Intermediate Target Research Articles

Risankizumab Is Associated With Normalization of Biomarkers in Patients With Crohn's Disease: Results From the Phase 3 ADVANCE, MOTIVATE, and FORTIFY Studies.

Normalization of high-sensitivity C-reactive protein [hs-CRP] and fecal calprotectin [FCP] are suggested Crohn's disease [CD] intermediate treatment targets. This analysis evaluates achievement of biomarker normalization and the relationship between improvements in biomarker concentrations and clinical and endoscopic outcomes among patients treated with risankizumab. This post hoc analysis included patients with moderately to severely active CD and elevated baseline hs-CRP [> 5mg/L] or FCP [> 250 µg/g] concentrations from the 12-week ADVANCE and MOTIVATE induction studies, and the 52-week FORTIFY maintenance study. We assessed the proportion of patients achieving biomarker normalization, defined as hs-CRP ≤ 5mg/L and FCP ≤ 250 µg/g, and the association between achieving biomarker normalization and improved clinical and endoscopic outcomes. Among 748 patients with elevated baseline hs-CRP or FCP concentrations, higher proportions of patients treated with risankizumab vs placebo achieved normalization of hs-CRP [week 12: placebo, 17.5%; risankizumab 600mg, 48.5%; week 52: placebo, 29.5%; risankizumab 180mg, 45.2%; risankizumab 360mg, 40.8%] and FCP [week 12: placebo, 9.1%; risankizumab 600mg, 26.0%; week 52: placebo, 28.0%; risankizumab 180mg, 43.0%; risankizumab 360mg, 44.0%; nominal p < 0.05 vs placebo for all comparisons]. Achievement of both clinical or endoscopic outcomes and improvement of biomarker concentrations occurred at higher rates among patients treated with risankizumab vs placebo, regardless of prior exposure to biologic therapies. Risankizumab treatment led to sustained normalization of inflammatory biomarkers with improved clinical and endoscopic results.

A cell-autonomous role for primary cilium-mediated signaling in long-range commissural axon guidance.

Ciliopathies are characterized by the absence or dysfunction of primary cilia. Despite the fact that cognitive impairments are a common feature of ciliopathies, how cilia dysfunction affects neuronal development has not been characterized in detail. Here, we show that primary cilium-mediated signaling is required cell-autonomously by neurons during neural circuit formation. In particular, a functional primary cilium is crucial during axonal pathfinding for the switch in responsiveness of axons at a choice point or intermediate target. Using different animal models and in vivo, ex vivo and in vitro experiments, we provide evidence for a crucial role of primary cilium-mediated signaling in long-range axon guidance. The primary cilium on the cell body of commissural neurons transduces long-range guidance signals sensed by growth cones navigating an intermediate target. In extension of our finding that Shh is required for the rostral turn of post-crossing commissural axons, we suggest a model implicating the primary cilium in Shh signaling upstream of a transcriptional change of axon guidance receptors, which in turn mediate the repulsive response to floorplate-derived Shh shown by post-crossing commissural axons.

Adapting to climate change and the European Union pursuit of a just transition

The European Green Deal was launched by the European Commission (EC) in December 2019, before being formally approved in 2020. It comprises a package of policy measures that aim to set the European Union (EU) on the path to a green transition, with the ultimate objective of achieving climate neutrality by 2050. Despite the EU’s longstanding commitment to reducing carbon emissions in support of climate change mitigation and the achievement of its net zero ambition, this paper focuses on the growing importance of climate change adaptation within its policy portfolio. With respect to the latter, the long-term vision is for the EU to become a climate-resilient society that is also fully adapted to the unavoidable impacts of climate change. Achieving climate neutrality and a climate-resilient society by 2050 will be more challenging for some EU member states and regions than for others, eg poorer regions and those highly dependent on fossil fuels or with carbon-intensive industries that employ significant numbers of people. To address such issues, the EU has introduced a Just Transition Mechanism to help level the playing field and provide financial and technical support to regions most adversely affected by the move towards a low carbon economy. The paper traces the evolution of the EU’s climate policy agenda leading up to the adoption of the Green Deal, outlines its proposed road map in pursuit of climate neutrality and a climate-resilient society by 2050, and questions the efficacy of some its intermediate targets including the adequacy and equity of its just transition aspirations. It also details and scrutinises the key role that the European Investment Bank (EIB) will play in supporting delivery of the strategy.1,2

