An EIL Family Transcription Factor From Switchgrass Affects Sulphur Assimilation and Root Development in Arabidopsis.

Sulphur limitation 1 (SLIM1), a member of ethylene-insensitive3-like (EIN3/EIL) protein family, is recognised as the pivotal transcription factor regulating sulphur assimilation, essential for maintaining sulphur homoeostasis in Arabidopsis. However, the function of its monocot homologues is largely unknown. In this study, we identified PvEIL3a, a homologous gene of AtSLIM1, from switchgrass (Panicum virgatum L.), a significant perennial bioenergy crop. Our results demonstrated that introducing PvEIL3a into Arabidopsis slim1 mutants significantly increased the expression of genes responsive to sulphur deficiency, and transgenic plants exhibited shortened root length and delayed development. Moreover, PvEIL3a activated the expression of AtAPR1, AtSULTR1;1 and AtBGLU30, which plays an important role in sulphur assimilation and glucosinolate metabolism. Results of transcriptome and metabonomic analysis further indicated a perturbation in the metabolic pathways of tryptophan-dependent indole glucosinolates (IGs), camalexin and auxin. In addition, PvEIL3a conservatively regulated sulphur assimilation and the biosynthesis of tryptophan pathway-derived secondary metabolites, which reduced the biosynthesis of indole-3-acetic acid (IAA) and inhibited the root elongation of transgenic Arabidopsis. In conclusion, this study highlights the functional difference of the ethylene-insensitive 3-like (EIL) family gene in monocot and dicot plants, thereby deepening the understanding of the specific biological roles of EIL3 in monocot plant species.

Population bottlenecks and sexual recombination shape diatom microevolution.

Diatoms are single-celled organisms that contribute approximately 20% of the global primary production and play a crucial role in biogeochemical cycles and trophic chains. Despite their ecological importance, our knowledge of microevolution is limited. We developed a model using the SLiM evolutionary framework to address this knowledge gap. As a reference, we used the diatom Pseudo-nitzschia multistriata, which has been extensively studied in the Gulf of Naples. Our model recapitulates what we observe in natural populations, with microevolutionary processes that occur annually during a three-stage bloom phase. Interestingly, we found that non-bloom phases allow the population to maintain sex-generated diversity produced during blooms. This finding suggests that non-bloom phases are critical to counteract bloom-related pressures and mitigate genetic divergence at the species level. Moreover, our model showed that despite the consistent genetic differentiation during bloom phases, the population tends to return to pre-bloom states. While our model is limited to neutral dynamics, our study provides valuable insights into diatoms' microevolution, paving the way to explore the ecological implications of the life history dynamics of these organisms.

A lightweight and efficient model for grape bunch detection and biophysical anomaly assessment in complex environments based on YOLOv8s.

As one of the most important economic crops, grapes have attracted considerable attention due to their high yield, rich nutritional value, and various health benefits. Identifying grape bunches is crucial for maintaining the quality and quantity of grapes, as well as managing pests and diseases. In recent years, the combination of automated equipment with object detection technology has been instrumental in achieving this. However, existing lightweight object detection algorithms often sacrifice detection precision for processing speed, which may pose obstacles in practical applications. Therefore, this thesis proposes a lightweight detection method named YOLOv8s-grape, which incorporates several effective improvement points, including modified efficient channel attention (MECA), slim-neck, new spatial pyramid pooling fast (NSPPF), dynamic upsampler (DySample), and intersection over union with minimum point distance (MPDIoU). In the proposed method, MECA and NSPPF enhance the feature extraction capability of the backbone, enabling it to better capture crucial information. Slim-neck reduces redundant features, lowers computational complexity, and effectively reuses shallow features to obtain more detailed information, further improving detection precision. DySample achieves excellent performance while maintaining lower computational costs, thus demonstrating high practicality and rapid detection capability. MPDIoU enhances detection precision through faster convergence and more precise regression results. Experimental results show that compared to other methods, this approach performs better in the grapevine bunch detection dataset and grapevine bunch condition detection dataset, with mean average precision (mAP50-95) increasing by 2.4% and 2.6% compared to YOLOv8s, respectively. Meanwhile, the computational complexity and parameters of the method are also reduced, with a decrease of 2.3 Giga floating-point operations per second and 1.5 million parameters. Therefore, it can be concluded that the proposed method, which integrates these improvements, achieves lightweight and high-precision detection, demonstrating its effectiveness in identifying grape bunches and assessing biophysical anomalies.

