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Abstract Lunsekimig is a novel, bispecific NANOBODY® molecule that inhibits both thymic stromal lymphopoietin (TSLP) and interleukin (IL)‐13, two key mediators of asthma pathophysiology. In this first‐in‐human study, we evaluated the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of lunsekimig in healthy adult participants. Participants received single ascending doses (SAD) of lunsekimig (10–400 mg intravenous [IV] or 400 mg subcutaneous [SC]) (SAD part) or multiple ascending doses (MAD part) of lunsekimig (100 or 200 mg, every 2 weeks [Q2W] for three SC doses), or placebo. Overall, 48 participants were randomized 3:1 in the SAD part and 4:1 in the MAD part for lunsekimig or placebo. The primary endpoint was safety and tolerability. The secondary endpoints included PK, antidrug antibodies (ADAs) and total target measurement. Lunsekimig was well tolerated and common treatment‐emergent adverse events were COVID‐19, nasopharyngitis, injection site reactions, and headache. Lunsekimig showed dose‐proportional increases in exposure and linear elimination. Mean t1/2z of lunsekimig was around 10 days across all IV and SC doses of the SAD and MAD parts of the study. Increases in the serum concentration of total TSLP and IL‐13 for lunsekimig versus placebo indicated target engagement. ADA of low titers were detected in four (11.1%) participants who received lunsekimig in the SAD, and seven (43.8%) in the MAD. In conclusion, lunsekimig was well tolerated in healthy participants with a linear PK profile up to single 400 mg IV and SC dose and multiple doses of 100 and 200 mg SC Q2W, with low immunogenicity.

Play of younger siblings of children with autism spectrum disorder (ASD) (siblings; n = 44), very preterm children (preterms; n = 44), and children at typical likelihood for ASD (n = 36) was observed at 24 months. Children with ASD and atypical development engaged less in spontaneous (pre-)symbolic play than typically developing children. Total duration of spontaneous and elicited (pre-)symbolic play was associated with later ASD traits in siblings. However, no association between most play variables and ASD traits was found in preterms. This suggests possible different ASD-trajectories between siblings and preterms. Thus, spontaneous (pre-)symbolic play may be indicative of developmental challenges across several populations, and results highlight the need to move beyond studying only siblings in order to broaden our understanding of ASD., Author(s): Floor Moerman [sup.1] , Petra Warreyn [sup.1] , Ellen Demurie [sup.1] , Sofie Boterberg [sup.1] , Julie Vermeirsch [sup.1] , Chloè Bontinck [sup.1] , Eva Bruyneel, Marjolein Muès, Liedewij [...]

The orange and cherry industries in New South Wales, Australia, are major horticulture industries with a high export value. Climate change has resulted in the carbon footprint of products being used by consumers to guide purchases meaning that products with a relatively high carbon footprint risk losing market access. The carbon footprint of cherry and orange production is unknown and there is no assessment of the success of climate change mitigation strategies to reduce the carbon footprint of their production and move production towards being carbon neutral. This study assesses the climate change mitigation potential of five management changes to on-farm cherry and orange production (revegetation, the use of nitrification inhibitors, renewable energy, green N fertilisers, and pyrolysis of orchard residues) over a 25-year period. for example, orchards in relevant growing regions. The results show that the carbon footprint of production can be reduced by 73 and 83% for cherries and oranges, respectively, when strategies that avoid emissions are included in their production. When strategies that sequester C from the atmosphere are also included, cherry and orange production becomes C negative in the first few years of the scenario. The economics of implementing these strategies are unfavourable, at present; however, our results indicate that the NSW cherry and orange industries can be confident in achieving emissions reductions in on-farm production to assure market access for their products.