Adapting to climate change and the European Union pursuit of a just transition

The European Green Deal was launched by the European Commission (EC) in December 2019, before being formally approved in 2020. It comprises a package of policy measures that aim to set the European Union (EU) on the path to a green transition, with the ultimate objective of achieving climate neutrality by 2050. Despite the EU’s longstanding commitment to reducing carbon emissions in support of climate change mitigation and the achievement of its net zero ambition, this paper focuses on the growing importance of climate change adaptation within its policy portfolio. With respect to the latter, the long-term vision is for the EU to become a climate-resilient society that is also fully adapted to the unavoidable impacts of climate change. Achieving climate neutrality and a climate-resilient society by 2050 will be more challenging for some EU member states and regions than for others, eg poorer regions and those highly dependent on fossil fuels or with carbon-intensive industries that employ significant numbers of people. To address such issues, the EU has introduced a Just Transition Mechanism to help level the playing field and provide financial and technical support to regions most adversely affected by the move towards a low carbon economy. The paper traces the evolution of the EU’s climate policy agenda leading up to the adoption of the Green Deal, outlines its proposed road map in pursuit of climate neutrality and a climate-resilient society by 2050, and questions the efficacy of some its intermediate targets including the adequacy and equity of its just transition aspirations. It also details and scrutinises the key role that the European Investment Bank (EIB) will play in supporting delivery of the strategy.1,2

The Impact of Monetary Policy in Achieving Exchange Rate Stability in the Iraqi Economy for The Period (1990 - 2023) an Econometric Study

The exchange rate is a monetary economic indicator that expresses a country's economic performance. The exchange rate is the basic foundation on which the economies of any country in the world are built, whether developed or developing. As a result, most governments seek to implement regulations that ensure the currency exchange rate remains stable. To avoid the radical changes that currencies will endure during another period. The exchange rate also plays a prominent role in monetary policy, due to its use as an intermediate target, or as a tool, or simply as an indicator of the competitiveness of countries through its impact on components of economic growth such as investment, the degree of economic openness, the inflation rate, the narrow money supply, and the volume of exports. And the volume of imports, and foreign exchange reserves. Therefore, the primary goal of this study was to try to identify the nature of the exchange rate. As a result, in the first section, we discussed the concept of monetary policy, its most important tools, its most important goals, the exchange rate, and Iraq’s experience in the field of exchange during the period (1990-2023). While the second section was devoted to measuring the impact of monetary policy in achieving stability in the exchange rate of the Iraqi dinar against the US dollar using the vector model. correcting the mistake. The study concluded with some recommendations to reduce exchange rate fluctuations.

Intermediate vs. High Oxygen Saturation Targets in Preterm Infants: A National Cohort Study

