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•BTKC481S was most common in both groups; in the acalabrutinib arm, low-VAF T474I (9/47; 8 co-occurring with C481S) but no L528W was seen.•More patients receiving acalabrutinib acquired BTKmutations, though overall, patients with BTKmutation did not fare worse vs those without.

Novel soil datasets and the application of pedotransfer functions provide soil hydraulic input data for modelling hydrological processes at different scales. We aimed to evaluate the reliability of soil hydraulic parameters derived by indirect methods in simulation of soil moisture time series and water budgets at profile level of three sites (Forest, Orchard and Grassland) from a Central European catchment (Lake Balaton, Hungary). Five soil-vegetation-atmosphere model variants were set up with the Hydrus-1D model for each site, differing only in the parametrization of input soil data: i) a calibrated reference, ii) measured values, iii) values predicted from measured basic soil properties, iv) values predicted from national soil map information, v) values derived from the 3D soil hydraulic dataset of Europe. Calibrated soil parameters led to Nash-Sutcliffe efficiency 0.50, 0.54 and 0.71 for the Forest, Orchard and Grassland Site respectively. The outcomes for model efficiency of soil moisture underline the superiority of local databases over regional ones and the need for more detailed vertical discretization during modelling. The model performance according to soil moisture and water budget accuracy led to different rank order of model variants. Water budget comparisons indicated moderate differences between the hydrologic fluxes simulated by the different model variants, emphasizing the uncertainties associated with soil hydraulic parametrization either at local or at watershed scale.

In this paper, novel application possibilities of CuO nanoparticles were investigated in SAC0307 solder alloy for composite soldering purposes. CuO nanoparticles in 0.25 and 0.5 wt% were mixed into the solder paste to produce composite solder joints. Solder joints were manufactured using standard surface mounting technology from different solder pastes. The solder joints were loaded in an 85 °C/85RH% temperature and humidity test for 4000 h. It was found that the CuO composite solder joints showed improved mechanical quality due to the microstructural refinement, which was studied using scanning electron microscopy (SEM) and focused ion beam (FIB) analysis. On the other hand, the corrosion resistance of CuO joints decreased, as they suffered localized corrosion extensively, which produced longer and more Sn whiskers on their surface than on the reference SAC0307. Density functional theory (DFT) calculations proved that CuO can bond to Sn, but CuO is not chemically inert in the solder bulk. CuO can start a cyclic reaction with the dispersed Cu6Sn5intermetallics, which produces SnO2in the solder bulk, ultimately enhancing corrosion. Therefore, CuO nanoparticles are suggested to be applied only in non-corrosive environments, such as space applications.

In this study, we detected and compared changes in the annual and daily captures of the Eurasian (Certhia familiaris)and Short-toed Treecreeper (C. brachydactyla)in the timing of their post-breeding movements, in the length of minimum stopover duration (MSD) in the area, and also in biometrics in western Hungary. The birds were captured and ringed, or recaptured from the end of July to the first weekend of November in all years from 2001 to 2023. The annual captures of both species indicated stable populations in this period, with milder February months having a positive effect on annual captures. There were similarities and differences in the movement strategies and habitat selection of the species. During the post-breeding season, the Eurasian Treecreeper was more strongly associated with the scrubland and forest edge than the Short-toed Treecreeper. There were two autumn capture waves in September and October for the Eurasian Treecreepers and just one in September for the Short-toed Treecreepers, which were primarily consisted of birds captured only once. There were no significant differences in wing length of the three capture intervals (July-August, September, October-November) in either species, which suggests that the dynamics of post-breeding movements cannot be explained on the bases of possible differences in the behavior of sexes, ages, or populations. The proportion of birds captured only once was about double of that of stopovers in both species each year. The average real length of stopover duration in the area for Eurasian Treecreepers was 94.25 days, and 84.31 days for Short-toed Treecreepers. The length of MSD in the area was not significantly associated with wing length and body mass in either species. Individuals of both species did not gain fat stores significantly during post-breeding season.

