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ABSTRACT Background Hip‐related pain (HRP) affects young to middle‐aged active adults and impacts physical activity, finances and quality of life. HRP includes conditions like femoroacetabular impingement syndrome and labral tears. Lateral hip muscle dysfunction and atrophy in HRP are more pronounced in advanced hip pathology, with limited evidence in younger populations. While MRI use for assessing hip muscle morphology is increasing, with automated deep‐learning techniques showing promise, studies assessing their accuracy are limited. Therefore, we aimed to compare hip intramuscular fat infiltrate (MFI) and muscle volume, in individuals with and without HRP as well as assess the reliability and accuracy of automated machine‐learning segmentations compared with human‐generated segmentation. Methods This cross‐sectional study included sub‐elite/amateur football players (Australian football and soccer) with a greater than 6‐month history of HRP [n = 180, average age 28.32, (standard deviation 5.88) years, 19% female] and a control group of sub‐elite/amateur football players without pain [n = 48, 28.89 (6.22) years, 29% female]. Muscle volume and MFI of gluteus maximus, medius, minimis and tensor fascia latae were assessed using MRI. Associations between muscle volume and group were explored using linear regression models, controlling for body mass index, age, sport and sex. A convolutional neural network (CNN) machine‐learning approach was compared with human‐performed muscle segmentations in a subset of participants (n = 52) using intraclass correlation coefficients and Sorensen–Dice index. Results When considering adjusted estimates of muscle volume, there were significant differences observed between groups for gluteus medius (adjusted mean difference 23 858 mm3 [95% confidence interval 7563, 40 137]; p = 0.004) and tensor fascia latae (6660 mm3 [2440, 13 075]; p = 0.042). No differences were observed between groups for gluteus maximus (18 265 mm3 [−21 209, 50 782]; p = 0.419) or minimus (3893 mm3 [−2209, 9996]; p = 0.21). The CNN was trained for 30 000 iterations and assessed its accuracy and reliability on an independent testing dataset, achieving high segmentation accuracy (mean Sorenson–Dice index >0.900) and excellent muscle volume and MFI reliability (ICC2,1 > 0.900). The CNN outperformed manual raters, who had slightly lower interrater accuracy (Sorensen–Dice index >0.800) and reliability (ICC2,1 > 0.800). Conclusions The increased muscle volumes in the symptomatic group compared with controls could be associated with increased myofibrillar size, sarcoplasmic hypertrophy or both. These changes may facilitate greater muscular efficiency for a given load, enabling the athlete to maintain their normal level of function. In addition, the CNNs for muscle segmentation was more efficient and demonstrated excellent reliability in comparison to manual segmentations.

Cholangiocarcinoma (CCA) is a highly aggressive form of liver cancer and is an increasing cause of cancer‐related death worldwide. Despite its increasing incidence globally and alarming mortality, treatment options for CCA have largely remained unchanged, stressing the importance of developing new effective therapies. YAP activation is common in CCA, and its major transcriptional signaling partners are the TEAD proteins. CA3 is a small‐molecule YAP‐TEAD disrupter discovered utilizing a TEAD reporter assay. Utilizing CCA, gastric cancer cell lines, and patient‐derived xenograft models (PDX), we demonstrate that CA3 is effective in inducing cell death and delaying tumor growth in both FGFR2 fusion and wild‐type models. CA3 was associated with on‐target decreases in YAP‐TEAD target gene expression, TEAD reporter activity, and overall TEAD levels. Hippo pathway signaling was not altered as there was no change in YAP phosphorylation status in the cells exposed to CA3. RNA sequencing of gastric cancer and CCA models demonstrated upregulation of an androgen receptor–mediated transcriptional program following exposure to CA3 in five unique models tested. Consistent with this upstream regulator analysis, CA3 exposure in CCA cells was associated with increased AR protein levels, and combinatorial therapy with CA3 and androgen receptor blockade was associated with increased cancer cell death. CA3 behaves functionally as a YAP‐TEAD disrupter in the models tested and demonstrated therapeutic efficacy. Exposure to CA3 was associated with compensatory androgen receptor signaling and dual inhibition improved the therapeutic effect.

Abstract Serpentinization, a consequence of water‐rock interaction in mafic and ultramafic rocks, refers to the hydrothermal alteration of olivine and pyroxene with serpentine as the typical product. Magnetite is produced in variable amounts during this serpentinization process. Here, we conducted a systematic rock magnetic study on the serpentinite of Ocean Drilling Program (ODP) Hole 1070A from the Iberia Abyssal Plain. From bottom to top, three units are distinguished rock‐magnetically: (a) serpentinized peridotite dominated by single‐domain (SD) ± multidomain (MD) magnetite particles; (b) gabbro with SD ± vortex state magnetite; (c) breccia dominated by MD ± vortex and SD ± vortex state maghemite/hematite and magnetite. Samples of the three units are highly serpentinized with serpentinization degrees >60%. The magnetite content increases exponentially with the degree of serpentinization. Two phases of serpentinization are proposed: (a) massive serpentinization that occurred before mantle exhumation and (b) maghemitization‐serpentinization that occurred near or at the seafloor after the final exhumation of mantle peridotites. The latter reduces the magnetization of the breccia unit significantly. Serpentinized peridotite associated with strong magnetization is the dominant contributor to the marine magnetic anomalies in ocean to continent transition areas.

Abstract Objectives (1) To plot the trajectory of humoral and cellular immune responses to the primary (two‐dose) COVID‐19 mRNA series and the third/booster dose in B‐cell‐depleted multiple sclerosis (MS) patients up to 2 years post‐vaccination; (2) to identify predictors of immune responses to vaccination; and (3) to assess the impact of intercurrent COVID‐19 infections on SARS CoV‐2‐specific immunity. Methods Sixty ocrelizumab‐treated MS patients were enrolled from NYU (New York) and University of Colorado (Anschutz) MS Centers. Samples were collected pre‐vaccination, and then 4, 12, 24, and 48 weeks post‐primary series, and 4, 12, 24, and 48 weeks post‐booster. Binding anti‐Spike antibody responses were assessed with multiplex bead‐based immunoassay (MBI) and electrochemiluminescence (Elecsys®, Roche Diagnostics), and neutralizing antibody responses with live‐virus immunofluorescence‐based microneutralization assay. Spike‐specific cellular responses were assessed with IFNγ/IL‐2 ELISpot (Invitrogen) and, in a subset, by sequencing complementarity determining regions (CDR)‐3 within T‐cell receptors (Adaptive Biotechnologies). A linear mixed‐effect model was used to compare antibody and cytokine levels across time points. Multivariate analyses identified predictors of immune responses. Results The primary vaccination induced an 11‐ to 208‐fold increase in binding and neutralizing antibody levels and a 3‐ to 4‐fold increase in IFNγ/IL‐2 responses, followed by a modest decline in antibody but not cytokine responses. Booster dose induced a further 3‐ to 5‐fold increase in binding antibodies and 4‐ to 5‐fold increase in IFNγ/IL‐2, which were maintained for up to 1 year. Infections had a variable impact on immunity. Interpretation Humoral and cellular benefits of COVID‐19 vaccination in B‐cell‐depleted MS patients were sustained for up to 2 years when booster doses were administered.

ABSTRACT Introduction Functional neurological disorder (FND) and autism spectrum disorder (ASD) are two complex neuropsychiatric conditions that have been historically classified within psychiatric domains, resulting in a lack of extensive research, insufficient clinical recognition, and persistent societal stigma. In recent years, there has been an increasing recognition among professionals and affected individuals of their possible overlap. This review explores the potential clinical and mechanistic overlap between FND and ASD, with particular attention to shared symptoms across sensory, motor, and psychiatric domains. Methods We conducted a narrative analysis utilizing the PubMed, CINAHL, MEDLINE, and ScienceDirect databases from inception to June 2024. The search employed specific MeSH terms related to ASD and FND. Given the limited data availability, we included all relevant articles that explored the potential connections between FND and ASD, focusing on established findings and theoretical hypotheses areas. Results Scientific evidence indicates that FND and ASD may co‐occur more frequently than previously acknowledged and with notable overlaps in their clinical presentations and pathophysiology. Theoretical models that have been applied to FND and ASD, such as the Bayesian brain theory and the tripartite model of autism, may provide valuable insights into the intersection of these conditions. Although much of the current evidence remains speculative, it underscores the need for hypothesis‐driven research to investigate these potential connections further. Conclusion ASD and FND are heterogeneous conditions that appear to co‐occur in a subset of individuals, with overlapping symptomatology and possibly shared underlying mechanisms. This hypothesis‐generating review emphasizes the need for further research to better understand these links, ultimately aiming to improve clinical recognition and develop targeted interventions that enhance the quality of life for affected individuals.

