Perceived benefits and challenges of school feeding program in Addis Ababa, Ethiopia: a qualitative study.

Addis Ababa initiated a universal Home-Grown School Feeding Program (HGSFP) in February 2019 to address hunger and improve the educational outcomes of schoolchildren. This study aimed to document the perceived benefits and challenges of the HGSFP in Addis Ababa, where such information was lacking. In May 2023, a qualitative phenomenological study was conducted to collect data from 20 schools participating in the HGSFP. Data were collected through key informant interviews and focus group discussions (FGDs) involving 98 purposively selected participants. The study encompassed 48 student mothers in 5 FGDs, 20 student interviews, 20 school principals, and 10 experts from the Ministry of Education, Sub-cities, and the School Feeding Agency for in-depth interviews. Data collected in the local language were transcribed, translated into English, and thematically analysed using ATLAS-TI software. The study's findings unveiled the transformative impact of the HGSFP in Addis Ababa, Ethiopia. It demonstrated remarkable improvements in attendance, concentration, academic performance, reduced dropout rates, financial relief, enhanced behaviour, and a safer learning environment. However, urgent measures are imperative to tackle pressing challenges such as underpaid kitchen workers, operational issues, reduced reading time, rising food costs, limited market access, inadequate infrastructure, and growing dependency. To ensure the enduring sustainability of HGSFP, addressing challenges like workload reduction, kitchen infrastructure enhancement, government guideline implementation, promoting self-reliance, overcoming budget limitations, and addressing school gardening obstacles is vital.

Hunger, Satiety, and Their Vulnerabilities.

The psychological states of hunger and satiety play an important role in regulating human food intake. Several lines of evidence suggest that these states rely upon declarative learning and memory processes, which are based primarily in the medial temporal lobes (MTL). The MTL, and particularly the hippocampus, is unusual in that it is especially vulnerable to insult. Consequently, we examine here the impact on hunger and satiety of conditions that: (1) are central to ingestive behaviour and where there is evidence of MTL pathology (i.e., habitual consumption of a Western-style diet, obesity, and anorexia nervosa); and (2) where there is overwhelming evidence of MTL pathology, but where ingestive behaviour is not thought central (i.e., temporal lobe epilepsy and post-traumatic stress disorder). While for some of these conditions the evidence base is currently limited, the general conclusion is that MTL impairment is linked, sometimes strongly, to dysfunctional hunger and satiety. This focus on the MTL, and declarative learning and memory processes, has implications for the development of alternative treatment approaches for the regulation of appetite.

A randomized feasibility trial of time-restricted eating during pregnancy in people with increased risk of gestational diabetes.

Time-restricted eating (TRE) is a nutritional intervention that confines the daily time-window for energy intake. TRE reduces fasting glucose concentrations in non-pregnant individuals, but whether this eating protocol is feasible and effective for glycemic control in pregnancy is unknown. The aim of this randomized controlled trial was to investigate the adherence to and effect of a 5-week TRE intervention (maximum 10 h daily eating window) among pregnant individuals at risk of gestational diabetes mellitus (GDM), compared with a usual-care control group. Participants underwent 2-h oral glucose tolerance tests and estimation of body composition, before and after the intervention. Interstitial glucose levels were continuously measured, and adherence rates and ratings of hunger were recorded daily. Thirty of 32 participants completed the trial. Participants allocated to TRE reduced their daily eating window from 12.3 (SD 1.3) to 9.9 (SD 1.0) h, but TRE did not affect glycemic measures, blood pressure, or body composition, compared with the control group. TRE increased hunger levels in the evening, but not in the morning, and induced only small changes in dietary intake. Adhering to a 5-week TRE intervention was feasible for pregnant individuals with increased risk of GDM but had no effect on cardiometabolic outcomes.

Influence of short-time resistance training on appetite and energy intake in young women with and without obesity.

