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Abstract Transitioning to renewables is critical to address the Caribbean's vulnerability to imported fossil fuel price volatility and concerns about climate change. This study presents a first‐of‐its‐kind comprehensive analysis of 17 illustrative pathways varying the impact of e‐fuel imports, grid interconnections and an accelerated energy transition towards the Caribbean's carbon neutrality by 2050. The research method is based on techno‐economic principles for designing a cost‐optimal energy system. An optimisation tool is used, the LUT Energy System Transition Model, to analyse the various pathways. The study finds that high uptake of renewables in Caribbean energy systems significantly lowers costs and enhances reliability, crucial for building competitive and resilient economies. Renewable energy dominated pathways show 7–24% lower cumulative costs compared to alternatives, with grid integration reducing costs by 1–10%. Accelerated transition pathways incur 3–12% higher costs than complete defossilisation by 2050. Solar photovoltaics, wind power, batteries, and electrolysers are pivotal for achieving carbon neutrality by 2050. Importing e‐fuels reduces system costs by 7–16% and supports local resource use. Offshore renewable energy overcome land limitations, driving sustainable development and a vibrant blue economy. High electrification levels with renewable energy, sector coupling, and Power‐to‐X solutions enhance system efficiency and flexibility. Given the dominance of solar photovoltaics, the Caribbean's energy transition could be more appropriately called a ‘Solar‐to‐X Economy’. This research contributes to the international perspective on sustainable energy transition for islands.

Abstract Adopting aggregation techniques in power sector modelling led to disregarding the key characteristics of regions in terms of resource use, which may not completely capture the bottlenecks in the energy transition. This study provides a holistic approach to estimate its impact on the transition of the European power system from the perspective of energy return on investment (EROI) by using six energy transition scenarios based on three different spatial representations. The findings indicate that EROI trends are highly dependent on the spatial representation, technology selection and energy mix. Further additional capacities of complementary technologies along with an upsurge in renewable capacities drive EROI values down. Disregarding the physical distances in the energy modelling results in large EROI enhancement due to the artificial smoothing effect of the aggregation method. EROI values of the aggregated scenarios remain between 18 and 24 by 2050. In the case of 20 independent sub‐regions, the lowest EROI is obtained at about 14 by 2050, due to the limitation on optimal resource utilisation. Interconnection of the sub‐regions, which represents the best proximation to the real situation, increases the EROI to 17 by 2050.

Abstract In chronic lymphocytic leukemia, the reliability of next‐generation sequencing (NGS) to detect TP53 variants ≤10% allelic frequency (low‐VAF) is debated. We tested the ability to detect 23 such variants in 41 different laboratories using their NGS method of choice. The sensitivity was 85.6%, 94.5%, and 94.8% at 1%, 2%, and 3% VAF cut‐off, respectively. While only one false positive (FP) result was reported at >2% VAF, it was more challenging to distinguish true variants

Abstract Introduction This study evaluates the clinical value of a deep learning–based artificial intelligence (AI) system that performs rapid brain volumetry with automatic lobe segmentation and age‐ and sex‐adjusted percentile comparisons. Methods Fifty‐five patients—17 with Alzheimer's disease (AD), 18 with frontotemporal dementia (FTD), and 20 healthy controls—underwent cranial magnetic resonance imaging scans. Two board‐certified neuroradiologists (BCNR), two board‐certified radiologists (BCR), and three radiology residents (RR) assessed the scans twice: first without AI support and then with AI assistance. Results AI significantly improved diagnostic accuracy for AD (area under the curve −AI: 0.800, +AI: 0.926, p

Abstract Effective photoinduced charge transfer makes molecular bimetallic assemblies attractive for applications as active light‐induced proton reduction systems. Developing competitive base metal dyads is mandatory for a more sustainable future. However, the electron transfer mechanisms from the photosensitizer to the proton reduction catalyst in base metal dyads remain so far unexplored. A Fe─Co dyad that exhibits photocatalytic H2 production activity is studied using femtosecond X‐ray emission spectroscopy, complemented by ultrafast optical spectroscopy and theoretical time‐dependent DFT calculations, to understand the electronic and structural dynamics after photoexcitation and during the subsequent charge transfer process from the FeII photosensitizer to the cobaloxime catalyst. This novel approach enables the simultaneous measurement of the transient X‐ray emission at the iron and cobalt K‐edges in a two‐color experiment. With this methodology, the excited state dynamics are correlated to the electron transfer processes, and evidence of the Fe→Co electron transfer as an initial step of proton reduction activity is unraveled.

