long-lasting insecticidal nets (LLINs) and treating confirmed cases with artemisinin-based combination therapy. These strategies have led to a sharp decline in the burden of malaria, which remains a significant public health problem in sub-Saharan countries. The objective of this study was to determine and compare the residual efficacy of LLINs recommended by the World Health Organization. Methods The study was conducted in six villages in two sites in Senegal located in the Sahelo-Sudanian area of the Thiès region, 70 km from Dakar and in Mbagame, a semi-urban zone in the Senegal River Valley. A census was conducted of all sleeping places in each household to be covered by LLINs. Five brands of LLIN were distributed, and every six months, retention rates, net use, maintenance, physical integrity, insecticide chemical content, and biological efficacy were examined for each type of LLIN. Results A total of 3012 LLINs were distributed in 1249 households in both sites, with an average coverage rate of 94% (95% CI 92.68–95.3). After 36 months, the average retention rate was 12.5% and this rate was respectively 20.5%, 15.1%, 10%, 7%, and 3% for Olyset Net®, Dawa Plus® 2.0, PermaNet® 2.0, NetProtect® and Life Net®, respectively. The proportion of LLINs with holes and the average number of holes per mosquito net increased significantly during each follow-up, with a large predominance of size 1 (small) holes for all types of LLINs distributed. During the three-year follow-up, bioassay mortality rates of a susceptible strain of insectary reared Anopheles coluzzii decreased in the following net types: in Dawa Plus® 2.0 (100% to 51.7%), PermaNet® 2.0 (96.6% to 83%), and Olyset Net® (96.6% to 33.3%). Mortality rates remained at 100% in Life Net® over the same time period. After 36 months, the average insecticide content per brand of LLIN decreased by 40.9% for Dawa Plus® 2.0, 31% for PermaNet® 2.0, 39.6% for NetProtect® and 51.9% for Olyset Net® and 40.1% for Life Net. Conclusions Although some net types retained sufficient insecticidal activity, based on all durability parameters measured, none of the net types survived longer than 2 years.

Under short-term submergence (7–15 days), submergence-tolerant rice genotypes (e.g. TDK1-Sub1) have been reported to be higher yielding than their intolerant equivalents without the Sub1 gene. This paper examined whether TDK1-Sub1 was superior to Other locally-preferred genotypes, with and without submergence, using 66 on-farm comparisons in southern Lao PDR. Data were examined for 2 genotype categories (TDK1-Sub1, Other) in 3 environment groups (Favourable, Drought, and Submergence), with 22 farms per group used as replicates. Farmers saved seeds of TDK1-Sub1, planted it again in flood-prone fields, and disseminated its seeds to relatives, neighbours and friends, but they did not do so in areas with lower flood risk. Grain yield was generally higher under Favourable conditions (2.42 ​t ​ha−1) than under Submergence (1.94 ​t ​ha−1) or Drought (1.90 ​t ​ha−1). Under Submergence, the grain yield of TDK1-Sub1 (2.22 ​t ​ha−1) was significantly higher than the Other genotype (1.65 ​t ​ha−1; P ​

Invasive fungal infections are a leading cause of death worldwide. Translating molecular insights into clinical benefits is challenging because fungal pathogens and their hosts share similar eukaryotic physiology. Consequently, current antifungal treatments have limited efficacy, may be poorly fungicidal in the host, can exhibit toxicity, and are increasingly compromised by emerging resistance. We have established that the phosphatase calcineurin (CaN) is required for invasive fungal disease and an attractive target for antifungal drug development. CaN is a druggable target, and there is vast clinical experience with the CaN inhibitors FK506 and cyclosporin A (CsA). However, while FK506 and its natural analog FK520 exhibit antifungal activity, they are also immunosuppressive in the host and thus not fungal-selective. We leverage our pathogenic fungal CaN-FK506-FKBP12 complex X-ray structures and biophysical data to support structure-based ligand design as well as structure-activity relationship analyses of broad-spectrum FK506/FK520 derivatives with potent antifungal activity and reduced immunosuppressive activity. Here, we apply molecular docking studies to develop antifungal C22-or C32-modified FK520 derivatives with improved therapeutic index scores. Among them, the C32-modified FK520 derivative JH-FK-44 (7) demonstrates a significantly improved therapeutic index compared to JH-FK-08, our lead compound to date. NMR binding studies with C32-derivatives are consistent with our hypothesis that C32 modifications disrupt the hydrogen bonding network in the human complex while introducing favorable electrostatic and cation-π interactions with the fungal FKBP12 R86 residue. These findings further reinforce calcineurin inhibition as a promising strategy for antifungal therapy. [ABSTRACT FROM AUTHOR]

