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Background and objectivePatients suspected to have lung cancer, undergo endobronchial ultrasound bronchoscopy (EBUS) for the purpose of diagnosis and staging. For presumptive curable patients, the EBUS bronchoscopy is planned based on images and data from computed tomography (CT) images and positron emission tomography (PET). Our study aimed to evaluate the feasibility of a multimodal electromagnetic navigation platform for EBUS bronchoscopy, integrating ultrasound and segmented CT, and PET scan imaging data.MethodsThe proof-of-concept study included patients with suspected lung cancer and pathological mediastinal/hilar lymph nodes identified on both CT and PET scans. Images obtained from these two modalities were segmented to delineate target lymph nodes and then incorporated into the CustusX navigation platform. The EBUS bronchoscope was equipped with a sensor, calibrated, and affixed to a 3D printed click-on device positioned at the bronchoscope's tip. Navigation accuracy was measured postoperatively using ultrasound recordings.ResultsThe study enrolled three patients, all presenting with suspected mediastinal lymph node metastasis (N1-3). All PET-positive lymph nodes were displayed in the navigation platform during the EBUS procedures. In total, five distinct lymph nodes were sampled, yielding malignant cells from three nodes and lymphocytes from the remaining two. The median accuracy of the navigation system was 7.7 mm.ConclusionOur study introduces a feasible multimodal electromagnetic navigation platform that combines intraoperative ultrasound with preoperative segmented CT and PET imaging data for EBUS lymph node staging examinations. This innovative approach holds promise for enhancing the accuracy and effectiveness of EBUS procedures.

Questionable research practices (QRP) are believed to be widespread, but empirical assessments are generally restricted to a few types of practices. Furthermore, conceptual confusion is rife with use and prevalence of QRPs often being confused as the same quantity. We present the hitherto most comprehensive study examining QRPs across scholarly fields and knowledge production modes. We survey perception, use, prevalence and predictors of QRPs among 3,402 researchers in Denmark and 1,307 in the UK, USA, Croatia and Austria. Results reveal remarkably similar response patterns among Danish and international respondents (τ = 0.85). Self-reported use indicates whether respondents have used a QRP in recent publications. 9 out of 10 respondents admitted using at least one QRP. Median use is three out of nine QRP items. Self-reported prevalence reflects the frequency of use. On average, prevalence rates were roughly three times lower compared to self-reported use. Findings indicated that the perceived social acceptability of QRPs influenced self-report patterns. Results suggest that most researchers use different types of QRPs within a restricted time period. The prevalence estimates, however, do not suggest outright systematic use of specific QRPs. Perceived pressure was the strongest systemic predictor for prevalence. Conversely, more local attention to research cultures and academic age was negatively related to prevalence. Finally, the personality traits conscientiousness and, to a lesser degree, agreeableness were also inversely associated with self-reported prevalence. Findings suggest that explanations for engagement with QRPs are not only attributable to systemic factors, as hitherto suggested, but a complicated mixture of experience, systemic and individual factors, and motivated reasoning.

[This corrects the article DOI: 10.1371/journal.pone.0284496.].

IntroductionImmune dysregulation with an excessive release of cytokines has been identified as a key driver in the development of severe COVID-19. The aim of this study was to evaluate the initial cytokine profile associated with 90-day mortality and respiratory failure in a cohort of patients hospitalized with COVID 19 that did not receive immunomodulatory therapy.MethodsLevels of 45 cytokines were measured in blood samples obtained at admission from patients with confirmed COVID-19. Logistic regression analysis was utilized to determine the association between cytokine levels and outcomes. The primary outcome was death within 90 days from admission and the secondary outcome was need for mechanical ventilation.ResultsA total of 132 patients were included during the spring of 2020. We found that one anti-inflammatory cytokine, one pro-inflammatory cytokine, and five chemokines were associated with the odds of 90-day mortality, specifically: interleukin-1 receptor antagonist, interleukin-6, interleukin-8, monocyte chemoattractant protein-1, macrophage inflammatory protein-3α, macrophage inflammatory protein-3β, and fractalkine. All but fractalkine were also associated with the odds of respiratory failure during admission. Monocyte chemoattractant protein-1 showed the strongest estimate of association with both outcomes.ConclusionWe showed that one anti-inflammatory cytokine, one pro-inflammatory cytokine, and five chemokines were associated with 90-day mortality in patients hospitalized with COVID-19 that did not receive immunomodulatory therapy.

Advanced optical neuromonitoring of cerebral hemodynamics with hybrid diffuse optical spectroscopy (DOS) and diffuse correlation spectroscopy (DCS) methods holds promise for non-invasive characterization of brain health in critically ill patients. However, the methods' fiber-coupled patient interfaces (probes) are challenging to apply in emergent clinical scenarios that require rapid and reproducible attachment to the head. To address this challenge, we developed a novel chassis-based optical probe design for DOS/DCS measurements and validated its measurement accuracy and reproducibility against conventional, manually held measurements of cerebral hemodynamics in pediatric swine (n = 20). The chassis-based probe design comprises a detachable fiber housing which snaps into a 3D-printed, circumferential chassis piece that is secured to the skin. To validate its reproducibility, eight measurement repetitions of cerebral tissue blood flow index (BFI), oxygen saturation (StO2), and oxy-, deoxy- and total hemoglobin concentration were acquired at the same demarcated measurement location for each pig. The probe was detached after each measurement. Of the eight measurements, four were acquired by placing the probe into a secured chassis, and four were visually aligned and manually held. We compared the absolute value and intra-subject coefficient of variation (CV) of chassis versus manual measurements. No significant differences were observed in either absolute value or CV between chassis and manual measurements (p > 0.05). However, the CV for BFI (mean ± SD: manual, 19.5% ± 9.6; chassis, 19.0% ± 10.8) was significantly higher than StO2 (manual, 5.8% ± 6.7; chassis, 6.6% ± 7.1) regardless of measurement methodology (p