Abstract This study presents a novel approach to analysing the Japanese energy system transition from a mostly fossil fuels‐based system as of today, to a sustainable renewable energy‐based system by 2050. This research uses a novel technology‐rich, multi‐regional, multi‐sectoral, and cost‐optimal energy system model for the analysis, describing pathways to achieving the Japanese climate neutrality vision by 2050 based on renewables in the most cost‐effective manner. The energy transition of Japan is analysed for both rapid and delayed defossilisation pathways, impact of demand sensitivity, and benefit of sustainable energy imports in the form of electricity from Russia and China or e‐fuels from countries like Australia. The results show that a self‐sufficient energy system is achievable; however, some sustainable energy imports in the form of electricity and e‐fuels can be beneficial in further reducing overall investments, relieve pressure to develop local renewable resources and improving energy system flexibility. In addition, this research highlights the critical advantage of a fully renewable pathway, sector coupling, and high electrification rates as the most cost‐efficient way of achieving the Japanese climate neutrality vision by 2050. The renewable pathway also delivers an energy system with high levels of efficiency gains through direct and indirect renewable electricity usage.

Abstract The British Isles, consisting of the United Kingdom and the Republic of Ireland, were investigated for a sustainable energy system transition towards 100% renewable energy in 2050. Under given framework conditions, three pathways comprising the entire energy system were investigated in 5‐year time steps and hourly resolution applying an advanced energy system modelling tool and identifying the lowest cost solutions. The British Isles were structured into 10 sub‐national regions. Special attention was paid to the high offshore wind potential of the British Isles, as well as the limited societal acceptance for onshore wind in the United Kingdom. The results indicate that a transition to 100% renewable energy is economically more attractive than the governmental strategy that involves nuclear power and fossil carbon capture and storage. The total annualised system costs can decrease to 63 b€ and a levelised cost of electricity of 40 €/MWh if onshore wind and solar photovoltaics are allowed to be built to a higher extend. High levels of electrification and sector coupling are the main reasons for decreasing primary energy demand. The multiple risks of nuclear technology can be avoided if dedicated action towards 100% renewable energy is taken.

Abstract Objective Self‐stigma is the internalization of unfavorable public perceptions, which people with epilepsy (PWE) frequently experience. PWE with strong self‐stigma have low self‐esteem and are less likely to engage in treatment behavior. The Epilepsy Self‐Stigma Scale (ESSS) has been developed and validated in Japan. We translated the ESSS into German for this study to examine its reliability and validity. Methods We created the German version of ESSS (ESSS‐G) based on the original Japanese version. From May to October 2022, we recruited out‐ and inpatients from Bethel Epilepsy Centre, University Hospital for Epileptology, for psychometric evaluation. Inclusion criteria were an age of ≥18 years, sufficient reading and speaking skills in German, and the ability to comprehend the German questionnaires. Participants also completed the Rosenberg Self‐Esteem Scale (RSES), Neurological Disorders Depression Inventory for Epilepsy (NDDI‐E), Generalized Anxiety Disorder 7 (GAD‐7), Epilepsy Knowledge Scale, and items on “overall quality of life (QOL)” and “overall health” (items from QOLIE‐31). Results One hundred twenty‐eight of 146 patients asked to participate granted informed consent and completed the study questionnaire (87.7% response rate). 115 cases were analyzed since 13 did not match the inclusion criteria. The analysis revealed a single factor explaining 49.2% of the total variance. All factor loadings were >0.40, and the reliability was high (Cronbach's α = 0.80). Higher ESSS total scores were associated with higher anxiety (GAD‐7, r = 0.54, P