Safety and Psychological Outcomes of Tandem t:Slim X2 Insulin Pump with Control-IQ Technology in Children, Adolescents, and Young Adults with Type 1 Diabetes: A Systematic Review.

The Tandem t:slim X2 insulin pump is a second-generation automated insulin delivery system with Control-IQ technology. It consists of an X2 insulin pump, an integrated Dexcom sensor, and an embedded 'Control-IQ' algorithm, which predicts glucose levels 30 min in the future, adapting the programmed basal insulin rates to get glucose levels between 112.5 and 160 mg/dl (8.9 mmol/l). The system delivers automatic correction boluses of insulin when glucose levels are predicted to rise > 180 mg/dl (10 mmol/l). It has been commercially available since 2016. We reviewed the current evidence about the psychological, safety, and exercise-related outcomes of this device in children, adolescents, and young adults living with type 1 diabetes. We screened 552 papers, but only 21 manuscripts were included in this review. Fear of hypoglycemia is significantly reduced in young people with diabetes and their parents. Interestingly, diabetes-related distress is decreased; thus, the system is well accepted by the users. The sleeping quality of subjects living with diabetes and their caregivers is improved to a lesser extent as well. Despite the small number of data, this system is associated with a low rate of exercise-related hypoglycemia. Finally, evidence from the literature shows that this system is safe and effective in improving psychological personal outcomes. Even if further steps toward the fully closed loop are still mandatory, this second-generation automated insulin delivery system reduces the burden of diabetes. It properly addresses most psychological issues in children, adolescents, and young adults with type 1 diabetes mellitus; thus, it appears to be well accepted.

Conditionally Deleterious Mutation Load Accumulates in Genomic Islands of Local Adaptation but Can Be Purged with Sufficient Genotypic Redundancy.

AbstractLocal adaptation frequently evolves in patches or environments that are connected via migration. In these cases, genomic regions that are linked to a locally adapted locus experience reduced effective migration rates. Via individual-based simulations of a two-patch system, we show that this reduced effective migration results in the accumulation of conditionally deleterious mutations, but not universally deleterious mutations, adjacent to adaptive loci. When there is redundancy in the genetic basis of local adaptation (i.e., genotypic redundancy), turnover of locally adapted polymorphisms allows conditionally deleterious mutation load to be purged. The amount of mutational load that accumulates adjacent to locally adapted loci is dependent on redundancy, recombination rate, migration rate, population size, strength of selection, and the phenotypic effect size of adaptive alleles. Our results highlight the need to be cautious when interpreting patterns of local adaptation at the level of phenotype or fitness, as the genetic basis of local adaptation can be transient, and evolution may confer a degree of maladaptation to nonlocal environments.

Elucidating the Gas-Phase Behavior of Nitazene Analog Protomers Using Structures for Lossless Ion Manipulations Ion Mobility-Orbitrap Mass Spectrometry.