Introduction: Optimal oxygen saturation targets remain unknown for extremely preterm infants. Methods: Cohort analysis of eligible preterm infants born <29 weeks’ gestation admitted between 2011 and 2018 to centers submitting data to the Canadian Neonatal Network (CNN) database. Site questionnaires to determine saturation targets, alarm settings, and date of change, allowed assignation of centers to intermediate (88–93%) or high (90–95%) saturation targets. A 6-month washout period was applied to sites which switched targets during the study period. Our primary outcome was survival free of major morbidity. Secondary outcomes were death, necrotizing enterocolitis (NEC), bronchopulmonary dysplasia (BPD), treated retinopathy of prematurity, and evidence of brain injury during admission. Generalized estimating equations were applied to compensate for demographic differences and site practices. Results: There were 2,739 infants in the high (mean gestational age [GA] 26 ± 1.6 weeks) and 6,813 infants in the intermediate (mean GA 26.2 ± 1.6 weeks) saturation target group. Survival without morbidity was higher in the intermediate target group (adjusted odds ratio [aOR] 1.59; 95% CI: 1.04, 2.45). There was no difference in mortality between groups (aOR 0.81; 95% CI: 0.59, 1.11), in NEC, treated retinopathy, or brain injury. On subgroup analysis, restricting data to sites which switched targets during the study, intermediate saturation targets were associated with lower rates of BPD (aOR 0.45; 95% CI: 0.28, 0.72). Conclusion: For neonates <29 weeks’ gestation, intermediate saturation target was associated with higher odds of survival without major morbidity compared to higher oxygen saturation target.

Hunting for the Intermolecular Diels-Alderase.

ConspectusThe Diels-Alder reaction is well known as a concerted [4 + 2] cycloaddition governed by the Woodward-Hoffmann rules. Since Prof. Otto Diels and his student Kurt Alder initially reported the intermolecular [4 + 2] cycloaddition between cyclopentadiene and quinone in 1928, it has been recognized as one of the most powerful chemical transformations to build C-C bonds and construct cyclic structures. This named reaction has been widely used in synthesizing natural products and drug molecules. Driven by the synthetic importance of the Diels-Alder reaction, identifying the enzyme that stereoselectively catalyzes the Diels-Alder reaction has become an intriguing research area in natural product biosynthesis and biocatalysis. With significant progress in sequencing and bioinformatics, dozens of Diels-Alderases have been characterized in microbial natural product biosynthesis. However, few are evolutionally dedicated to catalyzing an intermolecular Diels-Alder reaction with a concerted mechanism.This Account summarizes our endeavors to hunt for the naturally occurring intermolecular Diels-Alderase from plants. Our research journey started from the biomimetic syntheses of D-A-type terpenoids and flavonoids, showing that plants use both nonenzymatic and enzymatic intermolecular [4 + 2] cycloadditions to create complex molecules. Inspired by the biomimetic syntheses, we identify an intermolecular Diels-Alderase hidden in the biosynthetic pathway of mulberry Diels-Alder-type cycloadducts using a biosynthetic intermediate probe-based target identification strategy. This enzyme, MaDA, is an endo-selective Diels-Alderase and is then functionally characterized as a standalone intermolecular Diels-Alderase with a concerted but asynchronous mechanism. We also discover the exo-selective intermolecular Diels-Alderases in Morus plants. Both the endo- and exo-selective Diels-Alderases feature a broad substrate scope, but their mechanisms for controlling the endo/exo pathway are different. These unique intermolecular Diels-Alderases phylogenetically form a subgroup of FAD-dependent enzymes that can be found only in moraceous plants, explaining why this type of [4 + 2] cycloadduct is unique to moraceous plants. Further studies of the evolutionary mechanism reveal that an FAD-dependent oxidocyclase could acquire the Diels-Alderase activity via four critical amino acid mutations and then gradually lose its original oxidative activity to become a standalone Diels-Alderase during the natural evolution. Based on these insights, we designed new Diels-Alderases and achieved the diversity-oriented chemoenzymatic synthesis of D-A products using either naturally occurring or engineered Diels-Alderases.Overall, this Account describes our decade-long efforts to discover the intermolecular Diels-Alderases in Morus plants, particularly highlighting the importance of biomimetic synthesis and chemical proteomics in discovering new intermolecular Diels-Alderases from plants. Meanwhile, this Account also covers the evolutionary and catalytic mechanism study of intermolecular Diels-Alderases that may provide new insights into how to discover and design new Diels-Alderases as powerful biocatalysts for organic synthesis.

How aligned are industry strategy and government policy for the decarbonization of energy-intensive process industries?