The aim of this study was to investigate the effect of 6-weeks resistance training (RT) on appetite, energy intake and body composition in young women with and without obesity, and to examine the relationship between these variables. Thirty-five young women were divided according to the amount of body fat [with obesity (n = 16) and without obesity (n = 19)]. Appetite was assessed through self-reported hunger, fullness, desire to eat, satiety quotient, food frequency diary and motivations to eat palatable food (power of food scale) in both fasted and fed states (after a standardized breakfast). Energy intake and body composition were evaluated at pre- and post-6 weeks of RT. Results showed that self-reported hunger increased significantly in both fasted and fed states (p = 0.007 and p = 0.029, respectively), while self-reported fullness decreased at the fasted state (p = 0.030) in both groups. There were no significant effects for desire to eat fatty, sweet, savory and salty foods, motivation to eat palatable foods, or for total energy intake. Food frequency analysis indicated a decrease in consumption of soup and past (p = 0.045), vegetables and eggs (p = 0.034), and leafy vegetables (p = 0.022) in both groups. Fat-free mass increased significantly in both groups (p = 0.011 and p = 0.003), while fat mass did not show significant changes. There were no correlations between changes in appetite/energy intake and changes in body composition. In conclusion, following the 6-week RT program, both women with and without obesity exhibited increased self-reported hunger alongside decreased fullness, suggesting an increase in orexigenic drive. However, neither group showed an increase in energy intake and fat mass, while both groups experienced an increase in fat-free mass. Registered under Brazilian Registry of Clinical Trials n°. RBR-1024f4qs.

Lunch melodies: Investigating the impact of music on emotions, hunger, liking, and psychophysiology while viewing a lunch meal.

Sensory cues like music can influence our behaviour towards food. In the present study, the effect of music on hunger, fullness, desire to eat and liking of foods, while viewing real lunch food items, was investigated. To this end, emotions and physiological measures were obtained to understand the changes in hunger, fullness, desire to eat and liking. The study aimed to examine changes in hunger, fullness, desire to eat, and liking when viewing a lunch meal under silent and varying music conditions. Additionally, the study explored the potential role of emotions to explain these changes. A crossover experimental design was employed using 50 participants (17 males and 33 females) who observed lunch food items during a silent condition (control), or while listening to either liked or disliked music. The findings demonstrate the cross-modal influence of music on hunger and food liking ratings when viewing food. Hunger ratings were higher and more negative emotions were evoked while viewing lunch food items and listening to disliked music. In contrast, in the silent and liked music conditions, which elicited more positive emotions, there were increased ratings of healthy and unhealthy food pleasantness, overall food liking, and food satisfaction. Electrophysiological measures of heart rate (HR) and skin conductance (SC) were obtained while listening to music and viewing a lunch meal. Viewing food items while listening to disliked music evoked negative emotions and significantly increased SC compared to liked music or silent conditions. Viewing the food items under the silent condition evoked positive emotions and significantly increased HR compared to listening to liked and disliked music. This study showed that the participants' emotions, hunger level, liking, and electrophysiological responses when viewing food are influenced by music that varied with liking. Results from this study may assist in enhancing dining experiences, as well as influencing food choices and satisfaction with meals.

Improve the Hunger Games search algorithm to optimize the GoogleNet model.

The setting of parameter values will directly affect the performance of the neural network, and the manual parameter tuning speed is slow, and it is difficult to find the optimal combination of parameters. Based on this, this paper applies the improved Hunger Games search algorithm to find the optimal value of neural network parameters adaptively, and proposes an ATHGS-GoogleNet model. Firstly, adaptive weights and chaos mapping were integrated into the hunger search algorithm to construct a new algorithm, ATHGS. Secondly, the improved ATHGS algorithm was used to optimize the parameters of GoogleNet to construct a new model, ATHGS-GoogleNet. Finally, in order to verify the effectiveness of the proposed algorithm ATHGS and the model ATHGS-GoogleNet, a comparative experiment was set up. Experimental results show that the proposed algorithm ATHGS shows the best optimization performance in the three engineering experimental designs, and the accuracy of the proposed model ATHGS-GoogleNet reaches 98.1%, the sensitivity reaches 100%, and the precision reaches 99.5%.

Acute exercise might not affect subsequent appetite responses to a fixed meal in adolescents with obesity: The SMASH exploratory study.