BackgroundNeck pain remains a persistent challenge in modern society and is frequently encountered across a wide range of occupations, particularly those involving repetitive and monotonous tasks. It might be expected that patterns of trapezius muscle activity at work, characterized by few breaks and prolonged periods of sustained muscle activity, are linked to neck pain. However, previous cross-sectional studies have generally failed to establish a definitive association. While some longitudinal studies have suggested that extended periods of heightened muscle activity could be a risk factor for neck pain, these findings often relied on limited participant numbers or specific professional groups. This study aimed to investigate the relationship between trapezius muscle activity and neck pain by pooling data from seven Scandinavian research institutes encompassing a diverse range of occupational backgrounds.MethodsElectromyographic (EMG) data for the upper trapezius muscle, collected during working hours, were coupled with questionnaire responses pertaining to neck pain, individual characteristics, and potential confounding variables for a total of 731 subjects. Additionally, longitudinal data from 258 subjects were available. The various EMG datasets were consolidated into a standardized format, and efforts were made to harmonize inquiries about neck pain. Regression analyses, adjusting for sex and height, were conducted to explore the associations between muscle activity variables and neck pain. An exposure index was devised to quantify the cumulative neck load experienced during working hours and to differentiate between various occupational categories.ResultsThe cross-sectional data displayed a distinct pattern characterized by positive associations for brief periods of sustained muscle activity (SUMA) and negative associations for prolonged SUMA-periods and neck pain. The longitudinal data exhibited a contrasting trend, although it was not as pronounced as the cross-sectional findings. When employing the exposure index, notable differences in cumulative muscle load emerged among occupational groups, and positive associations with longitudinal neck pain were identified.DiscussionThe results suggest that individuals with neck pain experience higher cumulative workloads and extended periods of muscle activity over the long term. In the short term, they appear to compensate by taking frequent short breaks, resulting in a lower cumulative workload. Regardless of their occupation, it is crucial to distribute work breaks throughout the workday to ensure that the cumulative load remains manageable.

BackgroundDanish women-who were HPV-vaccinated as girls-are now reaching an age where they are invited to cervical cancer screening. Because of their expected lower cervical cancer risk, we must reassess our screening strategies. We analyzed Danish HPV-vaccinated women's outcomes after the first screening test at age 23.Methods and findingsOur study was embedded in Danish routine cytology-based screening. We conducted an observational study and included women born in 1994, offered the 4-valent HPV vaccine at age 14, and subsequently invited to screening at age 23. Cervical cytology was used for diagnostics and clinical management. Residual material was HPV tested with Cobas® 4800/6800. The most severe histology diagnosis within 795 days of screening was found through linkage with the Danish National Pathology Register. We calculated the number of women undergoing follow-up (repeated testing and/or colposcopy) per detected cervical intraepithelial neoplasia (CIN2+). A total of 6021 women were screened; 92% were HPV-vaccinated; 12% had abnormal cytology; 35% were high-risk HPV-positive, including 0.9% HPV16/18 positive, and 20% had follow-up. In women that were cytology-abnormal and HPV-positive (Cyt+/HPV+), 610 (98.5%) had been followed up, and 138 CIN2+ cases were diagnosed, resulting in 4.4 (95% CI 3.9-5.2) women undergoing follow-up per detected CIN2+. In contrast to recommendations, 182 (12.2%) cytology-normal and HPV-positive (Cyt-/HPV+) women were followed up within 795 days, and 8 CIN2+ cases were found, resulting in 22.8 (95% CI 13.3-59.3) women undergoing follow-up per detected CIN2+.ConclusionOverall, HPV prevalence was high in HPV-vaccinated women, but HPV16/18 had largely disappeared. In the large group of cytology-normal and HPV-positive women, 23 had been followed up per detected CIN2+ case. Our data indicated that primary HPV screening of young HPV-vaccinated women would require very effective triage methods to avoid an excessive follow-up burden.Trial registrationTrial registration number: NCT0304955.

BackgroundFour-weekly intramuscular (IM) benzathine penicillin G (BPG) injections to prevent acute rheumatic fever (ARF) progression have remained unchanged since 1955. A Phase-I trial in healthy volunteers demonstrated the safety and tolerability of high-dose subcutaneous infusions of BPG which resulted in a much longer effective penicillin exposure, and fewer injections. Here we describe the experiences of young people living with ARF participating in a Phase-II trial of SubCutaneous Injections of BPG (SCIP).MethodologyParticipants (n = 20) attended a clinic in Wellington, New Zealand (NZ). After a physical examination, participants received 2% lignocaine followed by 13.8mL to 20.7mL of BPG (Bicillin-LA®; determined by weight), into the abdominal subcutaneous tissue. A Kaupapa Māori consistent methodology was used to explore experiences of SCIP, through semi-structured interviews and observations taken during/after the injection, and on days 28 and 70. All interviews were recorded, transcribed verbatim, and thematically analysed.Principal findingsLow levels of pain were reported on needle insertion, during and following the injection. Some participants experienced discomfort and bruising on days one and two post dose; however, the pain was reported to be less severe than their usual IM BPG. Participants were 'relieved' to only need injections quarterly and the majority (95%) reported a preference for SCIP over IM BPG.ConclusionsParticipants preferred SCIP over their usual regimen, reporting less pain and a preference for the longer time gap between treatments. Recommending SCIP as standard of care for most patients needing long-term prophylaxis has the potential to transform secondary prophylaxis of ARF/RHD in NZ and globally.

The continued development in methylome analysis has enabled a more precise assessment of DNA methylation, but treatment of target tissue prior to analysis may affect DNA analysis. Prediction of age based on methylation levels in the genome (DNAmAge) has gained much interest in disease predisposition (biological age estimation), but also in chronological donor age estimation in crime case samples. Various epigenetic clocks were designed to predict the age. However, it remains unknown how the storage of the tissues affects the DNAmAge estimation. In this study, we investigated the storage method impact of DNAmAge by the comparing the DNAmAge of the two commonly used storage methods, freezing and formalin-fixation and paraffin-embedding (FFPE) to DNAmAge of fresh tissue. This was carried out by comparing paired heart tissue samples of fresh tissue, samples stored by freezing and FFPE to chronological age and whole blood samples from the same individuals. Illumina EPIC beadchip array was used for methylation analysis and the DNAmAge was evaluated with the following epigenetic clocks: Horvath, Hannum, Levine, Horvath skin+blood clock (Horvath2), PedBE, Wu, BLUP, EN, and TL. We observed differences in DNAmAge among the storage conditions. FFPE samples showed a lower DNAmAge compared to that of frozen and fresh samples. Additionally, the DNAmAge of the heart tissue was lower than that of the whole blood and the chronological age. This highlights caution when evaluating DNAmAge for FFPE samples as the results were underestimated compared with fresh and frozen tissue samples. Furthermore, the study also emphasizes the need for a DNAmAge model based on heart tissue samples for an accurate age estimation.