ABSTRACT Decarbonization of energy-intensive process industries (EPIs) is a central unresolved challenge for limiting global warming to 1.5°C or well-below 2°C. In this article, we investigate the alignment between government policy and applicable industry strategy in decarbonization efforts across six European countries – Denmark, Germany, Netherlands, Norway, Sweden and the United Kingdom. We distinguish between ‘target alignment’ (How comparable are the size of the emission reduction commitments?), ‘temporal alignment’ (How closely do the timelines match?) and ‘solution alignment’ (Are the same types of solutions prioritized?). Based on an analysis of national policy documents, company strategies of the 10 largest emitting EPI plants in each country, as well as secondary sources, we find high target alignment. However, we find substantially lower temporal alignment as emitters are reluctant to commit to intermediate targets that match the decarbonization timelines laid out in national government policy. Solution alignment is intermediate across all six countries as emitters generally pursue the decarbonization options prioritized in policy, but with most emitters remaining at the level of ambitions or plans and few examples of commercial investments so far.

Rac1 and Nectin3 are essential for PCP-directed axon guidance in the peripheral auditory system.

Our sense of hearing is critically dependent on the spiral ganglion neurons (SGNs) that connect the sound receptors in the organ of Corti (OC) to the cochlear nuclei of the hindbrain. Type I SGNs innervate inner hair cells (IHCs) to transmit sound signals, while type II SGNs (SGNIIs) innervate outer hair cells (OHCs) to detect moderate-to-intense sound. During development, SGNII afferents make a characteristic 90-degree turn toward the base of the cochlea and innervate multiple OHCs. It has been shown that the Planar Cell Polarity (PCP) pathway acts non-autonomously to mediate environmental cues in the cochlear epithelium for SGNII afferent turning towards the base. However, the underlying mechanisms are unknown. Here, we present evidence that PCP signaling regulates multiple downstream effectors to influence cell adhesion and the cytoskeleton in cochlear supporting cells (SCs), which serve as intermediate targets of SGNII afferents. We show that the core PCP gene Vangl2 regulates the localization of the small GTPase Rac1 and the cell adhesion molecule Nectin3 at SC-SC junctions through which SGNII afferents travel. Through in vivo genetic analysis, we also show that loss of Rac1 or Nectin3 partially phenocopied SGNII peripheral afferent turning defects in Vangl2 mutants, and that Rac1 plays a non-autonomous role in this process in part by regulating PCP protein localization at the SC-SC junctions. Additionally, epistasis analysis indicates that Nectin3 and Rac1 likely act in the same genetic pathway to control SGNII afferent turning. Together, these experiments identify Nectin3 and Rac1 as novel regulators of PCP-directed SGNII axon guidance in the cochlea.

Mechanism Design in Sport Matches: Competitive Balance, Intermediate Targets, and Effort Elicitation in a Three-Stage Contest Game

In sport, various examples of intermediate match targets exist that advantage the target-achieving party’s match outcome. We examine said targets within paired, multi-stage Tullock contest games, one a nested contest with intermediate target and one without. In equilibrium, the aggregate match-effort maximizing League sets a substantial subsequent match advantage to the target-achieving party. The nested Tullock contest with intermediate target elicits higher aggregate match effort than any one-shot Tullock contest. The effect of intermediate targets is fully consistent with that of an aggregate effort eliciting mechanism employed by leagues. Extant empirical literature finds clear demand for such a mechanism.

Impact of joint peer review with a specialist radiologist in head and neck cancer radiotherapy planning.