2-Benzylbenzimidazoles, or "nitazenes", are a class of novel synthetic opioids (NSOs) that are increasingly being detected alongside fentanyl analogs and other opioids in drug overdose cases. Nitazenes can be 20× more potent than fentanyl but are not routinely tested for during postmortem or clinical toxicology drug screens; thus, their prevalence in drug overdose cases may be under-reported. Traditional analytical workflows utilizing liquid chromatography-tandem mass spectrometry (LC-MS/MS) often require additional confirmation with authentic reference standards to identify a novel nitazene. However, additional analytical measurements with ion mobility spectrometry (IMS) may provide a path toward reference-free identification, which would greatly accelerate NSO identification rates in toxicology laboratories. Presented here are the first IMS and collision cross section (CCS) measurements on a set of fourteen nitazene analogs using a structures for lossless ion manipulations (SLIM)-orbitrap MS. All nitazenes exhibited two high intensity baseline-separated IMS distributions, which fentanyls and other drug and druglike compounds also exhibit. Incorporating water into the electrospray ionization (ESI) solution caused the intensities of the higher mobility IMS distributions to increase and the intensities of the lower mobility IMS distributions to decrease. Nitazenes lacking a nitro group at the R1 position exhibited the greatest shifts in signal intensities due to water. Furthermore, IMS-MS/MS experiments showed that the higher mobility IMS distributions of all nitazenes possessing a triethylamine group produced fragment ions with m/z 72, 100, and other low intensity fragments while the lower mobility IMS distributions only produced fragment ions with m/z 72 and 100. The IMS, solvent, and fragmentation studies provide experimental evidence that nitazenes potentially exhibit three gas-phase protomers. The cyclic IMS capability of SLIM was also employed to partially resolve four sets of structurally similar nitazene isomers (e.g., protonitazene/isotonitazene, butonitazene/isobutonitazene/secbutonitazene), showcasing the potential of using high-resolution IMS separations in MS-based workflows for reference-free identification of emerging nitazenes and other NSOs.

Safety of an anchor-based device for sacrospinous ligament fixation: A pilot case-control study.

INTRODUCTION AND HYPOTHESIS: Sacrospinous ligament fixation (SSLF) is a popular surgical technique for treating apical prolapse. The use of suture-capturing devices (SCD), or the more recently introduced anchor-based device (ABD), is useful for a posterior approach but essential for an anterior one. The aim of our study was to assess the safety of the ABD, which was recently introduced to our unit, compared to the traditionally used SCD. METHODS: This was a pilot case-control study of 40 patients who had a SSLF, 20 of these represented all the patients who had the procedure with the aid of the ABD and 20 patients who had the procedure using the SCD over approximately the same duration. The main safety endpoints of this pilot study were patient reported postoperative pain scores and perioperative complications rate. RESULTS: The population characteristics were similar. The mean postoperative pain scores differed significantly only on postoperative day 1 in favor of the suture capturing device (3.40 [2.60] vs 1.60 [1.64], p = 0.013). The mean highest pain score was similar in both groups. Peri-operative complications rates were low and comparable between both groups. According to POPQ at 6 weeks follow-up the median Ba point was higher in the ABD group and this difference was significant (-3.00 [-3.00; -2.25] vs. -2.00 [-3.00; -1.50]; p = 0.03). CONCLUSION: The anchor-based device for sacrospinal ligament fixation seems to have comparable safety profile to the traditionally used suture capturing devices.

Exploration of different electrode types inserted in a 3D model of a patient with incomplete partition type III inner ear malformation.

BACKGROUND: Incomplete partition type III (IP III) represents a rare malformation of the inner ear, posing challenges during cochlear implantation due to inevitable cerebrospinal fluid (CSF) leaks and the potential misplacement of electrodes within the internal auditory canal (IAC). Despite the absence of a consensus on electrode selection, literature suggests both straight and perimodiolar electrodes as viable options for proper insertion. Limited implantation series contribute to the ambiguity in electrode choice. In this study, we evaluated the insertion performance of three electrode types in a 3D model simulating an IP III patient's inner ear. METHODS: A 3D model replicating the inner ear of a patient with IP III undergoing surgery was created, incorporating a canal wall up mastoidectomy and an enlarged round window approach. Insertions were carried out using a straight electrode, a perimodiolar electrode, and a slim perimodiolar electrode, inserted through a sheath in the basal turn of the cochlea. Electrode positions were assessed after each insertion, with each type being tested 20 times. RESULTS: Successful insertion rates were 95 % for the slim perimodiolar electrode, 85 % for the perimodiolar electrode, and 75 % for the slim straight electrode. Notably, the slim perimodiolar electrode required an adapted insertion technique due to the altered cochlear position in IP III cases. Statistical analysis revealed the slim perimodiolar electrode's superiority over the slim straight electrode in achieving successful insertions. CONCLUSIONS: The 3D model of the IP III inner ear proved to be an effective tool for electrode testing and insertion training prior to surgery. Following multiple insertions in the 3D model, the slim perimodiolar electrode demonstrated the highest success rate, emphasizing its potential as the preferred choice for cochlear implantation in IP III cases.