Abstract Anthranilate and its derivatives are important basic chemicals for the synthesis of polyurethanes as well as various dyes and food additives. Today, anthranilate is mainly chemically produced from petroleum‐derived xylene, but this shikimate pathway intermediate could be also obtained biotechnologically. In this study, Corynebacterium glutamicum was engineered for the microbial production of anthranilate from a carbon source mixture of glucose and xylose. First, a feedback‐resistant 3‐deoxy‐arabinoheptulosonate‐7‐phosphate synthase from Escherichia coli, catalysing the first step of the shikimate pathway, was functionally introduced into C. glutamicum to enable anthranilate production. Modulation of the translation efficiency of the genes for the shikimate kinase (aroK) and the anthranilate phosphoribosyltransferase (trpD) improved product formation. Deletion of two genes, one for a putative phosphatase (nagD) and one for a quinate/shikimate dehydrogenase (qsuD), abolished by‐product formation of glycerol and quinate. However, the introduction of an engineered anthranilate synthase (TrpEG) unresponsive to feedback inhibition by tryptophan had the most pronounced effect on anthranilate production. Component I of this enzyme (TrpE) was engineered using a biosensor‐based in vivo screening strategy for identifying variants with increased feedback resistance in a semi‐rational library of TrpE muteins. The final strain accumulated up to 5.9 g/L (43 mM) anthranilate in a defined CGXII medium from a mixture of glucose and xylose in bioreactor cultivations. We believe that the constructed C. glutamicum variants are not only limited to anthranilate production but could also be suitable for the synthesis of other biotechnologically interesting shikimate pathway intermediates or any other aromatic compound derived thereof.

Abstract Background Acute graft‐versus‐host disease (aGvHD) is a major cause of death for patients following allogeneic hematopoietic stem cell transplantation (HSCT). Effective management of moderate to severe aGvHD remains challenging despite recent advances in HSCT, emphasizing the importance of prophylaxis and risk factor identification. Methods In this study, we analyzed data from 1479 adults who underwent HSCT between 2005 and 2017 to investigate the effects of aGvHD prophylaxis and time‐dependent risk factors on the development of grades II–IV aGvHD within 100 days post‐HSCT. Results Using a dynamic longitudinal time‐to‐event model, we observed a non‐monotonic baseline hazard overtime with a low hazard during the first few days and a maximum hazard at day 17, described by Bateman function with a mean transit time of approximately 11 days. Multivariable analysis revealed significant time‐dependent effects of white blood cell counts and cyclosporine A exposure as well as static effects of female donors for male recipients, patients with matched related donors, conditioning regimen consisting of fludarabine plus total body irradiation, and patient age in recipients of grafts from related donors on the risk to develop grades II–IV aGvHD. Additionally, we found that higher cumulative hazard on day 7 after allo‐HSCT are associated with an increased incidence of grades II–IV aGvHD within 100 days indicating that an individual assessment of the cumulative hazard on day 7 could potentially serve as valuable predictor for later grades II–IV aGvHD development. Using the final model, stochastic simulations were performed to explore covariate effects on the cumulative incidence over time and to estimate risk ratios. Conclusion Overall, the presented model showed good descriptive and predictive performance and provides valuable insights into the interplay of multiple static and time‐dependent risk factors for the prediction of aGvHD.

Abstract Introduction A prospective cohort study comparing peri‐ and postoperative outcomes for patients with predominantly anterior prostate cancer (APC) identified preoperatively against non‐anterior prostate cancer (NAPC) treated via robotic‐assisted radical prostatectomy (RARP). Patients and Methods Of the 757 RARP's completed between January 2016 and April 2018, two comparative cohorts for anterior and an equivalent group of non‐anterior prostate tumours each consisting of 152 patients were compared against each other. Data were collected on the following variables: patient age; operating consultant; preoperative PSA, ISUP grade, degree of nerve sparing; tumour staging; presence and location of positive surgical margins; PSA density, postoperative ISUP grade; treatment paradigm and postoperative PSA, erectile function, and continence outcomes with 2‐year follow‐up. Results APCs were found to have significantly lower ISUP grading postoperatively; increased diagnosis via active surveillance over new diagnosis; more frequently undertaken bilateral nerve‐sparing and long‐term poorer continence outcomes at 18 and 24 months postoperatively (p 0.05). Conclusion The lower ISUP grading could indicate APC as overall being less aggressive than NAPC, whereas the poorer long‐term continence outcomes require further investigating. The non‐significant differences amongst tumour staging, PSA density, preoperative PSA levels and PSM rates suggest that APC may not be as significant as predicted in diagnostic evaluation. Overall, this study provides useful information on the growing literature of anterior prostate cancer. Being the largest comparative cohort study to date on APC post‐RARP, these results indicate the true characteristics of anterior tumours and their functional outcomes to help improve education, patient expectations and management.