ObjectiveTo create a data-driven definition of post-COVID conditions (PCC) by directly measure changes in symptomatology before and after a first COVID episode.Materials and methodsRetrospective cohort study using Optum® de-identified Electronic Health Record (EHR) dataset from the United States of persons of any age April 2020-September 2021. For each person with COVID (ICD-10-CM U07.1 "COVID-19" or positive test result), we selected up to 3 comparators. The final COVID symptom score was computed as the sum of new diagnoses weighted by each diagnosis' ratio of incidence in COVID group relative to comparator group. For the subset of COVID cases diagnosed in September 2021, we compared the incidence of PCC using our data-driven definition with ICD-10-CM code U09.9 "Post-COVID Conditions", first available in the US October 2021.ResultsThe final cohort contained 588,611 people with COVID, with mean age of 48 years and 38% male. Our definition identified 20% of persons developed PCC in follow-up. PCC incidence increased with age: (7.8% of persons aged 0-17, 17.3% aged 18-64, and 33.3% aged 65+) and did not change over time (20.0% among persons diagnosed with COVID in 2020 versus 20.3% in 2021). For cases diagnosed in September 2021, our definition identified 19.0% with PCC in follow-up as compared to 2.9% with U09.9 code in follow-up.ConclusionSymptom and U09.9 code-based definitions alone captured different populations. Maximal capture may consider a combined approach, particularly before the availability and routine utilization of specific ICD-10 codes and with the lack consensus-based definitions on the syndrome.

The ADP-ribosylation factors (Arfs) constitute a family of small GTPases within the Ras superfamily, with a distinguishing structural feature of a hypervariable N-terminal extension of the G domain modified with myristate. Arf proteins, including Arf1, have roles in membrane trafficking and cytoskeletal dynamics. While screening for Arf1:small molecule co-crystals, we serendipitously solved the crystal structure of the non-myristoylated engineered mutation [L8K]Arf1 in complex with a GDP analogue. Like wild-type (WT) non-myristoylated Arf1•GDP, we observed that [L8K]Arf1 exhibited an N-terminal helix that occludes the hydrophobic cavity that is occupied by the myristoyl group in the GDP-bound state of the native protein. However, the helices were offset from one another due to the L8K mutation, with a significant change in position of the hinge region connecting the N-terminus to the G domain. Hypothesizing that the observed effects on behavior of the N-terminus affects interaction with regulatory proteins, we mutated two hydrophobic residues to examine the role of the N-terminal extension for interaction with guanine nucleotide exchange factors (GEFs) and GTPase Activating Proteins (GAPs. Different than previous studies, all mutations were examined in the context of myristoylated Arf. Mutations had little or no effect on spontaneous or GEF-catalyzed guanine nucleotide exchange but did affect interaction with GAPs. [F13A]myrArf1 was less than 1/2500, 1/1500, and 1/200 efficient as substrate for the GAPs ASAP1, ARAP1 and AGAP1; however, [L8A/F13A]myrArf1 was similar to WT myrArf1. Using molecular dynamics simulations, the effect of the mutations on forming alpha helices adjacent to a membrane surface was examined, yet no differences were detected. The results indicate that lipid modifications of GTPases and consequent anchoring to a membrane influences protein function beyond simple membrane localization. Hypothetical mechanisms are discussed.

Drought and heat are two stresses that often occur together and may pose significant risks to crops in future climates. However, the combined effects of these two stressors have received less attention than single-stressor investigations. This study used a rapid and straightforward phenotyping method to quantify the variation in 128 African eggplant genotype responses to drought, heat, and the combined effects of heat and drought at the seedling stage. The study found that the morphophysiological traits varied significantly among the 128 eggplants, highlighting variation in response to abiotic stresses. Broad-sense heritability was high (> 0.60) for chlorophyll content, plant biomass and performance index, electrolyte leakage, and total leaf area. Positive and significant relationships existed between biomass and photosynthetic parameters, but a negative association existed between electrolyte leakage and morpho-physiological traits. The plants underwent more significant stress when drought and heat stress were imposed concurrently than under single stresses, with the impact of drought on the plants being more detrimental than heat. There were antagonistic effects on the morphophysiology of the eggplants when heat and drought stress were applied together. Resilient genotypes such as RV100503, RV100501, JAMBA, LOC3, RV100164, RV100169, LOC 3, RV100483, GH5155, RV100430, GH1087, GH1087*, RV100388, RV100387, RV100391 maintained high relative water content, low electrolyte leakage, high Fv/Fm ratio and performance index, and increased biomass production under abiotic stress conditions. The antagonistic interactions between heat and drought observed here may be retained or enhanced during several stress combinations typical of plants' environments and must be factored into efforts to develop climate change-resilient crops. This paper demonstrates improvised climate chambers for high throughput, reliable, rapid, and cost-effective screening for heat and drought and combined stress tolerance in plants.