Background: Our knowledge is still limited about the characteristics and treatment of rare lung tumors. The aim of our study was to determine programmed cell death ligand-1 (PD-L1) and programmed cell death-1 (PD-1) expression in rare pulmonary tumors to assess the potential role of immunotherapy.Methods: 66 pathologically confirmed rare lung tumors including 26 mucoepidermoid carcinomas (MECs), 27 adenoid cystic carcinomas (ACCs), and 13 tracheobronchial papillomas (TBPs) were collected retrospectively. Immunohistochemical (IHC) staining was performed on formalin fixed paraffin embedded (FFPE) tumor tissues, and PD-L1 expression on tumor cells (TCs) and immune cells (ICs), and PD-1 expression on ICs were determined. The cut off value for positive immunostaining was set at 1% for all markers.Results: PD-L1 expression on TCs was observed in two cases of MEC (7.7%), one case of ACC (3.7%), and was absent in TBP samples. PD-L1 expression on ICs could be demonstrated in nine cases of MEC (34.6%), four cases of ACC (14.8%), and was absent in TBPs. All PD-L1 TC positive tumors were also PD-L1 IC positive. Higher expression level than 5% of PD-L1 TC and/or IC was observed only in one ACC and in two MEC patients. Among them, strong PD-L1 immunopositivity of >50% on TCs and of >10% on ICs could be demonstrated in one MEC sample. PD-L1 expression of ≥1% on ICs was significantly more common in MEC, than in TBP (p < 0.001). In MEC ≥1% PD-L1 TC or IC expressions were significantly more common in patients aged 55 or older, than in younger patients (p = 0.046, and p = 0.01, respectively). PD-1 expression on ICs was found in five cases of MEC (19.2%), four cases of ACC (14.8%), and in two cases of TBP (15.4%). Only one MEC case showed a higher than 5% expression level of PD-1 on ICs.Conclusion: This retrospective study comprehensively demonstrated the rare expression of PD-L1 and PD-1 in pulmonary MEC, ACC, and TBP. However, we found very strong PD-L1 immunopositivity on both TCs and ICs in one MEC sample, which warrants further investigations in a larger cohort.

PurposeThe use of computed tomography (CT) for routine surveillance to detect recurrence in patients with Wilms tumor (WT) has increased in recent years. The utility of CT, despite increased risk and cost, to improve outcome for these patients is unknown. We conducted a retrospective analysis with patients enrolled in the fifth National Wilms Tumor Study (NWTS-5) to determine if surveillance with CT correlates with improved overall survival (OS) after recurrence compared with chest x-ray (CXR) and abdominal ultrasound (US).Patients and methodsOverall, 281 patients with recurrent unilateral favorable-histology WT were reviewed to assess how WT recurrence was detected: sign/symptoms (SS), surveillance imaging (SI) with CT scan, or SI with CXR/US.ResultsThe estimated 5-year OS rate after relapse was 67% (95% CI, 61% to 72%). Twenty-five percent of recurrences were detected with SS; 48.5%, with CXR/US; and 26.5%, with CT. Patients with SS had a 5-year OS rate of 59% (95% CI, 46% to 72%) compared with 70% (95% CI, 63% to 77%; P = .23) for those detected by SI. Recurrences detected by CT had a shorter median time from diagnosis to recurrence (0.60 years) compared with SS (0.91 years) or CXR/US (0.86 years; P = .003). For recurrences detected by SI, more tumor foci at relapse ( P < .001) and size of the largest focus greater than 2 cm ( P = .02) were associated with inferior OS. However, there was no difference in OS after relapse when recurrence was detected by CT versus CXR/US (5-year OS rate, 65% v 73%; P = .20).ConclusionIn patients with favorable-histology WT, elimination of CT scans from surveillance programs is unlikely to compromise survival but would result in substantial reduction in radiation exposure and health care costs.

