A two-dose regimen of Qß virus-like particle-based vaccines elicit protective antibodies against heroin and fentanyl.

Opioid overdoses and the growing rate of opioid use disorder (OUD) are major public health concerns, particularly in the United States. Current treatment approaches for OUD have failed to slow the growth of the opioid crisis. Opioid vaccines have shown pre-clinical success in targeting multiple different opioid drugs. However, the need for many immunizations can limit their clinical implementation. In this study, we investigate the development of novel opioid vaccines by independently targeting fentanyl and the active metabolites of heroin using a bacteriophage virus-like particle (VLP) vaccine platform. We establish the successful conjugation of haptens to bacteriophage Qß VLPs and demonstrate immunogenicity of Qß-fentanyl, Qß-morphine, and Qß-6-acetylmorphine in animal models after one or two immunizations. We show that in independently or in combination, these vaccines elicit high-titer, high-avidity, and durable antibody responses. Moreover, we reveal their protective capacities against heroin or fentanyl challenge after two immunizations. Overall, these findings establish Qß-VLP conjugated vaccines for heroin and fentanyl as very promising opioid vaccine candidates.

Effects of Dietary Nitrate Supplementation on High-Intensity Cycling Sprint Performance in Recreationally Active Adults: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis investigated the influence of dietary nitrate supplementation on performance metrics during cycling sprint exercise according to the PRISMA guidelines. Searches were conducted on MEDLINE, PubMed, ScienceDirect, Scopus, and SPORTDiscus databases up to September 2023. Inclusion criteria were healthy recreationally active men and women who consumed nitrate-rich and nitrate-deficient beetroot juice to assess performance outcomes of mean power, peak power, time-to-peak power, and minimum power during 30-s cycling sprints. Risk of bias was assessed using the Cochrane Risk of Bias 2 and TESTEX tools and funnel plots. A random effects model was performed on six studies and showed that dietary nitrate had significant effects on time-to-peak power (SMD: -0.66, 95% CI: -1.127 to -0.192, p = 0.006) but not on mean power, peak power, or minimum power. Subgroup analysis revealed that an acute low nitrate dose improved time-to-peak power (SMD: -0.977, 95% CI: -1.524 to -0.430, p < 0.001) but not after a multiday moderate nitrate dose (SMD: -0.177, 95% CI: -0.619 to -0.264, p = 0.431). These data suggest that acute nitrate supplementation can benefit time-to-peak power during 30-s cycling sprints, but due to the limited availability of data and heterogeneity in methodology, these results should be interpreted with caution. There was insufficient data on women to analyze sex-based differences. Future studies are required to provide insight on how supplementation regimen and population impact the effects of dietary nitrate for enhancing cycling sprint performance.

TRIP13 localizes to synapsed chromosomes and functions as a dosage-sensitive regulator of meiosis.

Meiotic progression requires coordinated assembly and disassembly of protein complexes involved in chromosome synapsis and meiotic recombination. Mouse TRIP13 and its ortholog Pch2 are instrumental in remodeling HORMA domain proteins. HORMAD proteins are associated with unsynapsed chromosome axes but depleted from the synaptonemal complex (SC) of synapsed homologs. Here we report that TRIP13 localizes to the synapsed SC in early pachytene spermatocytes and to telomeres throughout meiotic prophase I. Loss of TRIP13 leads to meiotic arrest and thus sterility in both sexes. Trip13-null meiocytes exhibit abnormal persistence of HORMAD1 and HOMRAD2 on synapsed SC and chromosome asynapsis that preferentially affects XY and centromeric ends. These major phenotypes are consistent with reported phenotypes of Trip13 hypomorph alleles. Trip13 heterozygous mice exhibit meiotic defects that are less severe than the Trip13-null mice, showing that TRIP13 is a dosage-sensitive regulator of meiosis. Localization of TRIP13 to the synapsed SC is independent of SC axial element proteins such as REC8 and SYCP2/SYCP3. Terminal FLAG-tagged TRIP13 proteins are functional and recapitulate the localization of native TRIP13 to SC and telomeres. Therefore, the evolutionarily conserved localization of TRIP13/Pch2 to the synapsed chromosomes provides an explanation for dissociation of HORMA domain proteins upon synapsis in diverse organisms.