BackgroundStress during pregnancy is detrimental to maternal health, pregnancy and birth outcomes and various preventive relaxation interventions have been developed. This systematic review and meta-analysis aimed to evaluate their effectiveness in terms of maternal mental health, pregnancy and birth outcomes.MethodThe protocol for this review is published on PROSPERO with registration number CRD42020187443. A systematic search of major databases was conducted. Primary outcomes were maternal mental health problems (stress, anxiety, depression), and pregnancy (gestational age, labour duration, delivery mode) and birth outcomes (birth weight, Apgar score, preterm birth). Randomized controlled trials or quasi-experimental studies were eligible. Meta-analyses using a random-effects model was conducted for outcomes with sufficient data. For other outcomes a narrative review was undertaken.ResultWe reviewed 32 studies comprising 3,979 pregnant women aged 18 to 40 years. Relaxation interventions included yoga, music, Benson relaxation, progressive muscle relaxation (PMR), deep breathing relaxation (BR), guided imagery, mindfulness and hypnosis. Intervention duration ranged from brief experiment (~10 minutes) to 6 months of daily relaxation. Meta-analyses showed relaxation therapy reduced maternal stress (-4.1 points; 95% Confidence Interval (CI): -7.4, -0.9; 9 trials; 1113 participants), anxiety (-5.04 points; 95% CI: -8.2, -1.9; 10 trials; 1965 participants) and depressive symptoms (-2.3 points; 95% CI: -3.4, -1.3; 7 trials; 733 participants). Relaxation has also increased offspring birth weight (80 g, 95% CI: 1, 157; 8 trials; 1239 participants), explained by PMR (165g, 95% CI: 100, 231; 4 trials; 587 participants) in sub-group analysis. In five trials evaluating maternal physiological responses, relaxation therapy optimized blood pressure, heart rate and respiratory rate. Four trials showed relaxation therapy reduced duration of labour. Apgar score only improved significantly in two of six trials. One of three trials showed a significant increase in birth length, and one of three trials showed a significant increase in gestational age. Two of six trials examining delivery mode showed significantly increased spontaneous vaginal delivery and decreased instrumental delivery or cesarean section following a relaxation intervention.DiscussionWe found consistent evidence for beneficial effects of relaxation interventions in reducing maternal stress, improving mental health, and some evidence for improved maternal physiological outcomes. In addition, we found a positive effect of relaxation interventions on birth weight and inconsistent effects on other pregnancy or birth outcomes. High quality adequately powered trials are needed to examine impacts of relaxation interventions on newborns and offspring health outcomes.ConclusionIn addition to benefits for mothers, relaxation interventions provided during pregnancy improved birth weight and hold some promise for improving newborn outcomes; therefore, this approach strongly merits further research.

ObjectivesQuantitative sensory testing (QST) provides an assessment of cutaneous and deep tissue sensitivity and pain perception under normal and pathological settings. Approximately 2-4% of individuals undergoing groin hernia repair (GHR) develop severe persistent postsurgical pain (PPSP). The aims of this systematic review of PPSP-patients were (1) to retrieve and methodologically characterize the available QST literature and (2) to explore the role of QST in understanding mechanisms underlying PPSP following GHR.MethodsA systematic literature search was conducted from JAN-1992 to SEP-2022 in PubMed, EMBASE, and Google Scholar. For inclusion, studies had to report at least one QST-modality in patients with PPSP. Risk of bias assessment of the studies was conducted utilizing the Newcastle Ottawa Scale and Cochrane's Risk of Bias assessment tool 2.0. The review provided both a qualitative and quantitative analysis of the results. A random effects model was used for meta-analysis.ResultsTwenty-five studies were included (5 randomized controlled trials, 20 non-randomized controlled trials). Overall, risk of bias was low. Compared with the contralateral side or controls, there were significant alterations in somatosensory function of the surgical site in PPSP-patients. Following thresholds were significantly increased: mechanical detection thresholds for punctate stimuli (mean difference (95% CI) 3.3 (1.6, 6.9) mN (P = 0.002)), warmth detection thresholds (3.2 (1.6, 4.7) °C (P = 0.0001)), cool detection thresholds (-3.2 (-4.9, -1.6) °C (P = 0.0001)), and heat pain thresholds (1.9 (1.1, 2.7) °C (P = 0.00001)). However, the pressure pain thresholds were significantly decreased (-76 (-123, -30) kPa (P = 0.001)).ConclusionOur review demonstrates a plethora of methods used regarding outcome assessments, data processing, and data interpretation. From a pathophysiological perspective, the most consistent findings were postsurgical cutaneous deafferentation and development of a pain generator in deeper connective tissues.Trial registrationCRD42022331750.

Background and objectiveTreatments of lymphoma can lead to reduced physical functioning, cancer-related fatigue, depression, anxiety, and insomnia. These side effects can negatively impact the cancer survivor's quality of life. Mounting evidence indicates that physical activities are highly therapeutic in mitigating the short- and long-term side effects of cancer treatments. Yet, lymphoma survivors' participation in physical activities remains suboptimal, which has been further exacerbated by the deleterious effects of isolation during the COVID-19 pandemic. The Lymfit intervention aims to offer motivational support, expert guidance, and a personalized exercise prescription to optimize physical activities among lymphoma survivors. This proof-of-concept study explores implementation feasibility (retention, technical and safety), and the preliminary effects of Lymfit on various health outcomes.MethodThis was a single-armed trial with a pre-and post-test design. Twenty lymphoma survivors were recruited to participate in the 12-week Lymfit intervention. Wearable activity trackers (Fitbit) were given to participants as a motivational tool and for data collection purposes. Participants received a personalized exercise prescription designed by a kinesiologist. Physiologic metrics were collected by the Fitbit monitors and were stored in the Lymfit database. Self-reported questionnaires measuring health outcomes were collected at baseline and post-intervention.ResultsThe retention rate of this trial was 70%. Minimal technical issues and no adverse effects were reported. Lymfit led to significant improvements in sleep disturbances and the ability to participate in social activities and decreased fear of cancer recurrence. It also increased daily steps and decreased sedentary time in participants who did not meet the recommended physical activity guidelines.SignificanceWith access to resources and fitness centers being limited during the pandemic, the Lymfit intervention filled an immediate need to provide physical activity guidance to lymphoma survivors. Findings provide preliminary support that implementing the Lymfit intervention is feasible and demonstrated promising results.

