SGLT2 Inhibitors - The New Standard of Care for Cardiovascular, Renal and Metabolic Protection in Type 2 Diabetes: A Narrative Review.

A substantial evidence base supports the use of sodium-glucose cotransporter-2 inhibitors (SGLT2is) in the treatment of type 2 diabetes mellitus (T2DM). This class of medicines has demonstrated important benefits that extend beyond glucose-lowering efficacy to protective mechanisms capable of slowing or preventing the onset of long-term cardiovascular, renal and metabolic (CVRM) complications, making their use highly applicable for organ protection and the maintenance of long-term health outcomes. SGLT2is have shown cost-effectiveness in T2DM management and economic savings over other glucose-lowering therapies due to reduced incidence of cardiovascular and renal events. National and international guidelines advocate SGLT2i use early in the T2DM management pathway, based upon a plethora of supporting data from large-scale cardiovascular outcome trials, renal outcomes trials and real-world studies. While most people with T2DM would benefit from CVRM protection through SGLT2i use, prescribing hesitancy remains, potentially due to confusion concerning their place in the complex therapeutic paradigm, variation in licensed indications or safety perceptions/misunderstandings associated with historical data that have since been superseded by robust clinical evidence and long-term pharmacovigilance reporting. This latest narrative review developed by the Improving Diabetes Steering Committee (IDSC) outlines the place of SGLT2is within current evidence-informed guidelines, examines their potential as the standard of care for the majority of newly diagnosed people with T2DM and sets into context the perceived risks and proven advantages of SGLT2is in terms of sustained health outcomes. The authors discuss the cost-effectiveness case for SGLT2is and provide user-friendly tools to support healthcare professionals in the correct application of these medicines in T2DM management. The previously published IDSC SGLT2i Prescribing Tool for T2DM Management has undergone updates and reformatting and is now available as a Decision Tool in an interactive pdf format as well as an abbreviated printable A4 poster/wall chart.

Intersection of coral molecular responses to a localized mortality event and ex situ deoxygenation.

In July 2016, East Bank of Flower Garden Banks (FGB) National Marine Sanctuary experienced a localized mortality event (LME) of multiple invertebrate species that ultimately led to reductions in coral cover. Abiotic data taken directly after the event suggested that acute deoxygenation contributed to the mortality. Despite the large impact of this event on the coral community, there was no direct evidence that this LME was driven by acute deoxygenation, and thus we explored whether gene expression responses of corals to the LME would indicate what abiotic factors may have contributed to the LME. Gene expression of affected and unaffected corals sampled during the mortality event revealed evidence of the physiological consequences of the LME on coral hosts and their algal symbionts from two congeneric species (Orbicella franksi and Orbicella faveolata). Affected colonies of both species differentially regulated genes involved in mitochondrial regulation and oxidative stress. To further test the hypothesis that deoxygenation led to the LME, we measured coral host and algal symbiont gene expression in response to ex situ experimental deoxygenation (control = 6.9 ± 0.08 mg L-1, anoxic = 0.083 ± 0.017 mg L-1) in healthy O. faveolata colonies from the FGB. However, this deoxygenation experiment revealed divergent gene expression patterns compared to the corals sampled during the LME and was more similar to a generalized coral environmental stress response. It is therefore likely that while the LME was connected to low oxygen, it was a series of interconnected stressors that elicited the unique gene expression responses observed here. These in situ and ex situ data highlight how field responses to stressors are unique from those in controlled laboratory conditions, and that the complexities of deoxygenation events in the field likely arise from interactions between multiple environmental factors simultaneously.

Gene expression plasticity facilitates acclimatization of a long-lived Caribbean coral across divergent reef environments.

Local adaptation can increase fitness under stable environmental conditions. However, in rapidly changing environments, compensatory mechanisms enabled through plasticity may better promote fitness. Climate change is causing devastating impacts on coral reefs globally and understanding the potential for adaptive and plastic responses is critical for reef management. We conducted a four-year, three-way reciprocal transplant of the Caribbean coral Siderastrea siderea across forereef, backreef, and nearshore populations in Belize to investigate the potential for environmental specialization versus plasticity in this species. Corals maintained high survival within forereef and backreef environments, but transplantation to nearshore environments resulted in high mortality, suggesting that nearshore environments present strong environmental selection. Only forereef-sourced corals demonstrated evidence of environmental specialization, exhibiting the highest growth in the forereef. Gene expression profiling 3.5 years post-transplantation revealed that transplanted coral hosts exhibited profiles more similar to other corals in the same reef environment, regardless of their source location, suggesting that transcriptome plasticity facilitates acclimatization to environmental change in S. siderea. In contrast, algal symbiont (Cladocopium goreaui) gene expression showcased functional variation between source locations that was maintained post-transplantation. Our findings suggest limited acclimatory capacity of some S. siderea populations under strong environmental selection and highlight the potential limits of coral physiological plasticity in reef restoration.

