Explore the vast range of titles available.

Abstract One in ten severe acute respiratory syndrome coronavirus 2 infections result in prolonged symptoms termed long coronavirus disease (COVID), yet disease phenotypes and mechanisms are poorly understood 1 . Here we profiled 368 plasma proteins in 657 participants ≥3 months following hospitalization. Of these, 426 had at least one long COVID symptom and 233 had fully recovered. Elevated markers of myeloid inflammation and complement activation were associated with long COVID. IL-1R2, MATN2 and COLEC12 were associated with cardiorespiratory symptoms, fatigue and anxiety/depression; MATN2, CSF3 and C1QA were elevated in gastrointestinal symptoms and C1QA was elevated in cognitive impairment. Additional markers of alterations in nerve tissue repair (SPON-1 and NFASC) were elevated in those with cognitive impairment and SCG3, suggestive of brain–gut axis disturbance, was elevated in gastrointestinal symptoms. Severe acute respiratory syndrome coronavirus 2-specific immunoglobulin G (IgG) was persistently elevated in some individuals with long COVID, but virus was not detected in sputum. Analysis of inflammatory markers in nasal fluids showed no association with symptoms. Our study aimed to understand inflammatory processes that underlie long COVID and was not designed for biomarker discovery. Our findings suggest that specific inflammatory pathways related to tissue damage are implicated in subtypes of long COVID, which might be targeted in future therapeutic trials.

Protein-restricted diets promote health and longevity in many species. While the precise components of a protein-restricted diet that mediate the beneficial effects to longevity have not been defined, we recently showed that many metabolic effects of protein restriction can be attributed to reduced dietary levels of the branched-chain amino acids (BCAAs) leucine, isoleucine and valine. Here, we demonstrate that restricting dietary BCAAs increases the survival of two different progeroid mouse models, delays frailty and promotes the metabolic health of wild-type C57BL/6J mice when started in midlife, and leads to a 30% increase in life span and a reduction in frailty in male, but not female, wild-type mice when they undergo lifelong feeding. Our results demonstrate that restricting dietary BCAAs can increase health span and longevity in mice and suggest that reducing dietary BCAAs may hold potential as a translatable intervention to promote healthy aging. The authors find that mice fed a diet with reduced levels of branched-chain amino acids have improved metabolic health, and in males but not females, lifelong feeding of such a diet reduces frailty and extends life span.

For the construction of a common prime divisor graph, we consider an integer ζ = ∏ i = 1 k p i γ i ≥ 2 with its prime factorization, where p i ′ s are distinct primes and γ i ′ s are fixed positive integers. Every divisor of the integer ζ has the form x = ∏ i = 1 k p i x i , with 0 ≤ x i ≤ γ i . There are ∏ i = 1 k ( γ i + 1 ) distinct divisors of integer ζ . Let D ( ζ ) be the collection of all positive divisors of ζ other than integer 1. Then we can define a simple graph on the set of divisors D ( ζ ) of ζ , called a common prime divisor graph ℨ ( ζ ) with D ( ζ ) as the vertex set, and we insert an edge between two distinct divisors x and y of ζ if the gcd ( x , y ) = p i . In this article, we will introduce and discuss some basic properties of common prime divisor graphs and we will compute some indices of symmetries associated with a class of such graphs. This study will open a new domain of graphs to investigate their invariant and to explore such indices on the different classes of common prime divisor graphs.