Purpose The National Wilms Tumor Study (NWTS) treatment of favorable histology Wilms tumor with lung metastases was vincristine/dactinomycin/doxorubicin (DD4A) and lung radiation therapy (RT). The AREN0533 study applied a new risk stratification and treatment strategy to improve event-free survival (EFS) while reducing exposure to lung RT. Methods Patients with favorable histology Wilms tumor and isolated lung metastases showing complete lung nodule response (CR) after 6 weeks of DD4A continued receiving chemotherapy without lung RT. Patients with incomplete response (IR) or loss of heterozygosity at chromosomes 1p/16q received lung RT and four cycles of cyclophosphamide/etoposide in addition to DD4A drugs (Regimen M). AREN0533 was designed to preserve a 4-year EFS of 85% for lung nodule CR and improve 4-year EFS from 75% to 85% for lung nodule IR. Results Among 292 assessable patients, 133 had CR and 159 had IR. For patients with CR, 4-year EFS and overall survival (OS) estimates were 79.5% (95% CI, 71.2% to 87.8%) and 96.1% (95% CI, 92.1% to 100%), respectively. Expected versus observed event rates were 15% and 20.2% ( P = .052), respectively. For patients with IR, 4-year EFS and OS estimates were 88.5% (95% CI, 81.8% to 95.3%) and 95.4% (95% CI, 90.9% to 99.8%), respectively. Expected versus observed event rates were 25% and 12.2% ( P < .001), respectively. Overall, 4-year EFS and OS were 85.4% (95% CI, 80.5% to 90.2%) and 95.6% (95% CI, 92.8% to 98.4%) compared with 72.5% (95% CI, 66.9% to 78.1%; P < .001) and 84.0% (95% CI, 79.4% to 88.6%; P < .001), respectively, in the predecessor NWTS-5 study. Conclusion Excellent OS was achieved after omission of primary lung RT in patients with lung nodule CR, although there were more events than expected. EFS was significantly improved, with excellent OS, in patients with lung nodule IR using four cycles of cyclophosphamide/etoposide in addition to DD4A drugs. The overall AREN0533 treatment strategy yielded EFS and OS estimates that were superior to previous studies.

Thismia latiffiana Siti-Munirah & Dome, a new species from Terengganu, Peninsular Malaysia, is described and illustrated. The new species differs from all other species of Thismia, described so far, in having golden trichomes that are present on the outer surface of its floral tube and mitre, as well as pyramidal protuberances on the inner surface of the floral tube. Additionally, it is remarkable in its supraconnective apically bearing two long trichomes. Thismia latiffiana is assigned a preliminary conservation status as Critically Endangered (CR) according to IUCN Criteria.

Oncolytic virotherapy is a rapidly evolving approach that aims to selectively kill cancer cells. We designed a promising recombinant vaccinia virus, VV-GMCSF-Lact, for the treatment of solid tumors, including glioma. We assessed how VV-GMCSF-Lact affects human cells using immortalized and patient-derived glioma cultures and a non-malignant brain cell culture. Studying transcriptome changes in cells 12 h or 24 h after VV-GMCSF-Lact infection, we detected the common activation of histone genes. Additionally, genes associated with the interferon-gamma response, NF-kappa B signaling pathway, and inflammation mediated by chemokine and cytokine signaling pathways showed increased expression. By contrast, genes involved in cell cycle progression, including spindle organization, sister chromatid segregation, and the G2/M checkpoint, were downregulated following virus infection. The upregulation of genes responsible for Golgi vesicles, protein transport, and secretion correlated with reduced sensitivity to the cytotoxic effect of VV-GMCSF-Lact. Higher expression of genes encoding proteins, which participate in the maturation of pol II nuclear transcripts and mRNA splicing, was associated with an increased sensitivity to viral cytotoxicity. Genes whose expression correlates with the sensitivity of cells to the virus are important for increasing the effectiveness of cancer virotherapy. Overall, the results highlight molecular markers, biological pathways, and gene networks influencing the response of glioma cells to VV-GMCSF-Lact.