Menstrual cycles and the impact upon performance in elite British track and field athletes: a longitudinal study.

Objective: To assess the prevalence of menstrual disorders and the perceived effect of menstrual cycles upon performance in elite athletes. Methodology: A longitudinal survey in the form of a questionnaire was sent to female track and field athletes at British Athletics every 6 months, over a five-year period between 1st October 2014 and 1st October 2019 in the United Kingdom (UK). Results: 128 athletes completed an average of 4.2 ± 2.9 questionnaires across the study period. The mean age of menarche was 14.2 ± 1.4 years, 13.4 ± 1.3 years and 12.8 ± 1.4 years in endurance, power, and thrower athletes respectively (p < 0.05). Two-thirds (66%; n = 82) reported consistently regular cycles, 30% (n = 37) irregular at some point during the period of observation and 4% (n = 5) were amenorrhoeic. 87 athletes (68%) reported dysmenorrhoea and 40 (31%) menorrhagia. More than three quarters (76.8%; n = 96) described their cycle negatively affected performance. Amongst those who reported when the negative impact occurred (n = 91), 40% (n = 36) reported this in the late luteal phase and 35% (n = 32) during the early follicular phase. 79% (n = 100) of athletes reported at least one cyclical symptom, of which bloating, lower back and pelvic pain were most frequently experienced. Conclusion: This data highlights the complex interrelationship between women's health and elite athletic performance. Athletes perceive a negative impact from their menstrual cycles upon performance with a desire to manage these more effectively, particularly during competition. Female reproductive health expertise in the multi-disciplinary management of elite athletes is required.

Symbiosis modulates gene expression of symbionts, but not coral hosts, under thermal challenge.

Increasing ocean temperatures are causing dysbiosis between coral hosts and their symbionts. Previous work suggests that coral host gene expression responds more strongly to environmental stress compared to their intracellular symbionts; however, the causes and consequences of this phenomenon remain untested. We hypothesized that symbionts are less responsive because hosts modulate symbiont environments to buffer stress. To test this hypothesis, we leveraged the facultative symbiosis between the scleractinian coral Oculina arbuscula and its symbiont Breviolum psygmophilum to characterize gene expression responses of both symbiotic partners in and ex hospite under thermal challenges. To characterize host and in hospite symbiont responses, symbiotic and aposymbiotic O. arbuscula were exposed to three treatments: (1) control (18°C), (2) heat (32°C), and (3) cold (6°C). This experiment was replicated with B. psygmophilum cultured from O. arbuscula to characterize ex hospite symbiont responses. Both thermal challenges elicited classic environmental stress responses (ESRs) in O. arbuscula regardless of symbiotic state, with hosts responding more strongly to cold challenge. Hosts also exhibited stronger responses than in hospite symbionts. In and ex hospite B. psygmophilum both down-regulated gene ontology pathways associated with photosynthesis under thermal challenge; however, ex hospite symbionts exhibited greater gene expression plasticity and differential expression of genes associated with ESRs. Taken together, these findings suggest that O. arbuscula hosts may buffer environments of B. psygmophilum symbionts; however, we outline the future work needed to confirm this hypothesis.

Integrating cryptic diversity into coral evolution, symbiosis and conservation.

Understanding how diversity evolves and is maintained is critical to predicting the future trajectories of ecosystems under climate change; however, our understanding of these processes is limited in marine systems. Corals, which engineer reef ecosystems, are critically threatened by climate change, and global efforts are underway to conserve and restore populations as attempts to mitigate ocean warming continue. Recently, sequencing efforts have uncovered widespread undescribed coral diversity, including 'cryptic lineages'-genetically distinct but morphologically similar coral taxa. Such cryptic lineages have been identified in at least 24 coral genera spanning the anthozoan phylogeny and across ocean basins. These cryptic lineages co-occur in many reef systems, but their distributions often differ among habitats. Research suggests that cryptic lineages are ecologically specialized and several examples demonstrate differences in thermal tolerance, highlighting the critical implications of this diversity for predicting coral responses to future warming. Here, we draw attention to recent discoveries, discuss how cryptic diversity affects the study of coral adaptation and acclimation to future environments, explore how it shapes symbiotic partnerships, and highlight challenges and opportunities for conservation and restoration efforts.