Abstract Polar freshwater ecosystems are sensitive to climate change, facing increasing temperatures and its consequences such as glacier retreat. Phosphorus and/or fixed nitrogen are widely expected to limit primary production in most freshwater environments, however the role of micronutrients is largely un‐characterized. We measured dissolved nitrate and nitrite, phosphate, cobalt, iron, manganese and zinc in a selection of Greenland and Antarctic lakes, and report the first evaluation of cobalt regulating phytoplankton growth in these systems using bioassay incubations. Results showed cobalt potentially co‐limited phytoplankton in three of the eight sites tested. A time‐series of dissolved cobalt measured in Kobbefjord (southwest Greenland) runoff corroborated low cobalt availability during summer. This was in contrast to manganese and iron which remained at high concentrations throughout summer. We hypothesize that high manganese:cobalt and/or zinc:cobalt ratios in runoff, may impede cellular cobalt acquisition, meaning cobalt co‐limitation of primary production is plausible in many polar freshwater environments.

Abstract Objective Recent literature studying the impact of blood transfusion on outcomes in patients with head and neck cancer (HNC) have shown that blood transfusions are associated with increased risk of death and higher wound infection rates. The purpose of this study was to implement a lower transfusion threshold while comparing outcomes of free flap patients following initiation of a new transfusion guideline. Methods A retrospective study of all patients at a tertiary care academic center who underwent free tissue transfer after HNC resection between July 17, 2007 and June 7, 2021. Transfusion criteria were adjusted in 2014; the hematocrit threshold to transfuse was incrementally reduced from 30% in 2007 to 21% in 2017. The main outcomes of interest were overall survival (OS) and recurrence free survival (RFS). Results A total of 346 patients met the criteria for inclusion in the study. Groups 1 (less strict protocol – 30%) and 2 (stricter protocol – 21%) consisted of 171 and 175 patients, respectively. Fewer units of packed red cells were transfused per patient in group 2 (0.26 vs. 2.87 in group 1, p

Abstract Increasing evidence shows that wild bees, including bumble bees, are in decline due to a range of stressors, including pesticides. Our knowledge of pesticide impacts has consequently grown to enable the design of increasingly realistic risk assessment methods. However, one area where knowledge gaps may still hinder our ability to assess the full range of bee‐pesticide interactions is the field of exposure. Exposure has historically been linked to either direct contact with pesticides or the ingestion of contaminated pollen and nectar by bees. However, bumble bees, and other wild bees, may also be exposed to pesticides while using contaminated soil as an overwintering substrate. Yet knowledge of how soil‐mediated exposure affects bumble bee health is lacking. Here we take one of the first steps towards addressing this knowledge gap by designing a method for testing the effects of soil‐mediated pesticide exposure on bumble bee queen hibernation success. We measured hibernation survival, body weight change and abdominal fat content and found that none of these responses were affected by a field realistic soil exposure to the novel insecticide cyantraniliprole. Our study may help in developing a standardised method to test the effects of the soil‐mediated pesticide exposure route in bumble bee queens.

Abstract Palaeocurrent analysis is vital for basin analysis and helps in the interpretation of depositional environments (along‐slope or downslope). For that, it is crucial to have multiple measuring methods at hand to apply palaeocurrent analysis with a wide range of different datasets (outcrops, cores and photographs). Here, two relatively underexploited palaeocurrent measurement techniques are assessed when applied to trough cross‐stratification observed in the Arenazzolo Formation at Eraclea Minoa (Sicily). The first technique is a novel design of a qualitative approach to infer palaeocurrent directions from photographs of two‐dimensional sedimentary structures. The second technique involves measurements of the anisotropy of magnetic susceptibility from drilled samples. A broad agreement, with overlapping uncertainty boundaries, is observed between results from both techniques. This agreement validates the use of trough cross‐strata to infer palaeocurrent directions. Moreover, the addition of photographs improves reproducibility and prevents a bias towards the best‐exposed troughs. The application of both techniques to outcrops and sedimentary cores provides new opportunities for palaeocurrent analysis in any type of sedimentary environment.

Abstract Background Research on genetic and environmental influences on speech and/or language difficulties (SaLD) is sparse, with inconsistent heritability estimates. We aimed to estimate the prevalence of parental reported SaLD and the relative contributions of genetic and environmental factors for the phenotype using a Swedish population‐based twin sample. We hypothesized that there would be a stronger genetic than environmental effect on SaLD. Methods Data were collected from The Child and Adolescent Twin Study in Sweden. The study sample included 16,774 twin pairs (16,946 males, 16,602 females), of which 5141 were monozygotic, 5861 dizygotic (DZ), and 5772 opposite‐sex DZ pairs. The language items in the Autism–Tics, Attention‐Deficit Hyperactivity Disorder, and other Comorbidities inventory were used to categorize individuals as having parental‐reported SaLD. A classical twin design was used to estimate the relative contribution of genetic and environmental factors to the liability of SaLD. Results The prevalence of SaLD was 7.85% (95% confidence interval (CI) [7.57%–8.15%]) and 7.27% (95% CI [6.99%–7.55%]) when excluding individuals with autism and intellectual disability (ID). We also found that SaLD were significantly more prevalent in males than females with a ratio of 2:1. The heritability was estimated to be 75% (95% CI [67%–83%]) for SaLD. Shared environment played a significant role with an estimated contribution of 22% (95% CI [14%–30%]). The heritability estimate was reduced to 70% but with overlapping CI when excluding individuals with autism and ID. Conclusions We provide evidence that SaLD is common in the population and under strong genetic influence. Future studies should focus on mapping the genetic architecture of SaLD and related disorders.

Background Acute declines in estimated glomerular filtration rate (eGFR) occur commonly after starting angiotensin‐converting enzyme inhibitors. Whether declines in eGFR that occur after simultaneously starting angiotensin‐converting enzyme inhibitors with other antihypertensive agents modifies the benefits of these agents on cardiovascular outcomes is unclear. Methods and Results We identified predictors of acute declines in eGFR (>15% over 3 months) during randomization to benazepril plus amlodipine versus benazepril plus hydrochlorothiazide in the ACCOMPLISH (Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension) trial. We then determined the relation between declines in eGFR (treated as a binary variable, ≤15% versus >15% and separately, as a restricted spline variable) and the composite risk of fatal and nonfatal cardiovascular events using Cox proportional hazards models. We included 10 714 participants (median age 68 years [Q1 63, Q3 73]), of whom 1024 reached the trial end point over median follow‐up of 2.8 years. Predictors of acute declines in eGFR>15% over 3 months included assignment to hydrochlorothiazide (versus amlodipine) and higher baseline albuminuria. Overall, declines in eGFR ≥15% (versus

Abstract The interacting threats of invasive predators and altered fire regimes are key conservation issues for many native species globally. Artificial refuges have been proposed as a potential conservation tool to provide prey species with protection from invasive predators after fire, but we do not yet know whether they improve animal survival. To address this knowledge gap, we experimentally tested how small mammal abundance and species richness were influenced by the provision of artificial refuges after prescribed burns. We surveyed small mammals across five unburnt sites, seven burnt sites with artificial refuges, and eight burnt control sites following two prescribed fires in southeastern Australia. There were negative and neutral responses of small mammals to the burns, and relative abundance was positively correlated with structurally complex vegetation. Artificial refuges had no impact on abundance or species richness, irrespective of burn coverage. These findings suggest that this artificial refuge design may not be an effective tool for improving small mammal population persistence postfire, and as such we should not yet scale up their application. However, given the inherent context‐dependency of field experiments involving fire, which include difficult‐to‐control variables such as fire severity, predator activity, and population dynamics, we encourage researchers to undertake further experiments with artificial refuges in fire‐affected areas, including after severe wildfires when less vegetation cover remains. Such studies will help to build our understanding of their utility as a conservation tool across different ecosystems and fire types.