Abstract Purpose Our objective was to prioritise the psychosocial support needs of men on active surveillance for prostate cancer and to develop a consensus statement to provide guidance on best practice psychosocial support for men choosing active surveillance and their families. Subjects and methods We undertook a patient and public involvement Delphi process over two rounds, informed by qualitative data and a comprehensive literature review, to prioritise the information and support needs of men on active surveillance for prostate cancer. Two panels were surveyed, a patient/carer panel (n = 55) and a health care provider panel (n = 114). Based on the findings of the Delphi surveys, an expert active surveillance discussion group developed a consensus statement to guide best practice. Results Patients and health care professionals differed slightly in their ideas concerning priorities for active surveillance psychosocial support. Broadly, agreed priority areas included ‐patients being involved in decision‐making, continuity of care, more streamlined access to health care teams, improved understanding of the risk of prostate cancer progression and information and support provided through both health care professionals and peers. Based on the identified priorities, the expert discussion group agreed on 22 consensus statements for best practice in psychosocial care for active surveillance in respect of (1) principles of an active surveillance programme; (2) structure of consultations; (3) content of information and support; and (4) delivery of information. Conclusion This consensus statement provides a framework for patient‐focused psychosocial support, which, if adopted, should increase uptake and adherence to active surveillance among men with prostate cancer.

Abstract The UN's Paris Agreement goal of keeping global warming between 1.5 and 2°C is dangerously obsolete and needs to be replaced by a commitment to restore Earth's climate. We now know that continued use of fossil fuels associated with 1.5–2°C scenarios would result in hundreds of millions of pollution deaths and likely trigger multiple tipping elements in the Earth system. Unexpected advances in renewable power production and storage have radically expanded our climate response capacity. The cost of renewable technologies has plummeted at least 30‐year faster than projected, and renewables now dominate energy investment and growth. This renewable revolution creates an opportunity and responsibility to raise our climate ambitions. Rather than aiming for climate mitigation—making things less bad—we should commit to climate restoration—a rapid return to Holocene‐like climate conditions where we know humanity and life on Earth can thrive. Based on observed and projected energy system trends, we estimate that the global economy could reach zero emissions by 2040 and potentially return atmospheric CO2 to pre‐industrial levels by 2100–2150. However, this would require an intense and sustained rollout of renewable energy and negative emissions technologies on very large scales. We describe these clean electrification scenarios and outline technical and socioeconomic strategies that would increase the likelihood of restoring a Holocene‐like climate in the next 100 years. We invite researchers, policymakers, regulators, educators, and citizens in all countries to share and promote this positive message of climate restoration for human wellbeing and planetary stability.

Abstract Objective Assess the longer‐term efficacy and safety of adjunctive perampanel (up to 12 mg/day) in patients aged ≥12 years with generalized tonic–clonic (GTC) seizures from the Open‐label Extension (OLEx) Phase of Study 332 to determine whether responses obtained during the Core Study are maintained during long‐term treatment. Methods Patients with GTC seizures previously enrolled in a randomized placebo‐controlled trial of perampanel could enter an OLEx Phase comprising 6‐week blinded conversion (during which patients previously randomized to placebo‐switched to perampanel) and up to 136‐week maintenance periods (maximum perampanel dose of 12 mg/day). A 4‐week follow‐up period was completed by all patients after the last on‐treatment visit during the OLEx. We assessed seizure frequency outcomes from preperampanel baseline and the Core Study Pre‐randomization Phase, retention rates, doses selected, and treatment‐emergent adverse events (TEAEs). Results Overall, 138 patients entered the OLEx. Median percent reductions in GTC seizures per 28 days from preperampanel were 77% (Weeks 1‐13) and 90% (Weeks 40‐52). Retention rates were 88% (6 months) and 75% (12 months). Seizure‐freedom rates were maintained for at least 2 years regardless of prior treatment received during the Core Study. Most common modal daily dose was >4‐8 mg/day (n = 93). Across the Core and OLEx Phases, 120 (87%) patients experienced TEAEs; the most common was dizziness. Significance Perampanel was generally well‐tolerated, and the TEAEs reported here are consistent with the known safety profile of perampanel. Perampanel offers a long‐term treatment option for patients (aged ≥12 years) with GTC seizures.