IntroductionBehavioural and psychological symptoms of dementia (BPSD) should only rarely and briefly be treated with antipsychotics. Despite recommendations to the contrary, the use of antipsychotics in nursing home residents with dementia is widespread and followed by serious adverse effects. Intervention studies on methods to reduce the use of antipsychotics in persons with dementia are few and needed. The aim of this protocol is to describe the rationale and content of the intervention DEprescribing and Care to reduce Antipsychotics in DEmentia (DECADE)-a hybrid effectiveness-implementation pilot study.Materials and methodsThis is a protocol of a prospective hybrid effectiveness-implementation pilot study. The primary aim of DECADE is to reduce the use of antipsychotic drugs by 50% in 50% of nursing home residents with dementia while maintaining or improving BPSD. The intervention is implemented in six nursing homes including approximately 190 residents with dementia and consists of Academic Detailing, medication review, education of nursing home staff, and care plans. The evaluation of feasibility and potential effectiveness is an overall assessment of all clinical and process outcomes. Logistic regression analyses will be used to investigate factors characterizing situations with prescription of antipsychotics. BPSD is analysed with a before- and after design using self-controlled case series methods and the use of antipsychotics is analysed as interrupted time series.DiscussionThis protocol describes a study that will provide an indication of DECADE effectiveness and a model for upscaling and further evaluation in a controlled design.

It has been argued that persons with severe mental illness (SMI) receive poorer treatment for somatic comorbidities. This study assesses the treatment rates of glucose-lowering and cardiovascular medications among persons with incident type 2 diabetes (T2D) and SMI compared to persons with T2D without SMI. We identified persons ≥30 years old with incident diabetes (HbA1c ≥ 48 mmol/mol and/or glucose ≥ 11.0 mmol/L) from 2001 through 2015 in the Copenhagen Primary Care Laboratory (CopLab) Database. The SMI group included persons with psychotic, affective, or personality disorders within five years preceding the T2D diagnosis. Using a Poisson regression model, we calculated the adjusted rate ratios (aRR) for the redemption of various glucose-lowering and cardiovascular medications up to ten years after T2D diagnosis. We identified 1,316 persons with T2D and SMI and 41,538 persons with T2D but no SMI. Despite similar glycemic control at diagnosis, persons with SMI redeemed a glucose-lowering medication more often than persons without SMI in the period 0.5-2 years after the T2D diagnosis; for example, the aRR was 1.05 (95% CI 1.00-1.11) in the period 1.5-2 years after the T2D diagnosis. This difference was mainly driven by metformin. In contrast, persons with SMI were less often treated with cardiovascular medications during the first 3 years after T2D diagnosis, e.g., in the period 1.5-2 years after T2D diagnosis, the aRR was 0.96 (95% CI 0.92-0.99). For people with SMI in addition to T2D, metformin is more likely to be used in the initial years after T2D diagnosis, while our results suggest potential room for improvement regarding the use of cardiovascular medications.

Anthelmintic drugs are used to treat parasitic roundworm and flatworm infections in humans and other animals. Caenorhabditis elegans is an established model to investigate anthelmintics used to treat roundworms. In this study, we use C. elegans to examine the mode of action and the mechanisms of resistance against the flatworm anthelmintic drug praziquantel (PZQ), used to treat trematode and cestode infections. We found that PZQ inhibited development and that this developmental delay varies by genetic background. Interestingly, both enantiomers of PZQ are equally effective against C. elegans, but the right-handed PZQ (R-PZQ) is most effective against schistosome infections. We conducted a genome-wide association mapping with 74 wild C. elegans strains to identify a region on chromosome IV that is correlated with differential PZQ susceptibility. Five candidate genes in this region: cct-8, znf-782, Y104H12D.4, Y104H12D.2, and cox-18, might underlie this variation. The gene cct-8, a subunit of the protein folding complex TRiC, has variation that causes a putative protein coding change (G226V), which is correlated with reduced developmental delay. Gene expression analysis suggests that this variant correlates with slightly increased expression of both cct-8 and hsp-70. Acute exposure to PZQ caused increased expression of hsp-70, indicating that altered TRiC function might be involved in PZQ responses. To test if this variant affects development upon exposure to PZQ, we used CRISPR-Cas9 genome editing to introduce the V226 allele into the N2 genetic background (G226) and the G226 allele into the JU775 genetic background (V226). These experiments revealed that this variant was not sufficient to explain the effects of PZQ on development. Nevertheless, this study shows that C. elegans can be used to study PZQ mode of action and resistance mechanisms. Additionally, we show that the TRiC complex requires further evaluation for PZQ responses in C. elegans.

The Mekong River provides water, food security, and many other valuable benefits to the more than 60 million Southeast Asian residents living within its basin. However, the Mekong River Basin is increasingly stressed by changes in climate, land cover, and infrastructure. These changes can affect water quantity and quality and exacerbate related hazards such as land subsidence and saltwater intrusion, resulting in multiple compounding risks for neighboring communities. In this study, we demonstrate the connection between climate change, groundwater availability, and social vulnerability by linking the results of a numerical groundwater model to land cover and socioeconomic data at the Cambodia-Vietnam border in the Mekong River Delta region. We simulated changes in groundwater availability across 20 years and identified areas of potential water stress based on domestic and agriculture-related freshwater demands. We then assessed adaptive capacity to understand how communities may be able to respond to this stress to better understand the growing risk of groundwater scarcity driven by climate change and overextraction. This study offers a novel approach for assessing risk of groundwater scarcity by linking the effects of climate change to the socioeconomic context in which they occur. Increasing our understanding of how changes in groundwater availability may affect local populations can help water managers better plan for the future, leading to more resilient communities.

Introduction Racial disparities in breast cancer treatment contribute to Black women having the worst breast cancer survival rates in the U.S. We investigated whether differences in receipt of optimal locoregional treatment (OLT), defined as receipt of mastectomy, breast-conserving surgery, or no surgery when contraindicated, existed between Black and White women with early-stage breast cancer from 2008–2018. Methods In this retrospective cohort study, data from the Surveillance, Epidemiology, and End Results (SEER) Program Incidence Database was utilized to identify tumor cases from Black and White women aged 20–64 years old with stage I-II breast cancer. Logistic regression analyses were used to evaluate the associations between race and receipt of OLT as well as potential effect modification by tumor characteristics, and year of diagnosis. Results Among 177,234 women diagnosed with early-stage breast tumors, disparities in OLT between Black and White women were present from 2008–2010 (2008: 82.1% Black vs. 85.7% White, pConclusion Increased receipt of radiation therapy with breast-conserving surgery appeared to drive a substantial increase in OLT for Black women from 2010–2011 that lasted throughout the study period. Further research on the underlying mechanisms that reduced this disparity is warranted.