Background: Children with autism spectrum disorder (ASD) show substantial variability in their language development. Language problems are highly prevalent in these children. In addition, the quality of early language abilities contributes to the overall development of these children and is highly predictive of their adult outcome. Yet, little is known about language development in children at risk of ASD during the first years of life. Aims: To compare early receptive language (RL) and expressive language (EL) development in children at risk of ASD and determine predictors of language development. Methods & Procedures: Developmental trajectories of RL and EL were investigated from 10 to 36 months of age in younger siblings of typically developing children (LR-sibs, N = 30) and in younger siblings of children with ASD (HR-sibs, N = 31) using the Mullen Scales of Early Learning. Furthermore, both child and demographic characteristics were examined as possible predictors of language development. Outcomes & Results: Both groups showed similar growth curves for RL and EL and the majority of the children showed average (within ±1.5 SD of the mean) or above-average language abilities. Nevertheless, the mean growth of EL was lower and the variation in growth of both RL and EL was higher in HR-sibs than in LR-sibs. Furthermore, early child characteristics were predictive of language development in both groups. Yet, some child characteristics seemed to be of more importance in HR-sibs than in LR-sibs. Consequently, lower non-verbal abilities at 10 months in both groups and a higher degree of ASD characteristics at 14 months in HR-sibs may be indicative of difficulties in language development. Conclusions & Implications: HR-sibs show more variation in their language development than LR-sibs during the first 3 years of life. The majority of HR-sibs, however, did not present with below-average language abilities. Yet, early characteristics of ASD may be a red flag for difficulties in the language development of HR-sibs.

This study compared sibling interactions between 24-month-old children and their older sibling with ASD (high-risk; n = 24) with 24-month-old children and their typically developing older sibling (low-risk; n = 32). First, high-risk sibling pairs showed lower levels of positive behaviour and younger siblings of children with ASD imitated their older sibling less. Second, in the high-risk group positive interactions were positively associated with the youngest child's language abilities. However, this association was no longer significant after controlling for language abilities at 14 months. Third, more total interactions in the high-risk group, both negative and positive, were associated with more ASD characteristics. Thus, early sibling interactions might reveal interesting information in light of the (atypical) developmental trajectories of younger siblings of children with ASD.

Objective. Specific neck exercises are recommended in the rehabilitation of chronic nonspecific neck pain (CNNP). They are unfortunately often accompanied by acute pain flare-ups. Global exercises might be a beneficial addition, as they activate endogenous analgesia without overloading painful structures. However, it is still unclear which type of exercise is most effective. This randomized controlled trial was done to evaluate the effect of an online blended program of global and specific neck exercises, compared to programs including only 1 of both types of exercise. Methods. Forty-eight patients with CNNP were randomized into 3 groups. Online questionnaires were collected at baseline, at midtreatment, immediately after treatment, and at the 3-month follow-up. Quantitative sensory testing and actigraphy were assessed at baseline and after treatment. Linear mixed-model analyses were performed to evaluate treatment effects within and between groups. Neck pain-related disability after treatment was considered the primary outcome. Results. No time x treatment interaction effects were found. All groups improved in neck pain-related disability, pain intensity, self-reported symptoms of central sensitization, local pain sensitivity, physical activity, and pain medication use. No effects were found on quality of life, sleep quality, depression, anxiety, stress, widespread pain sensitivity, health economics, or actigraphy measurements. A higher global perceived effect was reported after performing the blended program, compared to the other groups. Conclusion. A blended exercise program was not superior to the stand-alone programs in reducing disability. Nevertheless, the global perceived effect of this type of exercise was higher. Future research necessitates larger sample sizes to adequately explore the optimal type of exercise for patients with CNNP. Impact. Exercise therapy should be an important part of the rehabilitation of patients with CNNP, regardless of the type of exercise. [ABSTRACT FROM AUTHOR]

Lunsekimig is a novel, bispecific NANOBODY® molecule that inhibits both thymic stromal lymphopoietin (TSLP) and interleukin (IL)‐13, two key mediators of asthma pathophysiology. In this first‐in‐human study, we evaluated the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of lunsekimig in healthy adult participants. Participants received single ascending doses (SAD) of lunsekimig (10–400 mg intravenous [IV] or 400 mg subcutaneous [SC]) (SAD part) or multiple ascending doses (MAD part) of lunsekimig (100 or 200 mg, every 2 weeks [Q2W] for three SC doses), or placebo. Overall, 48 participants were randomized 3:1 in the SAD part and 4:1 in the MAD part for lunsekimig or placebo. The primary endpoint was safety and tolerability. The secondary endpoints included PK, antidrug antibodies (ADAs) and total target measurement. Lunsekimig was well tolerated and common treatment‐emergent adverse events were COVID‐19, nasopharyngitis, injection site reactions, and headache. Lunsekimig showed dose‐proportional increases in exposure and linear elimination. Mean t1/2z of lunsekimig was around 10 days across all IV and SC doses of the SAD and MAD parts of the study. Increases in the serum concentration of total TSLP and IL‐13 for lunsekimig versus placebo indicated target engagement. ADA of low titers were detected in four (11.1%) participants who received lunsekimig in the SAD, and seven (43.8%) in the MAD. In conclusion, lunsekimig was well tolerated in healthy participants with a linear PK profile up to single 400 mg IV and SC dose and multiple doses of 100 and 200 mg SC Q2W, with low immunogenicity. [ABSTRACT FROM AUTHOR]