e18059 Background: Head and neck oncology is heavily dependent on interpretation of radiology. This raises the question whether input from radiology should be formally scheduled as part of the radiotherapy contouring processes. Our aim was to assess the impact of this practice through qualitative and quantitative analysis. Methods: H &amp; N patients treated with radiotherapy between May-2022 and August-2023 were reviewed by a specialist HN radiologist. Incidence of changes in T, N, M and TNM-stage, change as defined by The RCR guidance: 'major' (change in gross tumour volume and/or high-dose clinical target volume, dose/fractionation) or 'minor' (change in intermediate or elective dose clinical target volumes or organs at risk), was recorded. We evaluated whether any of these changes were time dependent (Time interval between MDT to RT Peer Review). Other clinical variables: age, gender, primary diagnosis, tumour site, significant incidental findings, post-operative pTNM, post-operative disease status in adjuvant setting on planning imaging (NIRADS), need for additional imaging. We also recorded number of scans reviewed per patient, types of imaging studies reviewed, time taken for review and number of radiologist PA’s required. Retrospective analysis of a prospective database was performed. Results: 410 patients (252-definitive, 137-adjuvant, 21-palliative) were reviewed of which 51.5%-oropharynx followed by 26.8%-Larynx &amp; Hypopharynx. Mean age was 66.14 yrs (SD 11.46) and M:F was 4:1. Baseline and Therapy planning imaging was reviewed for 100% patients of which baseline included: MR (91.7%), CT (96.1%), US (34.1%), PETCT (31%) and therapy planning (62%-CECT, 19%-MR&amp;CT, 15%-CT, 4%-PETCT). In all patients (n=410), T/N/M/TNM-stage percentage upstage was 27/36.8/8.3/42.2% and in definitive cohort (n=252), it was 41.7/56.7/7.1/59.5%. Reviewing RT-planning Imaging in adjuvant cohort (n=137), 76.6% were NIRADS-1, 11.7% NIRADS-3/4/loco-regional disease and 11.7% distant metastasis. T/N/M/TNM-stage upstage was time dependent and the mean time interval between MDT to RT was higher in upstaged patients (p &lt;0.001). Overall percentage change in treatment plan: no/minor/major/palliative was 40.5/33.9/17.3/8.3% and in definitive cohort 30.2/42.1/20.6/7.1%. Change in plan was not dependent on mean time interval between MDT to RT. Average 10 patients (4 imaging studies/patient) were reviewed by radiologist in 1PA (time to review and peer review meeting time). Conclusions: Routine head and neck radiologist input in radiotherapy peer review is feasible and resulted in a number of major and minor changes to treatment. Inputs not only eased the contouring for oncologists but also lead to updating of current disease stage just prior to treatment. Overall, our results suggest that this is a practice changing step in the radiotherapy workflow which has a direct impact on patient management.

Decarbonisation – how are we tracking against plans

Globally many countries have committed to reducing carbon dioxide emissions and their dependence on fossil fuels with most large emitting countries now committing to ‘net-zero’ targets sometime in the second half of this century and earlier intermediate targets in 2030. With only 6 years to go until the deadline to meet 2030 emission reduction targets, what is the verdict? How are Australian and global emission reduction projects tracking? World electricity demand in 2022 was 28,500 TWh with 39.3 billion tonnes of carbon dioxide emitted in the same year as a result. The global energy mix hasn’t changed much: fossil fuel consumption as a percentage of primary energy in 2022 remained steady at 82% and in July 2023 the International Energy Agency projected 2023 oil demand to be 102.1 million barrels a day, an all-time high. This paper will take a look at decarbonisation efforts around the world and provide an overview of what was targeted in previous years and compare it with what has actually been achieved. How far are we truly on the road to decarbonisation? Are decarbonisation initiatives including carbon capture, utilisation and storage, hydrogen projects, solar and wind farms providing the intended results? Incorporating recent key regulatory initiatives from governments around the world including the US, Australia and the EU, this paper will outline progress to date and attempt to show possible paths going forward in answering the question whether it is possible to achieve the proposed emission reduction targets in 6 years.

Oxygen-Saturation Targets and Cognitive and Functional Outcomes in Mechanically Ventilated Adults.