The Semmelweis Study is a prospective occupational cohort study that seeks to enroll all employees of Semmelweis University (Budapest, Hungary) aged 25 years and older, with a population of 8866 people, 70.5% of whom are women. The study builds on the successful experiences of the Whitehall II study and aims to investigate the complex relationships between lifestyle, environmental, and occupational risk factors, and the development and progression of chronic age-associated diseases. An important goal of the Semmelweis Study is to identify groups of people who are aging unsuccessfully and therefore have an increased risk of developing age-associated diseases. To achieve this, the study takes a multidisciplinary approach, collecting economic, social, psychological, cognitive, health, and biological data. The Semmelweis Study comprises a baseline data collection with open healthcare data linkage, followed by repeated data collection waves every 5 years. Data are collected through computer-assisted self-completed questionnaires, followed by a physical health examination, physiological measurements, and the assessment of biomarkers. This article provides a comprehensive overview of the Semmelweis Study, including its origin, context, objectives, design, relevance, and expected contributions.

Increasing the productivity of cereals such as maize while protecting the environment remains a fundamental impetus of healthy food production systems. The use of biostimulants is one of the sustainable strategies to achieve this balance, although the ability of biostimulants to enhance maize productivity varies. Moreover, research on the efficacy of biostimulants is ubiquitous with limited comprehensive global analysis. In this context, this systematic review evaluated the sole and interactive effects of biostimulants on the yield and quality of maize grain from a global perspective. Changes in yield (t ha-1), protein content (%), starch content (%) and oil content (%) of maize grain were assessed. Results revealed that sole and combined application of biostimulants significantly improved grain yield. Irrespective of the region, the highest and the lowest grain yields ranged between 16-20 t ha-1and 1-5 t ha-1, respectively. In sole application, the promising biostimulants were chicken feather (16.5 t ha-1), and endophyte Colletotrichum tofieldiae(14.5 t ha-1). Sewage sludge × NPK (15.4 t ha-1), humic acid × control release urea (12.4 t ha-1), Azospirillum brasilenseor Bradyrhizobium japonicum× maize hybrids (11.6 t ha-1), and Rhizophagus intraradices× earthworms (10.0 t ha-1) had higher yield for the interactive effects. The effects of biostimulants on grain quality were minimal, and all attributes improved in the range from 0.1 to 3.7%. Overall, biostimulants had a distinct improvement effect on yield, rather than on the quality of grain. As one way of maximising maize productivity, soil health, and the overall functioning of crop agroecosystems, the integrated application of synergistic microbial and non-microbial biostimulants could provide a viable option. However, the ability to produce consistent yield and quality of grain improvement remains a major concern.

There is a noteworthy overlap between the clinical picture of biliary acute pancreatitis (AP) and the 2018 Tokyo guidelines currently used for the diagnosis of cholangitis (AC) and cholecystitis (CC). This can lead to significant antibiotic and endoscopic retrograde cholangiopancreatography (ERCP) overuse. We aimed to assess the on‐admission prevalence of AC/CC according to the 2018 Tokyo guidelines (TG18) in a cohort of biliary AP patients, and its association with antibiotic use, ERCP and clinically relevant endpoints. We conducted a secondary analysis of the Hungarian Pancreatic Study Group's prospective multicenter registry of 2195 AP cases. We grouped and compared biliary cases (n= 944) based on the on‐admission fulfillment of definite AC/CC according to TG18. Aside from antibiotic use, we evaluated mortality, AC/CC/AP severity, ERCP performance and length of hospitalization. We also conducted a literature review discussing each criteria of the TG18 in the context of AP. 27.8% of biliary AP cases fulfilled TG18 for both AC and CC, 22.5% for CC only and 20.8% for AC only. Antibiotic use was high (77.4%). About 2/3 of the AC/CC cases were mild, around 10% severe. Mortality was below 1% in mild and moderate AC/CC patients, but considerably higher in severe cases (12.8% and 21.2% in AC and CC). ERCP was performed in 89.3% of AC cases, common bile duct stones were found in 41.1%. Around 70% of biliary AP patients fulfilled the TG18 for AC/CC, associated with a high rate of antibiotic use. Mortality in presumed mild or moderate AC/CC is low. Each of the laboratory and clinical criteria are commonly fulfilled in biliary AP, single imaging findings are also unspecific—AP specific diagnostic criteria are needed, as the prevalence of AC/CC are likely greatly overestimated. Randomized trials testing antibiotic use are also warranted.