Abstract Objective To report on the outcomes of urological cancer patients undergoing radical surgery between March–September 2020 (compared with 2019) in the European Institute of Oncology (IEO) in Milan and the South East London Cancer Alliance (SELCA). Materials and Methods Since March 2020, both institutions implemented a COVID‐19 minimal ‘green’ pathway, whereby patients were required to isolate for 14 days prior to admission and report a negative COVID‐19 polymerase chain reaction (PCR) test within 3 days of surgery. COVID‐19 positive patients had surgery deferred until a negative swab. Surgical outcomes assessed were: American Society of Anaesthesiologists (ASA) grade; surgery time; theatre time; intensive care unit (ICU) stay >24 h; pneumonia; length of stay (LOS); re‐admission. Postoperative COVID‐19 infection rates and associated mortality were also recorded. Results At IEO, uro‐oncological surgery increased by 4%, as compared with the same period in 2019 (n = 515 vs. 534). The main increase was observed for renal (16%, n = 98 vs. 114), bladder (24%, n = 45 vs. 56) and testicular (27%, n = 26 vs. 33). Patient demographics were all comparable between 2019 and 2020. Only one bladder cancer patient developed COVID‐19, reporting mild/moderate disease. There was no COVID‐19 associated mortality. In the SELCA cohort, uro‐oncological surgery declined by 23% (n = 403 vs. 312) compared with the previous year. The biggest decrease was seen for prostate (−42%, n = 156 vs. 91), penile (−100%, n = 4 vs. 0) and testicular cancers (−46%, n = 35 vs. 24). Various patient demographic characteristics were notably different when comparing 2020 versus 2019. This likely reflects the clinical decision of deferring COVID‐19 vulnerable patients. One patient developed COVID‐19, with no COVID‐19 related mortality. Conclusion The COVID‐19 minimal ‘green’ pathways that were put in place have shown to be safe for uro‐oncological patients requiring radical surgery. There were limited complications, almost no peri‐operative COVID‐19 infection and no COVID‐19‐related mortality in either cohort.

Abstract Pakistan is currently undertaking a substantial expansion of electricity generation capacity to provide electricity for all its end‐users and to satisfy a fast‐growing economy. Adoption of low‐cost, abundant and clean renewable energy will not only fulfil its growing electricity, heat, transportation and desalinated water demand but also help achieve the goals set under the Paris Agreement. A technology‐rich energy system model applied in hourly resolution has been used for investigating the transition in 5‐year periods until 2050. This study demonstrates that a 100% renewable energy system across the power, heat, transport and desalination sectors is not only technically feasible but also economically viable. Solar photovoltaics emerges as a key technology to generate electricity and contribute a share of 92% to the total primary energy demand across all sectors by 2050. The levelised cost of energy for a 100% renewable energy system is calculated as 56.1 €/MWh in 2050, lower than 70 €/MWh for the current fossil fuel‐based system. A key feature of Pakistan's future energy system is the huge increase in demand across all energy sectors, particularly for desalinated water, which is almost 19% of the final energy demand. This share of energy for desalination is among the highest in the world. Direct and indirect electrification across all demand sectors increases the efficiency of the future energy system. Moreover, GHG emissions from all the sectors will drop to zero by 2050 in a fully sustainable energy scenario.

Introduction. Elucent Medical has introduced a novel EnVisio™ Surgical Navigation system which uses SmartClips™ that generate a unique electromagnetic signal triangulated in 3 dimensions for real-time navigation. The purpose of this study was to evaluate the efficacy and feasibility of the EnVisio Surgical Navigation system in localizing and excising nonpalpable lesions in breast and axillary surgery. Methods. This pilot study prospectively examined patients undergoing breast and nodal localization using the EnVisio Surgical Navigation system. SmartClips were placed by designated radiologists using ultrasound (US) or mammographic (MMG) guidance. The technical evaluation focused on successful deployment and subsequent excision of all localized lesions including SmartClips and biopsy clips. Results. Eleven patients underwent localization using 27 SmartClips which included bracketed multifocal disease (n = 4) and clipped lymph node (n = 1). The bracketed cases were each localized with 2 SmartClips. Mammography and ultrasound were used (n = 8 and n = 19, respectively) to place the SmartClips. All 27 devices were successfully deployed within 5 mm of the targeted lesion or biopsy clip. All SmartClip devices were identified and retrieved intraoperatively. No patients required a second operation for margin excision. Conclusion. In a limited sample, the EnVisio Surgical Navigation system was a reliable technology for the localization of breast and axillary lesions planned for surgical excision. Further comparative studies are required to evaluate its efficacy in relation to the other existing localization modalities.

