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The objectives were to evaluate effects of human chorionic gonadotropin (hCG) (3,300 IU i.m.) administered on d 5 after AI on CL number, plasma progesterone concentration, conception rate, and pregnancy loss in high-producing dairy cows. Following the synchronization of estrus and AI, 406 cows were injected with either hCG or saline on d 5 after AI in a randomized complete block design. Blood sampling and ovarian ultrasonography were conducted once between d 11 and 16 after AI. Pregnancy diagnoses were performed on d 28 by ultrasonography and on d 45 and 90 after AI by rectal palpation. Treatment with hCG on d 5 resulted in 86.2% of the cows with more than one CL compared with 23.2% in controls. Plasma progesterone concentrations were increased by 5.0 ng/mL in hCG-treated cows. The presence of more than one CL increased progesterone concentration in hCG-treated cows but not in controls. Conception rates were higher for hCG-treated cows on d 28 (45.8 > 38.7%), 45 (40.4 > 36.3%), and 90 (38.4 > 31.9%) after AI. Treatment with hCG improved conception rate in cows losing body condition between AI and d 28 after AI. Pregnancy losses were similar between treatment groups. Treatment with hCG on d 5 after AI induces accessory CL, enhances plasma progesterone concentration, and improves conception rate of high-producing dairy cows. Key Words: hCG, Conception Rate, Dairy Cows, Pregnancy, Progesterone

Background: The 22Ne(α,n)25Mg reaction is one of the neutron sources for the s process in massive stars. The properties of levels in 26Mg above the α-particle threshold control the strengths of the 22Ne(α,n)25Mg and 22Ne(α,γ)26Mg reactions. The strengths of these reactions as functions of temperature are one of the major uncertainties in the s process. Purpose: Information on the existence, spin, and parity of levels in 26Mg can assist in constraining the strengths of the 22Ne(α,γ)26Mg and 22Ne(α,n)25Mg reactions, and therefore in constraining s-process abundances. Methods: Inelastically scattered α particles from a 26Mg target were momentum-analyzed in the K600 magnetic spectrometer at iThemba LABS, South Africa. The differential cross sections of states were deduced from the focal-plane trajectory of the scattered α particles. Based on the differential cross sections, spin and parity assignments to states are made. Results: A newly assigned 0+ state was observed in addition to a number of other states, some of which can be associated with states observed in other experiments. Some of the deduced Jπ values of the states observed in the present study show discrepancies with those assigned in a similar experiment performed at RCNP Osaka. The reassignments and additions of the various states can strongly affect the reaction rate at low temperatures. Conclusion: The number, location, and assignment of levels in 26Mg that may contribute to the 22Ne+α reactions are not clear. Future experimental investigations of 26Mg must have an extremely good energy resolution to separate the contributions from different levels. Coincidence experiments of 26Mg provide a possible route for future investigations. [ABSTRACT FROM AUTHOR]

Background: Aspects of the nuclear structure of light α-conjugate nuclei have long been associated with nuclear clustering based on α particles and heavier α-conjugate systems such as 12C and 16O. Such structures are associated with strong deformation corresponding to superdeformed or even hyperdeformed bands. Superdeformed bands have been identified in 40Ca and neighboring nuclei and find good description within shell model, mean-field, and α-cluster models. The utility of the α-cluster description may be probed further by extending such studies to more challenging cases comprising lighter α-conjugate nuclei such as 24Mg, 28Si, and 32S. Purpose: The purpose of this study is to look for the number and energy of isoscalar 0+ states in 28Si. These states are the potential bandheads for superdeformed bands in 28Si corresponding to the exotic structures of 28Si. Of particular interest is locating the 0+ bandhead of the previously identified superdeformed band in 28Si. Methods: α-particle inelastic scattering from a natSi target at very forward angles including 0° has been performed at the iThemba Laboratory for Accelerator-Based Sciences in South Africa. Scattered particles corresponding to the excitation energy region of 6 to 14 MeV were momentum-analysed in the K600 magnetic spectrometer and detected at the focal plane using two multiwire drift chambers and two plastic scintillators. Results: Several 0+ states have been identified above 9 MeV in 28Si. A newly identified 9.71 MeV 0+ state is a strong candidate for the bandhead of the previously discussed superdeformed band. The multichannel dynamical symmetry of the semimicroscopic algebraic model predicts the spectrum of the excited 0+ states. The theoretical prediction is in good agreement with the experimental finding, supporting the assignment of the 9.71-MeV state as the bandhead of a superdeformed band. Conclusion: Excited isoscalar 0+ states in 28Si have been identified. The number of states observed in the present experiment shows good agreement with the prediction of the multichannel dynamical symmetry. [ABSTRACT FROM AUTHOR]