Non‐alcoholic fatty liver disease (NAFLD) is a proven risk factor for acute pancreatitis (AP). However, NAFLD has recently been redefined as metabolic‐associated fatty liver disease (MAFLD). In this post hoc analysis, we quantified the effect of MAFLD on the outcomes of AP. We identified our patients from the multicentric, prospective International Acute Pancreatitis Registry of the Hungarian Pancreatic Study Group. Next, we compared AP patients with and without MAFLD and the individual components of MAFLD regarding in‐hospital mortality and AP severity based on the revised Atlanta classification. Lastly, we calculated odds ratios (ORs) with 95% confidence intervals (CIs) using multivariate logistic regression analysis. MAFLD had a high prevalence in AP, 39% (801/2053). MAFLD increased the odds of moderate‐to‐severe AP (OR = 1.43, CI: 1.09–1.89). However, the odds of in‐hospital mortality (OR = 0.89, CI: 0.42–1.89) and severe AP (OR = 1.70, CI: 0.97–3.01) were not higher in the MAFLD group. Out of the three diagnostic criteria of MAFLD, the highest odds of severe AP was in the group based on metabolic risk abnormalities (OR = 2.68, CI: 1.39–5.09). In addition, the presence of one, two, and three diagnostic criteria dose‐dependently increased the odds of moderate‐to‐severe AP (OR = 1.23, CI: 0.88–1.70, OR = 1.38, CI: 0.93–2.04, and OR = 3.04, CI: 1.63–5.70, respectively) and severe AP (OR = 1.13, CI: 0.54–2.27, OR = 2.08, CI: 0.97–4.35, and OR = 4.76, CI: 1.50–15.4, respectively). Furthermore, in patients with alcohol abuse and aged ≥60 years, the effect of MAFLD became insignificant. MAFLD is associated with AP severity, which varies based on the components of its diagnostic criteria. Furthermore, MAFLD shows a dose‐dependent effect on the outcomes of AP.

Janus kinase (JAK) inhibitors approved for myelofibrosis provide spleen and symptom improvements but do not meaningfully improve anaemia. Momelotinib, a first-in-class inhibitor of activin A receptor type 1 as well as JAK1 and JAK2, has shown symptom, spleen, and anaemia benefits in myelofibrosis. We aimed to confirm the differentiated clinical benefits of momelotinib versus the active comparator danazol in JAK-inhibitor-exposed, symptomatic patients with anaemia and intermediate-risk or high-risk myelofibrosis.

The effect of SiC nano-phases (nano-particles and nano-fibers) addition into SAC0307 solder paste was investigated on the thermal and microstructural properties of the composite solder joints. The nano-phases were used between 0.125 and 1 wt%, and they were mixed into the solder paste by ball milling process. For the study power MOSFET (metal oxide semiconductor field effect transistor) components were soldered onto metal core printed circuit boards (MCPCBs). The thermal impedance Zth(t) and thermal resistance Rthof MOSFETs were measured by an indirect electrical method. Furthermore, the void formation and the microstructure of solder joints were also studied. The solderability and voiding properties of the composite solder alloys were acceptable. It was found that in 0.5 wt% amount, SiC nano-particles have positive effects on the thermal parameters of the solder joints, which could be explained by the IMC (intermetallic compound) layer growth suppression effect of the nano-phases. The microstructural analysis revealed that the microstructural refinement of the composite solder joints differs in the case of nano-particles and nano-fibers.

Age-related macular degeneration (AMD) is a progressive neurodegenerative disease affecting the central area (macula lutea) of the retina. Research on the pathogenic mechanism of AMD showed complex cellular contribution governed by such risk factors as aging, genetic predisposition, diet, and lifestyle. Recent studies suggested that microbiota is a transducer and a modifier of risk factors for neurodegenerative diseases, and mitochondria may be one of the intracellular targets of microbial signaling molecules. This review explores studies supporting a new concept on the contribution of microbiota—mitochondria disorders to AMD. We discuss metabolic, vascular, immune, and neuronal mechanism in AMD as well as key alterations of photoreceptor cells, retinal pigment epithelium (RPE), Bruch’s membrane, choriocapillaris endothelial, immune, and neuronal cells. Special attention was paid to alterations of mitochondria contact sites (MCSs), an organelle network of mitochondria, endoplasmic reticulum, lipid droplets (LDs), and peroxisomes being documented based on our own electron microscopic findings from surgically removed human eyes. Morphometry of Bruch’s membrane lipids and proteoglycans has also been performed in early AMD and aged controls. Microbial metabolites (short-chain fatty acids, polyphenols, and secondary bile acids) and microbial compounds (lipopolysaccharide, peptidoglycan, and bacterial DNA)—now called postbiotics—in addition to local effects on resident microbiota and mucous membrane, regulate systemic metabolic, vascular, immune, and neuronal mechanisms in normal conditions and in various common diseases. We also discuss their antioxidant, anti-inflammatory, and metabolic effects as well as experimental and clinical observations on regulating the main processes of photoreceptor renewal, mitophagy, and autophagy in early AMD. These findings support an emerging concept that microbiota-mitochondria disorders may be a crucial pathogenic mechanism of early AMD; and similarly, to other age-related neurodegenerative diseases, new treatment approaches should be targeted at these disorders.