The study is aimed to examine the psychometric properties of the Urdu version of the Diabetes Quality-of-Life Brief Clinical Inventory. We adopted the forward-backward procedure to translate the Diabetes Quality-of-Life Brief Clinical Inventory (DQoL-BCI) into the Urdu language (lingua franca of Pakistan). The intraclass correlation (ICC) confirmed the consistency of retaining the items, and Cronbach's alpha established the test-re-test reliability. The confirmatory factor analysis (principal axis factoring extraction and oblique rotation with Kaiser normalization) validated the DQoL-BCI in Urdu. A two-time point with an interval of 2 weeks was used, and the Urdu version of DQoL-BCI was piloted accordingly. The 15-item translated version (DQoL-BCI-U) exhibited a satisfactory Cronbach's value of 0.866 (test) at week 1 and 0.850 at week 3 (re-test). Using the one-way random model with single measurements, the ICC for all 15 items exhibited coefficient values of >0.80. The Kaiser-Meyer-Olkin measure of sampling adequacy and Bartlett's Test of Sphericity revealed relationships of the data and suitability of CFA (0.899, <0.05). Seven factors explaining the total variance of 69% were extracted. With acceptable communalities, all 15 items of DQoL-BCI-U were retained. The study concludes that the translated version of DQoL-BCI-U is a valid instrument in regions, where Urdu is a communal language of communication and can examine quality-of-life issues during the typical patient-provider encounter.

Sparing the periprostatic neurovascular bundles during robot-assisted radical prostatectomy (RARP) improves postoperative erectile function and early urinary continence recovery. The NeuroSAFE technique, a standardised frozen section analysis, enables accurate real-time detection of positive surgical margins during nerve-sparing, increasing the likelihood of successful nerve preservation. However, the impact of the technique on patient outcomes remains uncertain. We aimed to assess the effect of NeuroSAFE-guided RARP versus standard RARP on erectile function and urinary continence. NeuroSAFE PROOF was a multicentre, patient-blinded, randomised, controlled phase 3 trial done at five National Health Service hospitals in the UK. Key eligibility criteria were a diagnosis of non-metastatic prostate cancer deemed suitable to undergo RARP, good erectile function (defined as a score of ≥22 on the first 5 items of the International Index of Erectile Function [IIEF]) without medical erectile function assistance, and no previous prostate cancer treatment. No age limits were applied. Participants were randomly assigned (1:1) to standard RARP or NeuroSAFE-guided RARP using block randomisation, stratified by site. Masking of participants to allocation was maintained throughout, but patients were informed of their nerve-sparing status after the operation. Due to the nature of the intervention, operating teams were aware of treatment group. Nerve-sparing was guided by a preoperative plan in the standard RARP group and by intraoperative NeuroSAFE assessment in the NeuroSAFE group. The primary outcome was erectile function at 12 months, assessed using the IIEF-5 score, in the modified intention-to-treat population, which included all randomly assigned participants who had surgery. Secondary endpoints were urinary continence scores at 3 and 6 months, evaluated using the International Consultation on Incontinence Questionnaire (ICIQ), and the erectile function domain of the IIEF (IIEF-6) scores at 12 months. The trial is registered at ClinicalTrials.gov, NCT03317990. Between Jan 6, 2019, and Dec 6, 2022, 407 patients were recruited, of whom 381 had surgery (190 participants in the NeuroSAFE group and 191 participants in the standard RARP group), and were included in the modified intention-to-treat population. Data for the primary outcome (IIEF-5 score at 12 months) were available for 344 participants (173 in the NeuroSAFE group and 171 participants in the standard RARP group). Median follow-up was 12·3 months (IQR 11·8–12·7). At 12 months, the mean IIEF-5 score was 12·7 (SD 8·0) in the NeuroSAFE group versus 9·7 (7·5) in the standard RARP group (adjusted mean difference 3·18 [95% CI 1·62 to 4·75]; p<0·0001). At 3 months, the ICIQ score was significantly lower in the NeuroSAFE group than the standard RARP group (adjusted mean difference –1·41 [95% CI –2·42 to –0·41]; p=0·006). At 6 months, no significant difference in ICIQ score was observed between groups (adjusted mean difference –0·37 [95% CI –1·35 to 0·62]; p=0·46). At 12 months, the mean IIEF-6 score was higher in the NeuroSAFE group than in the standard RARP group (15·3 [SD 9·7] vs 11·5 [SD 9·0]; adjusted mean difference 3·92 [95% CI 2·01 to 5·83]; p<0·0001). Serious adverse events occurred in six (3%) of 190 patients in the NeuroSAFE group, and and in five (3%) of 191 patients in the standard RARP group. All adverse events were postoperative complications; no serious adverse events or deaths were attributed to the study intervention. The use of NeuroSAFE to guide nerve-sparing during RARP improves patient-reported IIEF-5 scores at 12 months and short-term urinary continence. The erectile function benefit is enhanced in patients who would not otherwise have undergone bilateral nerve-sparing by standard practice. National Institute of Healthcare Research, JP Moulton Charitable Foundation, UCLH Charity, St Peters Trust, and Rosetrees Trust.