Fostering collaborative practice through interprofessional simulation for occupational therapy, physiotherapy, dietetics, and nursing students.

Literature regarding simulation for learning interprofessional collaborative practice (IPCP) indicates a need to include a range of health professions and to focus on students' development of team communication and conflict resolution skills in day-to-day healthcare delivery. This study evaluated the impact of interprofessional simulation for occupational therapy, physiotherapy, dietetics, and nursing students on interprofessional collaboration competencies, specifically collaborative communication and conflict resolution during day-to-day interactions, and their intention for IPCP during placement. A series of simulations featuring the potential for interprofessional conflict and involving explicit coaching on communication and conflict resolution were conducted. A single cohort pre-test post-test design included the Students' Perceptions of Interprofessional Clinical Education Revised (SPICE-R), the Interprofessional Collaborative Competencies Attainment Survey (ICCAS), and an open response survey question on future intended practice. A total of 237 students participated in the simulation experience. Overall scores and scores on all IPCP competencies in the ICASS (n = 193) and SPICE-R (n = 226) improved for all professions post-simulation. The mean score of the ICCAS increased for 98% of the respondents and similarly the mean score of the SPICE-R increased for 71% of the respondents. Open-ended responses indicated students' intentions to pursue self-leadership in IPCP. Students who participated in an interprofessional simulation reported perceived improvements in IPCP competencies and were encouraged to initiate IPCP when on placement in the practice setting.

Starvation differentially affects gene expression, immunity and pathogen susceptibility across symbiotic states in a model cnidarian.

Mutualistic symbioses between cnidarians and photosynthetic algae are modulated by complex interactions between host immunity and environmental conditions. Here, we investigate how symbiosis interacts with food limitation to influence gene expression and stress response programming in the sea anemone Exaiptasia pallida (Aiptasia). Transcriptomic responses to starvation were similar between symbiotic and aposymbiotic Aiptasia; however, aposymbiotic anemone responses were stronger. Starved Aiptasia of both symbiotic states exhibited increased protein levels of immune-related transcription factor NF-κB, its associated gene pathways, and putative target genes. However, this starvation-induced increase in NF-κB correlated with increased immunity only in symbiotic anemones. Furthermore, starvation had opposite effects on Aiptasia susceptibility to pathogen and oxidative stress challenges, suggesting distinct energetic priorities under food scarce conditions. Finally, when we compared starvation responses in Aiptasia to those of a facultative coral and non-symbiotic anemone, 'defence' responses were similarly regulated in Aiptasia and the facultative coral, but not in the non-symbiotic anemone. This pattern suggests that capacity for symbiosis influences immune responses in cnidarians. In summary, expression of certain immune pathways-including NF-κB-does not necessarily predict susceptibility to pathogens, highlighting the complexities of cnidarian immunity and the influence of symbiosis under varying energetic demands.

Pilot Study of Intensive Trismus Intervention Using Restorabite™ During Unilateral Adjuvant Radiation for Head and Neck Cancer.

Trismus commonly arises after surgery for head and neck cancer (HNC) and its severity is potentiated by postoperative radiotherapy. While the benefit of trismus rehabilitation after surgery and radiotherapy is well established, the evidence during radiotherapy is less clear. This may be due to poor adherence to trismus exercises secondary to acute mucositis. This study assessed the feasibility of using a novel trismus device during adjuvant radiotherapy for HNC in patients with acute postoperative trismus. Prospective single-arm cohort feasibility study. Eligible patients had undergone surgery with curative intent for HNC, planned for adjuvant radiotherapy, and were suitable for trismus rehabilitation. Participants completed a 10-week exercise program using a novel jaw stretching device. Study outcomes were adherence, maximal incisal opening (MIO), and trismus-related function and quality of life scores, assessed at baseline, 10 weeks, and 6 months after commencing exercises. Nine patients diagnosed with trismus after primary surgery were recruited. The mean increase in MIO at 10 weeks was 7.8 mm (range -4 to 15 mm, p = 0.03), and at 6 months was 10.6 mm (range 1-26 mm, p = 0.03). Significant improvements were observed in trismus-related quality of life (Gothenburg Trismus Questionnaire; p = 0.04). Adherence to the exercises was 100% in week 1-2, 67% in weeks 3-6, and 100% at 10 weeks (1 month post radiation). This study demonstrates the feasibility of using a novel jaw stretching device during adjuvant radiotherapy. Further evaluation is warranted to assess the effectiveness of early intervention and prevention of trismus during HNC radiotherapy.Level of Evidence: IV.