Background: Dissemination and outcome reporting biases are a significant problem in clinical research, with far-reaching implications for both scientific understanding and clinical decision-making. This study investigates the prevalence of dissemination- and outcome reporting biases in registered interventional malaria research., Methods: All malaria interventional trials registered on ClinicalTrials.gov from 2010 to 2020 were identified. Subsequently, publications that matched the registration were searched. The primary outcome measures were the percentage of registered studies that resulted in subsequent publication of study results, the concordance between registered outcomes, and reported outcomes. Secondary outcomes were compliance with WHO standards for timely publication (issued in 2017) of summary study results in the respective trial registry (within 12 months of study completion) or peer-reviewed publication (within 24 months of study completion) was evaluated., Results: A total of 579 trials were identified on ClinicalTrials.gov, of which 544 met the inclusion criteria. Notably, almost 36.6% of these trials (199/544) were registered retrospectively, with 129 (23.7%) registered after the first patient enrolment and 70 (12.9%) following study completion. Publications were identified for 351 out of 544 registered trials (64.5%), involving 1,526,081 study participants. Conversely, publications were not found for 193 of the 544 registrations (35.5%), which aimed to enrol 417,922 study participants. Among these 544 registrations, 444 (81.6%) did not meet the WHO standard to post summary results within 12 months of primary study completion (the last visit of the last subject for collection of data on the primary outcome), while 386 out of 544 registrations (71.0%) failed to publish their results in a peer-reviewed journal within 24 months of primary study completion. Discrepancies were noted in the reported primary outcomes compared to the registered primary outcomes in 47.6% (222/466) of the published trials, and an even higher discordance rate of 73.2% (341/466 publications) for secondary outcomes., Conclusions: Non-dissemination remains a significant issue in interventional malaria research, with most trials failing to meet WHO standards for timely dissemination of summary results and peer-reviewed journal publications. Additionally, outcome reporting bias is highly prevalent across malaria publications. To address these challenges, it is crucial to implement strategies that enhance the timely reporting of research findings and reduce both non-dissemination and outcome reporting bias., (© 2024. The Author(s).)

Importance: The incidence of melanoma in situ (MIS) has increased significantly over the past decades, and traditional guidelines for treatment of MIS have been excision with a 5-mm clinical margin; however, current Australian and other guidelines now recommend 5- to 10-mm margins. This changed recommendation was largely driven by the outcomes of studies using Mohs micrographic surgery, and recent studies using Mohs micrographic surgery are advocating for even wider excisions up to 18 mm for clearance., Objective: To assess the rate of recurrence of MIS excised with a 5-mm margin., Design, Setting, and Participants: This case series studied all MIS lesions from a single private dermatology clinic between January 1, 2011, and November 30, 2018. The criteria for inclusion were a documented 5-mm excisional margin on operation report and more than 5 years of site-specific follow-up after wide local excision. Lesions were excluded if the excisional margin was more than 5 mm or undocumented, there was less than 5 years of follow-up, or they required more than 1 wide local excision. Data analysis was performed January 30 to February 25, 2024., Intervention: Wide local excision with 5-mm margin., Results: A total of 351 MISs were identified from 292 patients (mean [SD] age, 60.3 [11.8] years; 162 females [55.5%]). Superficial spreading melanoma was the most common subtype diagnosed (177 lesions [50.4%]), followed by lentigo maligna (107 lesions [30.5%]) and lentiginous MIS (67 lesions [19.1%]). The trunk was the most common location of lesions (168 lesions [47.9%]), followed by upper limb (96 lesions [27.4%]) and lower limb (59 lesions [16.8%]). Scalp was the least common location (2 lesions [0.6%]). Most of the lesions were small, with 274 lesions (78.1%) having a length less than 10 mm and 312 lesions (88.9%) having a width less than 10 mm. A total of 348 lesions (99.1%) did not have clinical recurrence after excision with a 5-mm clinical margin following then current guidelines. A total of 3 lesions (0.9%) experienced local recurrence with no metastatic spread., Conclusions and Relevance: This case series found that excision with a 5-mm margin for MIS of smaller size (<10 mm) on low-risk body sites had a low rate of recurrence. Conservative 5-mm excisional margin is likely to be suitable for small MIS on lower-risk body sites.