IntroductionGeriatric co-management is known to improve treatment of older adults in various clinical settings, however, widespread application of the concept is limited due to restricted resources. Digitalization may offer options to overcome these shortages by providing structured, relevant information and decision support tools for medical professionals. We present the SURGE-Ahead project (Supporting SURgery with GEriatric co-management and Artificial Intelligence) addressing this challenge.MethodsA digital application with a dashboard-style user interface will be developed, displaying 1) evidence-based recommendations for geriatric co-management and 2) artificial intelligence-enhanced suggestions for continuity of care (COC) decisions. The development and implementation of the SURGE-Ahead application (SAA) will follow the Medical research council framework for complex medical interventions. In the development phase a minimum geriatric data set (MGDS) will be defined that combines parametrized information from the hospital information system with a concise assessment battery and sensor data. Two literature reviews will be conducted to create an evidence base for co-management and COC suggestions that will be used to display guideline-compliant recommendations. Principles of machine learning will be used for further data processing and COC proposals for the postoperative course. In an observational and AI-development study, data will be collected in three surgical departments of a University Hospital (trauma surgery, general and visceral surgery, urology) for AI-training, feasibility testing of the MGDS and identification of co-management needs. Usability will be tested in a workshop with potential users. During a subsequent project phase, the SAA will be tested and evaluated in clinical routine, allowing its further improvement through an iterative process.DiscussionThe outline offers insights into a novel and comprehensive project that combines geriatric co-management with digital support tools to improve inpatient surgical care and continuity of care of older adults.Trial registrationGerman clinical trials registry (Deutsches Register für klinische Studien, DRKS00030684), registered on 21st November 2022.

IntroductionThe association between occupational mechanical exposures and chronic low back pain (LBP) has been widely studied, however, few systematic reviews have evaluated the evidence of an association. Furthermore, little is known of the impact of occupational psychosocial exposures on chronic LBP. The aim of this systematic review and meta-analysis is to study the association between occupational mechanical and psychosocial exposures and chronic LBP.MethodsThe study will be conducted as a systematic review using another systematic review published in 2014 as basis and has been registered in the International Prospective Register of Systematic Reviews (PROSPERO) with registration number CRD42021281996. A systematic literature search will be performed in 6 scientific databases to identified potential relevant studies published after 2014. Studies will systematically be excluded through a screening process performed independently by 2 reviewers. Exposures will include occupational mechanical and psychosocial exposures, and outcome will include chronic LBP (LBP ≥3 months, "degenerative" diseases, and lumbosacral radiculopathy). Study population will include persons in or above working age, and study designs will comprise cohort and case-control studies. The quality of each included study will be methodologically assessed by 2 independent reviewers and level of evidence of an association will be graded using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) system. In meta-analyses, effect sizes will be addressed using random-effect models, sensitivity analyses will explore the robustness of the meta-analysis, and heterogeneity assessed.DiscussionThis systematic review and meta-analysis will assess the evidence available of the association between occupational mechanical and psychosocial exposures and chronic LBP. The review can provide essential knowledge on the association, exposure-response relationships, thresholds, which may pave the way for political decisions on the occupational environment and the labour market insurance policy.

Background and aimWith multimorbidity becoming increasingly prevalent in the ageing population, addressing the epidemiology and development of multimorbidity at a population level is needed. Individuals subject to chronic heart disease are widely multimorbid, and population-wide longitudinal studies on their chronic disease trajectories are few.MethodsDisease trajectory networks of expected disease portfolio development and chronic condition prevalences were used to map sex and socioeconomic multimorbidity patterns among chronic heart disease patients. Our data source was all Danish individuals aged 18 years and older at some point in 1995-2015, consisting of 6,048,700 individuals. We used algorithmic diagnoses to obtain chronic disease diagnoses and included individuals who received a heart disease diagnosis. We utilized a general Markov framework considering combinations of chronic diagnoses as multimorbidity states. We analyzed the time until a possible new diagnosis, termed the diagnosis postponement time, in addition to transitions to new diagnoses. We modelled the postponement times by exponential models and transition probabilities by logistic regression models.FindingsAmong the cohort of 766,596 chronic heart disease diagnosed individuals, the prevalence of multimorbidity was 84.36% and 88.47% for males and females, respectively. We found sex-related differences within the chronic heart disease trajectories. Female trajectories were dominated by osteoporosis and male trajectories by cancer. We found sex important in developing most conditions, especially osteoporosis, chronic obstructive pulmonary disease and diabetes. A socioeconomic gradient was observed where diagnosis postponement time increases with educational attainment. Contrasts in disease portfolio development based on educational attainment were found for both sexes, with chronic obstructive pulmonary disease and diabetes more prevalent at lower education levels, compared to higher.ConclusionsDisease trajectories of chronic heart disease diagnosed individuals are heavily complicated by multimorbidity. Therefore, it is essential to consider and study chronic heart disease, taking into account the individuals' entire disease portfolio.

The use of fresh tissue for molecular studies is preferred but often impossible. Instead, frozen or formalin-fixed, paraffin-embedded (FFPE) tissues are widely used and constitute valuable resources for retrospective studies. We assessed the utility of cardiac tissue stored in different ways for gene expression analyses by whole transcriptome sequencing of paired fresh, frozen, and FFPE tissues. RNA extracted from FFPE was highly degraded. Sequencing of RNA from FFPE tissues yielded higher proportions of intronic and intergenic reads compared to RNA from fresh and frozen tissues. The global gene expression profiles varied with the storage conditions, particularly mitochondrial and long non-coding RNAs. However, we observed high correlations among protein-coding transcripts (ρ > 0.94) with the various storage conditions. We did not observe any significant storage effect on the allele-specific gene expression. However, FFPE had statistically significantly (p < 0.05) more discordant variant calls compared to fresh and frozen tissue. In conclusion, we found that frozen and FFPE tissues can be used for reliable gene expression analyses, provided that proper quality control is performed and caution regarding the technical variability is withheld.

