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Summary: Steroids are a mainstay in the treatment of acute lymphoblastic leukaemia (ALL) in children and adolescents; however, their use can cause clinically significant steroid‐related neuropsychiatric symptoms (SRNS). As current knowledge on SRNS during ALL treatment is limited, we mapped the phenotypes, occurrence and treatment strategies using a database created by the international Ponte di Legno Neurotoxicity Working Group including data on toxicity in the central nervous system (CNS) in patients treated with frontline ALL protocols between 2000 and 2017. Ninety‐four of 1813 patients in the CNS toxicity database (5.2%) experienced clinically significant SRNS with two peaks: one during induction and one during intensification phase. Dexamethasone was implicated in 86% of SRNS episodes. The most common symptoms were psychosis (52%), agitation (44%) and aggression (31%). Pharmacological treatment, mainly antipsychotics and benzodiazepines, was given to 87% of patients while 38% were hospitalised due to their symptoms. Recurrence of symptoms was reported in 29% of patients and two previously healthy patients required ongoing pharmacological treatment at the last follow up. Awareness of SRNS during ALL treatment and recommendation on treatment strategies merit further studies and consensus. [ABSTRACT FROM AUTHOR]

The article in the British Journal of Haematology discusses a case study of a 79-year-old man with myelodysplastic syndrome (MDS) and a 5q deletion who was effectively treated with luspatercept after failing to respond to other treatments. The patient showed significant improvements in blood counts and bone marrow characteristics after luspatercept treatment, even after discontinuation. The study highlights the potential mechanisms of action of luspatercept beyond late-stage erythropoiesis enhancement, suggesting broader effects on hematopoiesis and inflammation. The findings suggest a need for further research on the complex actions of luspatercept in MDS patients with specific genetic abnormalities. [Extracted from the article]

This article presents a study on the use of an optimized oligonucleotide library to identify virus-specific T-cell receptors (TCRs) using Epstein-Barr virus (EBV) as an example. The researchers used HEK293T cells and human T cells to study T-cell activation. They constructed an oligonucleotide library covering the entire EBV proteome and optimized the length of the library oligonucleotides for T-cell activation. The study found that minigenes with a length of 50 amino acids resulted in the strongest T-cell activation, and cell surface CD137 staining was the most effective method for detecting T-cell activation. This methodology provides a systematic approach for studying T-cell immunology in various conditions. [Extracted from the article]

In this article we propose and study one‐ and two‐sided control charts for monitoring a first order binomial integer‐valued ARCH process. This model can be used for modeling integer‐valued time series of counts with a finite support, which also exhibit overdispersion. We consider Shewhart as well as exponentially weighted moving average control charts. The performance of both schemes is investigated for various shifts in process parameters, which result in an upward or a downward shift in process mean level. Practical guidelines concerning the statistical design of the proposed charts are given as well. The case of two‐sided control charts is also considered. Finally, we describe the implementation of the proposed schemes by using a real dataset about the monthly inflation of the Eurozone members. [ABSTRACT FROM AUTHOR]

The related literature highlighted the impact of COVID‐19 on agri‐food entrepreneurship, the government measures and support on agri‐food entrepreneurship, and the shift of agri‐food entrepreneurship towards digitization, innovative ideas, and new market solutions. Agri‐food entrepreneurship faces numerous challenges, but at the same time, the crisis can generate opportunities. The studies made so far indicate that COVID‐19 can cause transformational changes to agri‐food entrepreneurship, although further research is needed to clarify open issues. [ABSTRACT FROM AUTHOR]