Abstract Introduction Recent evidence has raised questions about whether newer HIV treatment regimens, including dolutegravir (DTG) and tenofovir alafenamide (TAF), are associated with increases in blood pressure (BP). Methods We assessed changes in BP by treatment regimen and evaluated the relative contribution of kidney function and weight gain to these changes among participants in the ADVANCE phase‐3 trial clinical trial in South Africa (study dates: January 2017–February 2022). Our primary outcome of interest was a change in systolic BP (SBP) at 96 and 192 weeks, among those not receiving antihypertensive medication. The secondary outcome was treatment‐emergent hypertension at these same time points, defined as BP ≥140/90 mmHg on two occasions, or initiation of antihypertensive medication after week 4 among individuals without hypertension at enrolment. We used linear regression to evaluate the relationship between change in estimated glomerular filtration rate (eGFR) and change in SBP; and Poisson regression to evaluate the relationship between change in eGFR and treatment‐emergent hypertension at each time point. All models were adjusted for age, sex, treatment group and change in body mass index (BMI). Results Over 96 weeks, the average changes in SBP were 1.7 mmHg (95% CI: 0.0−3.4), −0.5 mmHg (95% CI: −2.2 to 1.7) and −2.1 mmHg (95% CI: −3.8 to 0.4) in the TAF/emtricitabine (FTC)/DTG, tenofovir disoproxil fumarate (TDF)/FTC/DTG and TDF/FTC/efavirenz (EFV) groups, respectively. This difference was significant for the TAF/FTC/DTG compared to the TDF/FTC/EFV group (p = 0.002). Over 96 weeks, 18.2% (95% CI: 13.4–22.9), 15.4% (95% CI: 11.0–19.9) and 13.3% (95% CI: 8.9–17.6) of participants developed treatment‐emergent hypertension, respectively. In adjusted models, there was no significant relationship between change in eGFR and either outcome. Change in BMI was significantly associated with an increase in SBP, while age was associated with an increased risk of treatment‐emergent hypertension. Adjustment for BMI also mitigated the unadjusted relationship between HIV treatment regimen and SBP where present. Conclusions In the ADVANCE cohort, weight gain and age accounted for increases in BP and risk of treatment‐emergent hypertension. HIV treatment programmes may need to integrate the management of obesity and hypertension into routine care. Clinical Trial Number NCT03122262

Abstract Introduction The advent of disease‐modifying therapies for Alzheimer's disease (AD) has raised many questions and debates in the field as to the clinical benefits, risks, and costs of such therapies. The controversies have resulted in the perception that many clinicians are apprehensive about prescribing these medications to their patient populations. There also remains widespread uncertainty as to the economic impact, cost benefit ratio, and safety oversight for use of these medications in standard clinical care settings. Methods To contextualize such issues, the present study compared anti‐amyloid biologic therapy (lecanemab) to four commonly used biologic agents in other fields, including trastuzumab for breast cancer, bevacizumab for lung cancer, etanercept for rheumatoid arthritis, and ocrelizumab for multiple sclerosis. Results The data presented demonstrate comparable costs, clinical benefits, and risks for these biologic agents in their disparate disease states. Discussion These results provide context for the costs, clinical benefits, and safety regarding the mainstream use of anti‐amyloid biologic agents for the prevention of cognitive loss. While the era of disease‐modifying therapies for AD is now in its infancy, there is an expectation that these discoveries will be followed by improved therapies and combination treatments leading to greater efficacy in ameliorating the clinical trajectory of AD. Highlights Anti‐amyloid therapy costs are comparable to other commonly used biologics. Anti‐amyloid therapy efficacy is comparable to other commonly used biologics. Anti‐amyloid therapy safety is compatible with other commonly used biologics.

Abstract Aims Many heart failure (HF) patients do not receive optimal guideline‐directed medical therapy (GDMT) despite clear benefit on morbidity and mortality outcomes. Digital consults (DCs) have the potential to improve efficiency on GDMT optimization to serve the growing HF population. The investigator‐initiated ADMINISTER trial was designed as a pragmatic multicenter randomized controlled open‐label trial to evaluate efficacy and safety of DC in patients on HF treatment. Methods and results Patients (n = 150) diagnosed with HF with a reduced ejection fraction will be randomized to DC or standard care (1:1). The intervention group receives multifaceted DCs including (i) digital data sharing (e.g. exchange of pharmacotherapy use and home‐measured vital signs), (ii) patient education via an e‐learning, and (iii) digital guideline recommendations to treating clinicians. The consults are performed remotely unless there is an indication to perform the consult physically. The primary outcome is the GDMT prescription rate score, and secondary outcomes include time till full GDMT optimization, patient and clinician satisfaction, time spent on healthcare, and Kansas City Cardiomyopathy Questionnaire. Results will be reported in accordance to the CONSORT statement. Conclusions The ADMINISTER trial will offer the first randomized controlled data on GDMT prescription rates, time till full GDMT optimization, time spent on healthcare, quality of life, and patient and clinician satisfaction of the multifaceted patient‐ and clinician‐targeted DC for GDMT optimization.

Abstract Background Evidence for substance use‐related problems in individuals with mild intellectual disability is sparse and mainly limited to selected psychiatric populations. We evaluated the risk of substance use‐related problems in individuals with mild intellectual disability compared to the general population. Additionally, we have performed secondary sibling comparison analyses to account for familial confounding. Methods We conducted a population‐based cohort study of individuals born in Sweden between 1973 and 2003. A total of 18,307 individuals with mild intellectual disability were compared to 915,350 reference individuals from the general population and 18,996 full siblings of individuals with mild intellectual disability. Information on mild intellectual disability and substance use‐related problems was obtained from several Swedish national and regional school and healthcare registers. Substance use‐related problems were measured via corresponding diagnostic and legal codes and included alcohol use disorder, drug use disorder, alcohol‐related somatic disease, conviction for a substance‐related crime, and substance‐related death. Results Individuals with mild intellectual disability had a higher risk of any substance use‐related problem compared to the general population (HR, 1.81; 95% CI, 1.72–1.91), both in males (HR, 1.76; 95% CI, 1.65–1.89) and females (HR, 1.89; 95% CI, 1.74–2.05). The risks of substance use‐related problems were particularly elevated among individuals with mild intellectual disability and psychiatric comorbidities (HR, 2.21–8.24). The associations were attenuated in the sibling comparison models. Conclusions Individuals with mild intellectual disability, especially those with psychiatric comorbidity, are at an elevated risk of substance use‐related problems. Familial factors shared by full siblings contribute considerably to the association between mild intellectual disability and substance use‐related problems.

Abstract Introduction As access to effective antiretroviral therapy (ART) has improved globally, tobacco‐related illnesses, including cardiovascular disease, cancer and chronic respiratory conditions, account for a growing proportion of deaths among people with HIV (PWH). We estimated the impact of tobacco smoking and smoking cessation on life expectancy among PWH in South Africa. Methods In a microsimulation model, we simulated 18 cohorts of PWH with virologic suppression, each homogenous by sex, initial age (35y/45y/55y) and smoking status (current/former/never). Input parameters were from data sources published between 2008 and 2022. We used South African data to estimate age‐stratified mortality hazard ratios: 1.2−2.3 (females)/1.1−1.9 (males) for people with current versus never smoking status; and 1.0−1.3 (females)/1.0−1.5 (males) for people with former versus never smoking status, depending on age at cessation. We assumed smoking status remains unchanged during the simulation; people who formerly smoked quit at model start. Simulated PWH face a monthly probability of disengagement from care and virologic non‐suppression. In sensitivity analysis, we varied smoking‐associated and HIV‐associated mortality risks. Additionally, we estimated the total life‐years gained if a proportion of all virologically suppressed PWH stopped smoking. Results Forty‐five‐year‐old females/males with HIV with virologic suppression who smoke lose 5.3/3.7 life‐years compared to PWH who never smoke. Smoking cessation at age 45y adds 3.4/2.4 life‐years. Simulated PWH who continue smoking lose more life‐years from smoking than from HIV (females, 5.3 vs. 3.0 life‐years; males, 3.7 vs. 2.6 life‐years). The impact of smoking and smoking cessation increase as smoking‐associated mortality risks increase and HIV‐associated mortality risks, including disengagement from care, decrease. Model results are most sensitive to the smoking‐associated mortality hazard ratio; varying this parameter results in 1.0−5.1 life‐years gained from cessation at age 45y. If 10−25% of virologically suppressed PWH aged 30−59y in South Africa stopped smoking now, 190,000−460,000 life‐years would be gained. Conclusions Among virologically suppressed PWH in South Africa, tobacco smoking decreases life expectancy more than HIV. Integrating tobacco cessation interventions into HIV care, as endorsed by the World Health Organization, could substantially improve life expectancy.