BACKGROUND: The occurrence of brain metastases (at diagnosis or at relapse) in patients with Wilms tumor is very rare. METHODS: We retrospectively reviewed the clinical characteristics of patients with Wilms tumor and relapse to the brain enrolled on the National Wilms Tumor Studies (NWTSs) 1-5. RESULTS: Intracranial relapse was documented in 47 patients (0.5%). Of the 45 patients with adequate data, 26 (58%) patients were male. Thirty-eight (84%) patients had favorable histology Wilms tumor. In 30 patients (67%), the appearance of intracranial disease was preceded by relapse at another site. Ten patients did not have any disease-directed therapy. Surgical resection was attempted in 15 patients; gross total resection was achieved in 11 patients. Twenty-nine patients received brain irradiation; the median dose was 3,000 cGy (range 1,080-4,000 cGy). Twenty-seven patients received chemotherapy. The 5-year overall survival from the time of intracranial relapse was 28.7% (95% confidence interval: 14.4-43.1%). Nine patients (all favorable histology Wilms tumor) were alive with a median follow-up from brain relapse of 140 months (range 35-381 months). All nine survivors received radiation therapy, eight received chemotherapy, and four underwent surgery (two gross total resection, two partial resection). The overall survival after brain metastases of the NWTS-5 patients was significantly higher than the overall survival of the NWTS 1-4 patients (P value = 0.029, log-rank test). CONCLUSIONS: Patients with Wilms tumor recurrence involving the brain may have durable survival, particularly those treated in recent years. Multimodality therapy including radiation and chemotherapy should be considered for these patients.

Los frutos climatéricos, como el kiwi, deben cosecharse una vez que alcanzan la madurez fisiológica, a fin de no comprometer su calidad gustativa. El propósito del presente trabajo fue determinar la instancia del desarrollo cuando los frutos del cv. 'Hayward' alcanzaron la madurez fisiológica, mediante la medición de índices de madurez objetivos. Para tal fin, un lote comercial de kiwi cv 'Hayward' situado en el sudeste de la provincia de Buenos Aires (Argentina) s e c o s e c h ó s e m a n a l m e n t e d e s d e l a s 11 semanas después de plena floración (sdpf) hasta la cosecha comercial, a las 18 sdpf. La fruta fue analizada a la cosecha y después de un período de almacenamiento (53 días a 2°C) y maduración (7 días a 20°C). A cosecha, el contenido de materia seca de la fruta, la firmeza de la pulpa y la acidez titulable del jugo no sufrieron cambios significativos a partir de las 16 sdpf. Al final del período de almacenamiento y maduración, los sólidos solubles y la acidez titulable, así como la pérdida de peso de los frutos, no variaron significativamente en frutos cosechados a partir de las 16 sdpf. Estos resultados sugieren que la madurez fisiológica se alcanzó dos semanas antes de la cosecha comercial. Con mayores exigencias protocolares de contenido de materia seca, la madurez comercial se habría logrado recién a las 18 sdpf. A madurez fisiológica, los índices de madurez registraron los siguientes valores: 5,4% sólidos solubles, 1,18% acidez titulable, 14,2% materia seca y 49% semillas negras.

We describe an extraordinary new species in the genus Thismia from the Terengganu State of Malaysia in the Malay Peninsula. The new species, which we name Thismia sitimeriamiae, is distinct from all other Thismia species known to science, most notably in its unique mitre configuration formed by the inner tepals and its floral surface morphology characterised by conspicuous orange trichomes. We discuss our findings in the context of underestimated species diversity in the genus Thismia and implications for their conservation. We recommend assigning T. sitimeriamiae the conservation status as Critically Endangered (CR) according to IUCN criteria.