Many horses, just before and during their athletic career, show vertical movement asymmetries, to the same degree as clinically lame horses. It is unknown whether these asymmetries are caused by pain or have alternative explanations, such as inherent biological variation. In the latter case, movement asymmetries would be expected to be present at a very young age. This study aimed to investigate the prevalence of movement asymmetries in foals. Motion analysis, using an inertial measurement unit-based system (Equinosis), was performed on 54 foals (31 Swedish Warmbloods, 23 Standardbreds) during straight-line trot. The foals were between 4-13 weeks old and considered sound by their owners. Differences between the vertical minimum and maximum values recorded for the head (HDmin, HDmax) and pelvis (PDmin, PDmax) between left and right stance were calculated for each stride and an average was computed for each trial. Thresholds for asymmetry were defined as absolute trial mean >6 mm for HDmin and HDmax, and >3 mm for PDmin and PDmax. These thresholds were exceeded for one or several parameters by 83% of Standardbred foals and 45% of Swedish Warmblood foals, demonstrating surprisingly high prevalence of asymmetries in young foals, although the risk of repetitive strain injuries and cumulative risk of trauma injuries was expected to be low in this age group. Standardbred foals showed similar prevalence of asymmetries to that reported previously for yearling Standardbred trotters, so relatively higher prevalence of movement asymmetries may be expected among trotters as a breed. In general, vertical head and pelvic movement asymmetries can be anticipated among foals considered sound by their owners. A better understanding of the aetiology of asymmetries is needed for correct interpretation of objective symmetry measurements in different populations of horses.

We investigate the water sources for a perennial spring, "Little Black Pond," located at Expedition Fiord, Axel Heiberg Island in the Canadian High Arctic based on dissolved gases. We measured the dissolved O2 in the likely sources Phantom Lake and Astro Lake and the composition of noble gases (3He/4He, 4He, Ne,36Ar, 40Ar, Kr, Xe), N2, O2, CO2, H2S, CH4, and tritium dissolved in the outflow water and bubbles emanating from the spring. The spring is associated with gypsum-anhydrite piercement structures and occurs in a region of thick, continuous permafrost (400-600 m). The water columns in Phantom and Astro lakes are uniform and saturated with O2. The high salinity of the water emanating from the spring, about twice sea water, affects the gas solubility. Oxygen in the water and bubbles is below the detection limit. The N2/Ar ratio in the bubbles and the salty water is 89.9 and 40, respectively, and the relative ratios of the noble gases, with the exception of Neon, are consistent with air dissolved in lake water mixed with air trapped in glacier bubbles as the source of the gases. The Ne/Ar ratio is ~62% of the air value. Our results indicate that about half (0.47±0.1) of the spring water derives from the lakes and the other half from subglacial melt. The tritium and helium results indicate that the groundwater residence time is over 70 years and could be thousands of years.

IntroductionThroughout recent years the demand for prehospital emergency care has increased significantly. Non-traumatic chest pain is one of the most frequent complaints. Our aim was to investigate the trend in frequency of the most urgent ambulance patients with chest pain, subsequent acute myocardial infarction (AMI) diagnoses, and 48-hour and 30-day mortality of both groups.MethodsPopulation-based historic cohort study in the North Denmark Region during 2012-2018 including chest pain patients transported to hospital by highest urgency level ambulance following a 1-1-2 emergency call. Primary diagnoses (ICD-10) were retrieved from the regional Patient Administrative System, and descriptive statistics (distribution, frequency) performed. We evaluated time trends using linear regression, and mortality (48 hours and 30 days) was assessed by the Kaplan Meier estimator.ResultsWe included 18,971 chest pain patients, 33.9% (n = 6,430) were diagnosed with"Diseases of the circulatory system" followed by the non-specific R- (n = 5,288, 27.8%) and Z-diagnoses (n = 3,634; 19.2%). AMI was diagnosed in 1,967 patients (10.4%), most were non-ST-elevation AMI (39.7%). Frequency of chest pain patients and AMI increased 255 and 22 patients per year respectively, whereas the AMI proportion remained statistically stable, with a tendency towards a decrease in the last years. Mortality at 48 hours and day 30 in chest pain patients was 0.7% (95% CI 0.5% to 0.8%) and 2.4% (95% CI 2.1% to 2.6%).ConclusionsThe frequency of chest pain patients brought to hospital during 2012-2018 increased. One-tenth were diagnosed with AMI, and the proportion of AMI patients was stable. Almost 1 in of 4 high urgency level ambulances was sent to chest pain patients. Only 1 of 10 patients with chest pain had AMI, and overall mortality was low. Thus, monitoring the number of chest pain patients and AMI diagnoses should be considered to evaluate ambulance utilisation and triage.

Lung cancer is a product of inflammation and a dysfunctional immune system, and depression has similar dysregulation. Depression disproportionately affects lung cancer patients, having the highest rates of all cancers. Systemic inflammation and depression are both predictive of non-small cell lung cancer (NSCLC) survival, but the existence and extent of any co-occurrence is unknown. Studied is the association between systemic inflammation ratio (SIR) biomarker levels and patients' depressive symptoms, with the hypothesis that depression severity would be significantly associated with prognostically poor inflammation. Newly diagnosed stage-IV non-small cell lung cancer (NSCLC; N = 186) patients were enrolled (ClinicalTrials.gov Identifier: NCT03199651) and blood draws and depression self-reports (Patient Health Questionnaire-9) were obtained. For SIRs, cell counts of neutrophils (N), lymphocytes (L), and platelets (P) were abstracted for ratio (R) calculations for NLR, PLR, and the Advanced Lung cancer Inflammation Index (ALI). Patients were followed and biomarkers were tested as predictors of 2-year overall survival (OS) to confirm their relevance. Next, multivariate linear regressions tested associations of depression with NLR, PLR, and ALI. Overall 2-year mortality was 61% (113/186). Cox model analyses confirmed higher NLR [hazard ratio (HR) = 1.91; p = 0.001] and PLR (HR = 2.08; p