While an intensity-dependent post-exercise decrease in energy intake (EI) has been described in adolescents with obesity, studies invariably used ad libitum meals, limiting then any conclusions regarding the effect of exercise on post-meal appetitive responses that can be also impacted by the ad libitum nature of the meal. This study analyses appetite and food-reward related responses to a fixed meal after an acute exercise, also exploring the associations between substrate use during exercise and overall daily EI in adolescents with obesity. Thirteen adolescents with obesity (12-16 years, 5 males) randomly complete 2 experimental sessions: (i) a control condition (CON); (ii) a 30-min moderate intensity (65% VO2peak) cycling condition (EX). Energy expenditure and substrate oxidation were measured during both 30 min of rest (CON) or exercise (EX). Ad libitum EI, macronutrient intake and relative EI were assessed at dinner, subjective appetite sensations taken at regular intervals and food reward measured before and after lunch as well as before dinner. Energy and macronutrient intake did not differ between conditions, as well as appetite feelings. A time effect (p = 0.012) was observed between pre and post meal for choice fat bias in both conditions but was only significant within the CON condition (p = 0.004). CHO oxidation during exercise was found correlated with both EI (r = 0.586, p = 0.045), pre-lunch hunger (r = 0.624, p = 0.030), daily AUC for hunger and DTE (r = 0.788, p = 0.002 and r = 0.695; p = 0.012 respectively). This exploratory study highlights that acute exercise might not affect subsequent appetite responses when using a fixed test meal in adolescents with obesity.

Exploring factors influencing late evening eating and barriers and enablers to changing to earlier eating patterns in adults with overweight and obesity.

Late evening eating is a potential risk factor for overconsumption and weight gain. However, there is limited qualitative research investigating the complex factors that influence late evening eating in adults living with obesity. Identifying the factors that influence late evening eating can inform interventions to reduce late evening eating and associated health risks. Therefore, this study aimed to: i) explore factors that contribute to eating late, and ii) apply the Capability, Opportunity, and Motivation Behaviour (COM-B) model to understand the barriers and enablers to changing to earlier food intake timings in UK adults who report eating late. Semi-structured interviews with seventeen participants [32.47 ± 6.65 years; 34.68 ± 7.10 kg/m2; 71% female (n = 12); 41% White (n = 7)] investigated reasons for late evening eating and the potential barriers and enablers to changing to earlier eating patterns. Thematic analysis identified four main contributors to late evening eating: 1) internal signals (e.g., feeling hungry in the evening); 2) external and situational factors (e.g., work schedules and the food-rich environment); 3) social factors (e.g., interactions with family) and 4) behavioural and emotional factors (e.g., personal preferences and negative feelings in the evening). Time constraints and work schedules were identified as main barriers to changing to earlier eating patterns. Whereas, having high motivation (e.g., contentment with eating earlier in the evening) and interpersonal support were identified as main enablers to eating earlier. This study provides in-depth insights into the psychological, social, and environmental factors contributing to late evening eating. The findings highlight potential targets for future interventions to facilitate earlier eating times in individuals at risk of overweight and obesity.

Cross-sectional association of food insecurity with loneliness in older adults: The role of sex, age, and psychosomatic factors.

OBJECTIVE: Food insecurity (FI) is a critical social determinant of poor psychosocial health. While data on the specific roles of sex and age in the FI-loneliness link among older adults are limited, the underlying mechanisms are largely unknown. This study examines the age-sex-specific associations of FI with loneliness among older adults in Ghana and quantifies the extent to which psychosomatic factors mediate the association. METHODS: We analyzed cross-sectional data from the Aging, Health, Psychological, and Health-seeking Behavior Study in Ghana. The past 30-day FI was assessed using items on hunger and breakfast skipping frequency due to a lack of resources. We assessed loneliness severity with the University of California, Los Angeles 3-item Loneliness Scale. Multivariable OLS regressions and bootstrapping mediation analysis using the Hayes PROCESS macro plug-in were used to evaluate the associations. RESULTS: We included 1,201 individuals aged ≥50 years (mean = 62.9 [SD = 11.9]; women = 63.3%). The prevalence of loneliness was 17.7%. The prevalence of moderate and severe FI was 44.0% and 8.5%, respectively. In the adjusted model, greater FI was significantly associated with loneliness severity (B = .22, SE = .029, p < .001). We found significant interactive effects of FI × age (B = -.17, SE = .023, p < .01) and FI × sex (B = -.28, SE = .036, p < .001) on loneliness. Thus, the FI-loneliness link was respectively more marked among women (B = .25, SE = .035, p < .001) and ≥65 age groups (B = .34, SE = .041, p < .001) than men (B = .16, SE = .051, p < .01) and those aged 50-64 (B = .22; SE = .040, p < .001). Finally, comorbid depression/anxiety (41.07%), hopelessness (48.6%), worthlessness (42.1%), functional limitations (8.2%), and pain severity (6.4%) mediated the FI-loneliness association. CONCLUSIONS: Age- and sex-specific associations between FI and loneliness exist among older Ghanaians. Addressing FI in concert with psychosomatic problems in older adults may contribute meaningfully to reducing loneliness in later life.