Dimethyl Fumarate Mediates Sustained Vascular Smooth Muscle Cell Remodeling in a Mouse Model of Cerebral Aneurysm.

Cerebral aneurysms (CA) are a type of vascular disease that causes significant morbidity and mortality with rupture. Dysfunction of the vascular smooth muscle cells (VSMCs) from circle of Willis (CoW) vessels mediates CA formation, as they are the major cell type of the arterial wall and play a role in maintaining vessel integrity. Dimethyl fumarate (DMF), a first-line oral treatment for relapsing-remitting multiple sclerosis, has been shown to inhibit VSMC proliferation and reduce CA formation in a mouse model. Potential unwanted side effects of DMF on VSMC function have not been investigated yet. The present study characterizes the impact of DMF on VSMC using single-cell RNA-sequencing (scRNA-seq) in CoW vessels following CA induction and further explores its role in mitochondrial function using in vitro VSMC cultures. Two weeks of DMF treatment following CA induction impaired the transcription of the glutathione redox system and downregulated mitochondrial respiration genes in VSMCs. In vitro, DMF treatment increased lactate formation and enhanced the mitochondrial production of reactive oxygen species (ROS). These effects rendered VSMCs vulnerable to oxidative stress and led to mitochondrial dysfunction and enhancement of apoptosis. Taken together, our data support the concept that the DMF-mediated antiproliferative effect on VSMCs is linked to disturbed antioxidative functions resulting in altered mitochondrial metabolism. This negative impact of DMF treatment on VSMCs may be linked to preexisting alterations of cerebrovascular function due to renal hypertension. Therefore, before severe adverse effects emerge, it would be clinically relevant to develop indices or biomarkers linked to this disturbed antioxidative function to monitor patients undergoing DMF treatment.

Diastereoselective Synthesis of the HIV Protease Inhibitor Darunavir and Related Derivatives via a Titanium Tetrachloride-Mediated Asymmetric Glycolate Aldol Addition Reaction.

Darunavir is a potent HIV protease inhibitor that has been established as an effective tool in the fight against the progression of HIV/AIDS in the global community. The successful application of this drug has spurred the development of derivatives wherein strategic regions (e.g., P1, P1', P2, and P2') of the darunavir framework have been structurally modified. An alternate route for the synthesis of darunavir and three related P1 and P1' derivatives has been developed. This synthetic pathway involves the use of a Crimmins titanium tetrachloride-mediated oxazolidine-2-thione-guided asymmetric glycolate aldol addition reaction. The resultant aldol adduct introduces the P1 fragment of darunavir via an aldehyde. Transamidation with a selected amine (isobutylamine or 2-ethyl-1-butylamine) to cleave the auxiliary yields an amide wherein the P1' component is introduced. From this stage, the amide is reduced to the corresponding ß-amino alcohol and the substrate is then bis-nosylated to introduce the requisite p-nitrobenzenesulfonamide component and activate the secondary alcohol for nucleophilic substitution. Treatment with sodium azide yielded the desired azides, and the deprotection of the p-methoxyphenoxy group is achieved with the use of ceric ammonium nitrate. Finally, hydrogenation to reduce both the aniline and azide functionalities with concurrent acylation yields darunavir and its derivatives.

Agenesis of the left hepatic lobe: a cadaveric case report.

Agenesis of the left hepatic lobe is a rare anomaly described as the absence of liver tissue on the left side of the gallbladder fossa or falciform ligament. Here we report a case of agenesis of the left hepatic lobe identified during educational dissection of an 84-year-old male formalin-fixed cadaver. The gross anatomical characteristics, embryological origin, and clinical relevance of this rare variation are described in this report.