Boosting prairie dog optimizer for optimal planning of multiple wind turbine and photovoltaic distributed generators in distribution networks considering different dynamic load models.

Deploying distributed generators (DGs) supplied by renewable energy resources poses a significant challenge for efficient power grid operation. The proper sizing and placement of DGs, specifically photovoltaics (PVs) and wind turbines (WTs), remain crucial due to the uncertain characteristics of renewable energy. To overcome these challenges, this study explores an enhanced version of a meta-heuristic technique called the prairie dog optimizer (PDO). The modified prairie dogs optimizer (mPDO) incorporates a novel exploration phase inspired by the slime mold algorithm (SMA) food approach. The mPDO algorithm is proposed to analyze the substantial effects of different dynamic load characteristics on the performance of the distribution networks and the designing of the PV-based and WT-based DGs. The optimization problem incorporates various operational constraints to mitigate energy loss in the distribution networks. Further, the study addresses uncertainties related to the random characteristics of PV and WT power outputs by employing appropriate probability distributions. The mPDO algorithm is evaluated using cec2020 benchmark suit test functions and rigorous statistical analysis to mathematically measure its success rate and efficacy while considering different type of optimization problems. The developed mPDO algorithm is applied to incorporate both PV and WT units, individually and simultaneously, into the IEEE 69-bus distribution network. This is achieved considering residential, commercial, industrial, and mixed time-varying voltage-dependent load demands. The efficacy of the modified algorithm is demonstrated using the standard benchmark functions, and a comparative analysis is conducted with the original PDO and other well-known algorithms, utilizing various statistical metrics. The numerical findings emphasize the significant influence of load type and time-varying generation in DG planning. Moreover, the mPDO algorithm beats the alternatives and improves distributed generators' technical advantages across all examined scenarios.

A long-term growth stable Halomonas sp. deleted with multiple transposases guided by its metabolic network model Halo-ecGEM.

Microbial instability is a common problem during bio-production based on microbial hosts. Halomonas bluephagenesis has been developed as a chassis for next generation industrial biotechnology (NGIB) under open and unsterile conditions. However, the hidden genomic information and peculiar metabolism have significantly hampered its deep exploitation for cell-factory engineering. Based on the freshly completed genome sequence of H. bluephagenesis TD01, which reveals 1889 biological process-associated genes grouped into 84 GO-slim terms. An enzyme constrained genome-scale metabolic model Halo-ecGEM was constructed, which showed strong ability to simulate fed-batch fermentations. A visible salt-stress responsive landscape was achieved by combining GO-slim term enrichment and CVT-based omics profiling, demonstrating that cells deploy most of the protein resources by force to support the essential activity of translation and protein metabolism when exposed to salt stress. Under the guidance of Halo-ecGEM, eight transposases were deleted, leading to a significantly enhanced stability for its growth and bioproduction of various polyhydroxyalkanoates (PHA) including 3-hydroxybutyrate (3HB) homopolymer PHB, 3HB and 3-hydroxyvalerate (3HV) copolymer PHBV, as well as 3HB and 4-hydroxyvalerate (4HB) copolymer P34HB. This study sheds new light on the metabolic characteristics and stress-response landscape of H. bluephagenesis, achieving for the first time to construct a long-term growth stable chassis for industrial applications. For the first time, it was demonstrated that genome encoded transposons are the reason for microbial instability during growth in flasks and fermentors.

The LC3-interacting region of NBR1 is a protein interaction hub enabling optimal flux.