Investigation of setmelanotide, an MC4R agonist, for obesity in individuals with Smith-Magenis syndrome.

BACKGROUND: Smith Magenis Syndrome (SMS) is a rare genetic disorder caused by RAI1 haploinsufficiency. Obesity in people with SMS is believed partially due to dysfunction of the proximal melanocortin 4 receptor (MC4R) pathway. We therefore studied effects of treatment with the MC4R agonist setmelanotide on obesity and hunger, as well as metabolic, cardiac and safety, in individuals with SMS. METHODS: People with SMS received once-daily setmelanotide injections, with the dose titrated bi-weekly to a maximum of 3 mg over ∼1 month; and a full-dose treatment duration of 3mo. The primary outcome was percent change in body weight. Secondary outcomes included hunger, waist circumference, body composition, and safety. RESULTS: 12 individuals, ages 11-39 y, enrolled and 10 completed the full-dose treatment phase. Mean percent change in body weight at end-treatment was - 0.28 % [(95 % CI, -2.1 % to 1.5 %; n = 12; P = 0.66]. Participants experienced a significant decrease in total cholesterol associated with a significant decrease in HDL-cholesterol and a trend for lower LDL-cholesterol. Self-reported hunger was reduced at end-treatment (p = 0.011). All participants reported adverse events (AEs), most commonly injection-site reactions and skin hyperpigmentation. No AEs led to withdrawal or death. CONCLUSIONS: In this trial, setmelanotide did not significantly reduce body weight in participants with SMS. Participants reported significant differences in hunger, but such self-reports are difficult to interpret without a placebo-treated group. The changes in lipid profiles require further investigation. Results of this study do not suggest that dysfunction of the proximal MC4R pathway is the main etiology for obesity in people with SMS.

Volitionally Regulated Breathing with Prolonged Expiration Influences Food Craving and Impulsivity.

INTRODUCTION: Previously, an intervention involving volitional slow breathing reduced trait food craving with protective effects on cardiac vagal activity (CVA). Breathing with a low inspiration-to-expiration (i/e) ratio also increases CVA. High CVA was separately associated with low unregulated eating and lesser impulsivity. Hence, the present study assessed breathing with a low i/e for effects on state food craving, hunger and satiety, state impulsivity, and heart rate variability (HRV) in healthy obese persons. METHODS: Forty obese persons were randomized to two groups. The intervention group (mean age ± SD, 41.15 ± 12.63, M:F, 10:10) practiced metronome-regulated breathing with low i/e at 12 breaths per minute (expiration 72% of total breath duration) and attained expiration 55.8% of total breath duration, while the active control group (mean age ± SD, 44.45 ± 11.06, M:F, 13:07) sat motionless and directed their gaze and awareness to the stationary metronome without modifying their breath consciously. The HRV was recorded before, during, and after breathing intervention (or control) (standard limb lead I, acquisition at 2,000 Hz, with an LF filter = 0.5 Hz and HF filter = 50 Hz). Time-domain and frequency-domain HRV parameters were obtained with Kubios software. State food craving, and hunger and satiety were recorded before and after the intervention/control. RESULTS: The intervention group decreased total state food craving scores and the sub-domains (i.e., desire to eat, positive reinforcement, lack of control and hunger), increased current satisfaction with food, decreased total state impulsivity (repeated measures ANOVA, p < 0.05 in all cases), increased HF-HRV and RMSSD (linear mixed model analyses with age and gender as fixed factors; p < 0.05 in all cases) during the intervention compared to the preceding baseline. The intervention group also showed an increase in positive mood and a decrease in aroused and negative mood states. CONCLUSION: Changes in state food craving and impulsivity could be related to an increase in HRV or to changes in subjective relaxation and positive mood or to both.

Plant synthetic biology as a tool to help eliminate hidden hunger.