Protective role for kidney TREM2high macrophages in obesity- and diabetes-induced kidney injury.

Diabetic kidney disease (DKD), the most common cause of kidney failure, is a frequent complication of diabetes and obesity, and yet to date, treatments to halt its progression are lacking. We analyze kidney single-cell transcriptomic profiles from DKD patients and two DKD mouse models at multiple time points along disease progression-high-fat diet (HFD)-fed mice aged to 90-100 weeks and BTBR ob/ob mice (a genetic model)-and report an expanding population of macrophages with high expression of triggering receptor expressed on myeloid cells 2 (TREM2) in HFD-fed mice. TREM2high macrophages are enriched in obese and diabetic patients, in contrast to hypertensive patients or healthy controls in an independent validation cohort. Trem2 knockout mice on an HFD have worsening kidney filter damage and increased tubular epithelial cell injury, all signs of worsening DKD. Together, our studies suggest that strategies to enhance kidney TREM2high macrophages may provide therapeutic benefits for DKD.

Impact of drone-specific dispatch instructions on the safety and efficacy of drone-delivered emergency medical treatments: A randomized simulation pilot study.

Introduction: Medical drones have potential for improving the response times to out-of-hospital emergencies. However, widespread adoption is hindered by unanswered questions surrounding medical dispatch and bystander safety. This study evaluated the impact of novel drone-specific dispatch instructions (DSDI) on bystanders' ability to interact effectively with a medical drone and provide prompt, safe, and high-quality treatment in a simulated emergency scenario. We hypothesized DSDI would improve bystanders' performance and facilitate safer bystander-drone interactions. Methods: Twenty-four volunteers were randomized to receive either DSDI and standard Medical Priority Dispatch (MPD) instructions or MPD alone in a simulated out-of-hospital cardiac arrest (OHCA) or pediatric anaphylaxis.,3 Participants in the DSDI group received detailed instructions on locating and interacting with the drone and its enclosed medical kit. The simulations were video recorded. Participants completed a semi-structured interview and survey. Results: The addition of DSDI did not lead to statistically significant changes to the overall time to provide care in either the anaphylaxis or OHCA simulations. However, DSDI did have an impact on bystander safety. In the MPD only group, 50% (6/12) of participants ignored the audio and visual safety cues from the drone instead of waiting for it to be declared safe compared to no DSDI participants ignoring these safety cues. Conclusions: All participants successfully provided patient care. However, this study indicates that DSDI may be useful to ensure bystander safety and should be incorporated in the continued development of emergency medical drones.

Bystander interaction with a novel multipurpose medical drone: A simulation trial.

Intro: Medical drones are an emerging technology which may facilitate rapid treatment in time-sensitive emergencies. However, drones rely on lay rescuers, whose interactions with multipurpose medical drones have not been studied, and the optimal drone design remains unclear. Methods: We conducted 24 simulations of adult out-of-hospital cardiac arrest (OHCA) and pediatric anaphylaxis with a prototype drone equipped with spoken and visual cues and a multipurpose medical kit. 24 layperson volunteers encountered one of the two scenarios and were supported through administering treatment by a simulated 911 dispatcher. Bystander-drone interactions were evaluated via a convergent parallel mixed methods approach using surveys, video event review, and semi-structured interviews. Results: 83% (20/24) of participants voiced comfort interacting with the drone. 96% (23/24) were interested in future interaction. Participants appreciated the drone's spoken instructions but found visual cues confusing. Participants retrieved the medical kit from the drone in a mean of 5 seconds (range 2-14) of drone contact; 79% (19/24) found this step easy or very easy. The medical kit's layered design caused difficulty in retrieving appropriate equipment. Participants expressed a wide range of reactions to the unique drone design. Conclusions: Laypeople can effectively and comfortably interact with a medical drone with a novel design. Feedback on design elements will result in further refinements and valuable insights for other drone designers. A multipurpose medical kit created more challenges and indicates the need for further refinement to facilitate use of the equipment.