Adult and juvenile survival are important factors affecting the population dynamics of small passerines. Understanding variation in the population dynamics and survival rates is critical for ecological studies and nature conservation. The aim of this study was to investigate the annual capture-recapture, apparent survival and capture probabilities of the Blue Tit Cyanistes caeruleusand the Great Tit Parus majoroccurring in western Hungary. Data from 8,628 Blue Tits and 7,727 Great Tits came from a constant-effort ringing scheme, using three ringing periods, spanning 24 years (1998 to 2021). The annual captures did not show a significant linear trend from 1998 to 2021 in the study site for both tit species. The temporal variation of annual captures and the annual capture-recapture proportions of different ages and sexes of the tit species were similar. This indicated that the migration strategies of these two partial migrant species did not differ significantly. According to the best standard Cormack-Jolly-Seber model, apparent survival of first-year birds was lower than that for adults. The CJS model selection for the dataset indicated that the time and sex had no effect on apparent survival probabilities for both tit species. Capture probability in the juvenile groups was not significantly higher than that in the adult groups for both species.

•Levels of von Willebrand factor (VWF) in both patient groups were the highest at engraftment during hematopoietic stem cell transplantation.•Platelet counts decreased and C-reactive protein increased antiparallel in both groups.•Remission state was associated with pretreatment VWF level in patients with lymphoma.•Pretreatment VWF level should be measured to assess the probability of remission.

The main joining process of the electronic industry is still soldering with different alloys of Sn. This work studied the relationship between Sn whisker growth and corrosion resistance of 99Sn0.3Ag0.7Cu–TiO2/ZnO (0.25wt%) composite solder alloys in a corrosive environment via scanning electron microscopy and focused ion beam techniques. The corrosive environment test showed that the application of TiO2and ZnO nano-particles almost totally suppressed the Sn whisker growth and improved the corrosion resistance of the composite solder alloys compared to the reference 99Sn0.3Ag0.7Cu alloy. The microstructural analysis of the reference 99Sn0.3Ag0.7Cu solder alloy showed that the volumetric increase of the corroded β-Sn grains resulted in local mechanical stress in the solder joints, which was released by Sn whisker development. However, in the composite solder joints, the increased grain boundary fraction and segregation of the TiO2and ZnO nano-particles to the grain boundaries resulted in a relatively uniform and compact protective oxide layer at the β-Sn grain boundaries. This suppressed the formation of SnOx, and via this, the corrosion-induced whisker growth.

Elotuzumab plus lenalidomide and dexamethasone has shown improved progression-free and overall survival versus lenalidomide and dexamethasone in patients with relapsed or refractory multiple myeloma. We aimed to assess these regimens in patients with newly diagnosed multiple myeloma who are ineligible for haematopoietic stem-cell transplantation (HSCT).

Background: Percutaneous transhepatic gallbladder drainage (PTGBD) plays an important role in the treatment of elderly patients and/or patients in poor health with acute cholecystitis (AC). The primary aim of this study is to determine how these factors influence the clinical outcome of PTGBD. Moreover, we assessed the timing and results of subsequent cholecystectomies. Patients and Methods: We retrospectively examined the results of 162 patients undergoing PTGBD between 2010 and 2020 (male–female ratio: 51.23% vs.48.77%; mean age: 71.43 ± 13.22 years). Patient’s performance status and intervention outcomes were assessed with clinical success rates (CSR) and in-hospital mortality. The conversion rate (CR) of possible urgent or delayed, elective laparoscopic cholecystectomies (LC) after PTGBD were analysed. Results: PTGBD was the definitive treatment in 42.18% of patients, while it was a bridging therapy prior to cholecystectomy (CCY) for the other patients. CSR was 87.97%, it was only 64.29% in grade III AC. In 9.87% of the cases, urgent LC was necessary after PTGBD, and its conversion rate was approximately equal to that of elective LC (18.18 vs.17.46%, respectively, p= 0.2217). Overall, the post-PTGBD in-hospital mortality was 11.72%, while the same figure was 0% for grade I AC, 7.41% for grade II and 40.91% for grade III. Based on logistic regression analyses, in-hospital mortality (OR 6.07; CI 1.79–20.56), clinical progression (OR 7.62; CI 2.64–22.05) and the need for emergency CCY (OR 14.75; CI 3.07–70.81) were mostly determined by AC severity grade. Conclusion: PTGBD is an easy-to-perform intervention with promising clinical success rates in the treatment of acute cholecystitis. After PTGBD, the level of gallbladder inflammation played a decisive role in the course of AC. In a severe, grade III inflammation, we have to consider low CSR and high mortality.