The importance of ammonia in the fertilizer industry has been widely acknowledged over the past decades. In view of the upcoming increase of world population and, in turn, food demand, its production rate is likely to increase exponentially. However, considering the high dependence on natural resources and the intensive emission profile of the contemporary ammonia synthesis route, as well as the rigid environmental laws being enforced at a global level, the need to develop a sustainable alternative production route becomes quite imperative. A novel approach toward the synthesis of ammonia has been realized by means of non‐thermal plasma technology under ambient operating conditions. Because the given technology is still under development, carrying out a life cycle assessment (LCA) is highly recommended as a means of identifying areas of the chemical process that could be potentially improved for an enhanced environmental performance. For that purpose, in the given research study, a process design for a small‐scale plasma‐assisted ammonia plant is being proposed and evaluated environmentally for specific design scenarios against the conventional ammonia synthesis employing steam reforming and water electrolysis for hydrogen generation. On the basis of the LCA results, the most contributory factor to the majority of the examined life cycle impact categories for the plasma‐assisted process, considering an energy efficiency of 1.9 g NH3/kWh, is the impact of the power consumption of the plasma reactor with its share ranging from 15% to 73%. On a comparative basis, the plasma process powered by hydropower has demonstrated a better overall environmental profile over the two benchmark cases for the scenarios of a 5% and 15% NH3 yield and an energy recovery of 5% applicable to all examined plasma power consumption values. [ABSTRACT FROM AUTHOR]

Summary: Background: Invasive mould infections (IMIs) are very rare in patients with lymphoid malignancies. However, IMIs, mostly due to Aspergillus species, have been increasingly reported in such patients receiving ibrutinib (IBR). There is paucity of information regarding non‐Aspergillus invasive mould infections (NAIMIs) in this setting, Objectives: To review our recent experience and the published literature on the topic. Patients/Methods: We present a case of invasive sinusitis caused by Fusarium in a patient with refractory chronic lymphocytic leukaemia (CLL) who was treated with IBR and review the 12 published cases of NAIMIs during IBR. Results: Nearly all cases of NAIMIs in the setting of IBR use were encountered in patients with CLL. Mixed fungal infections, brain involvement and late‐onset infections were common. Conclusions: Although rare, NAIMIs should be considered in patients who receive IBR. [ABSTRACT FROM AUTHOR]

Perfusion and oxygenation are critical parameters of muscle metabolism in health and disease. They have been both the target of many studies, in particular using near‐infrared spectroscopy (NIRS). However, difficulties with quantifying NIRS signals have limited a wide dissemination of the method to the clinics. Our aim was to investigate whether clinical multispectral optoacoustic tomography (MSOT) could enable the label‐free imaging of muscle perfusion and oxygenation under clinically relevant challenges: the arterial and venous occlusion. We employed a hybrid clinical MSOT/ultrasound system equipped with a hand‐held scanning probe to visualize hemodynamic and oxygenation changes in skeletal muscle under arterial and venous occlusions. Four (N = 4) healthy volunteers were scanned over the forearm for both 3‐minute occlusion challenges. MSOT‐recorded pathophysiologically expected results during tests of disturbed blood flow with high resolution and without the need for contrast agents. During arterial occlusion, MSOT‐extracted Hb‐values showed an increase, while HbO2‐ and total blood volume (TBV)‐values remained roughly steady, followed by a discrete increase during the hyperemic period after cuff deflation. During venous occlusion, results showed a clear increase in intramuscular HbO2, Hb and TBV within the segmented muscle area. MSOT was found to be capable of label‐free non‐invasive imaging of muscle hemodynamics and oxygenation under arterial and venous occlusion. We introduce herein MSOT as a novel modality for the assessment of vascular disorders characterized by disturbed blood flow, such as acute limb ischemia and venous thrombosis. [ABSTRACT FROM AUTHOR]