The orange and cherry industries in New South Wales, Australia, are major horticulture industries with a high export value. Climate change has resulted in the carbon footprint of products being used by consumers to guide purchases meaning that products with a relatively high carbon footprint risk losing market access. The carbon footprint of cherry and orange production is unknown and there is no assessment of the success of climate change mitigation strategies to reduce the carbon footprint of their production and move production towards being carbon neutral. This study assesses the climate change mitigation potential of five management changes to on-farm cherry and orange production (revegetation, the use of nitrification inhibitors, renewable energy, green N fertilisers, and pyrolysis of orchard residues) over a 25-year period. for example, orchards in relevant growing regions. The results show that the carbon footprint of production can be reduced by 73 and 83% for cherries and oranges, respectively, when strategies that avoid emissions are included in their production. When strategies that sequester C from the atmosphere are also included, cherry and orange production becomes C negative in the first few years of the scenario. The economics of implementing these strategies are unfavourable, at present; however, our results indicate that the NSW cherry and orange industries can be confident in achieving emissions reductions in on-farm production to assure market access for their products. [ABSTRACT FROM AUTHOR]

Because virtually all proteins interact with other proteins, studying protein–protein interactions (PPIs) is fundamental in understanding protein function. This is especially true when studying specific developmental processes, in which proteins often make developmental stage- or tissue specific interactions. However, studying these specific PPIs in planta can be challenging. One of the most widely adopted methods to study PPIs in planta is affinity purification coupled to mass spectrometry (AP/MS). Recent developments in the field of mass spectrometry have boosted applications of AP/MS in a developmental context. This review covers two main advancements in the field of affinity purification to study plant developmental processes: increasing the developmental resolution of the harvested tissues and moving from affinity purification to affinity enrichment. Furthermore, we discuss some new affinity purification approaches that have recently emerged and could have a profound impact on the future of protein interactome analysis in plants.

Although sibling interactions play an important role in children's early development, they are rarely studied in very young children with an older brother or sister with autism spectrum disorder (ASD). This study used a naturalistic, observational method to compare interactions between 18-month-old infants and their older sibling with ASD (n = 22) with a control group of 18-month-old infants and their typically developing (TD) older sibling (n = 29). In addition, role (a)symmetry and the influence of gender were evaluated. Sibling interactions in ASD-dyads were characterized by higher levels of negativity. Although somewhat less pronounced in ASD-dyads, role asymmetry was present in both groups, with the older child taking the dominant position. Finally, siblings pairs with an older sister were characterized by more positive behaviours. Since differences in sibling interactions may alter the developmental trajectories of both siblings, these early relationships should be taken into account in future ASD research and interventions.

While a number of authors have suggested that patients with palilalia typically show a tendency to repeat words or phrases with an increasing rate, others maintain that an accelerating speech rate is not essential. The present paper reports the results of an instrumental analysis of the reiterations in a 60-year-old man with palilalia. Results indicate that there is not necessarily an increasing rapidity in palilalia. Duration of the repetition trains, duration of the pauses between the trains, and average number and average duration of the components within a train were variable but did not show a pattern indicative of a systematically increasing rate. The variation in the reiterations suggests that novel or varying motor processes are deployed to produce the elements in a sequence rather than an invariant motor program.