Abstract Ocean island basalts (OIBs) are generated by mantle plumes, with their geochemistry controlled by a combination of source composition, temperature, and thickness of overlying lithosphere. For example, OIBs erupting onto thicker, older oceanic lithosphere are expected to exhibit signatures indicative of higher average melting pressures. Here, we quantitatively investigate this relationship using a global data set of Neogene and younger OIB compositions. Local lithospheric thicknesses are estimated using theoretical plate‐cooling models and Bayes factors are applied to identify trends. Our findings provide compelling evidence for a correlation between OIB geochemistry and lithospheric thickness, with some variables (SiO2, Al2O3, FeO, Lu) showing linear trends that can be attributed to increasing average melting pressure, whereas others (CaO, La, λ0, and λ1) require a bi‐linear fit with a change in gradient at ∼55 km. Observed variations in highly incompatible elements are consistent with degrees of melting that decrease with increasing lithospheric thickness, as expected. Nevertheless, at thicknesses beyond ∼55 km, the implied degree of melting does not decrease as rapidly as is suggested by theoretical expectations. This observation is robust across different lithospheric thickness estimates, including those derived from seismic constraints. We infer that at thicknesses exceeding ∼55 km, weak plumes fail to effectively thin overlying lithosphere and/or produce insufficient melt to erupt. This is supported by independent estimates of plume buoyancy flux, indicating that OIB magmatism on older lithosphere may be biased toward hotter plumes. In addition, we find evidence for a “memory effect” of incomplete homogenization of melts during their ascent.

Abstract Fire shapes animal communities by altering resource availability and species interactions, including between predators and prey. In Australia, there is particular concern that two highly damaging invasive predators, the feral cat (Felis catus) and European red fox (Vulpes vulpes), increase their activity in recently burnt areas and exert greater predation pressure on the native prey due to their increased exposure. We tested how prescribed fire occurrence and extent, along with fire history, vegetation, topography, and distance to anthropogenic features (towns and farms), affected the activity (detection frequency) of cats, foxes, and the native mammal community in south‐eastern Australia. We used camera traps to quantify mammal activity before and after a prescribed burn and statistically tested how the fire interacted with these habitat variables to affect mammal activity. We found little evidence that the prescribed fire influenced the activity of cats and foxes and no evidence of an effect on kangaroo or small mammal (

Abstract Background and Aims Osteoarthritis (OA) is one of the most common debilitating diseases among the aging population. Nigella sativa is one potential treatment for OA. Here, we sought to evaluate the efficacy and safety of Nigella sativa for treating patients with OA. Methods PubMed, Scopus, Embase, and Web of Science were searched up to October 20, 2022. The primary outcome was changes in the pain score after receiving Nigella sativa or control agents based on the results of randomized controlled trials (RCTs). The secondary outcome was set as the frequency of adverse events reported during the follow‐up period. Results Six RCTs involving a total of 370 patients with knee OA were included in the present systematic review. Among the four screened studies, the topical administration of Nigella sativa oil was found to be more effective than the placebo in relieving pain in three trials. Additionally, the oral use of Nigella sativa oil was assessed in two trials, and an improvement in pain score relative to placebo was documented in only one of the studies. Also, the trial that evaluated the effectiveness of Nigella sativa oral capsules did not demonstrate any difference in pain reduction between the intervention and placebo groups. Overall, either topical or oral administration of Nigella sativa was well tolerated, and no serious adverse events were reported. Conclusion Nigella sativa is generally safe, but conflicting findings from low‐quality studies hinder the ability to make clinical recommendations for or against treating OA. Robust trials are needed for informed decisions.

Abstract Coronavirus disease 2019 (COVID‐19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), can manifest itself in several ways, including coagulopathy and thrombosis. These complications can be the first and sometimes only manifestations of SARS‐CoV‐2 infection and can occur early or late in the course of the disease. However, these symptoms are more prevalent in hospitalized patients with venous thromboembolism, particularly those admitted to intensive care units. Moreover, various forms of arterial and venous thrombosis, or micro‐ or macro‐vasculature embolisms, have been reported during the current pandemic. They have led to harmful consequences, such as neurological and cardiac events, nearly all resulting from the hypercoagulable state caused by this viral infection. The severe hypercoagulability observed in patients with COVID‐19 accounts for most cases of the disease that become critical. Therefore, anticoagulants seem to be one of the most vital therapeutics for treating this potentially life‐threatening condition. In the current paper, we present a thorough review of the pathophysiology of COVID‐19‐induced hypercoagulable state and the use of anticoagulants to treat SARS‐CoV‐2 infections in different patient groups, as well as their pros and cons.

Abstract Precipitation is an essential climate variable and a fundamental part of the global water cycle. Given its importance to society, precipitation is often assessed in climate monitoring activities, such as in those led by the Copernicus Climate Change Service (C3S). To undertake these activities, C3S predominantly uses ERA5 reanalysis precipitation. Research has shown that short‐range forecasts for precipitation made from this reanalysis can provide valuable estimates of the actual (observed) precipitation in extratropical regions but can be less useful in the tropics. While some of these limitations will be reduced with future reanalyses because of the latest advancements, there is potentially a more immediate way to improve the precipitation estimate. This is to use the precipitation modelled in the Four‐Dimensional Variational (4D‐Var) data assimilation window of the reanalysis, and it is the aim of this study to evaluate this approach. Using observed 24‐h precipitation accumulations at 5637 stations from 2001 to 2020, results show that smaller root‐mean‐square errors (RMSEs) and mean absolute errors are generally found by using the ERA5 4D‐Var precipitation. For example, for all available days from 2001 to 2020, 87.5% of stations have smaller RMSEs. These improvements are driven by reduced random errors in the 4D‐Var precipitation because it is better constrained by observations, which are themselves sensitive to or influence precipitation. However, there are regions (e.g., Europe) where larger biases occur, and via the decomposition of the Stable Equitable Error in Probability Space score, this is shown to be because the 4D‐Var precipitation has a wetter bias on ‘dry’ days than the standard ERA5 short‐range forecasts. The findings also highlight that the 4D‐Var precipitation does improve the discrimination of ‘heavy’ observed events. In conclusion, an improved ERA5 precipitation estimate is largely obtainable, and these results could prove useful for C3S activities and for future reanalyses, including ERA6.

Abstract The Pampean flat slab in central Chile and Argentina is characterized by the inland migration and subsequent cessation of arc volcanism since the mid‐Miocene. Slab flattening also affects the distribution and number of intermediate‐depth earthquakes and the evolution of the overlying continental thermal structure. In this study, we combine thermal‐mechanical models with petrological models to examine temporal changes in pressure, temperature, and composition during flat‐slab subduction and estimate water carrying capacity, predicted melt distributions and predicted changes in melt composition. Model results indicate that the present‐day flattened Nazca plate carries water to ∼700 km inland from the trench and could cause flux melting if the material above the slab remains fertile. Observed slab seismicity matches areas where hydrated materials have ∼>3 wt% H2O in the oceanic crust and mantle lithosphere. Seismicity increases as slab water carrying capacity decreases (slab dehydration). As P‐T conditions and compositions of the rock trapped above the slab change during slab flattening, flux melting switches from a peridotite‐dominated early phase to a combined mid‐ocean ridge basalt/eclogite and peridotite melting at ∼8 Ma. The results provide broad consistency with known earthquake distributions, seismic velocities, and observed temporal and spatial changes in volcanic patterns above the Pampean flat slab and point toward the role of melt depletion in the decrease and ultimate cessation of arc volcanism in this region.