Background and Objective: Currently, there is a trend towards a healthy lifestyle. Interest in specialty foods is increasing due to the desire for a balanced diet. One of the main food products of the population is bread and bakery products. These products often have an unbalanced composition. Therefore bakery products are enriched with easily digestible and bioavailable free amino acids and peptides to increase the nutritional value. This study aims to develop new types of bakery products using the mechanoenzymatic hydrolysis technology and assess their quality. Material and Methods: A distinctive feature of the study was that the production line involved mechanical pretreatment of the biomass in the presence of the enzyme. Mechanical pretreatment of pea seeds without adding the enzyme product (when the enzymes were added immediately before the hydrolysis and did not undergo mechanical treatment) reduced the hydrolysis rate almost twofold compared to that in the system “biomass + enzyme treated simultaneously.” A complex enzyme product Protosubtilin G3x exhibiting protease, xylanase, β-glucanase, and pectinase activities was used for hydrolysis of biomass. Results and Conclusion: The optimal hydrolysis parameters (enzyme concentration and duration of the process) were determined. The finished hydrolysate of the mechanically treated pea seed biomass was added to dough to enrich bakery products with macro- and micronutrients. The sponge-and-dough method was the optimal dough mixing method according to a combination of sensory and physicochemical parameters. Quality parameters of the pre-ferment depending on yeast and hydrolysis contents was assessed using mathematical modeling. Regression equations were derived to predict the formation of water-soluble substances during fermentation of the dough semi-finished product. The action of the selected enzyme was found to be efficient as the finished products were enriched in free amino acids, while the protein content was reduced. The finished products were classified as functional food products due to the optimal content of minerals and vitamins. The new products are recommended to be included in the diet of people allergic to legume proteins and healthy individuals to increase the digestibility of plant-based proteins.

Pleural mesothelioma (PM) is an aggressive malignancy that develops in a unique tumor microenvironment (TME). However, cell models for studying the TME in PM are still limited. Here, we have generated and characterized novel human telomerase reverse transcriptase (hTERT)-transduced mesothelial cell and mesothelioma-associated fibroblast (Meso-CAF) models and investigated their impact on PM cell growth. Pleural mesothelial cells and Meso-CAFs were isolated from tissue of pneumothorax and PM patients, respectively. Stable expression of hTERT was induced by retroviral transduction. Primary and hTERT-transduced cells were compared with respect to doubling times, hTERT expression and activity levels, telomere lengths, proteomes, and the impact of conditioned media (CM) on PM cell growth. All transduced derivatives exhibited elevated hTERT expression and activity, and increased mean telomere lengths. Cell morphology remained unchanged, and the proteomes were similar to the corresponding primary cells. Of note, the CM of primary and hTERT-transduced Meso-CAFs stimulated PM cell growth to the same extent, while CM derived from mesothelial cells had no stimulating effect, irrespective of hTERT expression. In conclusion, all new hTERT-transduced cell models closely resemble their primary counterparts and, hence, represent valuable tools to investigate cellular interactions within the TME of PM.

The objective of this study is to report the long‐term timing and patterns of relapse for children enrolled in Children's Oncology Group AREN0534, a multicenter phase III clinical trial conducted from 2009 to 2015. Participants included children with bilateral Wilms tumor (BWT) or unilateral WT with genetic predisposition to develop BWT followed for up to 10 years. Smoothed hazard (risk) functions for event‐free survival (EFS) were plotted so that the timing of events could be visualized, both overall and within pre‐specified groups. Two hundred and twenty‐two children (190 BWT and 32 unilateral WT with BWT predisposition) were followed for a median of 8.6 years. Fifty events were reported, of which 48 were relapse/progression. The overall 8‐year EFS was 75% (95% confidence interval: 69%–83%). The highest risk for an EFS event was immediately after diagnosis with a declining rate over 2 years. A second peak of events was observed around 4 years after diagnosis, and a small number of events were reported until the end of the follow‐up period. In subset analyses, later increases in risk were more commonly observed in patients with female sex, anaplastic histology, negative lymph nodes or margins, and favorable histology Wilms tumor patients with post‐chemotherapy intermediate risk. Among relapses that occurred after 2 years, most were to the kidney. These patterns suggest that late events may be second primary tumors occurring more commonly in females, although more investigation is required. Clinicians may consider observation of patients with BWT beyond 4 years from diagnosis. [ABSTRACT FROM AUTHOR]