Cohort profile: Born in Wales-a birth cohort with maternity, parental and child data linkage for life course research in Wales, UK.

PURPOSE: Using Wales's national dataset for maternity and births as a core dataset, we have linked related datasets to create a more complete and comprehensive entire country birth cohort. Data of anonymised identified persons are linked on the individual level to data from health, social care and education data within the Secure Anonymised Information Linkage (SAIL) Databank. Each individual is assigned an encrypted Anonymised Linking Field; this field is used to link anonymised individuals across datasets. We present the descriptive data available in the core dataset, and the future expansion plans for the database beyond its initial development stage. PARTICIPANTS: Descriptive information from 2011 to 2023 has been gathered from the National Community Child Health Database (NCCHD) in SAIL. This comprehensive dataset comprises over 400 000 child electronic records. Additionally, survey responses about health and well-being from a cross-section of the population including 2500 parents and 30 000 primary school children have been collected for enriched personal responses and linkage to the data spine. FINDINGS TO DATE: The electronic cohort comprises all children born in Wales since 2011, with follow-up conducted until they finish primary school at age 11. The child cohort is 51%: 49% female: male, and 7.8% are from ethnic minority backgrounds. When considering age distribution, 26.8% of children are under the age of 5, while 63.2% fall within the age range of 5-11. FUTURE PLANS: Born in Wales will expand by 30 000 new births annually in Wales (in NCCHD), while including follow-up data of children and parents already in the database. Supplementary datasets complement the existing linkage, including primary care, hospital data, educational attainment and social care. Future research includes exploring the long-term implications of COVID-19 on child health and development, and examining the impact of parental work environment on child health and development.

The impact of jejunostomy feeding on nutritional outcomes after oesophagectomy.

BACKGROUND: Nutritional status is compromised long-term following oesophagectomy. Controversy surrounds the optimal route for nutrition support postoperatively and there is wide variation in the use of feeding jejunostomy tubes. METHODS: A retrospective service evaluation was conducted for all consecutive adults who underwent oesophagectomy for a cancer diagnosis within a specialist centre between April 2016 and July 2019 (n = 165). Nutritional and clinical outcomes were compared for patients who received jejunostomy feeding (n = 24), versus those who did not (n = 141). RESULTS: Patients with feeding jejunostomy lost significantly less weight at both 6 and 12 months postoperatively compared to those without jejunostomy (p ≤ 0.001 and p = 0.001, respectively). This remained statistically significant in multiple regression, controlling for age, gender, preoperative tumour staging and adjuvant treatment (p ≤ 0.001 and p = 0.03, respectively). Median length of home enteral feeding was 10 weeks after discharge in the jejunostomy group. We observed minor jejunostomy tube-related complications in four patients (16.7%). Of those readmitted within 90 days of surgery in the non-jejunostomy group, nutritional failure was a factor in 43.2% of these readmissions. "Rescue tube feeding" was required by 8.5% of the non-jejunostomy group within the first postoperative year, including 6.4% within 90 days of surgery. CONCLUSIONS: Use of short-term supplementary jejunal feeding in addition to oral intake after hospital discharge is beneficial for maintaining weight after oesophagectomy. We suggest a future randomised-controlled trial to confirm these findings.

Identifying factors associated with user retention and outcomes of a digital intervention for substance use disorder: a retrospective analysis of real-world data.