Abstract Impacts of long‐term fertilization and cultivation were evaluated on nematode communities associated with tall fescue turfgrass following 11 years of treatment applications. Fertilizer treatments of biosolid, synthetic, and plant‐based fertilizers and cultivation treatments of 0×, 1×, and 2× aerification passes were applied to randomized and replicated tall fescue plots at the University of Maryland Paint Branch Turfgrass facility in College Park, Maryland. Free‐living and plant‐parasitic nematodes were identified, enumerated, and categorized into functional groups. Nematode count data were compared using generalized linear mixed modeling with negative binomial distribution and two‐way ANOVA was used to compare nematode ecological indices. Biosolid treatments resulted in lower omnivore‐predator densities than plant‐based fertilizer treatments (p ≤ .001) and significantly greater Hoplolaimus densities than plant‐based fertilizer plots (p ≤ .05). Synthetic fertilizer applications resulted in the greatest Eucephalobus (p ≤ .05) and total bacterivore densities (p ≤ .001) of all fertilizer treatments. Plant‐based fertilizer‐treated plots had the largest Maturity Index cp 2‐5 and Structure Index (p ≤ .05). Cultivation of 1× resulted in fewer total bacterivore densities than 2× (p ≤ .01) while omnivore‐predator densities were greater in 1× than 0× (p ≤ .001). Plant health, as measured by NDVI, was lowest in biosolid‐treated turfgrass (p ≤ .05). These findings suggest that long‐term turfgrass management practices can have variable impacts on nematode abundance and community structure in tall fescue and provide insights into ecological impacts of turfgrass management practices.

Background The objective of the PERSONAL‐CovidBP (Personalised Electronic Record Supported Optimisation When Alone for Patients With Hypertension: Pilot Study for Remote Medical Management of Hypertension During the COVID‐19 Pandemic) trial was to assess the efficacy and safety of smartphone‐enabled remote precision dosing of amlodipine to control blood pressure (BP) in participants with primary hypertension during the COVID‐19 pandemic. Methods and Results This was an open‐label, remote, dose titration trial using daily home self‐monitoring of BP, drug dose, and side effects with linked smartphone app and telemonitoring. Participants aged ≥18 years with uncontrolled hypertension (5–7 day baseline mean ≥135 mm Hg systolic BP or ≥85 mm Hg diastolic BP) received personalized amlodipine dose titration using novel (1, 2, 3, 4, 6, 7, 8, 9 mg) and standard (5 and 10 mg) doses daily over 14 weeks. The primary outcome of the trial was mean change in systolic BP from baseline to end of treatment. A total of 205 participants were enrolled and mean BP fell from 142/87 (systolic BP/diastolic BP) to 131/81 mm Hg (a reduction of 11 (95% CI, 10–12)/7 (95% CI, 6–7) mm Hg, P

Conclusion: Care should be taken to prevent drills from plunging beyond the medial femoral cortex during surgery. Cautious observation of patient’s vitals and clinical course can allow for early detection of vascular complication.

Objective. To examine one academic institution’s experiences with SpaceOAR placement, its associated complications, and periprocedural characteristics that affect outcomes for the purpose of quality improvement. Materials and Methods. We conducted a retrospective review of 233 patients who received SpaceOAR from four surgeons and one radiation oncologist between 2018 and 2021. Variables such as demographics, oncologic parameters, radiation plan, and radiographic assessment of hydrogel placement were recorded. The Charlson Comorbidity Index (CCI) was used to assess comorbidity risk. Mann–Whitney and Fisher’s exact tests were performed to compare patients with and without complications. Results. Of the 233 patients who received SpaceOAR, 24 (10.3%) experienced toxicity. All complications were Clavien I or II, such as pelvic pain postplacement, pelvic fullness, bleeding, and lower urinary tract symptoms. 16 patients (6.9%) had some portion of the hydrogel injected into the rectal wall, but it was never clinically significant. The average CCI was 3.2 ± 0.95 for patients who experienced complications; the average CCI was 3.6 ± 1.6 (p=0.48) in the group without complications. Of the physicians with higher procedure volumes, Physician #1 had the highest rate of patient-reported complications at 11 out of 68 (16.2%) and Physician #2 had the lowest rate of complications at 4 out of 96 placements (4.2%). Multivariate analysis found that patients who had received hormone therapy previously had less odds of reporting complications after SpaceOAR placement. Conclusions. The listed attending on the procedure had a significant correlation to complications with SpaceOAR placement on univariate analysis, and hormone therapy had some benefits to the tolerance for the procedure on multivariate analysis. Overall, the hydrogel placement was well tolerated with low incidence of mild and transient procedure-related toxicity.

Abstract Objective In vitro data prompted U.S Food and Drug Administration warnings that lamotrigine, a common sodium channel modulating anti‐seizure medication (NaM‐ASM), could increase the risk of sudden death in patients with structural or ischaemic cardiac disease, however, its implications for Sudden Unexpected Death in Epilepsy (SUDEP) are unclear. Methods This retrospective, nested case–control study identified 101 sudden unexpected death in epilepsy (SUDEP) cases and 199 living epilepsy controls from Epilepsy Monitoring Units (EMUs) in Australia and the USA. Differences in proportions of lamotrigine and NaM‐ASM use were compared between cases and controls at the time of admission, and survival analyses from the time of admission up to 16 years were conducted. Multivariable logistic regression and survival analyses compared each ASM subgroup adjusting for SUDEP risk factors. Results Proportions of cases and controls prescribed lamotrigine (P = 0.166), one NaM‐ASM (P = 0.80), or ≥2NaM‐ASMs (P = 0.447) at EMU admission were not significantly different. Patients taking lamotrigine (adjusted hazard ratio [aHR] = 0.56; P = 0.054), one NaM‐ASM (aHR = 0.8; P = 0.588) or ≥2 NaM‐ASMs (aHR = 0.49; P = 0.139) at EMU admission were not at increased SUDEP risk up to 16 years following admission. Active tonic–clonic seizures at EMU admission associated with >2‐fold SUDEP risk, irrespective of lamotrigine (aHR = 2.24; P = 0.031) or NaM‐ASM use (aHR = 2.25; P = 0.029). Sensitivity analyses accounting for incomplete ASM data at follow‐up suggest undetected changes to ASM use are unlikely to alter our results. Significance This study provides additional evidence that lamotrigine and other NaM‐ASMs are unlikely to be associated with an increased long‐term risk of SUDEP, up to 16 years post‐EMU admission.

Abstract Tetrahydrobiopterin (BH4) is an essential cofactor for nitric oxide (NO) synthases in which its production of NO is crucial for cardiac function. However, non‐canonical roles of BH4 have been discovered recently and the cell‐specific role of cardiomyocyte BH4 in cardiac function and metabolism remains to be elucidated. Therefore, we developed a novel mouse model of cardiomyocyte BH4 deficiency, by cardiomyocyte‐specific deletion of Gch1, which encodes guanosine triphosphate cyclohydrolase I, a required enzyme for de novo BH4 synthesis. Cardiomyocyte (cm)Gch1 mRNA expression and BH4 levels from cmGch1 KO mice were significantly reduced compared to Gch1flox/flox (WT) littermates. Transcriptomic analyses and protein assays revealed downregulation of genes involved in fatty acid oxidation in cmGch1 KO hearts compared with WT, accompanied by increased triacylglycerol concentration within the myocardium. Deletion of cardiomyocyte BH4 did not alter basal cardiac function. However, the recovery of left ventricle function was improved in cmGch1 KO hearts when subjected to ex vivo ischaemia–reperfusion (IR) injury, with reduced infarct size compared to WT hearts. Metabolomic analyses of cardiac tissue after IR revealed that long‐chain fatty acids were increased in cmGch1 KO hearts compared to WT, whereas at 5 min reperfusion (post‐35 min ischaemia) fatty acid metabolite levels were higher in WT compared to cmGch1 KO hearts. These results indicate a new role for BH4 in cardiomyocyte fatty acid metabolism, such that reduction of cardiomyocyte BH4 confers a protective effect in response to cardiac IR injury. Manipulating cardiac metabolism via BH4 could play a therapeutic role in limiting IR injury.