Background: Immune‐checkpoint inhibitors have been shown to improve survival in melanoma patients, but can also trigger immune‐related endocrinopathies, especially hypophysitis and thyroid dysfunction. Methods: To assess the incidence and the spectrum of endocrinopathies in melanoma patients treated with immunotherapy a prospective observational study was conducted. Forty out of 339 patients, treated with immune‐checkpoint inhibitors, developed endocrinopathies. All patients had hormonal functional tests at screening (before the initiation of immunotherapy) and during follow‐up. Results: The total incidence of endocrinopathies was 11.8%, 13.4% due to anti‐PD1/PDL1, 5% due to anti‐CTLA4, and 18.5% due to sequential and/or combination treatment. Twenty‐one patients (6.2%) presented with isolated anterior hypophysitis, eleven (3.2%) with primary thyroid dysfunction and eight (2.4%) with both abnormalities. The most frequent anterior pituitary hormone deficiency was central adrenal insufficiency, followed by central hypothyroidism and hypogonadotrophic hypogonadism. None of the patients with corticotroph axis failure recovered during follow‐up. Endocrinopathies occurred after a median of 22 weeks (range: 4‐156) from treatment initiation. Of note, sequential and/or combination therapy with anti‐CTLA4 and anti‐PD1/anti‐PDL1 led to an almost threefold incidence of hypophysitis compared to either monotherapy. Only one of 120 patients receiving anti‐CTLA4 monotherapy developed primary hypothyroidism. Conclusions: Our cohort demonstrated an increased incidence of hypophysitis with anti‐PD1/anti‐PDL1 in contrast to the rarity of primary thyroid dysfunction with anti‐CTLA4 treatment. These results could be attributed to genetic/ethnic differences. Sequential treatment is, for the first time to our knowledge, reported to increase the risk of developing hypophysitis to a level as high as that of combination therapy. [ABSTRACT FROM AUTHOR]

We report a 44-year-old male, who was diagnosed with hypogonadotropic hypogonadism after complaining of erectile dysfunction, depression, and fatigue. He was started on testosterone replacement therapy. He persistently complained of fatigue despite increasing the dose of testosterone over two years and having therapeutic testosterone levels. He was found to have homozygous C677T methylenetetrahydrofolate reductase (MTHFR) gene mutation. After treatment with folate and B12, his symptoms resolve completely. MTHFR is a key enzyme in the folate pathway, and it plays an essential role in homocysteine metabolism. Homozygous C677T individuals have decreased activity of MTHFR enzyme with increased homocysteine levels, which is associated with increased risk of thrombosis. An association has been reported between C677T variant and male infertility. Patients identified to have hyperhomocysteinemia should be treated with B-complex vitamin supplements. Our case emphasizes other possible etiologies for fatigue and erectile dysfunction in a male with hypogonadism on testosterone therapy. Also, it shows possible association between MTHFR gene mutation and male hypogonadism. [ABSTRACT FROM AUTHOR]

Objectives To study the behavior of specific coagulation factors in different types of non-metastatic urological cancers, and to identify their possible role as diagnostic and prognostic markers. Methods This was a prospective controlled study, which included three cancer patient groups and a control group of healthy individuals. The cancer subgroups consisted of renal ( n = 44), prostate ( n = 56) and bladder cancer ( n = 47). We excluded patients receiving anticoagulant therapy, or with significant comorbidity. In all patients, certain coagulation parameters were measured (prothrombin time, international normalized ratio, partial thromboplastin time, D-dimers, fibrinogen, F1 + 2, thrombin-antithrombin complex). Statistical analysis was carried out to explore the association of hemostasis markers with tumor-nodes-metastasis stage, Gleason score, transitional cell carcinoma grade, Fuhrman grade and prostate-specific antigen. Results Our final sample consisted in 58 control patients and 147 patients with urological cancer. We found specific patterns of increased coagulation factors in the different cancers that were statistically significant. Renal cancer showed increased levels of D-dimers, partial thromboplastin time and fibrinogen. D-dimers and fibrinogen were increased in prostate cancer; whereas in bladder cancer, only fibrinogen was elevated. Correlations were found between certain factors and tumor stage and grading, with D-dimers being independently associated with higher tumor grade. Thrombin-antithrombin complex was associated with Gleason score. Furthermore, D-dimers, fibrinogen and F1 + 2 were associated with higher tumor stages (II-IV). Conclusions The coagulation pathway seems to be activated in urological malignancies. Specific panels of coagulation factors might play a role as screening or prognostic tools in earlier stages of renal, prostate and bladder cancer. Further research should also focus on their role in the association of cancer with thromboembolic events. [ABSTRACT FROM AUTHOR]