Background: The presence of atrial fibrillation (AF) in heart failure (HF) patients with reduced ejection fraction is common and associated with an increased risk of stroke, hospitalization and mortality. Recent research findings indicate that a reduction in nicotinamide adenine dinucleotide (NAD + ) levels results in mitochondrial dysfunction, DNA damage and consequently cardiomyocyte impairment in experimental and clinical HF and AF. The HF-AF ENERGY trial aims to investigate the cardioprotective effects of the NAD + precursor nicotinamide riboside (NR) treatment in ischemic heart disease patients diagnosed with AF., Study Design: The HF-AF ENERGY trial is a prospective intervention study. The study consists of a (retrospective) 4 months observation period and a 4 months intervention period. The cardioprotective effect of NR on AF burden is investigated by remote monitoring software of implantable cardiac defibrillators (ICDs), which enables continuous atrial rhythm monitoring detection. Cardiac dimension and function are examined by echocardiography. Laboratory blood analysis is performed to determine mitochondrial function markers and energy metabolism. All the study parameters are assessed at two fixed time points (pre- and post-treatment). Pre- and post-treatment outcomes are compared to determine the effects of NR treatment on AF burden, mitochondrial function markers and energy metabolism., Conclusion: The HF-AF ENERGY trial investigates the cardioprotective effects of NR on AF burden and whether NR normalizes blood-based mitochondrial function markers and energy metabolites of the NAD metabolome in ischemic heart disease patients diagnosed with AF. The study outcomes elucidate whether NAD + metabolism can be used as a future therapy for HF patients with AF., (© 2022. The Author(s).)