Abstract Camera traps are increasingly used in wildlife monitoring and citizen science to address an array of ecological questions on a wide variety of species. However, despite the ability of modern camera traps to capture high‐quality video, the majority of studies collect still images, in part because of concerns with video performance. We conducted a camera trap survey of a forested landscape in the UK, using a grid of paired camera traps, to quantify the impact of using video compared to photos on the outcomes of ecological research and for participation and engagement of citizen scientists. Ecological outputs showed no difference between photo and video datasets, but comparison between expert and citizen science classifications showed citizen scientists were able to classify videos more accurately (average accuracy of 95% for video, 86% for photo). Furthermore, citizen scientists were more likely to volunteer additional information on age (provided for 61% videos and 30% photos) and sex (provided for 63% videos and 45% photos) of animals in video footage. Concerns over slow trigger speeds for videos did not appear to affect our datasets or the inferences gained. When combined with citizen science, video datasets are likely to be of higher quality due to increased classification accuracy. Consequently, we encourage researchers to consider the use of video for future camera‐trapping projects.

Abstract Background The present study reported the cancer deaths and disability‐adjusted life years (DALYs) that were attributable to high fasting plasma glucose (HFPG) in the Middle East and North Africa (MENA) region by country, age, sex, cancer type and Socio‐demographic Index (SDI), from 1990 to 2019. Methods Global Burden of Disease (GBD) 2019 data were used to report the cancer‐related deaths and DALYs that were attributable to HFPG, for all MENA countries over the period 1990–2019. The results were presented as numbers, population attributable fractions (PAFs) and rates (per 100,000) with 95% uncertainty intervals. Results In 2019, there were an estimated 19.8 thousand (5.5–40.2) cancer deaths attributable to HFPG in MENA, which represents 4.7% (1.3–9.3) of all cancer‐related deaths. The number of regional DALYs due to HFPG‐related cancers was 462.2 thousand (127.3–959.5), which represents 3.8% (1.1–7.6) of all cancer‐related DALYs in 2019. From 1990 to 2019, the age‐standardized DALY rate of cancers attributable to HFPG (per 100,000) grew from 56.3 (14.6–121.1) to 107.0 (29.8–220.8), which was a 90.1% (64.4–127.8) increase. In 2019, the highest age‐standardized DALY rate of cancers attributable to HFPG was in Qatar (270.4) and the lowest was in Sudan (75.3). The DALY rate of cancers attributable to HFPG increased with age, peaking for males in the 70–74 age group and for females in the 75–79 age group, and then decreased for both sexes. A broadly positive relationship was found between the national SDI and the national age‐standardized DALY rate of all cancers attributable to FPG over the measurement period. Conclusions The burden of HFPG‐related cancers has increased over the past three decades in MENA, and was higher than the global average in multiple age groups. Implementing a battery of preventive measures and therapeutic interventions is suggested to address the adverse effects of this modifiable risk factor.

Abstract The rituximab biosimilar CT‐P10 is approved for the treatment of non‐Hodgkin lymphoma. Previous studies have demonstrated clinical similarity between CT‐P10 and reference rituximab. However, real‐world data relating to treatment in patients with DLBCL with rituximab biosimilars are limited. This study collected real‐world data relating to the effectiveness and safety of CT‐P10 treatment from the medical records of 389 patients with DLBCL (24 centers, five European countries). For the primary outcome (clinical effectiveness), overall survival (OS), progression‐free survival (PFS), and best response (BR) were assessed. The percentage (95% confidence interval [95% CI]) of patients alive at 12‐, 18‐, and 30 months postindex (initiation of CT‐P10) was 86% (82.4%–89.4%), 81% (76.9%–84.9%), and 76% (71.2%–80.1%), respectively. The PFS rate (percent, [95% CI]) at 12‐, 18‐, and 30 months postindex was 78% (74.2%–82.5%), 72% (67.9%–76.9%), and 67% (61.9%–71.7%), respectively. Median OS/PFS was not reached. For 82% (n = 312) of patients, the BR to CT‐P10 was a complete response. Adverse events were consistent with known effects of chemotherapy. This international, multicenter study provides real‐world data on the safety and effectiveness profile of CT‐P10 for DLBCL treatment and supports the adoption of CT‐P10 for the treatment of DLBCL.

Abstract Neurodegenerative diseases such as Parkinson's disease (PD), Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS) are traditionally considered strictly neurological disorders. However, clinical presentation is not restricted to neurological systems, and non‐central nervous system (CNS) manifestations, particularly gastrointestinal (GI) symptoms, are common. Our objective was to understand the systemic distribution of pathology in archived non‐CNS tissues, taken as part of routine clinical practice during life from people with ALS. We examined tissue from 13 people who went on to develop ALS; including sporadic ALS (n = 12) and C9orf72 hexanucleotide repeat expansion (n = 1). The tissue cohort consisted of 68 formalin‐fixed paraffin embedded samples from 21 surgical cases (some patients having more than one case over their lifetimes), from 8 organ systems, which we examined for evidence of phosphorylated TDP‐43 (pTDP‐43) pathology. We identified pTDP‐43 aggregates in multiple cell types of the GI tract, including macrophages and dendritic cells within the lamina propria; as well as ganglion/neuronal and glial cells of the myenteric plexus. Aggregates were also noted within lymph node parenchyma, blood vessel endothelial cells, and chondrocytes. We note that in all cases with non‐CNS pTDP‐43 pathology, aggregates were present prior to ALS diagnosis and in some instances preceded neurological symptom onset by more than 10 years. These data imply that patients with microscopically unexplained non‐CNS symptoms could have occult protein aggregation that could be detected many years prior to neurological involvement.

Abstract Hypertension is the main cause of cardiovascular disease, especially in women. Black women (58%) are affected by higher rates of hypertension than other racial/ethnic groups contributing to increased cardio‐metabolic disorders. To decrease blood pressure (BP) in this population, a pilot randomized controlled trial was conducted to examine the effects of Interactive Technology Enhanced Coaching (ITEC) versus Interactive Technology (IT) alone in achieving BP control, adherence to antihypertensive medication, and adherence to lifestyle modifications among Black women diagnosed with and receiving medication for their hypertension. Participants completed a 6‐week Chronic Disease Self‐Management Program (CDSMP), and 83 participants were randomly assigned to ITEC versus IT. Participants were trained to use three wireless tools and five apps that were synchronized to smartphones to monitor BP, weight, physical activity (steps), diet (caloric and sodium intake), and medication adherence. Fitbit Plus, a cloud‐based collaborative care platform was used to collect, track, and store data. Using a mixed‐effects repeated measures model, the main effect of group means indicated no significant difference between the treatment and referent groups on study variables. The main effect of time indicated significant differences between repeated measures for systolic BP (p

Abstract Genomic selection has been utilized for genetic improvement in both plant and animal breeding and is a favorable technique for quantitative trait development. Within this study, genomic selection was evaluated within a breeding program, using novel validation methods in addition to plant materials and data from a commercial soybean (Glycine max) breeding program. A total of 1501 inbred lines were used to test multiple genomic selection models for multiple traits. Validation included cross‐validation, inter‐environment, and empirical validation. The results indicated that the extended genomic best linear unbiased prediction (EGBLUP) model was the most effective model tested for yield, protein, and oil in cross‐validation with accuracies of 0.50, 0.68, and 0.64, respectively. Increasing marker number from 1000 to 3000 to 6000 single nucleotide polymorphism markers leads to statistically significant increases in accuracy. Cross‐environment predictions were statistically lower than cross‐validation with accuracies of 0.24, 0.54, and 0.42 for yield, protein, and oil, respectively, using the extended genomic BLUP model. Empirical validation, predicting the yield of 510 soybean lines, had a prediction accuracy of 0.34, with the inclusion of a maturity covariate leading to a notable increase in accuracy. Genomic selection identified high‐performance lines in inter‐environment predictions: 34% of lines within the upper quartile of yield, and 51% and 48% of the highest quartile protein and oil lines, respectively. Statistically similar results occurred comparing rankings in empirical validation and selection for advancements in yield trials. These results indicate that genomic selection is a useful tool for selection decisions.