•Food safety controls were conducted over a period of 4 months in 10 school kitchens.•Internal staff, internal auditor and external auditor completed the same checklist.•External auditors evaluated the kitchens significantly lower.•Issues related to personal hygiene, storage, and cleaning were judged divergently.•Food handlers perceive their practices to be safer than they actually are.

The paper deals with the international circular migration which has globally become a buzzword in scientific, political, and administrative circles since the new century. The article concentrates on an unknown feature of the circular migration, namely its dialectic nature, which encompasses both event and system characteristics. This would be the common root of false ideas surrounding human circulation. The literature echoes wide variety of conceptualisations of international circular migration. However, the investigation and application of double characteristic is absent. On one hand, circular migration is a type of migration as a simple event, on the other hand that is a repeat process or a complete system. The main aim of the article is to discuss the event-system dilemma in general and to provide a sort of practical solution with empirical evidence that comes from Hungary in particular. Moreover, the authors contribute to the clarification of the general concept of human circular mobilities.

A hierarchical lane-keeping controller of passenger cars is analyzed, with the consideration of feedback delay in the control loop. The higher-level controller generates the desired steering angle based on the delayed feedback of the lateral position and yaw angle of the vehicle. The feedback delay of the lateral position and the yaw angle are treated separately in the model, therefore more general sensor setups and estimation algorithms can be handled. A lower-level proportional-integral-derivative power steering controller ensures that the desired steering angle signal is followed properly. The linear stability analysis of the resulting closed-loop system is performed, with a focus on the controller parameters and the delay values. The optimal control gains, leading to the fastest decay of the solution are also investigated in detail. The results are showcased with the help of stability charts and numerical simulations.

Graphical abstract:

Annual captures and biometric parameters of the Goldcrest (Regulus regulus) were studied at Tömörd, western Hungary. We used records of 4,284 individuals trapped and ringed between August and November within the study period (1998–2020). The Goldcrest was determined to be a regular partial migrant species with highly intensive migration in 2000, 2001, 2008, 2014 and 2019. The catching results showed very high number fluctuations at Tömörd, but the smoothed curves were distinctly wave-like in all age and sex classes. There were significant positive correlations between annual captures of age and sex classes. The average proportion of immature Goldcrests was 90%, the average proportion of male individuals was 63% and both proportions were stable between 1998 and 2020. There were similar decreasing trends in the average annual wing length and body mass of males and females from 1998 to 2020. This may indicate that the migration strategies of females may be modified by global climate change.

The author tries to investigate the thoughts and politics in literature about international circular migration in the lights of European Union (EU) initiatives related to Visegrad Four Countries (V4) with special attention to Hungary. The cross-border circular flows have become relatively frequent during life stages of people differentiated by previous migratory experiences, and next aspirations. The popularity of international circular migration erected from the hypothesis of ’triple win solution’ without any empirical verifications. Basically, two sorts of circular migration system exist: homogenous and heterogenous. The homogenous human circular migration system consists of the same kind of moves with similar time rhythm from statistical angles. It seems to us that the practice of life-long international circular migration characterises few long-term circulators. However, the heterogenous circular migration systems combine with other spatial mobility forms function during whole individual life cycle due to one of the symptoms of human beings. The main aim of the contribution is to explore some elements of similar ideas and politics on international circulatory flows interfered between Western and Eastern Europe. Moreover, we propose some old-new innovativesolutions for V4 to reform the rigid EU migration policies.