Abstract The eosin‐5′‐maleimide (EMA) binding test is widely used as diagnostic test for hereditary spherocytosis (HS), one of the most common haemolytic disorders in Caucasian populations. We recently described the advantages of replacing the use of healthy control blood samples with fluorescent beads in a modified EMA binding assay. In this study we further explore this novel approach. We performed targeted next‐generation sequencing, modified EMA binding test and osmotic gradient ektacytometry on consecutive individuals referred to our laboratory on the suspicion of HS. In total, 33 of 95 carried a (likely) pathogenic variant, and 24 had variants of uncertain significance (VUS). We identified a total 79 different (likely) pathogenic variants and VUS, including 43 novel mutations. Discarding VUS and recessive mutations in STPA1, we used the occurrence of (likely) pathogenic variants to generate a diagnostic threshold for our modified EMA binding test. Twenty‐one of 23 individuals with non‐SPTA1 (likely) pathogenic variants had EMA ≥ 43.6 AU, which was the optimal threshold in receiver operating characteristic (ROC) analysis. Accuracy was excellent at 93.4% and close to that of osmotic gradient ektacytometry (98.7%). In conclusion, we were able to simplify the EMA‐binding test by using rainbow beads as reference and (likely) pathogenic variants to define an accurate cut‐off value.

Abstract The paper provides a comprehensive overview of possible strategies for the repair of cracked polyamide‐based backsheets. A repair process has been developed that comprises the following steps: (i) cleaning, (ii) pretreatment, and (iii) repair process (crack filling and sealing). The important topic of long‐term reliability is still under investigation. Two different repair strategies have been addressed in this article: (i) repairing damage by restoring electrical insulation properties and (ii) preventing further growth of the surface near microcracks. From a technical point of view, several of the repair solutions examined met the defined requirements for compatibility and applicability. On the one hand, repair tapes/films sealed the surface and only covered the cracks. The adhesive did not penetrate into the cavities that had opened through the cracks in the backsheet material. Therefore, adhesive tapes/films are not suitable for the repair of large‐scale damage and the permanent restoration of the electrical insulation properties. On the other hand, several repair coatings based on polyurethane, epoxy, silicone and synthetic rubber were identified which, after a two‐step application process, showed complete crack filling and sealing of the surface. The required insulation resistance of the aged modules could be restored. Since the new and artificial reliability tests are still running, no final conclusions on the long‐term behavior of the repair and its life‐extending effect of PV modules can be drawn at the moment.

Abstract Objectives To determine the safety of urological admissions and procedures during the height of the COVID‐19 pandemic using “hot” and “cold” sites. The secondary objective is to determine risk factors of contracting COVID‐19 within our cohort. Patients and methods A retrospective cohort study of all consecutive patients admitted from March 1 to May 31, 2020 at a high‐volume tertiary urology department in London, United Kingdom. Elective surgery was carried out at a “cold” site requiring a negative COVID‐19 swab 72‐hours prior to admission and patients were required to self‐isolate for 14‐days preoperatively, while all acute admissions were admitted to the “hot” site. Complications related to COVID‐19 were presented as percentages. Risk factors for developing COVID‐19 infection were determined using multivariate logistic regression analysis. Results A total of 611 patients, 451 (73.8%) male and 160 (26.2%) female, with a median age of 57 (interquartile range 44‐70) were admitted under the urology team; 101 (16.5%) on the “cold” site and 510 (83.5%) on the “hot” site. Procedures were performed in 495 patients of which eight (1.6%) contracted COVID‐19 postoperatively with one (0.2%) postoperative mortality due to COVID‐19. Overall, COVID‐19 was detected in 20 (3.3%) patients with two (0.3%) deaths. Length of stay was associated with contracting COVID‐19 in our cohort (OR 1.25, 95% CI 1.13‐1.39). Conclusions Continuation of urological procedures using “hot” and “cold” sites throughout the COVID‐19 pandemic was safe practice, although the risk of COVID‐19 remained and is underlined by a postoperative mortality.