Abstract Repetitive transcranial magnetic stimulation (rTMS) is an effective and well tolerable biological intervention in major depressive disorder (MDD) contributing to rapid symptom improvement. Molecular mechanisms underpinning the therapeutic effects of rTMS have still not been clarified. Recently published animal data implicated relevant associations with changes in endocannabinoid (eCB) brain levels during rTMS treatment, human studies, however, have not been published. In our study we assessed the detailed phenotypic spectrum of MDD and serum 2-arachidnoylglycerol (2-AG) and anandamide (AEA) levels in 18 patients with treatment-resistant depression before, immediately following, and two weeks after completion of a 10-day rTMS treatment. We found significant associations between serum 2-AG level changes from pretreatment to 2 weeks after treatment and symptom reduction. The greater the increase of 2-AG levels, the greater the improvement of depressive (p = 0.031), anxious (p = 0.007) and anhedonia symptoms (p = 0.047). Here we report for the first time a significant association of human circulating eCB and antidepressant effect of rTMS. Our data may indicate that direct stimulation of targeted brain areas can rapidly alleviate depressive complaints via activation of the eCB system.

Abstract Background Early metastasis is a hallmark of small cell lung cancer (SCLC). However, the mechanisms and resulting patterns of SCLC dissemination are unclear. Our aim was thus to investigate the organ specificity and timing of blood‐borne metastases in a comprehensive large cohort of SCLC patients. Methods In this retrospective non‐interventional cross‐sectional study of 1009 Caucasian SCLC patients, we investigated the correlation between the distinct locations of the primary tumor and metastatic sites. Results The onset of bone (p

Introduction Depression and suicidal behaviour are major public health problems everywhere but particularly in Hungary where until 2000 the suicide rate was among the highest in the world. Objectives To analyse the possible causes of declining national suicide rate of Hungary. Methods Review of the scientific literature on Hungarian suicide scene published in the last 40 years. Results The peak of Hungarian national suicide rate was in 1985 (46/100.000) but due to a steady and continuous, year by year decline, in 2019 it was only 16/100.000, which represents a more than 65% decrease. Rate of unrecognised/untreated mood disorders, availability of health/psychiatric care, antidepressant and lithium prescription, unemployment, smoking and alcohol consumption as well as lithium and arsenic contents of drinking water were the most investigated possible determinants of suicide mortality of the country. More widespread and effective treatment of psychiatric/mood disorder patients, decreased rate of unemployment and smoking as well as the continuously improving living standards were the most important contributors to the great decline of the national suicide rate. However, in 2020 – the first year of the COVID-19 pandemic – the national suicide rate rose by 16%, which was almost totally accounted for by the increase of suicides among males. Conclusions Suicidal behaviour is preventable in many cases, but as it is a complex, multicausal phenomenon, its prevention should involve several medical/psychiatric, psychosocial and community interventions. Disclosure No significant relationships.

Background Metastatic lung cancer is a debilitating disease, but with the advances in immunotherapy, therapeutic options have vastly increased. Numerous complete blood count parameters (CBC) have been described as easily accessible biomarkers that might predict response to immunotherapy. However, to date, no comprehensive study has been performed on the longitudinal changes of these parameters during cancer progression. Methods The clinicopathological variables and CBC parameters of 986 advanced stage lung cancer patients were retrospectively analyzed. Blood tests were performed as part of the routine checkup and the results were recorded at the time of the diagnosis of the primary tumor, the diagnosis of brain or bone metastases, and also during the last available follow‐up. Results In the experimental subcohort, 352 and 466 patients were diagnosed with brain and bone metastases, respectively. The control group consisted of 168 patients without clinically detectable or other distant organ metastases. In our longitudinal analyses, we found significantly decreasing absolute lymphocyte count (ALC: P