Agricultural systems are under increasing pressure from declining environmental conditions, a growing population, and changes in consumer preferences, resulting in widespread malnutrition-related illnesses. Improving plant nutritional content through biotechnology techniques such as synthetic biology is a promising strategy to help combat hidden hunger caused by the lack of affordable and healthy foods in human diets. Production of compounds usually found in animal-rich diets, such as vitamin D or omega-3 fatty acids, has been recently demonstrated in planta. Here, we review recent biotechnological approaches to biofortifying plants with vitamins, minerals, and other metabolites, and summarise synthetic biology advances that offer the opportunity to build on these early biofortification efforts.

Caregivers' Attention Toward, and Response to, Their Child's Interoceptive Hunger and Thirst Cues.

People can use their internal state to determine if they are hungry or thirsty. Although the meaning of some interoceptive cues may be innate (e.g., pain), it is possible that others-including those for hunger and thirst-are acquired. There has been little exploration of this idea in humans. Consequently, we conducted a survey among child caregivers to determine if the basic conditions necessary for interoceptive learning were present. Two-hundred and thirty-five caregivers of children aged 1-12 years were asked if they had recently noticed stomach rumbling, hunger-related irritability, and a dry mouth in their child. They were also asked how they would respond. The impact of several moderating variables, especially caregiver beliefs about the causes of hunger, fullness, and thirst, was also explored. Fifteen percent of caregivers had recently noticed stomach rumbling in their child, 28% hunger-related irritability, and 14% a dry mouth. Forty-four percent of caregivers had noticed at least one of these three cues. Noticing hunger cues was significantly moderated by caregiver beliefs about their cause, by child age, and in one case by temporal context (around vs. outside mealtimes). Key caregiver responses were providing the need (e.g., offer food) and/or asking the child if they had a need (e.g., hungry?). Each type of response could potentially support a different form of interoceptive learning. In conclusion, we suggest the necessary conditions for children to learn interoceptive hunger and thirst cues, are present in many caregiver-offspring dyads.

Post-COVID-19 Changes in Appetite-An Exploratory Study.

In this analysis, we aimed to investigate the effect of COVID-19 disease on eating behavior. A total of 55 right-handed adults, <50 years of age, without overweight or obesity, from two cross-sectional studies were included. The first one enrolled subjects between September 2018 and December 2019 (non-COVID-19 group). The second one included subjects enrolled between March 2022 and May 2023; for this analysis, 28 with a history of COVID-19 (COVID-19 group) were retained. Hunger, TFEQ-18, plasma ghrelin, neuropeptide Y (NPY) and resting-state fMRI were assessed during fasting. Intraregional neuronal synchronicity and connectivity were assessed by voxel-based regional homogeneity (ReHo) and degree of centrality (DC). Significantly higher ghrelin and NPY levels were observed in the COVID-19 group than in the non-COVID-19 group (ghrelin 197.5 pg/mL vs. 67.1 pg/mL, p < 0.001; NPY 128.0 pg/mL vs. 84.5 pg/mL, p = 0.005). The NPY levels positively correlated with the DC and ReHo in the left lingual (r = 0.67785 and r = 0.73604, respectively). Similar scores were noted for cognitive restraint, uncontrolled eating and emotional eating in both groups according to the TFEQ-18 questionnaire results (p > 0.05 for all). Our data showed increased levels of appetite-related hormones, correlated with activity in brain regions involved in appetite regulation, persisting long after COVID-19 infection.

Benefits of using both the Hunger Vital Sign and brief nutrition security screener in health-related social needs screening.

Food security is a commonly screened for health-related social need at hospitals and community settings, and until recently, there were no tools to additionally screen for nutrition security. The purpose of this study was to assess the potential advantage of including a one-item brief nutrition security screener (BNSS) alongside the commonly used two-item Hunger Vital Sign (HVS) food security screener for identifying individuals with diet-related health risks. Cross-sectional survey data were collected from April to June 2021. Generalized linear mixed models were used to assess associations between screening status and dietary and health variables. Recruitment was done across five states (California, Florida, Maryland, North Carolina, and Washington) from community-based organizations. Participants (n = 435) were, on average, 44.7 years old (SD = 14.5), predominantly women (77%), and racially/ethnically diverse. In adjusted analyses, being in the food insecure and nutrition insecure group (but not the food insecure and nutrition secure or food secure and nutrition insecure groups) was associated with significantly increased odds for self-reported "fair" or "poor" general health [OR = 2.914 (95% CI = 1.521-5.581)], reporting at least one chronic condition [2.028 (1.024-4.018)], and "low" fruit and vegetable intake [2.421 (1.258-4.660)], compared with the food secure and nutrition secure group. These findings support using both the HVS and BNSS simultaneously in health-related social needs screening to identify participants at the highest risk for poor dietary and health outcomes and warrant further investigation into applying these screeners to clinical and community settings.