Rationale: Among mechanically ventilated critically ill adults, the PILOT (Pragmatic Investigation of Optimal Oxygen Targets) trial demonstrated no difference in ventilator-free days among lower, intermediate, and higher oxygen-saturation targets. The effects on long-term cognition and related outcomes are unknown.Objectives: To compare the effects of lower (90% [range, 88-92%]), intermediate (94% [range, 92-96%]), and higher (98% [range, 96-100%]) oxygen-saturation targets on long-term outcomes.Methods: Twelve months after enrollment in the PILOT trial, blinded neuropsychological raters conducted assessments of cognition, disability, employment status, and quality of life. The primary outcome was global cognition as measured using the Telephone Montreal Cognitive Assessment. In a subset of patients, an expanded neuropsychological battery measured executive function, attention, immediate and delayed memory, verbal fluency, and abstraction.Measurements and Main Results: A total of 501 patients completed follow-up, including 142 in the lower, 186 in the intermediate, and 173 in the higher oxygen target groups. Median (interquartile range) peripheral oxygen saturation values in the lower, intermediate, and higher target groups were 94% (91-96%), 95% (93-97%), and 97% (95-99%), respectively. Telephone Montreal Cognitive Assessment score did not differ between lower and intermediate (adjusted odds ratio [OR], 1.36 [95% confidence interval (CI), 0.92-2.00]), intermediate and higher (adjusted OR, 0.90 [95% CI, 0.62-1.29]), or higher and lower (adjusted OR, 1.22 [95% CI, 0.83-1.79]) target groups. There was also no difference in individual cognitive domains, disability, employment, or quality of life.Conclusions: Among mechanically ventilated critically ill adults who completed follow-up at 12 months, oxygen-saturation targets were not associated with cognition or related outcomes.

Are we ready to use new endoscopic scores for ulcerative colitis?

For ulcerative colitis (UC), the variability in inflammatory activity along the colon poses a challenge in management. The focus on achieving endoscopic healing in UC is evident, where the UC Endoscopic Index of Severity and Mayo Endoscopic Subscore are commonly used for evaluation. However, these indices primarily consider the most severely affected region. Liu et al recent study validates the Toronto Inflammatory Bowel Disease Global Endoscopic Reporting (TIGER) score offering a comprehensive assessment of inflammatory activity across diverse segments of the colon and rectum and a reliable index correlating strongly with UC Endoscopic Index of Severity and moderately with Mayo Endoscopic Subscore (MES). Despite recommendation, certain aspects warrant further investigation. Fecal calprotectin, an intermediate target, correlates with TIGER and should be explored. Determining TIGER scores defining endoscopic remission and response, evaluating agreement with histological activity, and assessing inter-endoscopist agreement for TIGER require scrutiny. Exploring the correlation between TIGER and intestinal ultrasound, akin to MES, adds value.

Electron Absorbed Fractions and S Factors for Intermediate Size Target Volumes: Comparison of Analytic Calculations and Monte Carlo Simulations

The absorbed fraction and the S factor represent fundamental quantities in MIRD-based dosimetry of radiopharmaceutical therapy (RPT). Although Monte Carlo (MC) simulations represent the gold standard in RPT dosimetry, dose point kernels (DPK) obtained from analytic range–energy relations offer a more practical alternative for charged-particle dosimetry (β- or α-emitters). In this work, we perform DPK- and MC-based calculations of the self-absorbed fractions and S factors for monoenergetic electrons uniformly distributed in intermediate-size target volumes (~mm to cm) relevant to micrometastasis and disseminated disease. Specifically, the aim of the present work is as follows: (i) the development of an analytic range–energy relation, effective over a broad energy range (100 keV–20 MeV) covering most applications of radiotherapeutic interest; (ii) the application of the new formula to DPK-based calculations of the absorbed fraction and S factor and comparison against MC simulations (both published and present work data) as well as the MIRDcell V2.0.16 software, which uses a similar analytic methodology; and (iii) the study of the influence of simulation parameters (step-size, tracking/production cut-off energies, and ionization model) in Geant4-based calculations of S factors. It is shown that the present DPK-based calculations are in excellent agreement (within 1.5%) with the MIRDcell software, while also being in fair agreement with published MC data as well as with the new Geant4 simulations, with average differences of ~20% for the (sub) mm-sized volumes and ~10% for the cm-sized volumes. The effect of the choice of Geant4 simulation parameters was found to be negligible for the examined target volumes (~mm), except for the use of the Penelope ionization model, which may exhibit noticeable discrepancies (up to ~20%) against the Standard and Livermore models. The present work provides quantitative information that may be useful to both the MC- and DPK-based beta dosimetry of micrometastasis and disseminated disease, which represents an important field of application of RPT.