Abstract The Congo River supplies vast quantities of trace metals (TMs) to the South Atlantic Ocean, but TM budgets for the Congo plume derived using radium isotopes for GEOTRACES cruise GA08 suggest additional input other than the river outflow. Considering the tight correlations between most dissolved TMs and salinity in the plume and the high rainfall during the wet season over the Congo shelf, we hypothesized that wet atmospheric deposition is a TM source to the Congo plume. Observed TM concentrations in rainwaters across the Congo shelf were mostly comparable to values from previous work in the North Atlantic and Mediterranean Sea. Wet deposition contributed the equivalent of 43% dCd, 21% dCu, 20% dPb and 68% dZn of the Congo River fluxes. Our findings show an important role of wet deposition in supplying TMs to the South Atlantic overlapping with the region that receives substantial TM fluxes from the Congo River.

Abstract Background and Objective Obesity has historically been seen as a sign of wealth and social privilege, as can be inferred from studying the ancient works. We aimed to report the causes, diagnostic approaches, and treatment among the authentic books of traditional Iranian medicine. Methods We searched the original versions of historical books and used a narrative approach to report the history of obesity. Results Obesity was often seen as an indicator of complete health. Obesity in healthy women was a requirement for beauty, based on descriptions of women from the Zoroaster period and from antiquity to the late Qajar period. This point of view existed during various ages. However, after the constitutional period, the view of obesity changed into that of an illness, due to modern ideas and offshore role models, especially during the Pahlavi era. This change led to serious attempts to treat obesity. Obesity is a critical problem that needs immediate attention to prevent substantial health consequences. Different medical paradigms have presented their criteria and foundations throughout history. The emphasis of Iranian alternative medicine was on prevention and the maintenance of health, with the next step being treatment. Prevention, treatment, consuming medicinal plants, and recovery have often been written about in the traditional books of medicine. Conclusions Throughout the traditional Iranian medical texts, physicians have made recommendations about maintaining an appropriate body weight. The best treatment was prevention and a healthy lifestyle. The treatments for controlling and restricting obesity included paying attention to nourishment, mobility, and even the habitat.

Abstract Background Neck pain is a complex musculoskeletal disorder that can result in substantial morbidity. The present article presents the neck pain burden in Iranians who were at least 70 years old, from 1990 to 2019, by sex, age group, and province. Methods Publicly available information on the prevalence, incidence, and years lived with disability (YLD) caused by neck pain was extracted from the Global Burden of Disease study 2019. The estimates were all provided as counts and age‐standardized rates (per 100,000), and included 95% uncertainty intervals. Results The point prevalence of neck pain in 2019 was 8710.6, while the incidence rate was 1334.7 per 100,000 population. That same year, there were number of 27.8 thousand YLDs and an YLD rate of 801.7 per 100,000. The prevalence, incidence, and YLD rates did not change substantially over the measurement period (1990–2019). The highest YLD rate was found in Tehran (960.9 per 100,000), while Kohgiluyeh and Boyer‐Ahmad had the lowest (730.5 per 100,000). Females had slightly higher prevalent cases, incident cases, and YLDs, as well as their corresponding rates in 2019. In 2019, the number of prevalent cases, incident cases, and YLDs peaked in the 70–74 age group, for both sexes, and in all cases they reduced with age. In both 1990 and 2019, Iran had a higher YLD rate than that found among elderly adults in the Middle East and North Africa region. Conclusions The burden of neck pain in Iran has decreased slightly over the last three decades, but it still imposes a substantial burden and is higher than that found in the rest of the region. Therefore, preventive programs should be initiated at a young age to reduce the attributable burden later in life.

Abstract Siderite (FeCO3) is an important ferrous iron carbonate in the geochemical cycling of iron, as it is a sink for iron under reducing conditions. However, its detection is not straightforward with classical analytical approaches because in natural samples it is often fine‐grained and/or occurs in low concentrations. In this study, we explore the analytical potential of low‐temperature magnetometry. Synthetic siderites with a limited amount of associated ferric iron of up to 5 mol% and some natural siderites were subjected to investigation. Maxima in the cooling curves in a 5 T magnetic field shows that the Néel temperature of siderite is at 37 K in agreement with literature data. Those maxima appear at a higher temperature in the synthetic siderites with associated/sorbed ferric iron; it is 45 K for the 5 mol% Fe3+ synthesis. With the increasing amount of ferric iron, the synthetic siderites show an increasingly prominent remanence tail beyond the nominal Néel temperature in field‐cooled (FC) and zero‐field‐cooled (ZFC) warming curves of the remanent magnetization acquired in 5 T at 5 K. Fine‐grained siderite alters in air on laboratory time scales which is manifested by more pronounced remanence tails up to higher temperatures. Siderite's presence is best diagnosed by evaluating a combination of FC warming curves and a FC/ZFC remanence ratio >3 at 5 K. Standard addition experiments of FC warming curves enable the determination of siderite down to 0.1 wt%.

Abstract Low cloud feedback in global warming projections by climate models is characterized by its positive sign, the mechanism of which is not well understood. Here we propose that the positive sign is primarily caused by the increase in upward longwave radiation from the sea surface. We devise numerical experiments that enable separation of the feedback into components coming from physically distinct causes. Results of these experiments with a climate model indicate that increases in upward longwave radiation from the sea surface cause warming and absolute drying in the boundary layer, leading to the positive low cloud feedback. The absolute drying results from decrease in surface evaporation, and also from decrease in inversion strength which enhances vertical mixing of drier free tropospheric air into the boundary layer. This mechanism is different from previously proposed understanding that positive low cloud feedback is caused by increases in surface evaporation or vertical moisture contrast.

Abstract Despite numerous published studies on the wear of dental composites, few have considered the influence of temperature on the two‐body wear process. Additionally, no previous work has considered the influence of temperature on dominant wear mechanisms during the consumption of hot substances, hence the focus of this study. Reciprocating wear tests were carried out at varying artificial saliva lubricant temperatures (37 and 57°C) and material loss was quantified using profilometry. The wear tracks were analysed using FIB/SEM/TEM. Results reveal that the wear rate of a dental composite can significantly increase with temperature, with fatigue/delamination and ploughing acting as dominant mechanisms.

Abstract Objective To compare “hybrid immunity” (prior COVID‐19 infection plus vaccination) and post‐vaccination immunity to SARS CoV‐2 in MS patients on different disease‐modifying therapies (DMTs) and to assess the impact of vaccine product and race/ethnicity on post‐vaccination immune responses. Methods Consecutive MS patients from NYU MS Care Center (New York, NY), aged 18–60, who completed primary COVID‐19 vaccination series ≥6 weeks previously were evaluated for SARS CoV‐2‐specific antibody responses with electro‐chemiluminescence and multiepitope bead‐based immunoassays and, in a subset, live virus immunofluorescence‐based microneutralization assay. SARS CoV‐2‐specific cellular responses were assessed with cellular stimulation TruCulture IFNγ and IL‐2 assay and, in a subset, with IFNγ and IL‐2 ELISpot assays. Multivariate analyses examined associations between immunologic responses and prior COVID‐19 infection while controlling for age, sex, DMT at vaccination, time‐to‐vaccine, and vaccine product. Results Between 6/01/2021 and 11/11/2021, 370 MS patients were recruited (mean age 40.6 years; 76% female; 53% non‐White; 22% with prior infection; common DMT classes: ocrelizumab 40%; natalizumab 15%, sphingosine‐1‐phosphate receptor modulators 13%; and no DMT 8%). Vaccine‐to‐collection time was 18.7 (±7.7) weeks and 95% of patients received mRNA vaccines. In multivariate analyses, patients with laboratory‐confirmed prior COVID‐19 infection had significantly increased antibody and cellular post‐vaccination responses compared to those without prior infection. Vaccine product and DMT class were independent predictors of antibody and cellular responses, while race/ethnicity was not. Interpretation Prior COVID‐19 infection is associated with enhanced antibody and cellular post‐vaccine responses independent of DMT class and vaccine type. There were no differences in immune responses across race/ethnic groups.