The Heart of Borneo (HoB) initiative facilitates conservation and environment protection while enhancing sustainable development that safeguards the welfare of natural resources and inhabitants of the island. The HoB research expeditions conducted in the Long Banga and Tama Abu were aimed to document the highland orchid species inhabited in one of the largest remaining transboundary rainforests in the world, which are racing dissolution from their habitat. Thus the resolution for their conservation in situ and ex situ could be drafted meritoriously. The research expeditions in the protected transboundary forest areas revealed a total of 206 species and 59 genera. A total of 118 species of 46 genera were recorded during the HoB Long Banga 2016 expedition, while 117 species in 46 genera were found from the HoB Tama Abu 2017 expedition. Roughly 70% of the species documented were epiphytes. A few of them were mycoheterotrophs, such as Aphyllorchis pallida, Cystorchis aphylla, and Tropidia saprophytica, and several «jewel» orchids, including Cystorchis stenoglossa and Macodes petola. Astonishingly, we discovered a number of endemic and newly recorded orchid species for Borneo. In Long Banga, the riverine forests are home to a higher number of orchids than the inland forests, owing to the presence of host trees with a spreading crown structure and moist bark texture suited epiphyte colonisation. In addition, the riverine forests are banked by a swampy alluvial vegetation that encourage the terrestrial species to grow in. Sites of the inland forests were seen disturbed with wide canopy gaps lacking of the emergent layer. Contrarily, in Tama Abu, the inland forest perceived as the more preferable habitats for orchids to thrive in as it was an undisturbed forested belt. In addition, they had a higher humidity essential for the orchid growth. It was not surprisingly, that a high abundance of orchid species was encountered in the undisturbed inland hill forest roofed with dense tree canopy cover. The hills transitioned into a montane vegetation with a lower number of species. This parameter peaked in a mossy forest, a distinct habitat harbouring endemic and rare species. In addition, ten endemic species are assessed as EN B2b(iii). Herewith, our discovery infers the need for a continuous biodiversity monitoring and conservation assessment to maintain orchid species survival and to reveal the accurate species richness within the highland habitats of Sarawak. Additionally, underlined herein is the need for establishment of an arboretum or a conservation centre for orchids to accommodate the botanical study.

Abstract Background Although increasing data supports the use of transbronchial lung cryobiopsies (TBLCs) for the diagnosis of diffuse parenchymal lung diseases (DPLDs), its role as an alternative to surgical lung biopsy (SLB) is still under debate. The aim of this study was to assess the benefit of additional SLBs performed in selected patients after TBLCs. Method We conducted a multicentric Belgian prospective trial in which SLBs were performed after TBLCs when the pathological diagnosis was uncertain or if a nonspecific interstitial pneumonia (NSIP) pattern was observed hypothesizing that SLB could provide additional information and that a co-existent UIP pattern could be missed. Results Eighty-one patients with TBLCs performed for a DPLD were included in the study between April 2015 and December 2019. A specific histological diagnosis was obtained in 52 patients (64%) whereas no pathological diagnosis following TBLCs was obtained in 13 patients (16%) and a pattern suggestive of a NSIP was observed in 16 patients (20%). Fourteen out of these 29 patients had SLBs after TBLCs. SLBs showed a UIP pattern in 11 (79%), a pattern suggestive of a hypersensitivity pneumonitis in two (14%) and a NSIP pattern in one patient (7%). Among the 16 patients with pathological NSIP following TBLCs, six underwent a SLBs showing a UIP in five and confirming a NSIP in one patient only. A retrospective pathological analysis of patients having both procedures showed a lower diagnostic confidence and agreement among pathologists for TBLCs compared to SLBs. Major factors underlying the added value of SLBs were the bigger size of the sample as well as the subpleural localization of the biopsies. Conclusions TBLCs are useful in the setting of DPLDs with a good diagnostic yield. However, our study suggests that SLB provides critical additional information in case TBLCs are inconclusive or show a pattern suggestive of a NSIP, questioning the accuracy of TBLC to adequately identify this histological pattern.