Carotid artery stenosis (CAS) is a consequence of systemic atherosclerotic disease affecting the aging populations of the Western world. CAS is frequently associated with cognitive impairment. However, the mechanisms contributing to the development of vascular cognitive impairment (VCI) associated with CAS are multifaceted and not fully understood. In addition to embolization and decreased blood flow due to the atherosclerotic lesion in the carotid artery, microcirculatory dysfunction in the cerebral circulation also plays a critical role in CAS-related VCI. To better understand the microvascular contributions to cognitive decline associated with CAS and evaluate microvascular protective effects of therapeutic interventions, it is essential to examine the structural and functional changes of the microvessels in the central nervous system (CNS). However, there are some limitations of in vivo brain vascular imaging modalities. The retinal microvasculature provides a unique opportunity to study pathogenesis of cerebral small vessel disease and VCI, because the cerebral circulation and the retinal circulation share similar anatomy, physiology and embryology. Similar microvascular pathologies may manifest in the brain and the retina, thus ocular examination can be used as a noninvasive screening tool to investigate pathological changes in the CNS associated with CAS. In this review, ocular signs of CAS and the retinal manifestations of CAS-associated microvascular dysfunction are discussed. The advantages and limitation of methods that are capable of imaging the ocular circulation (including funduscopy, fluorescein angiography, Doppler sonography, optical coherence tomography [OCT] and optical coherence tomography angiography [OCTA]) are discussed. The potential use of dynamic retinal vessel analysis (DVA), which allows for direct visualization of neurovascular coupling responses in the CNS, for understanding microvascular contributions to cognitive decline in CAS patients is also considered.

Innovation plays great role in organizational competitiveness and sustainable business processes and it should be a key success policy for small and medium-sized enterprises (SMEs) all over the world. To this effect, the purpose of this study is to present a comprehensive understanding of the scientific studies made on the field of innovation and its effect on small and medium enterprises performance. A bibliometric study was used to analyze articles published between 1976 and 2020 and create an illustrative map of innovation in small and medium enterprises; a sample of papers gathered through Web of Science Core Collection database. Accordingly, there were found 2219 documents which were published in 332 sources. VOS viewer was employed to portray network analysis of, authorship, keywords visualization, citations, and countries dealing with the subject. SCIMAT software was also used to do longitudinal thematic analysis. Even though many countries, universities, research institutes, funding agencies, and authors contributed for the growth of this field of study, almost all are from developed nations. This study is one amongst the very few studies made using bibliometric analysis in this field. Moreover, the thematic network diagram reveals two other new themes in the subject, which are taken as knowledge seed, and have high potential for a future study.

Despite advances in the treatment of Hodgkin lymphoma with the introduction of PET-adapted regimens, practical challenges prevent more widespread use of these approaches. The ECHELON-1 study assessed the safety and efficacy of front-line A+AVD (brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine) versus ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) in patients with stage III or IV classical Hodgkin lymphoma. The primary analysis showed improved modified progression-free survival with A+AVD. We present an updated analysis of ECHELON-1 at 5 years, an important landmark for this patient population.

Objective Follicular lymphoma (FL) is an indolent, lymphoproliferative disease of B-cell origin that has a heterogeneous disease course with varying outcomes. Certain patients may undergo autologous stem cell transplantation. We investigated the outcome of autologous stem cell transplantation in patients with FL.Methods Patients who received autologous stem cell transplantation at the University of Debrecen’s Department of Hematology between 2004 and 2021 were retrospectively analyzed. The overall survival (OS) and progression-free survival (PFS) after transplantation of patients with FL were examined. Prognostic factors that may influence the course of the disease were chosen.Results Data were collected from 49 patients. OS was influenced only by age, whereas PFS was affected by age and the lymphocyte/monocyte ratio. The combination of age and lymphocyte/monocyte ratio defined a patient population with a particularly unfavorable prognostic risk profile: patients over 47 years of age with a pre-transplant lymphocyte/monocyte ratio greater than or equal to 2.675.Conclusion Age and lymphocyte/monocyte ratio were identified as useful prognostic factors for PFS in patients with FL following autologous stem cell transplantation.