Abstract Understanding plankton dynamics in marine ecosystems has been advanced using in situ molecular and imaging instrumentation. A range of research objectives have been addressed through high‐resolution autonomous sampling, from food web characterization to harmful algal bloom dynamics. When used together, molecular and imaging sensors can cover the full‐size range, genetic identity, and life stages of plankton. Here, we briefly review a selection of in situ instrumentation developed for the collection of molecular and imaging information on plankton communities in marine ecosystems. In addition, we interviewed a selection of instrumentation developers to determine if the transfer of sensor technology from marine to freshwater ecosystems is feasible and to describe the process of creating in situ sensors. Finally, we discuss the status of in situ molecular and imaging sensors in freshwater ecosystems and how some of the reviewed sensors could be used to address basic and applied research questions.

Abstract Background A minority of breast cancer (BC) patients suffer from severe reaction to adjuvant radiotherapy (RT). Although deficient DNA double‐strand break repair is considered the main basis for the reactions, pretreatment identification of high‐risk patients has been challenging. Methods To retrospectively determine the etiology of severe local reaction to RT in a 39‐year‐old woman with BC, we performed next‐generation sequencing followed by further clinical and functional studies. Results We found a −4 intronic variant (c.2251‐4A>G) in trans with a synonymous (c.3576G>A) variant affecting the ATM DNA‐repair gene (NG_009830.1, NM_000051.3) which is linked to autosomal recessive ataxia–telangiectasia (A–T). We verified abnormal transcripts resulting from both variants, next to a minor wild‐type transcript leading to a residual ATM kinase activity and genomic instability. Follow‐up examination of the patient revealed no classic sign of A–T but previously unnoticed head dystonia and mild dysarthria, a family history of BC and late‐onset ataxia segregating with the variants. Additionally, her serum level of alpha‐fetoprotein (AFP) was elevated similar to A–T patients. Conclusion Considering the variable presentations of A–T and devastating impact of severe reactions to RT, we suggest a routine measurement of AFP in RT‐candidate BC patients followed by next‐generation sequencing with special attention to non‐canonical splice site and synonymous variants in ATM.

Breast cancer is the most common cancer in women worldwide. The tumor microenvironment contributes to tumor progression by inducing cell dissemination from the primary tumor and metastasis. TGFβ signaling is involved in breast cancer progression and is specifically elevated during metastatic transformation in aggressive breast cancer. In this study, we performed genomewide correlation analysis of TGFBR2 expression in a panel of 51 breast cancer cell lines and identified that MET is coregulated with TGFBR2. This correlation was confirmed at the protein level in breast cancer cell lines and human tumor tissues. Flow cytometric analysis of luminal and basal‐like breast cancer cell lines and examination of 801 tumor specimens from a prospective cohort of breast cancer patients using reverse phase protein arrays revealed that expression of TGFBR2 and MET is increased in basal‐like breast cancer cell lines, as well as in triple‐negative breast cancer tumor tissues, compared to other subtypes. Using real‐time cell analysis technology, we demonstrated that TGFβ1 triggered hepatocyte growth factor (HGF)‐induced and MET‐dependent migration in vitro. Bioinformatic analysis predicted that TGFβ1 induces expression of C‐ets‐1 as a candidate transcription factor regulating MET expression. Indeed, TGFβ1‐induced expression of ETS1 and breast cancer cell migration was blocked by knockdown of ETS1. Further, we identified that MET is a direct target of miR‐128‐3p and that this miRNA is negatively regulated by TGFβ1. Overexpression of miR‐128‐3p reduced MET expression and abrogated HGF‐induced cell migration of invasive breast cancer cells. In conclusion, we have identified that TGFβ1 regulates HGF‐induced and MET‐mediated cell migration, through positive regulation of C‐ets‐1 and negative regulation of miR‐128‐3p expression in basal‐like breast cancer cell lines and in triple‐negative breast cancer tissue.