During autophagy, potentially toxic cargo is enveloped by a newly formed autophagosome and trafficked to the lysosome for degradation. Ubiquitinated protein aggregates, a key target for autophagy, are identified by multiple autophagy receptors. NBR1 is an archetypal autophagy receptor and an excellent model for deciphering the role of the multivalent, heterotypic interactions made by cargo-bound receptors. Using NBR1 as a model, we find that three critical binding partners - ATG8-family proteins, FIP200, and TAX1BP1 - each bind to a short linear interaction motif (SLiM) within NBR1. Mutational peptide arrays indicate that these binding events are mediated by distinct overlapping determinants, rather than a single, convergent, SLiM. AlphaFold modeling underlines the need for conformational flexibility within the NBR1 SLiM, as distinct conformations mediate each binding event. To test the extent to which overlapping SLiMs exist beyond NBR1, we performed peptide binding arrays on >100 established LC3-interacting regions (LIRs), revealing that FIP200 and/or TAX1BP1 binding to LIRs is a common phenomenon and suggesting LIRs as protein interaction hotspots. Comparative analysis of phosphomimetic peptides highlights that while FIP200 and Atg8-family binding are generally augmented by phosphorylation, TAX1BP1 binding is nonresponsive, suggesting differential regulation of these binding events. In vivo studies confirm that LIR-mediated interactions with TAX1BP1 enhance NBR1 activity, increasing autophagosomal delivery by leveraging an additional LIR from TAX1BP1. In sum, these results reveal a one-to-many binding modality in NBR1, providing key insights into the cooperative mechanisms among autophagy receptors. Furthermore, these findings underscore the pervasive role of multifunctional SLiMs in autophagy, offering substantial avenues for further exploration into their regulatory functions.

SLIM-Based High-Resolution Ion Mobility Reveals New Structural Insights into Isomeric Vitamin D Metabolites and their Isotopologues.

Testing for vitamin D deficiency remains a high-volume clinical assay, much of which is done using mass spectrometry-based methods to alleviate challenges in selectivity associated with immunoassays. Ion mobility-mass spectrometry (IM-MS) has been proposed as a rapid alternative to traditional LC-MS/MS methods, but understanding the structural ensemble that contributes to the ion mobility behavior of this molecular class is critical. Herein we demonstrate the first application of high-resolution Structures for Lossless Ion Manipulations (SLIM) IM separations of several groups of isomeric vitamin D metabolites. Despite previous IM studies of these molecules, the high resolving power of SLIM (Rp ∼ 200) has revealed additional conformations for several of the compounds. The highly similar collision cross sections (CCS), some differing by as little as 0.7%, precluded adequate characterization with low-resolution IM techniques where, in some cases, wider than expected peak widths and/or subtle shoulders may have hinted at their presence. Importantly, these newly resolved peaks often provided a unique mobility that could be used to separate isomers and provides potential for their use in quantification. Lastly, the contribution of isotopic labeling to arrival time distribution for commonly used 13C- and deuterium-labeled internal standards was explored. Minor shifts of ∼0.2-0.3% were observed, and in some instances these shifts were specific to the conformer being measured (i.e., "closed" vs "open"). Accounting for these shifts is important during raw data extraction to ensure reproducible peak area integration, which will be a critical consideration in future quantitative applications.

Research on improved YOLOv8n based potato seedling detection in UAV remote sensing images.

Introduction: Accurate detection of potato seedlings is crucial for obtaining information on potato seedlings and ultimately increasing potato yield. This study aims to enhance the detection of potato seedlings in drone-captured images through a novel lightweight model. Methods: We established a dataset of drone-captured images of potato seedlings and proposed the VBGS-YOLOv8n model, an improved version of YOLOv8n. This model employs a lighter VanillaNet as the backbone network in-stead of the original YOLOv8n model. To address the small target features of potato seedlings, we introduced a weighted bidirectional feature pyramid network to replace the path aggregation network, reducing information loss between network layers, facilitating rapid multi-scale feature fusion, and enhancing detection performance. Additionally, we incorporated GSConv and Slim-neck designs at the Neck section to balance accuracy while reducing model complexity. Results: The VBGS-YOLOv8n model, with 1,524,943 parameters and 4.2 billion FLOPs, achieves a precision of 97.1%, a mean average precision of 98.4%, and an inference time of 2.0ms. Comparative tests reveal that VBGS-YOLOv8n strikes a balance between detection accuracy, speed, and model efficiency compared to YOLOv8 and other mainstream networks. Specifically, compared to YOLOv8, the model parameters and FLOPs are reduced by 51.7% and 52.8% respectively, while precision and a mean average precision are improved by 1.4% and 0.8% respectively, and the inference time is reduced by 31.0%. Discussion: Comparative tests with mainstream models, including YOLOv7, YOLOv5, RetinaNet, and QueryDet, demonstrate that VBGS-YOLOv8n outperforms these models in terms of detection accuracy, speed, and efficiency. The research highlights the effectiveness of VBGS-YOLOv8n in the efficient detection of potato seedlings in drone remote sensing images, providing a valuable reference for subsequent identification and deployment on mobile devices.