Objectives: Successful delivery of digital health interventions is affected by multiple real-world factors. These factors may be identified in routinely collected, ecologically valid data from these interventions. We propose ideas for exploring these data, focusing on interventions targeting complex, comorbid conditions. Materials and Methods: This study retrospectively explores pre-post data collected between 2016 and 2019 from users of digital cognitive behavioral therapy (CBT)-containing psychoeducation and practical exercises-for substance use disorder (SUD) at UK addiction services. To identify factors associated with heterogenous user responses to the technology, we employed multivariable and multivariate regressions and random forest models of user-reported questionnaire data. Results: The dataset contained information from 14 078 individuals of which 12 529 reported complete data at baseline and 2925 did so again after engagement with the CBT. Ninety-three percent screened positive for dependence on 1 of 43 substances at baseline, and 73% screened positive for anxiety or depression. Despite pre-post improvements independent of user sociodemographics, women reported more frequent and persistent symptoms of SUD, anxiety, and depression. Retention-minimum 2 use events recorded-was associated more with deployment environment than user characteristics. Prediction accuracy of post-engagement outcomes was acceptable (Area Under Curve [AUC]: 0.74-0.79), depending non-trivially on user characteristics. Discussion: Traditionally, performance of digital health interventions is determined in controlled trials. Our analysis showcases multivariate models with which real-world data from these interventions can be explored and sources of user heterogeneity in retention and symptom reduction uncovered. Conclusion: Real-world data from digital health interventions contain information on natural user-technology interactions which could enrich results from controlled trials.

Work engagement, psychological empowerment and relational coordination in long-term care: A mixed-method examination of nurses' perceptions and experiences.

Nurse engagement, empowerment and strong relationships among staff, residents and families, are essential to attract and retain a suitably qualified and skilled nursing workforce for safe, quality care. There is, however, limited research that explores engagement, empowerment and relational coordination in long-term care (LTC). Nurses from an older persons' mental health and dementia LTC unit in Australia participated in this study. Forty-one nurses completed a survey measuring psychological empowerment, work engagement and relational coordination. Twenty-nine nurses participated in individual interviews to further explore these concepts. Although nurses reported high psychological empowerment and work engagement, their relationships with key stakeholders varied. Our findings suggest that nurses in LTC require both supports and opportunities to contribute as active members of the multiprofessional care team that includes tailored education, professional development and positive interactions within the care team. Regular support is needed to enable nurses to feel empowered, foster relationships and communication, and facilitate work engagement. Based on these findings, we suggest that it is important to find ways to ensure that all who provide care perceive that they are part of the whole care team and able to contribute to the care and well-being of people in LTC.

Longitudinal relationships between lifestyle risk factors and neurodevelopment in early adolescence.

OBJECTIVE: The goal of this study is to investigate the cross-sectional and longitudinal relationships between clustered lifestyle risk factors (sleep, physical activity, body mass index [BMI], and screen time) and neurodevelopment over the early adolescent period. METHOD: Data from the ABCD Study Data Release 3.0 consisted of 11,878 participants (aged 9-10 years) at baseline and 6,571 participants (aged 11-12 years) at 2-year follow-up. The interrelationships between lifestyle risk factors and brain structure were analyzed using bivariate multiple indicator latent change score models. Using confirmatory factor analysis, a single lifestyle risk factor domain (measured by sleep, physical activity, BMI, and screen time) was shown to fit the data well. Using exploratory and confirmatory factor analysis, seven brain structure domains were extracted and labeled as temporal-parietal, frontotemporal, occipital, orbitofrontal, temporal, cingulate, parietal, and cuneus domains. All bivariate latent change score models accounted for age, sex at birth, race/ethnicity, parental education, and marital status. RESULTS: Higher lifestyle risk was associated with smaller brain volume at baseline. Higher baseline lifestyle risk was also associated with a greater rate of change (i.e., greater decreases) in brain volume for the temporal-parietal, frontotemporal, orbitofrontal, parietal, and cuneus domains. Effects were not reciprocal; baseline brain volume did not predict changes in lifestyle behaviors over time. CONCLUSION: These findings are important for understanding the biological mechanisms underpinning health risk factors and can be used to target interventions and improve brain health during this critical developmental phase. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Marine heatwaves threaten cryptic coral diversity and erode associations among coevolving partners.