Theragnostics represent cutting-edge, multi-disciplinary strategies that combine diagnostics with therapeutics in order to generate personalized therapies that improve patient outcome. In oncology, the approach is aimed at more accurate diagnosis of cancer, optimization of patient selection to identify those most likely to benefit from a specific therapy and to generate effective therapeutics that enhance patient survival. MicroRNAs (miRNAs) are master regulators of the human genome that orchestrate myriad cellular pathways to control growth during physiologic and pathologic conditions. Compelling evidence shows that miRNA deregulation promotes events linked to tumor initiation, metastasis and drug resistance as seen in multiple myeloma (MM), an invariably fatal hematologic malignancy. miRNAs are readily detected in body fluids, for example, serum, plasma, urine, as well as circulating tumor cells to demonstrate their potential as readily accessible, non-invasive diagnostic and prognostic biomarkers and potential therapeutics. Specific miRNAs are aberrantly expressed early in myelomagenesis and may more readily detect high-risk disease than current methods. Although only recently discovered miRNAs have rapidly advanced from preclinical studies to evaluation in human clinical trials. The development of miRNA theragnostics should provide widely applicable tools for the targeted delivery of personalized medicines to improve the outcome of patients with MM.

Background Robotic radical prostatectomy (RARP) is a first-line curative treatment option for localized prostate cancer. Postoperative erectile dysfunction and urinary incontinence are common associated adverse side effects that can negatively impact patients’ quality of life. Preserving the lateral neurovascular bundles (NS) during RARP improves functional outcomes. However, selecting men for NS may be difficult when there is concern about incurring in positive surgical margin (PSM) which in turn risks adverse oncological outcomes. The NeuroSAFE technique (intra-operative frozen section examination of the neurovascular structure adjacent prostate margin) can provide real-time pathological consult to promote optimal NS whilst avoiding PSM. Methods NeuroSAFE PROOF is a single-blinded, multi-centre, randomised controlled trial (RCT) in which men are randomly allocated 1:1 to either NeuroSAFE RARP or standard RARP. Men electing for RARP as primary treatment, who are continent and have good baseline erectile function (EF), defined by International Index of Erectile Function (IIEF-5) score > 21, are eligible. NS in the intervention arm is guided by the NeuroSAFE technique. NS in the standard arm is based on standard of care, i.e. a pre-operative image-based planning meeting, patient-specific clinical information, and digital rectal examination. The primary outcome is assessment of EF at 12 months. The primary endpoint is the proportion of men who achieve IIEF-5 score ≥ 21. A sample size of 404 was calculated to give a power of 90% to detect a difference of 14% between groups based on a feasibility study. Oncological outcomes are continuously monitored by an independent Data Monitoring Committee. Key secondary outcomes include urinary continence at 3 months assessed by the international consultation on incontinence questionnaire, rate of biochemical recurrence, EF recovery at 24 months, and difference in quality of life. Discussion NeuroSAFE PROOF is the first RCT of intra-operative frozen section during radical prostatectomy in the world. It is properly powered to evaluate a difference in the recovery of EF for men undergoing RARP assessed by patient-reported outcome measures. It will provide evidence to guide the use of the NeuroSAFE technique around the world. Trial registration NCT03317990 (23 October 2017). Regional Ethics Committee; reference 17/LO/1978.