Understanding the distribution of genetic diversity in the light of past demographic events linked with climatic shifts will help to forecast evolutionary trajectories of ecosystems within the current context of climate change. In this study, mitochondrial sequences and microsatellite loci were analysed using traditional population genetic approaches together with Bayesian dating and the more recent approximate Bayesian computation scenario testing. The genetic structure and demographic history of a commercial fish, the black scorpionfish, Scorpaena porcus, was investigated throughout the Mediterranean and Black Seas. The results suggest that the species recently underwent population expansions, in both seas, likely concomitant with the warming period following the Last Glacial Maximum, 20 000 years ago. A weak contemporaneous genetic differentiation was identified between the Black Sea and the Mediterranean Sea. However, the genetic diversity was similar for populations of the two seas, suggesting a high number of colonizers entered the Black Sea during the interglacial period and/or the presence of a refugial population in the Black Sea during the glacial period. Finally, within seas, an east/west genetic differentiation in the Adriatic seems to prevail, whereas the Black Sea does not show any structured spatial genetic pattern of its population. Overall, these results suggest that the Black Sea is not that isolated from the Mediterranean, and both seas revealed similar evolutionary patterns related to climate change and changes in sea level. [ABSTRACT FROM AUTHOR]

The development and function of B lymphocytes is regulated by numerous signaling pathways, some emanating from the B-cell antigen receptor ( BCR). The spleen tyrosine kinase (Syk) plays a central role in the activation of the BCR, but less is known about its contribution to the survival and maintenance of mature B cells. We generated mice with an inducible and B-cell-specific deletion of the Syk gene and found that a considerable fraction of mature Syk-negative B cells can survive in the periphery for an extended time. Syk-negative B cells are defective in BCR, RP105 and CD38 signaling but still respond to an IL-4, anti- CD40, CpG or LPS stimulus. Our in vivo experiments show that Syk-deficient B cells require BAFF receptor and CD19/ PI3K signaling for their long-term survival. These studies also shed a new light on the signals regulating the maintenance of the normal mature murine B-cell pool. [ABSTRACT FROM AUTHOR]

Diet and feeding strategy of the blackmouth catshark Galeus melastomus in the deep waters of the eastern Ionian Sea were investigated. Sampling was carried out using experimental bottom longline fishing at depths ranging from 300 to 855 m in summer and autumn 2010. Diet variability with fish size, season, area, sex and depth zone was tested and only season was found to significantly affect the diet of the species. Of the 870 stomachs examined, only 1·4% were empty. Cumulative prey curves showed that the sample sizes were adequate to describe the main prey items of the diet for both seasons. Prey identified belonged primarily to three major groups: fishes, cephalopods and dendrobranchiatan and caridean shrimps. In autumn, the above three major groups were found as principal prey, whereas in summer cephalopods followed by fishes were the principal prey and shrimps were found as secondary prey. SIMPER analysis indicated high dissimilarity between seasons and highlighted that Sepiolidae, Myctophidae, fishes, cephalopods, shrimps and other crustaceans contributed to seasonal differences in the diet of G. melastomus. The prey diversity index was higher in autumn than in summer. A high dietary overlap was observed between the two seasons. Galeus melastomus behaved as an opportunistic predator with a variety of unimportant prey in its diet. Feeding strategy indicated that G. melastomus holds a generalist niche with a considerable specialization at the individual level. This strategy seems to be an adaptation to a food-scarce environment, as typified in deep-water habitats. [ABSTRACT FROM AUTHOR]