Abstract Accurate and precise density estimates are crucial for effective species management and conservation. However, efficient monitoring of mammal densities over large spatial and temporal scales is challenging. In the United Kingdom, published density estimates for many mammals, including species considered to be common, are imprecise. Camera trap distance sampling (CTDS) can estimate densities of multiple species at a time and has been used successfully in a small number of studies. However, CTDS has typically been used over relatively homogeneous landscapes, often over large time scales, making monitoring changes (by repeating surveys) difficult. In this study, we deployed camera traps at 109 sites across an area of 2725 km2 of varied habitat in North‐East England, United Kingdom. The 4‐month survey generated 51 447 photos of wild mammal species. Data were sufficient for us to use CTDS to estimate the densities of eight mammal species across the whole‐survey area and within four specific habitats. Both survey‐wide and habitat‐specific density estimates largely fell within previously published density ranges and our estimates were amongst the most precise produced for these species to date. Lower precision for some species was typically due to animals being missed by the camera at certain distances, highlighting the need for careful consideration of practical and methodological decisions, such as how high to set cameras and where to left‐truncate data. Although CTDS is a promising methodology for determining densities of multiple species from one survey, species‐specific decisions are still required and these cannot always be generalized across species types and locations. Taking the United Kingdom as a case study, our study highlights the potential for CTDS to be used on a national scale, although the scale of the task suggests that it would need to be integrated with a citizen science approach.

Abstract Aims Exercise training (ET) has been consistently shown to increase peak oxygen consumption (V̇O2) in patients with heart failure with preserved ejection fraction (HFpEF); however, inter‐individual responses vary significantly. Because it is unlikely that ET‐induced improvements in peak V̇O2 are significantly mediated by an increase in peak heart rate (HR), we aimed to investigate whether baseline peak O2‐pulse (V̇O2 × HR−1, reflecting the product of stroke volume and arteriovenous oxygen difference), not baseline peak V̇O2, is inversely associated with the change in peak V̇O2 (adjusted by body weight) following ET versus guideline control (CON) in patients with HFpEF. Methods and results This was a secondary analysis of the OptimEx‐Clin (Optimizing Exercise Training in Prevention and Treatment of Diastolic Heart Failure, NCT02078947) trial, including all 158 patients with complete baseline and 3 month cardiopulmonary exercise testing measurements (106 ET, 52 CON). Change in peak V̇O2 (%) was analysed as a function of baseline peak V̇O2 and its determinants (absolute peak V̇O2, peak O2‐pulse, peak HR, weight, haemoglobin) using robust linear regression analyses. Mediating effects on change in peak V̇O2 through changes in peak O2‐pulse, peak HR and weight were analysed by a causal mediation analysis with multiple correlated mediators. Change in submaximal exercise tolerance (V̇O2 at the ventilatory threshold, VT1) was analysed as a secondary endpoint. Among 158 patients with HFpEF (66% female; mean age, 70 ± 8 years), changes in peak O2‐pulse explained approximately 72% of the difference in changes in peak V̇O2 between ET and CON [10.0% (95% CI, 4.1 to 15.9), P = 0.001]. There was a significant interaction between the groups for the influence of baseline peak O2‐pulse on change in peak V̇O2 (interaction P = 0.04). In the ET group, every 1 mL/beat higher baseline peak O2‐pulse was associated with a decreased mean change in peak V̇O2 of −1.45% (95% CI, −2.30 to −0.60, P = 0.001) compared with a mean change of −0.08% (95% CI, −1.11 to 0.96, P = 0.88) following CON. None of the other factors showed significant interactions with study groups for the change in peak V̇O2 (P > 0.05). Change in V̇O2 at VT1 was not associated with any of the investigated factors (P > 0.05). Conclusions In patients with HFpEF, the easily measurable peak O2‐pulse seems to be a good indicator of the potential for improving peak V̇O2 through exercise training. While changes in submaximal exercise tolerance were independent of baseline peak O2‐pulse, patients with high O2‐pulse may need to use additional therapies to significantly increase peak V̇O2.

Abstract Digital health technology is receiving increasing attention in cardiology. The rise of accessibility of digital health tools including wearable technologies and smart phone applications used in medical practice has created a new era in healthcare. The coronavirus pandemic has provided a new impetus for changes in delivering medical assistance across the world. This Consensus document discusses the potential implementation of digital health technology in older adults, suggesting a practical approach to general cardiologists working in an ambulatory outpatient clinic, highlighting the potential benefit and challenges of digital health in older patients with, or at risk of, cardiovascular disease. Advancing age may lead to a progressive loss of independence, to frailty, and to increasing degrees of disability. In geriatric cardiology, digital health technology may serve as an additional tool both in cardiovascular prevention and treatment that may help by (i) supporting self‐caring patients with cardiovascular disease to maintain their independence and improve the management of their cardiovascular disease and (ii) improving the prevention, detection, and management of frailty and supporting collaboration with caregivers. Digital health technology has the potential to be useful for every field of cardiology, but notably in an office‐based setting with frequent contact with ambulatory older adults who may be pre‐frail or frail but who are still able to live at home. Cardiologists and other healthcare professionals should increase their digital health skills and learn how best to apply and integrate new technologies into daily practice and how to engage older people and their caregivers in a tailored programme of care.

Abstract Background and Aims Low back pain (LBP) is one of the most debilitating and prevalent disorders. The prevalence of LBP ranges from 30% to 80%, depending on the population, and increases with age. Causes of LBP are typically classified as spinal and non‐spinal. The main goal of this study was to investigate the non‐spinal causes of LBP, since neglecting these factors leads to increases in the financial, psychological, and physical burden of LBP on individuals as well as on society. Methods The data were extracted after searching the PubMed database and Google Scholar search engine up to October 27, 2021. We included all studies that were conducted on a human population and assessed the effects of epidemiological, biological, psychological, and sociodemographic factors on the incidence or progression of LBP. Results The most common causes of non‐spinal LBP were diseases such as nephrolithiasis, endometriosis, tumors, fibromyalgia, and conditions like psychological disorders and pregnancy. Nevertheless, the perceived intensity of the pain can be affected by factors such as socioeconomic level, genetics, age, habits, diet, and psychological status. Conclusion The epidemiology, etiologies, and risk factors associated with LBP should be more clearly recognized to better prevent, diagnose, and treat the underlying disease and to reduce the burden of LBP.

Background Among patients with an implantable cardioverter‐defibrillator, a high prevalence of atrial fibrillation (AF) is present. Identification of AF predictors in this patient group is of clinical importance to initiate appropriate preventive therapeutic measures to reduce the risk of AF‐related complications. This study assesses whether cardiac magnetic resonance imaging–derived atrial characteristics are associated with AF development in patients with a dual‐chamber implantable cardioverter‐defibrillator or cardiac resynchronization therapy defibrillator, as detected by the cardiac implantable electronic device. Methods and Results This single‐center retrospective study included 233 patients without documented AF history at the moment of device implantation (dual‐chamber implantable cardioverter‐defibrillator [63.5%] or cardiac resynchronization therapy defibrillator [36.5%]). All patients underwent cardiac magnetic resonance imaging before device implantation. Cardiac magnetic resonance–derived features of left atrial (LA) remodeling were evaluated in all patients. Detection of AF episodes was based on cardiac implantable electronic device interrogation. During a median follow‐up of 6.1 years, a newly diagnosed AF episode was detected in 88 of the 233 (37.8%) patients with an ICD. In these patients, increased LA volumes and impaired LA function (LA emptying fraction and LA strain) were found as compared with patients without AF during follow‐up. However, a significant association was only found in patients with dilated cardiomyopathy and not in patients with ischemic cardiomyopathy. Conclusions LA remodeling characteristics were associated with development of AF in patients with dilated cardiomyopathy but not patients with ischemic cardiomyopathy, suggesting different mechanisms of AF development in ischemic cardiomyopathy and dilated cardiomyopathy. Assessment of LA remodeling before device implantation might identify high‐risk patients for AF.