"Slim-Mesh" Technique for Diastasis Recti Abdominis, Including Obesity-Related Cases.

Background and Objective: We operated on a series of mostly obese patients with diastasis recti abdominis using the "Slim-Mesh" technique to repair/reinforce the diastasis and linea alba/recti muscles without plicating and traumatizing them. Additional objectives were to decrease operation time and intra- and postoperative complications. Methods: We considered T1 cases diastasis after pregnancy and T2 cases obesity (BMI ≥ 30 mg/kg2); D1, D2, and D3 when the diastasis measured 2-3, 3-5, and ≥ 5 cm, respectively; H0 and H1 without and concomitant umbilical and/or epigastric hernia, respectively. At our Department, between May 2010 and November 2022, 47 patients with diastasis recti were operated on with the "Slim-Mesh" technique to reinforce/repair the traumatized linea alba/recti muscles, without plicating them. This was a prospective (83%)-retrospective study. Results: We studied 23 males and 24 females. Mean age and BMI was 58 years and 29 kg/m2, respectively. Groups D1, D2, and D3 comprised 6, 23 and 18 patients, respectively; groups T1, T2, H0 and H1 comprised 22, 25, 13 and 34 patients, respectively. Mean operation time for all cases was 100 minutes. Mean length of hospital stay was 2.3 days and follow-up time was 5 years. We had 6 late postoperative complications: 3 hernia recurrences and 3 trocar site hernias. Conclusion: Considering the lack of agreement on the best surgery for diastasis recti abdominis repair, in our experience the "Slim-Mesh" technique is a valid, safe and easy-to-reproduce way to save, repair and reinforce linea alba/recti muscles in diastasis recti patients, including the obese population (53%).

Overexpression of SLIM1 transcription factor accelerates vegetative development in Arabidopsis thaliana.

The transcription factor Sulfur Limitation 1 (SLIM1) belongs to the plant-specific Ethylene Insenstive3-Like transcription factor family and is known to coordinate gene expression in response to sulfur deficiency. However, the roles of SLIM1 in nutrient-sufficient conditions have not been characterized. Employing constitutive SLIM1 overexpression (35S::SLIM1) and CRISPR/Cas9 mutant plants (slim1-cr), we identified several distinct phenotypes in nutrient-sufficient conditions in Arabidopsis thaliana. Overexpression of SLIM1 results in plants with approximately twofold greater rosette area throughout vegetative development. 35S::SLIM1 plants also bolt earlier and exhibit earlier downregulation of photosynthesis-associated genes and earlier upregulation of senescence-associated genes than Col-0 and slim1-cr plants. This suggests that overexpression of SLIM1 accelerates development in A. thaliana. Genome-wide differential gene expression analysis relative to Col-0 at three time points with slim1-cr and two 35S::SLIM1 lines allowed us to identify 1,731 genes regulated directly or indirectly by SLIM1 in vivo.

A Detailed Numerical Model for a New Composite Slim-Floor Slab System.