Evolutionary process of changing marine fuels - transition fuels on the way to the hydrogen era

The article presents the ongoing transformation of marine fuels - from fossil fuels to transition fuels and the final target - hydrogen. This process was forced by the legal regulations of the International Maritime Organization and the European Union Parliament. The target year is 2050, but intermediate targets should be achieved in 2030 and 2040. The base year is 2008. By the end of 2022, an increasing trend of interest in more environmentally friendly fuels was observed. However, it is far from expectations. Analyzing ships under construction and those ordered, a much higher share of renewable fuels intended for propulsion of ships is observed. The shipowners took precautionary measures. They order ships for transitional fuels, which reduce investment and operating costs, assuming that far-reaching changes will take place after overcoming significant technological problems, lowering the prices of equipment and fuel. The article analyzes the ongoing processes, justifying the sense of the actions taken. The regulations being introduced have a significant impact on the ongoing transformation processes of marine fuels. It was noted that they may have serious consequences for maritime transport, indicating potential threats.

The impact of collaborative processes on target text quality in translator training

ABSTRACT This article explores the impact of collaboration on target text quality in translator training. By comparing team translations with those by individual peers, and analysing the highest and lowest scoring teams, the authors aimed to understand the impact of collaboration on quality. The comparison indicates that translations in a skills lab setting marginally outperform individual translations, but that carelessness is more likely to be observed in the intermediate individual target texts produced in a collaborative setting.

A GARP transcription factor SlGCC positively regulates lateral root development in tomato via auxin-ethylene interplay.

SlGCC, a GARP transcription factor, functions as a root-related transcriptional repressor. SlGCC synchronizes auxin and ethylene signaling involving SlPIN3 and SlIAA3 as intermediate targets sketching a molecular map for lateral root development in tomato. The root system is crucial for growth and development of plants as it performs basic functions such as providing mechanical support, nutrients and water uptake, pathogen resistance and responds to various stresses. SlGCC, a GARP family transcription factor (TF), exhibited predominant expression in age-dependent (initial to mature stages) tomato root. SlGCC is a transcriptional repressor and is regulated at a transcriptional and translational level by auxin and ethylene. Auxin and ethylene mediated SlGCC protein stability is governed via proteasome degradation pathway during lateral root (LR) growth development. SlGCC over-expressor (OE) and under-expressed (UE) tomato transgenic lines demonstrate its role in LR development. This study is an attempt to unravel the vital role of SlGCC in regulating tomato LR architecture.

TRImodal DEfinitive invasive vagiNal carcinoma Treatment (TRIDENT protocol): how a standardized approach may change prognostic outcomes

ObjectiveVaginal carcinoma is a rare malignancy accounting for 1–2% of all gynecological cancers. Surgery has a limited role, while definitive radiotherapy–chemotherapy followed by interventional radiotherapy is considered a valid alternative....

Decarbonisation of Road Transport as a Key Element for Achieving Climate Neutrality

Abstract This article considers the issue of climate neutrality, which is becoming increasingly important in view of current European Union (EU) policies. It is necessary to mention the requirement that EU countries achieve climate neutrality by 2050, with the intermediate target being the reduction of harmful exhaust gases to 55 per cent compared to 1990. The achievement of climate neutrality particularly affects transport, which is one of the most crucial sectors of the economy in this regard. Therefore, the author will point out the process of decarbonisation of road transport in the context of both public and private transport, highlighting the most important barriers to the development of this process, using Poland as an example.