Rapid, high-capacity adsorption of iodine from aqueous environments with amide functionalized covalent organic frameworks.

The uses and production of radionuclides in nuclear energy production and medical therapy are becoming more significant in today's world. While these applications have many benefits, they can produce harmful pollutants, such as radioactive iodine, that need to be sequestered. Effective capture and storage of radioactive iodine waste remains a major challenge for nuclear energy generation and nuclear medicine. Here we report the highly efficient capture of iodine in a series of mesoporous, two-dimensional (2D) covalent organic frameworks, called COFamides, which contain amide sidechains in their pores. COFamides are capable of rapidly removing iodine from aqueous solution at concentrations as low as 50 ppm, with total capacities greater than 650 wt%. In order to explain the high affinity of the COFamide series for iodine and iodide species in water, we performed a computational analysis of the interactions between the COFamide framework and iodine guests. These studies suggest that the origin of the large iodine capacity in these materials can be explained by the presence of multiple, cooperative, non-covalent interactions between the framework and both iodine, and iodide species.

The N-terminal modification of HORMAD2 causes its ectopic persistence on synapsed chromosomes without meiotic blockade.

In brief: The dissociation of HORMA domain protein 2 (HORMAD2) from the synaptonemal complex is tightly regulated. This study reveals that the N-terminal region of HORMAD2 is critical for its dissociation from synapsed meiotic chromosomes. Abstract: During meiosis, homologous chromosomes undergo synapsis and recombination. HORMA domain proteins regulate key processes in meiosis. Mammalian HORMAD1 and HORMAD2 localize to unsynapsed chromosome axes but are removed upon synapsis by the TRIP13 AAA+ ATPase. TRIP13 engages the N-terminal region of HORMA domain proteins to induce an open conformation, resulting in the disassembly of protein complexes. Here, we report introduction of a 3×FLAG-HA tag to the N-terminus of HORMAD2 in mice. Coimmunoprecipitation coupled with mass spectrometry identified HORMAD1 and SYCP2 as HORMAD2-associated proteins in the testis. Unexpectedly, the N-terminal tagging of HORMAD2 resulted in its abnormal persistence along synapsed regions in pachynema and ectopic localization to telomeres in diplonema. Super-resolution microscopy revealed that 3×FLAG-HA-HORMAD2 was distributed along the central region of the synaptonemal complex, whereas wild-type HORMAD1 persisted along the lateral elements in 3×FLAG-HA-HORMAD2 meiocytes. Although homozygous mice completed meiosis and were fertile, homozygous males exhibited a significant reduction in sperm count. Collectively, these results suggest that the N-terminus of HORMAD2 is important for its timely removal from meiotic chromosome axes.

It appears on my feed! Differences in intentionality of fitspiration exposure by weight/shape concerns, disordered eating, and self-compassion in women.

Viewing fitspiration (fitness inspiration) has been found to increase body dissatisfaction and negative affect; however, minimal research has examined how body dissatisfaction and related variables differ based on intentionality of fitspiration exposure. This study's aim was to examine differences in levels of weight/shape concerns, disordered eating, and self-compassion according to type of fitspiration exposure. Participants included 234 female undergraduate students who completed online questionnaires. We created three groups of fitspiration exposure based on their self-report of Instagram exposure: unexposed (neither view nor post fitspiration; n = 43), incidentally exposed (report seeing fitspiration content unintentionally; n = 119), and intentionally exposed (intentionally view and/or post fitspiration; n = 72). Weight/shape concerns, disordered eating, and self-compassion were significantly worse in the intentionally exposed group and incidentally exposed group compared to the unexposed group. These results suggest that exposure to fitspiration, regardless of intention, may be problematic and should be limited.