The paper concerns the numerical modelling of a new slim-floor system with innovative steel-concrete composite beams called "hybrid beams". Hybrid beams consist of a high-strength TT inverted cross-section steel profile and a concrete core made of high-performance concrete and are jointed with prestressed hollow core slabs by infill concrete and tie reinforcement. Such systems are gaining popularity since they allow the integration of the main structural members within the ceiling depth, shorten the execution time, and reduce the use of concrete and steel. A three-dimensional finite element model is proposed with all parts of the system taken into account and detailed geometry reproduction. Advanced constitutive models are adopted for steel and concrete. Special attention is paid to the proper characterisation of interfaces. The new approach to calibration of damaged elastic traction-separation constitutive model for cohesive elements is applied to concrete-to-concrete contact zones. The model is validated with outcomes of experimental field tests and analytical calculations. A satisfactory agreement between different assessment methods is obtained. The model can be used in the development phase of a new construction system, for instance, to plan further experimental campaigns or to calibrate simplified design formulas.

Control-IQ Technology Use in Individuals With High Insulin Requirements: Results From the Multicenter Higher-IQ Trial.

BACKGROUND: Control-IQ technology version 1.5 allows for a wider range of weight and total daily insulin (TDI) entry, in addition to other changes to enhance performance for users with high basal rates. This study evaluated the safety and performance of the updated Control-IQ system for users with basal rates >3 units/h and high TDI in a multicenter, single arm, prospective study. METHODS: Adults with type 1 diabetes (T1D) using continuous subcutaneous insulin infusion (CSII) and at least one basal rate over 3 units/h (N = 34, mean age = 39.9 years, 41.2% female, diabetes duration = 21.8 years) used the t:slim X2 insulin pump with Control-IQ technology version 1.5 for 13 weeks. Primary outcome was safety events (severe hypoglycemia and diabetic ketoacidosis (DKA)). Central laboratory hemoglobin A1c (HbA1c) was measured at system initiation and 13 weeks. Participants continued using glucagon-like peptide-1 (GLP-1) receptor agonists, sodium-glucose transport protein 2 (SGLT-2) inhibitors, or other medications for glycemic control and/or weight loss if on a stable dose. RESULTS: All 34 participants completed the study. Fifteen participants used a basal rate >3 units/h for all 24 hours of the day. Nine participants used >300 units TDI on at least one day during the study. There were no severe hypoglycemia or DKA events. Time in range 70-180 mg/dL was 64.8% over the 13 weeks, with 1.0% time <70 mg/dL. Hemoglobin A1c decreased from 7.69% at baseline to 6.87% at 13 weeks (-0.82%, P < .001). CONCLUSIONS: Control-IQ technology version 1.5, with wider range of weight and TDI input and enhancements for users with high insulin requirements, was safe in individuals with T1D in this study.

Identification of Unique Fragmentation Patterns of Fentanyl Analog Protomers Using Structures for Lossless Ion Manipulations Ion Mobility-Orbitrap Mass Spectrometry.

The opioid crisis in the United States is being fueled by the rapid emergence of new fentanyl analogs and precursors that can elude traditional library-based screening methods, which require data from known reference compounds. Since reference compounds are unavailable for new fentanyl analogs, we examined if fentanyls (fentanyl + fentanyl analogs) could be identified in a reference-free manner using a combination of electrospray ionization (ESI), high-resolution ion mobility (IM) spectrometry, high-resolution mass spectrometry (MS), and higher-energy collision-induced dissociation (MS/MS). We analyzed a mixture containing nine fentanyls and W-15 (a structurally similar molecule) and found that the protonated forms of all fentanyls exhibited two baseline-separated IM distributions that produced different MS/MS patterns. Upon fragmentation, both IM distributions of all fentanyls produced two high intensity fragments, resulting from amine site cleavages. The higher mobility distributions of all fentanyls also produced several low intensity fragments, but surprisingly, these same fragments exhibited much greater intensities in the lower mobility distributions. This observation demonstrates that many fragments of fentanyls predominantly originate from one of two different gas-phase structures (suggestive of protomers). Furthermore, increasing the water concentration in the ESI solution increased the intensity of the lower mobility distribution relative to the higher mobility distribution, which further supports that fentanyls exist as two gas-phase protomers. Our observations on the IM and MS/MS properties of fentanyls can be exploited to positively differentiate fentanyls from other compounds without requiring reference libraries and will hopefully assist first responders and law enforcement in combating new and emerging fentanyls.