Food security and nutrition security are related to a household's ability to get enough food and to get food that is good for their health, respectively. Patients at hospitals, or clients who go to food pantries for help, are often asked about their food security status. This is referred to as screening. On the basis of their answers, they may get help such as referral to a food pantry and/or consultation with a dietitian. While there is a standard tool to screen for food security status, until recently, there has not been one for nutrition security. We used both the commonly used Hunger Vital Sign (HVS) food security screener and the newly developed brief nutrition security screener to identify food and nutrition security screening status. Being in the food insecure and nutrition insecure groups (but not the food insecure and nutrition secure or food secure and nutrition insecure groups) was associated with significantly increased odds for poor dietary and health outcomes. These findings support using both the HVS and brief nutrition security screener simultaneously in health-related social needs screening to identify participants at the highest risk.

Acute Consumption of Cooked Green Banana Pulp Beverage (Musa cavendishii) Decreases Plasma Glucose in Healthy Women: A Cross-Sectional Controlled Study.

This study aimed at comparing the carbohydrate composition of three banana varieties (cv. Nanica, Nanicão, and Prata) and investigating the effect of a single dose of cooked green banana pulp beverage (GBPd) on plasma glycemic homeostasis indexes (glucose, PYY, GIP, insulin) and hunger and satiety sensation (visual analog scale-VAS). The bananas were classified according to the color scale. The fiber, total carbohydrate, and resistant starch (RS) were determined using validated methods. Glucose homeostasis indexes and hunger/satiety sensation were determined in ten healthy women in two stages before and after intake: (1) glucose solution (250 g/L); (2) one week later, consumption of the glucose solution plus 75 g/L of GBPd. Blood samples were collected twice in stage-1 and every 15 min for 2 h in stage-2. Cv. Nanicão was selected, because it presented a higher content in RS and dietary fiber on dry base than the other cultivars. Thus, it was used to test glycemic response. After 2 h of GBPd intake, no difference was observed in hunger/satiety sensation and plasma glycemic homeostasis indexes, except for a decrease in plasma glucose concentration (-15%, p = 0.0232) compared to stage-1. These results suggest that cv. Nanicão has a higher potential as a functional ingredient and can influence the reduction in the glycemic index of a meal compared to other cultivars. However, it had not a short-term effect on hormones GIP and PYY in healthy women. Further research is needed to understand the long-term effects and mechanisms of green banana on glycemic control and satiety.

Effect of coffee intake on appetite parameters in woman with overweight or obesity: A pilot crossover randomized trial.

INTRODUCTION: Coffee consumption has demonstrated an effect on the regulation of appetite, causing less hunger and/or greater satiety; however, its effects are not well known in woman with overweight or obesity. Therefore, this study aimed to evaluate the effect of coffee consumption on hunger, satiety, sensory specific desire (SSD), and dietary intake in women with overweight or obesity. METHODOLOGY: A randomized crossover clinical trial was realized in 3 sessions: in the first session a clinical history, anthropometric measurements and body composition analysis were performed; in sessions 2 and 3 the participants randomly consumed 240mL of coffee with 6mg/caffeine/kg of weight or 240mL of water along with a standardized breakfast. At fasting and every 30min after breakfast for the next 3h, appetite sensations and SSD were recorded using visual analog scales. Blood samples were taken at fasting, 30 and 180min after breakfast. Dietary intake was recorded in the rest of the intervention days. RESULTS: In the coffee intervention there was an increased desire for sweet foods, higher fructose intake during the rest of the day, and higher triglyceride levels than with the water intervention. No differences were detected in ghrelin or cholecystokinin. CONCLUSIONS: Coffee consumption may lead to higher triglycerides and higher intake of simple sugars, mainly fructose, through changes in the SSD. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/NCT05774119.