Aims: Areas of conduction inhomogeneity (CI) during sinus rhythm may facilitate the initiation and perpetuation of atrial fibrillation (AF). Currently, no tool is available to quantify the severity of CI. Our aim is to develop and validate a novel tool using unipolar electrograms (EGMs) only to quantify the severity of CI in the atria., Methods and Results: Epicardial mapping of the right atrium (RA) and left atrium, including Bachmann's bundle, was performed in 235 patients undergoing coronary artery bypass grafting surgery. Conduction inhomogeneity was defined as the amount of conduction block. Electrograms were classified as single, short, long double (LDP), and fractionated potentials (FPs), and the fractionation duration of non-single potentials was measured. The proportion of low-voltage areas (LVAs, <1 mV) was calculated. Increased CI was associated with decreased potential voltages and increased LVAs, LDPs, and FPs. The Electrical Fingerprint Score consisting of RA EGM features, including LVAs and LDPs, was most accurate in predicting CI severity. The RA Electrical Fingerprint Score demonstrated the highest correlation with the amount of CI in both atria (r = 0.70, P < 0.001)., Conclusion: The Electrical Fingerprint Score is a novel tool to quantify the severity of CI using only unipolar EGM characteristics recorded. This tool can be used to stage the degree of conduction abnormalities without constructing spatial activation patterns, potentially enabling early identification of patients at high risk of post-operative AF or selection of the appropriate ablation approach in addition to pulmonary vein isolation at the electrophysiology laboratory., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Dendritic cells (DCs) are mediators between innate and adaptive immunity and vital in initiating and modulating antigen-specific immune responses. The most important site for induction of tolerance is the gut mucosa, where TGF-β, retinoic acid, and aryl hydrocarbon receptors collaborate in DCs to induce a tolerogenic phenotype. To mimic this, a novel combination of compounds - the synthetic aryl hydrocarbon receptor (AhR) agonist IGN-512 together with TGF-β and retinoic acid - was developed to create a platform technology for induction of tolerogenic DCs intended for treatment of several conditions caused by unwanted immune activation. These in vitro -generated cells, designated ItolDCs, are phenotypically characterized by their low expression of co-stimulatory and activating molecules along with high expression of tolerance-associated markers such as ILT3, CD103, and LAP, and a weak pro-inflammatory cytokine profile. When co-cultured with T cells and/or B cells, ItolDC-cultures contain higher frequencies of CD25+Foxp3+ regulatory T cells (Tregs), CD49b+LAG3+ 'type 1 regulatory (Tr1) T cells, and IL-10-producing B cells and are less T cell stimulatory compared to cultures with matured DCs. Factor VIII (FVIII) and tetanus toxoid (TT) were used as model antigens to study ItolDC antigen-loading. ItolDCs can take up FVIII, process, and present FVIII peptides on HLA-DR. By loading both ItolDCs and mDCs with TT, antigen-specific T cell proliferation was observed. Cryo-preserved ItolDCs showed a stable tolerogenic phenotype that was maintained after stimulation with LPS, CD40L, or a pro-inflammatory cocktail. Moreover, exposure to other immune cells did not negatively impact ItolDCs' expression of tolerogenic markers. In summary, a novel protocol was developed supporting the generation of a stable population of human DCs in vitro that exhibited a tolerogenic phenotype with an ability to increase proportions of induced regulatory T and B cells in mixed cultures. This protocol has the potential to constitute the base of a tolDC platform for inducing antigen-specific tolerance in disorders caused by undesired antigen-specific immune cell activation., Competing Interests: Authors LP, PE, HR and MW are co-inventors of the technology of the patent application (now acquired and further developed by Cell4Cure AB) regarding the generation of ItolDC. Authors GD, LP, PE, TH, AS, KT, HR, and MW were employed by Idogen AB. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Dao Nyesiga, Pool, Englezou, Hylander, Ohlsson, Appelgren, Sundstedt, Tillerkvist, Romedahl and Wigren.)

Background: The current paradigm is that fibrosis promotes electrophysiological disorders and drives atrial fibrillation (AF). In this current study, we investigated the relation between the degree of fibrosis in human atrial tissue samples of controls and patients in various stages of AF and the degree of electrophysiological abnormalities., Methods: The degree of fibrosis was measured in the atrial tissue and serum of patients in various stages of AF and the controls. Hereto, picrosirius and H&E staining were performed to quantify degree of total, endo-perimysial fibrosis, and cardiomyocyte diameter. Western blot quantified fibrosis markers: neural cell adhesion molecule, tissue inhibitor of metalloproteinase, lysyl oxidase, and α-smooth muscle actin. In serum, the ratio carboxyl-terminal telopeptide of collagen/matrix-metalloproteinase1 was determined. High-resolution epicardial mapping evaluated low-voltage areas and conduction abnormalities., Results: No significant differences were observed in the degree of fibrosis between the groups. Finally, no significant correlation-absolute nor spatial-was observed between all electrophysiological parameters and histological fibrosis markers., Conclusions: No differences in the degree of fibrosis were observed in patients from various stages of AF compared to the controls. Moreover, electrophysiological abnormalities did not correlate with any of the fibrosis markers. The findings indicate that fibrosis is not the hallmark of structural remodeling in AF.