Human hepatocellular carcinoma (HCC) is the most common and recurrent type of primary adult liver cancer without any effective therapy. Plant-derived compounds acting as anticancer agents can induce apoptosis by targeting several signaling pathways. Strigolactone (SL) is a novel class of phytohormone, whose analogues have been reported to possess anticancer properties on a panel of human cancer cell lines through inducing cell cycle arrest, destabilizing microtubular integrity, reducing damaged in the DNA repair machinery, and inducing apoptosis. In our previous study, we reported that a novel SL analogue, TIT3, reduces HepG2 cell proliferation, inhibits cell migration, and induces apoptosis. To decipher the mechanisms of TIT3-induced anticancer activity in HepG2, we performed RNA sequencing and the differential expression of genes was analyzed using different tools. RNA-Seq data showed that the genes responsible for microtubule organization such as TUBB, BUB1B, TUBG2, TUBGCP6, TPX2, and MAP7 were significantly downregulated. Several epigenetic modulators such as UHRF1, HDAC7, and DNMT1 were also considerably downregulated, and this effect was associated with significant upregulation of various proapoptotic genes including CASP3, TNF-α, CASP7, and CDKN1A (p21). Likewise, damaged DNA repair genes such as RAD51, RAD52, and DDB2 were also significantly downregulated. This study indicates that TIT3-induced antiproliferative and proapoptotic activities on HCC cells could involve several signaling pathways. Our results suggest that TIT3 might be a promising drug to treat HCC.

Abstract Background Our objectives were (1) to test the association between the report of subjective cognitive decline (SCD) and prospective objective cognitive performance in high age individuals and (2) to study the course of longitudinal cognitive performance before and after the first report of SCD. Methods Cognitively normal elderly participants of the German Study on Ageing, Cognition, and Dementia study (N = 2330) with SCD (subjective decline in memory with and without associated concerns) and without SCD at baseline were assessed over 8 years with regard to immediate and delayed verbal recall, verbal fluency, working memory, and global cognition. Baseline performance and cognitive trajectories were compared between groups. In addition, cognitive trajectories before and after the initial report of SCD (incident SCD) were modelled in those without SCD at baseline. Results Baseline performance in the SCD group was lower and declined more steeply in immediate and delayed verbal recall than in the control group (no SCD at baseline). This effect was more pronounced in the SCD group with concerns. Incident SCD was preceded by decline in immediate and delayed memory and word fluency. Conclusions SCD predicts future memory decline. Incident SCD is related to previous cognitive decline. The latter finding supports the concept of SCD indicating first subtle decline in cognitive performance that characterizes preclinical Alzheimer's disease.

Ebstein’s anomaly is a rare congenital heart disease that presents with apical displacement of the septal and posterior leaflets of the tricuspid valve. It has a wide spectrum of clinical presentations and has been shown to manifest itself any time from birth to adulthood. Our patient is a 43-year-old male with a history of intravenous heroin abuse who presented to the emergency department with worsening shortness of breath and lower extremity edema. He denied any prior cardiac history. A transthoracic echo showed normal left ventricular function, but a large 2.2 × 2.1 cm echodensity on the septal leaflet of the tricuspid valve consistent with vegetation with severe tricuspid regurgitation and probable leaflet perforation. It also demonstrated severe right heart enlargement with atrialization of the right ventricle and apical displacement of the tricuspid valve consistent with Ebstein’s anomaly. This is a rare case of an adult who presented with asymptomatic Ebstein’s anomaly. There have been few reports of tricuspid valve endocarditis with Ebstein’s anomaly in the literature. To our knowledge, this represents the fifth reported case of a new diagnosis of Ebstein’s anomaly in the setting of endocarditis and the second case of Ebstein’s anomaly and endocarditis in an intravenous drug abuser.

Background: The QT intervals accuracy for predicting arrhvthmic death varies between studies, possibly due to differences in the selection of the lead used for measurement of the QT interval. The purpose of this study was to analyze the prognostic accuracy of all known ways to select the lead. Methods and Results: Three institutions that used different methods for measuring QT intervals provided their QT databases. They included more than 3500 twelve‐lead surface ECGs. The data represented low‐ and high‐risk patients of the normal population (survivors vs dead from cardiovascular causes), acute myocardial infarction (survivors versus death from all causes) and remote myocardial infarction (with vs without a history of ventricular arrhythmia). The prognostic accuracy was defined as the area under the Receiver Operator Curve (ROC‐area). The most accurate standard leads were I and aVL and the least accurate was AVR. The most accurate precordial lead was V4. The prognostic accuracy of the longest QT interval was higher than for any standard lead. The prognostic accuracv of the mean of the three longest QT intervals was equal to or slightly lower than for the longest QT interval. Conclusions: The highest prognostic accuracy is obtained with the longest QT interval. The accuracies of the lead selection methods are so different that it can explain a substantial part of the differences between otherwise similar studies in the literature. We recommend the use of the mean value of the three longest QT intervals. A.N.E. 2002;7(1):10–16