Early intranasal medication administration in out-of-hospital cardiac arrest: Two randomized simulation trials.

Objective: Intranasal medications have been proposed as adjuncts to out-of-hospital cardiac arrest (OHCA) care. We sought to quantify the effects of intranasal medication administration (INMA) in OHCA workflows. Methods: We conducted separate randomized OHCA simulation trials with lay rescuers (LRs) and first responders (FRs). Participants were randomized to groups performing hands-only cardiopulmonary resuscitation (CPR)/automated external defibrillator with or without INMA during the second analysis phase. Time to compression following the second shock (CPR2) was the primary outcome and compression quality (chest compression rate (CCR) and fraction (CCF)) was the secondary outcome. We fit linear regression models adjusted for CPR training in the LR group and service years in the FR group. Results: Among LRs, INMA was associated with a significant increase in CPR2 (mean diff. 44.1 s, 95% CI: 14.9, 73.3), which persisted after adjustment (p = 0.005). We observed a significant decrease in CCR (INMA 95.1 compressions per min (cpm) vs control 104.2 cpm, mean diff. -9.1 cpm, 95% CI -16.6, -1.6) and CCF (INMA 62.4% vs control 69.8%, mean diff. -7.5%, 95% CI -12.0, -2.9). Among FRs, we found no significant CPR2 delays (mean diff. -2.1 s, 95% CI -15.9, 11.7), which persisted after adjustment (p = 0.704), or difference in quality (CCR INMA 115.5 cpm vs control 120.8 cpm, mean diff. -5.3 cpm, 95% CI -12.6, 2.0; CCF INMA 79.6% vs control 81.2% mean diff. -1.6%, 95% CI -7.4, 4.3%). Conclusions: INMA in LR resuscitation was associated with diminished resuscitation performance. INMA by FR did not impede key times or quality.

Malignant Epithelioid Mesothelioma of the Tunica Vaginalis Testis Presenting as Hydrocele in a Kidney Transplant Recipient.

Mesotheliomas of the tunica vaginalis testis are rare malignant tumors that can present as a scrotal mass or hydrocele. These tumors are typically aggressive with high rates of recurrence and metastasis. Suspected risk factors for malignant mesothelioma include asbestos exposure, chronic inflammation, trauma, and persistent hydrocele. We report the case of a malignant epithelioid mesothelioma of the tunica vaginalis testis that presented as a finding at hydrocelectomy and was ultimately treated with radical inguinal orchiectomy. This patient was on chronic immunosuppression therapy with tacrolimus and mycophenolate mofetil secondary to a kidney transplant but had none of the common risk factors for mesothelioma formation. To our knowledge, this is the first case describing a possible connection between chronic immunosuppression and mesothelioma of the tunica vaginalis. However, future studies are needed to investigate this association and discern whether this could have played a role in our patient or if his mesothelioma formation was coincidental.

Extreme heat reduces host and parasite performance in a butterfly-parasite interaction.

Environmental temperature fundamentally shapes insect physiology, fitness and interactions with parasites. Differential climate warming effects on host versus parasite biology could exacerbate or inhibit parasite transmission, with far-reaching implications for pollination services, biocontrol and human health. Here, we experimentally test how controlled temperatures influence multiple components of host and parasite fitness in monarch butterflies (Danaus plexippus) and their protozoan parasites Ophryocystis elektroscirrha. Using five constant-temperature treatments spanning 18-34°C, we measured monarch development, survival, size, immune function and parasite infection status and intensity. Monarch size and survival declined sharply at the hottest temperature (34°C), as did infection probability, suggesting that extreme heat decreases both host and parasite performance. The lack of infection at 34°C was not due to greater host immunity or faster host development but could instead reflect the thermal limits of parasite invasion and within-host replication. In the context of ongoing climate change, temperature increases above current thermal maxima could reduce the fitness of both monarchs and their parasites, with lower infection rates potentially balancing negative impacts of extreme heat on future monarch abundance and distribution.