Objective: This systematic review summarizes the relevant literature on the effectiveness of tailored interventions in non‐specific low back pain (NSLBP). Methods: The search strategy has been executed in December 2019 in the electronic databases PubMed, Web of Science and Embase. Study selection, data extraction and quality assessment were done independently by two authors. Results: A total six eligible studies were identified. Five out of six articles used a classification system to subgroup patients. All active patient tailored interventions had similar or better results than the non‐patient tailored interventions, most importantly on pain (short‐ and mid‐term, not for long term follow‐up). Two motor control interventions revealed sustained or increased effects at 12 months follow‐up for disability. For cost‐effectiveness, medication use and work absenteeism, results were inconclusive. Global rating of change evaluation confirmed significant between‐group results at 10 weeks to 4 months follow‐up, but results were not maintained at 12‐month evaluation. Discussion & conclusion: Our findings support the preliminary evidence for the use of patient tailored treatment for reductions in pain and disability. However, our results are of very low to moderate quality evidence and the observed effects strongly depend on the subgroups and the chosen interventions. More high‐quality RCT's with homogenous designs and larger sample sizes are needed. [ABSTRACT FROM AUTHOR]

SAMBA has been identified as a plant-specific regulator of the anaphase-promoting complex/cyclosome (APC/C) that controls unidirectional cell cycle progression in Arabidopsis (Arabidopsis thaliana), but so far its role has not been studied in monocots. Here, we show the association of SAMBA with the APC/C is conserved in maize (Zea mays). Two samba genome edited mutants showed growth defects, such as reduced internode length, shortened upper leaves with erect leaf architecture, and reduced leaf size due to an altered cell division rate and cell expansion, which aggravated with plant age. The two mutants differed in the severity and developmental onset of the phenotypes, because samba-1 represented a knockout allele, while translation re-initiation in samba-3 resulted in a truncated protein that was still able to interact with the APC/C and regulate its function, albeit with altered APC/C activity and efficiency. Our data are consistent with a dosage-dependent role for SAMBA to control developmental processes for which a change in growth rate is pivotal. [ABSTRACT FROM AUTHOR]

Background and Objective: After whiplash injury, some patients develop chronic whiplash‐associated disorders. The exact pathophysiology of this chronification is still unclear and more knowledge is needed regarding the different post‐injury phases. Therefore, studies were searched that examined temporal changes in pain processing, measured by Quantitative Sensory Testing (QST). Databases and Data Treatment: This systematic review searched three electronic databases (Medline, Web of Science and Embase) for articles meeting the eligibility requirements. Risk of bias was assessed according to a modified Newcastle–Ottawa Scale. Results: The 12 included studies presented moderate to good methodological quality. These studies showed altered pain processing within the first month after injury and normalization within 3 months in 59%–78% of the patients. After 3 months, recovery stagnates during the following years. Thermal and widespread mechanical hyperalgesia occur already in the acute phase, but only in eventually non‐recovered patients. Conclusions: Differences in pain processing between recovering and non‐recovering patients can be observed already in the acute phase. Early screening for signs of altered pain processing can identify patients with high risk for chronification. These insights in temporal changes show the importance of rehabilitation in the acute phase. Future research should target to develop a standardized (bed‐site) QST protocol and collect normative data which could, in relation with self‐reported pain parameters, allow clinicians to identify the risk for chronification. Significance: Altered pain processing is present soon after whiplash injury, but usually recovers within 3 months. Non‐recovering patients show little to no improvements in the following years. Differences between recovering and non‐recovering patients can be observed by Quantitative Sensory Testing already in the acute phase. Therefore, it is considered a feasible and effective tool that can contribute to the identification of high‐risk patients and the prevention of chronification. [ABSTRACT FROM AUTHOR]

Autism is frequently associated with difficulties with top-down attentional control, which impact on individuals' mental health and quality of life. The developmental processes involved in these attentional difficulties are not well understood. Using a data-driven approach, 2 samples (N = 294 and 412) of infants at elevated and typical likelihood of autism were grouped according to profiles of parent report of attention at 10, 15 and 25 months. In contrast to the normative profile of increases in attentional control scores between infancy and toddlerhood, a minority (7–9%) showed plateauing attentional control scores between 10 and 25 months. Consistent with pre-registered hypotheses, plateaued growth of attentional control was associated with elevated autism and ADHD traits, and lower adaptive functioning at age 3 years. [ABSTRACT FROM AUTHOR]