Climate change-amplified marine heatwaves can drive extensive mortality in foundation species. However, a paucity of longitudinal genomic datasets has impeded understanding of how these rapid selection events alter cryptic genetic structure. Heatwave impacts may be exacerbated in species that engage in obligate symbioses, where the genetics of multiple coevolving taxa may be affected. Here, we tracked the symbiotic associations of reef-building corals for 6 years through a prolonged heatwave, including known survivorship for 79 of 315 colonies. Coral genetics strongly predicted survival of the ubiquitous coral, Porites (massive growth form), with variable survival (15 to 61%) across three morphologically indistinguishable-but genetically distinct-lineages. The heatwave also disrupted strong associations between these coral lineages and their algal symbionts (family Symbiodiniaceae), with symbiotic turnover in some colonies, resulting in reduced specificity across lineages. These results highlight how heatwaves can threaten cryptic genotypes and decouple otherwise tightly coevolved relationships between hosts and symbionts.

Emergency paediatric medicine consultation-a practical guide to a consultation with refugee and asylum-seeking children within the paediatric emergency department.

There are increasing numbers of refugee and asylum-seeking children entering the UK annually who face significant barriers to accessing healthcare services. Clinicians working in the emergency department should have an awareness of the journeys children may have taken and the barriers they face in accessing care and have a holistic approach to care provision. We conducted a narrative literature review and used experiential knowledge of paediatricians working in the Paediatric Emergency Department to formulate a step-by-step screening tool. We have formulated a step-by-step screening tool, CCHILDS (Communication, Communicable diseases, Health-physical and mental, Immunisation, Look after (safeguarding), Deficiencies, Sexual health) which can be used by healthcare professionals in the emergency department. CONCLUSION: Due to increasing numbers of refugee and asylum-seeking children, it is important that every point of contact with healthcare professionals is an impactful one on their health, well-being and development. Future work would include validation of our tool. WHAT IS KNOWN: •The number of refugees globally are rapidly increasing, leading to an increase in the number of presentations to the PED. These patients are often medically complex and may have unique and sometimes unexpected presentations that could be attributed to by their past. There are a multitude of resources available outlining guidance on the assessment and management of refugee children. WHAT IS NEW: •This review aims to succinctly summarise the guidance surrounding the assessment of refugee children presenting to the PED and ensure that healthcare professionals are aware of the pertinent information regarding this cohort. It introduces the CCHILDS assessment tool which has been formulated through a narrative review of the literature and acts as a mnemonic to aid professionals in their assessment of refugee children in the PED.

The Influence of Storage and Cooking on the Vitamin D Content of 25-Hydroxyvitamin D3-Enriched Eggs.

Food fortification is an effective approach to improve vitamin D (VD) concentrations in foods. Eggs are a useful food vehicle for enrichment with VD via its hydroxylated metabolite, 25-hydroxyvitamin D (25-D3), in hen feed. This study determined the impact of time of lay, storage conditions (ambient and refrigeration) and common cooking methods (boiling, frying, scrambling, poaching and microwaving) on the vitamin D metabolite concentration of eggs enriched with 25-D3. Processed samples were freeze-dried and analysed for D3 and 25-D3 using an HPLC-MS(/MS) method. The results indicated that storage and cooking practices influence VD metabolites, with 25-D3 showing true retention of 72-111% and concentrations of 0.67-0.96 µg/100 g of whole egg. Vitamin D3 showed true retention of 50-152% and concentrations of 0.11-0.61 µg/100 g of whole egg. Depending on the storage and method of cooking applied, the calculated total VD activity of enriched eggs ranged from 3.45 to 5.43 µg/100 g of whole egg and was 22-132% higher in comparison to standardised VD content for non-enriched British eggs. The study suggests that 25-D3 is a stable metabolite in eggs following storage and cooking, and that 25-D3-enriched eggs may serve as a potent dietary source of VD.

Co-crystallisation and humanisation of an anti-HER2 single-domain antibody as a theranostic tool.

Human epidermal growth factor receptor-2 (HER2) is a well-recognised biomarker associated with 25% of breast cancers. In most cases, early detection and/or treatment correlates with an increased chance of survival. This study, has identified and characterised a highly specific anti-HER2 single-domain antibody (sdAb), NM-02, as a potential theranostic tool. Complete structural description by X-ray crystallography has revealed a non-overlapping epitope with current anti-HER2 antibodies. To reduce the immunogenicity risk, NM-02 underwent a humanisation process and retained wild type-like binding properties. To further de-risk the progression towards chemistry, manufacturing and control (CMC) we performed full developability profiling revealing favourable thermal and physical biochemical 'drug-like' properties. Finally, the application of the lead humanised NM-02 candidate (variant K) for HER2-specific imaging purposes was demonstrated using breast cancer HER2+/BT474 xenograft mice.