A bacteriophage virus-like particle vaccine against oxycodone elicits high-titer and long-lasting antibodies that sequester drug in the blood.

Opioid use disorder (OUD) and opioid overdoses are public health emergencies. In 2021, 80,000 opioid overdose associated deaths were reported in the United States. Despite the availability of treatment strategies, including medications for opioid use disorder (MOUD) and naloxone, opioid overdoses continue to increase at an alarming rate. Opioid vaccines are a novel approach to combat the growing crisis with several candidates recently entering human clinical trials. In this study, we investigated Qß bacteriophage virus-like particles (VLPs) as a vaccine platform for immunogenic display of oxycodone. A derivative of oxycodone was conjugated to pre-formed Qß VLPs using a sulfhydryl-amine reactive heterobifunctional crosslinker with high loading of oxycodone. In mice, intramuscular immunization with Qß-oxycodone elicited high-titer, high-avidity and long-lasting antibody responses. Qß-oxycodone was also immunogenic after storage at ambient room temperature for over two weeks, demonstrating that the vaccine is highly thermostable. In mice, immunization with Qß-oxycodone elicited antibodies that sequester oxycodone in the serum, an important mechanism for preventing the adverse effects of opioid activity. Finally, Qß-oxycodone is immunogenic in nonhuman primates, eliciting serum oxycodone antibodies after intramuscular immunization of rhesus macaques. These data establish Qß-oxycodone as a promising opioid vaccine candidate.

Different nutritional systems influence the tenderness and lipid oxidation of ewe lamb meat without altering gene expression.

Feeding is a determining factor in the various characteristics of sheep meat and animal performance, the objectives were to evaluate the effect of supplementation of ewe lambs finished in different nutritional planes on the gene expression of CASP3, CAPN1, CAPN2 and CAST and its possible association with meat quality. Samples of the Longissimus lumborum muscle of 24 ewe lambs were used, distributed in 3 groups (n=8): P (pasture), PS (pasture and supplement) and F (feedlot). Physicochemical analyses were performed for centesimal analysis, pH, lipid oxidation, Warner-Bratzler shear force and RT-qPCR for the analysis of relative gene expression of the following genes: CASP3, CAPN1, CAPN2 and CAST. There is an increase in daily weight gain and ethereal extract values in the meat of confined animals, due to the greater energy intake in the nutrition of these animals. Animals kept only on pasture have lower lipid oxidation in meat than other treatments because of the lower percentage of lipids. The Warner-Bratzler shear force is considerably higher in the meat of animals kept only on pasture but is still considered tender. The different nutritional systems do not interfere with the gene expression of CASP3, CAPN1, CAPN2 and CAST in ewe lambs.

Automated oxygen delivery for preterm infants with respiratory dysfunction.