Spatial distribution and life history aspects of Pagellus bogaraveo in the eastern Ionian Sea were investigated using the data from 13 different studies carried out in the area from 1983 to 2010. The spatial patterns of the abundance, biomass and mean size showed that the species inhabits the shallow waters of the shelf (<170 m depth) as juveniles up to a certain size (<180 mm total length, LT), moving to deeper waters of the slope (mainly 400-500 m depth) as adults. The spatial pattern of abundance indicated a continuous distribution of the species in deep waters, with hot-spot areas of high values, whereas in shallow waters distribution was more discontinuous, with higher concentrations of juveniles in estuaries and brackish waters. The study of biological aspects of the species revealed (1) a difference in the increase in mass between males and females, (2) protandrous hermaphroditism, accompanied by the presence of primary females and males that do not change sex, (3) a sex ratio in favour of females >250 mm LT, (4) the presence of hermaphrodites between 200 and 370 mm, (5) a long reproduction period from June to March, (6) a size at first maturity around 300 mm and (7) a diet composition of adults based mainly on fishes, and also on opportunistic behaviour in the food scarce environment of deep waters. The results suggest that the species' distribution and feeding strategies are the most appropriate for the oligotrophic eastern Ionian waters and that these conditions result in smaller sizes of the species in the east Mediterranean Sea compared to the west basin and the east Atlantic Ocean, with implications for the growth and reproductive biology of the species. [ABSTRACT FROM AUTHOR]

Age, growth, and mortality of the edible crab, Cancer pagurus, were determined for the native population in South Wales ( UK). Sampling was carried out on a monthly basis between February 2001 and September 2002. Carapace width ranged between 10.4 and 163 mm. Based on the carapace width frequency distribution, the Swansea and Gower population was composed mainly of males belonging to the first and second age-class (1 and 2), and of females belonging to the third and fourth age-class (3 and 4). Sex ratio was 1.126 ± 0.27 in favour of males. Carapace width frequency distributions and weight-at-age data were used to estimate the von Bertalanffy growth equation parameters. For the population as a whole, these were: L∞ = 199 mm, W∞ = 1179.56 g, K = 0.24 year−1, t0 = −0.1004 years. The overall carapace width-weight relationship was: W = 0.38( CW2.69). Analysis of covariance indicated a significant difference in the carapace width-weight relationship between males and females in the study area. Total mortality Z and natural mortality M rates for combined sexes were 1.245 year−1 and 0.567 year−1, respectively. The exploitation ratio E was estimated to be 54.43%. [ABSTRACT FROM AUTHOR]

The feeding ecology of Chlorophthalmus agassizi from the North Ionian Sea was examined in specimens caught during daylight hours on a seasonal basis from December 1996 to November 1997, at depths between 250 and 800 m (92 stations, total). Chlorophthalmus agassizi showed a mixed feeding strategy, exploiting a wide range of prey including mesopelagic, benthic and endobenthic organisms. Crustaceans and fishes were dominant food items in the diet year round. Diet composition showed slight seasonal fluctuations; these variations were correlated with food availability and reproductive activity. However, ontogenetic changes in the diet were relatively clear, despite the high overlap observed between small, medium and large individuals. Larger individuals are more efficient hunters that exhibit selection of prey with good swimming capabilities; smaller individuals consume prey with low mobility. Chlorophthalmus agassizi seem to be adapted to a food-scarce environment, as typified in the deep-water habitats of the Ionian Sea, and exploit all available niches. [ABSTRACT FROM AUTHOR]

The distribution and population structure of the shortnose green eye, Chlorophthalmus agassizi, were studied in the Greek Ionian Sea using data collected during experimental trawl surveys carried out from December 1996 to November 1997. The length–frequency distribution ranged between 45 and 201 mm total length (TL). The significant increase in average size linked with depth has been observed, supporting the general ‘bigger-deeper’ phenomenon. Specifically, 1528 individuals were measured in the 300–400 m depth zone with a mean TL = 101 mm, 2351 individuals in the 400–500 m depth zone with a mean TL = 132 mm and 1889 individuals in the 500–600 depth zone with a mean TL = 145 mm. Age and growth of the population were determined by otolith readings. Twelve age groups were identified. The von Bertalanffy growth function (VBGF) parameters were L∞=202.22 mm, K=0.20 and to=−1.6 years. Natural mortality was estimated at 0.285 per year, while total mortality was estimated at 0.65. The reproductive period of C. agassizi extends from spring to autumn, with greater activity in the summer. [ABSTRACT FROM AUTHOR]