The phase 2 CAVALLI (NCT02055820) study assessed efficacy and safety of venetoclax, a selective B-cell lymphoma-2 (Bcl-2) inhibitor, with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in first-line (1L) diffuse large B-cell lymphoma (DLBCL), including patients demonstrating Bcl-2 protein overexpression by immunohistochemistry (Bcl-2 IHC+). Eligible patients were ≥18 years of age and had previously untreated DLBCL, Eastern Cooperative Oncology Group performance status ≤2, and International Prognostic Index 2 to 5. Venetoclax 800 mg (days 4-10, cycle 1; days 1-10, cycles 2-8) was administered with rituximab (8 cycles) and cyclophosphamide, doxorubicin, vincristine, and prednisone (6-8 cycles) in 21-day cycles. Primary end points were safety, tolerability, and complete response (CR) at end of treatment (EOT). Secondary end points were progression-free survival (PFS) and overall survival. Comparative analyses used covariate-adjusted R-CHOP controls from the GOYA/BO21005 study, an appropriate contemporary benchmark for safety and efficacy. Safety and efficacy analyses included 206 patients. CR rate at EOT was 69% in the overall population and was maintained across Bcl-2 IHC+ subgroups. With a median follow-up of 32.2 months, trends were observed for improved investigator-assessed PFS for venetoclax plus R-CHOP in the overall population (hazard ratio [HR], 0.61; 95% confidence interval [CI], 0.43-0.87) and Bcl-2 IHC+ subgroups (HR, 0.55; 95% CI, 0.34-0.89) vs R-CHOP. Despite a higher incidence of grade 3/4 hematologic adverse events (86%), related mortality was not increased (2%). Chemotherapy dose intensity was similar in CAVALLI vs GOYA. The addition of venetoclax to R-CHOP in 1L DLBCL demonstrates increased, but manageable, myelosuppression and the potential of improved efficacy, particularly in high-risk Bcl-2 IHC+ patient subgroups.

Mid-infrared (IR) ellipsometry of thin films and molecule layers at solid–liquid interfaces has been a challenge because of the absorption of light in water. It has been usually overcome by using configurations utilizing illumination through the solid substrate. However, the access to the solid–liquid interface in a broad spectral range is also challenging due to the limited transparency of most structural materials in the IR wavelength range. In this work, we propose a concept of a microfabricated analysis cell based on an IR-transparent Si membrane with advantages of a robust design, flexible adaptation to existing equipment, small volume, multiple-angle capabilities, broad wavelength range, and opportunities of multilayer applications for adjusted ranges of high sensitivity. The chamber was prepared by 3D micromachining technology utilizing deep reactive ion etching of a silicon-on-insulator wafer and bonded to a polydimethylsiloxane microfluidic injection system resulting in a cell volume of approximately 50 μL. The mechanical stability of the 2 and 5 μm-thick membranes was tested using different “backbone” reinforcement structures. It was proved that the 5 μm-thick membranes are stable at lateral cell sizes of 5 mm by 20 mm. The cell provides good intensity and adjustment capabilities on the stage of a commercial mid-IR ellipsometer. The membrane configuration also provides optical access to the sensing interfaces at a broad range of incident angles, which is a significant advantage in many potential sensing structure configurations, such as plasmonic, multilayer, 2D, or metamaterial applications.

Carotid artery stenosis (CAS) is among the leading causes of mortality and permanent disabilities in the Western world. CAS is a consequence of systemic atherosclerotic disease affecting the majority of the aging population. Optical coherence tomography angiography (OCTA) is a novel imaging technique for visualizing retinal blood flow. It is a noninvasive, fast method for qualitative and quantitative assessment of the microcirculation. Cerebral and retinal circulation share similar anatomy, physiology, and embryology; thus, retinal microvasculature provides a unique opportunity to study the pathogenesis of cerebral small vessel disease in vivo. In this study, we aimed to analyze the effect of systemic risk factors on retinal blood flow in the eyes of patients with significant carotid artery stenosis using OCT angiography. A total of 112 eyes of 56 patients with significant carotid stenosis were included in the study. We found that several systemic factors, such as decreased estimated glomerular filtration rate (eGFR), hypertension, and carotid occlusion have a significant negative effect on retinal blood flow, while statin use and carotid surgery substantially improve ocular microcirculation. Neither diabetes, clopidogrel or acetylsalicylic acid use, BMI, serum lipid level, nor thrombocyte count showed a significant effect on ocular blood flow. Our results demonstrate that a systematic connection does exist between certain systemic risk factors and retinal blood flow in this patient population. OCTA could help in the assessment of cerebral circulation of patients with CAS due to its ability to detect subtle changes in retinal microcirculation that is considered to represent changes in intracranial blood flow.