BACKGROUND: Many preterm infants require respiratory support to maintain an optimal level of oxygenation, as oxygen levels both below and above the optimal range are associated with adverse outcomes. Optimal titration of oxygen therapy for these infants presents a major challenge, especially in neonatal intensive care units (NICUs) with suboptimal staffing. Devices that offer automated oxygen delivery during respiratory support of neonates have been developed since the 1970s, and individual trials have evaluated their effectiveness. OBJECTIVES: To assess the benefits and harms of automated oxygen delivery systems, embedded within a ventilator or oxygen delivery device, for preterm infants with respiratory dysfunction who require respiratory support or supplemental oxygen therapy. SEARCH METHODS: We searched CENTRAL, MEDLINE, CINAHL, and clinical trials databases without language or publication date restrictions on 23 January 2023. We also checked the reference lists of retrieved articles for other potentially eligible trials. SELECTION CRITERIA: We included randomised controlled trials and randomised cross-over trials that compared automated oxygen delivery versus manual oxygen delivery, or that compared different automated oxygen delivery systems head-to-head, in preterm infants (born before 37 weeks' gestation). DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our main outcomes were time (%) in desired oxygen saturation (SpO2) range, all-cause in-hospital mortality by 36 weeks' postmenstrual age, severe retinopathy of prematurity (ROP), and neurodevelopmental outcomes at approximately two years' corrected age. We expressed our results using mean difference (MD), standardised mean difference (SMD), and risk ratio (RR) with 95% confidence intervals (CIs). We used GRADE to assess the certainty of evidence. MAIN RESULTS: We included 18 studies (27 reports, 457 infants), of which 13 (339 infants) contributed data to meta-analyses. We identified 13 ongoing studies. We evaluated three comparisons: automated oxygen delivery versus routine manual oxygen delivery (16 studies), automated oxygen delivery versus enhanced manual oxygen delivery with increased staffing (three studies), and one automated system versus another (two studies). Most studies were at low risk of bias for blinding of personnel and outcome assessment, incomplete outcome data, and selective outcome reporting; and half of studies were at low risk of bias for random sequence generation and allocation concealment. However, most were at high risk of bias in an important domain specific to cross-over trials, as only two of 16 cross-over trials provided separate outcome data for each period of the intervention (before and after cross-over). Automated oxygen delivery versus routine manual oxygen delivery Automated delivery compared with routine manual oxygen delivery probably increases time (%) in the desired SpO2 range (MD 13.54%, 95% CI 11.69 to 15.39; I2 = 80%; 11 studies, 284 infants; moderate-certainty evidence). No studies assessed in-hospital mortality. Automated oxygen delivery compared to routine manual oxygen delivery may have little or no effect on risk of severe ROP (RR 0.24, 95% CI 0.03 to 1.94; 1 study, 39 infants; low-certainty evidence). No studies assessed neurodevelopmental outcomes. Automated oxygen delivery versus enhanced manual oxygen delivery There may be no clear difference in time (%) in the desired SpO2 range between infants who receive automated oxygen delivery and infants who receive manual oxygen delivery (MD 7.28%, 95% CI -1.63 to 16.19; I2 = 0%; 2 studies, 19 infants; low-certainty evidence). No studies assessed in-hospital mortality, severe ROP, or neurodevelopmental outcomes. Revised closed-loop automatic control algorithm (CLACfast) versus original closed-loop automatic control algorithm (CLACslow) CLACfast allowed up to 120 automated adjustments per hour, whereas CLACslow allowed up to 20 automated adjustments per hour. CLACfast may result in little or no difference in time (%) in the desired SpO2 range compared to CLACslow (MD 3.00%, 95% CI -3.99 to 9.99; 1 study, 19 infants; low-certainty evidence). No studies assessed in-hospital mortality, severe ROP, or neurodevelopmental outcomes. OxyGenie compared to CLiO2 Data from a single small study were presented as medians and interquartile ranges and were not suitable for meta-analysis. AUTHORS' CONCLUSIONS: Automated oxygen delivery compared to routine manual oxygen delivery probably increases time in desired SpO2 ranges in preterm infants on respiratory support. However, it is unclear whether this translates into important clinical benefits. The evidence on clinical outcomes such as severe retinopathy of prematurity are of low certainty, with little or no differences between groups. There is insufficient evidence to reach any firm conclusions on the effectiveness of automated oxygen delivery compared to enhanced manual oxygen delivery or CLACfast compared to CLACslow. Future studies should include important short- and long-term clinical outcomes such as mortality, severe ROP, bronchopulmonary dysplasia/chronic lung disease, intraventricular haemorrhage, periventricular leukomalacia, patent ductus arteriosus, necrotising enterocolitis, and long-term neurodevelopmental outcomes. The ideal study design for this evaluation is a parallel-group randomised controlled trial. Studies should clearly describe staffing levels, especially in the manual arm, to enable an assessment of reproducibility according to resources in various settings. The data of the 13 ongoing studies, when made available, may change our conclusions, including the implications for practice and research.