A bstract The cross section for coherent photonuclear production of J/ ψ is presented as a function of the electromagnetic dissociation (EMD) of Pb. The measurement is performed with the ALICE detector in ultra-peripheral Pb-Pb collisions at a centre-of-mass energy per nucleon pair of s NN = 5.02 TeV. Cross sections are presented in five different J/ ψ rapidity ranges within | y | < 4, with the J/ ψ reconstructed via its dilepton decay channels. In some events the J/ ψ is not accompanied by EMD, while other events do produce neutrons from EMD at beam rapidities either in one or the other beam direction, or in both. The cross sections in a given rapidity range and for different configurations of neutrons from EMD allow for the extraction of the energy dependence of this process in the range 17 < W γ Pb , n < 920 GeV, where W γ Pb , n is the centre-of-mass energy per nucleon of the γ Pb system. This range corresponds to a Bjorken- x interval spanning about three orders of magnitude: 1.1 × 10 − 5 < x < 3.3 × 10 − 2 . In addition to the ultra-peripheral and photonuclear cross sections, the nuclear suppression factor is obtained. These measurements point to a strong depletion of the gluon distribution in Pb nuclei over a broad, previously unexplored, energy range. These results, together with previous ALICE measurements, provide unprecedented information to probe quantum chromodynamics at high energies.

The aim of the study was to assess the influence of flap designs (Envelope flap (EF) and Szmyd flap (SF)) for impacted mandibular third molar extraction, on periodontal pocket depth (PPD), clinical attachment loss (CAL) and bone levels (BL) of second molar. Sixty patients indicated for third molar extractions with healthy second molars were allocated into two groups: EF and SF (n = 30). Third molars were assessed for angulation, root patterns, depth of impactions and relation with ramus (Pell and Gregory classification). Extraction of third molars was performed and PPD, CAL and BL around second molars at 0, 3 and 6 month (mon) follow-ups (FU) were assessed clinically and radiographically. ANOVA, Chi-square and Fisher’s exact test were employed to compare periodontal factors between EF and SF groups, considering p ≤ 0.05 as significant. Sixty participants with a mean age of 23.22 ± 3.17 were included in the study. Based on angulation, the most common impaction in the EF and SF groups was mesio-angular (EF, 50%; SF, 36.7%). Buccal and distal PPD showed a significant increase (p < 0.001) in both EF and SF patients from baseline to 6 mon. EF patients showed significantly higher distal and buccal CAL (6.67 ± 0.18 mm; 6.91 ± 0.17 mm) and BL (7.64 ± 0.16 mm; 7.90 ± 0.15 mm) as compared to SF patients (CAL, 6.76 ± 0.26 mm; 6.91 ± 0.17 mm-BL, 7.42 ± 0.38 mm; 7.34 ± 0.34 mm) at 6 mon FU. SF showed better soft tissue attachment (PPD and CAL) and bone stability (less bone loss) around second molars compared to EF after third molar extractions regardless of the patient, tooth and operator factors.

This paper describes a measurement of light-by-light scattering based on Pb+Pb collision data recorded by the ATLAS experiment during Run 2 of the LHC. The study uses 2.2 nb(-1) of integrated luminosity collected in 2015 and 2018 at root sNN = 5.02TeV. Light-by-light scattering candidates are selected in events with two photons produced exclusively, each with transverse energy E-T(gamma) > 2.5 GeV, pseudorapidity vertical bar eta(gamma)vertical bar < 2.37, diphoton invariant mass m(gamma gamma) > 5 GeV, and with small diphoton transverse momentum and diphoton acoplanarity. The integrated and differential fiducial cross sections are measured and compared with theoretical predictions. The diphoton invariant mass distribution is used to set limits on the production of axion-like particles. This result provides the most stringent limits to date on axion-like particle production for masses in the range 6-100 GeV. Cross sections above 2 to 70 nb are excluded at the 95% CL in that mass interval.