ABSTRACTIntroductionPolycythemia vera (PV) is a Philadelphia chromosome-negative chronic myeloproliferative neoplasm (MPN). A newly developed PV treatment option, ropeginterferon alfa-2b, contains recombinant human alfa monoisomer as an active ingredient, resulting in a novel pharmacologic profile and improved tolerability. Efficacy studies conclude remarkable long-term hematological response and sustained JAK2V617F allele burden reduction. Ropeginterferon alfa-2b compound has been approved for the treatment of polycythemia vera without symptomatic splenomegaly.Areas coveredCurrent clinical trials are investigating the role of ropeginterferon alfa-2b in the first-line setting of treatment for PV. The safety and efficacy results of completed trials are summarized in this review. Metabolic, pharmacokinetic issues are also discussed of ropeginterferon alfa-2b.Expert opinionRopeginterferon alfa-2b is a targeted therapeutic option in the treatment of PV, representing a significant improvement compared to conventional cytoreductive therapies. The single isomer entity of the recombinant human interferon alfa-2b and the mono-pegylation method imparts favorable properties to the compound. The use of ropeginterferon alfa-2b allows extended dosing interval, reduces side effects, and may increase the overall survival of PV patients by reducing the risk of progression to myelofibrosis or acute leukemia. Clinical data suggests that the compound may provide a disease-modifying option for PV patients with asymptomatic splenomegaly.

The phase 3 ECHELON-1 study demonstrated that brentuximab vedotin (A) with doxorubicin, vinblastine, and dacarbazine (AVD; A+AVD) exhibited superior modified progression-free survival (PFS) vs doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) for frontline treatment of patients with stage III/IV classical Hodgkin lymphoma (cHL). Maturing positron emission tomography (PET)-adapted trial data highlight potential limitations of PET-adapted approaches, including toxicities with dose intensification and higher-than-expected relapse rates in PET scan after cycle 2 (PET2)-negative (PET2−) patients. We present an update of the ECHELON-1 study, including an exploratory analysis of 3-year PFS per investigator. A total of 1334 patients with stage III or IV cHL were randomized 1:1 to receive 6 cycles of A+AVD (n = 664) or ABVD (n = 670). Interim PET2 was required. At median follow-up of 37 months, 3-year PFS rates were 83.1% with A+AVD and 76.0% with ABVD; 3-year PFS rates in PET2−patients aged <60 years were 87.2% vs 81.0%, respectively. A beneficial trend in PET2+patients aged <60 years on A+AVD was also observed, with a 3-year PFS rate of 69.2% vs 54.7% with ABVD. The benefit of A+AVD in the intent-to-treat population appeared independent of disease stage and prognostic risk factors. Upon continued follow-up, 78% of patients with peripheral neuropathy on A+AVD had either complete resolution or improvement compared with 83% on ABVD. These data highlight that A+AVD provides a durable efficacy benefit compared with ABVD for frontline stage III/IV cHL, consistent across key subgroups regardless of patient status at PET2, without need for treatment intensification or bleomycin exposure. This trial was registered at www.clinicaltrials.govas #NCT01712490 (EudraCT no. 2011-005450-60).

Accurate classification of liver disease stages provides crucial insights into patient prognosis, aiding in the prediction of disease outcomes and influencing clinical decision-making. There is an urgent need for non-invasive methods to diagnose various stages of liver dysfunction and uncover hidden pattern based on individual disease characteristics.

•There was no clear survival benefit for guadecitabine over standard-of-care in patients with relapsed/refractory AML.•Guadecitabine produced higher clinical response rates, with potential survival benefit in several prespecified subgroups.

Silica-supported Ni catalyst (6.6 wt% Ni) was prepared and tested in solvent-free hydroconversion of levulinic acid (LA) using flow-through fixed-bed tube-type microreactor at 250 and 275 °C in the pressure and space time range of 1–30 bar and 0.1–1.0 gcatgLA−1h, respectively. The catalyst was characterized by XRD, adsorption/desorption N2isotherms, temperature-programmed H2-reduction (H2-TPR), FT-IR spectra of adsorbed pyridine (Py), and temperature-programmed H2desorption (H2-TPD). At 250 °C and 1 bar total pressure LA was dehydrated to α-angelica lactone (AL) intermediate that was hydrogenated to γ-valerolactone (GVL). At space time 0.25 gcatgLA−1h 82% GVL selectivity was achieved at virtually full LA conversion. The GVL became partially converted to pentanoic acid (PA). At longer space time, 1.0 gcatgLA−1h, the PA selectivity increased to 37%. At pressure > 1 bar the favored reaction of GVL was the hydrogenolysis of its ester bond and dehydration of the intermediate 1,4-pentanediol (1,4-PD) to 2-methyltetrahydrofuran (2-MTHF). At 250 °C and 30 bar the yield of 2-MTHF was 56 mol%. The product distribution is controlled by the relative activity of the Ni/SiO2catalyst in the hydrogenolysis of the GVL C–O bonds.