BackgroundAttempts to manage the COVID-19 pandemic have involved a massive flow of guidelines and information to health professionals on how to reorganize clinical work and handle patients with COVID-19. The aim of this paper is to investigate how Danish general practitioners (GPs) made sense of and worked with guidelines and associated information on COVID-19 in the first months of the pandemic.MethodsWe conducted qualitative interviews with 13 GPs in the beginning of the pandemic and again approximately three months later. Between the two interviews, they wrote daily notes for 20 days. Interviews were audio-recorded and transcribed, and the material was analyzed using thematic network analysis.ResultsThe interviewed GPs found the situation urgent and serious, and they spent a lot of time reading and working with COVID-19 related guidelines and associated information. Keeping up-to-date with and implementing guidelines was challenging due to the many sources of information and the constant guideline revisions. The GPs were able to assess patients' risk status but were challenged by the changing guidelines regarding this. The GPs found that deciding whether a COVID-19 patient needed to be admitted to hospital was relatively straightforward. An important final challenge was discrepancies between the government's public announcements regarding which patients could be tested for COVID-19, the guidelines provided to GPs, and the local testing capacities, which gave GPs extra work.ConclusionIn an urgent situation like the COVID-19 pandemic it is crucial to secure good communication between the government, health authorities, professional medical societies, and health professionals. Improved practices of collaboration between health authorities and professional societies could improve communication in future health crises and relieve GPs of some of the work involved in keeping up-to-date with information flows, constantly reviewing new guidelines, and dealing with communicative inconsistencies.

Recycling human waste for beneficial use has been practiced for millennia. Aerobic (thermophilic) composting of sewage sludge has been shown to reduce populations of opportunistically pathogenic bacteria and to inactivate both Ascaris eggs and culturable Escherichia coli in raw waste, but there is still a question about the fate of most fecal bacteria when raw material is composted directly. This study undertook a comprehensive microbial community analysis of composting material at various stages collected over 6 months at two composting facilities in Haiti. The fecal microbiota signal was monitored using a high-density DNA microarray (PhyloChip). Thermophilic composting altered the bacterial community structure of the starting material. Typical fecal bacteria classified in the following groups were present in at least half the starting material samples, yet were reduced below detection in finished compost: Prevotella and Erysipelotrichaceae (100% reduction of initial presence), Ruminococcaceae (98-99%), Lachnospiraceae (83-94%, primarily unclassified taxa remained), Escherichia and Shigella (100%). Opportunistic pathogens were reduced below the level of detection in the final product with the exception of Clostridium tetani, which could have survived in a spore state or been reintroduced late in the outdoor maturation process. Conversely, thermotolerant or thermophilic Actinomycetes and Firmicutes (e.g., Thermobifida, Bacillus, Geobacillus) typically found in compost increased substantially during the thermophilic stage. This community DNA-based assessment of the fate of human fecal microbiota during thermophilic composting will help optimize this process as a sanitation solution in areas where infrastructure and resources are limited.

Background and objective: Patients suspected to have lung cancer, undergo endobronchial ultrasound bronchoscopy (EBUS) for the purpose of diagnosis and staging. For presumptive curable patients, the EBUS bronchoscopy is planned based on images and data from computed tomography (CT) images and positron emission tomography (PET). Our study aimed to evaluate the feasibility of a multimodal electromagnetic navigation platform for EBUS bronchoscopy, integrating ultrasound and segmented CT, and PET scan imaging data. Methods: The proof-of-concept study included patients with suspected lung cancer and pathological mediastinal/hilar lymph nodes identified on both CT and PET scans. Images obtained from these two modalities were segmented to delineate target lymph nodes and then incorporated into the CustusX navigation platform. The EBUS bronchoscope was equipped with a sensor, calibrated, and affixed to a 3D printed click-on device positioned at the bronchoscope's tip. Navigation accuracy was measured postoperatively using ultrasound recordings. Results: The study enrolled three patients, all presenting with suspected mediastinal lymph node metastasis (N1-3). All PET-positive lymph nodes were displayed in the navigation platform during the EBUS procedures. In total, five distinct lymph nodes were sampled, yielding malignant cells from three nodes and lymphocytes from the remaining two. The median accuracy of the navigation system was 7.7 mm. Conclusion: Our study introduces a feasible multimodal electromagnetic navigation platform that combines intraoperative ultrasound with preoperative segmented CT and PET imaging data for EBUS lymph node staging examinations. This innovative approach holds promise for enhancing the accuracy and effectiveness of EBUS procedures. [ABSTRACT FROM AUTHOR]

Questionable research practices (QRP) are believed to be widespread, but empirical assessments are generally restricted to a few types of practices. Furthermore, conceptual confusion is rife with use and prevalence of QRPs often being confused as the same quantity. We present the hitherto most comprehensive study examining QRPs across scholarly fields and knowledge production modes. We survey perception, use, prevalence and predictors of QRPs among 3,402 researchers in Denmark and 1,307 in the UK, USA, Croatia and Austria. Results reveal remarkably similar response patterns among Danish and international respondents (τ = 0.85). Self-reported use indicates whether respondents have used a QRP in recent publications. 9 out of 10 respondents admitted using at least one QRP. Median use is three out of nine QRP items. Self-reported prevalence reflects the frequency of use. On average, prevalence rates were roughly three times lower compared to self-reported use. Findings indicated that the perceived social acceptability of QRPs influenced self-report patterns. Results suggest that most researchers use different types of QRPs within a restricted time period. The prevalence estimates, however, do not suggest outright systematic use of specific QRPs. Perceived pressure was the strongest systemic predictor for prevalence. Conversely, more local attention to research cultures and academic age was negatively related to prevalence. Finally, the personality traits conscientiousness and, to a lesser degree, agreeableness were also inversely associated with self-reported prevalence. Findings suggest that explanations for engagement with QRPs are not only attributable to systemic factors, as hitherto suggested, but a complicated mixture of experience, systemic and individual factors, and motivated reasoning. [ABSTRACT FROM AUTHOR]

Advanced optical neuromonitoring of cerebral hemodynamics with hybrid diffuse optical spectroscopy (DOS) and diffuse correlation spectroscopy (DCS) methods holds promise for non-invasive characterization of brain health in critically ill patients. However, the methods' fiber-coupled patient interfaces (probes) are challenging to apply in emergent clinical scenarios that require rapid and reproducible attachment to the head. To address this challenge, we developed a novel chassis-based optical probe design for DOS/DCS measurements and validated its measurement accuracy and reproducibility against conventional, manually held measurements of cerebral hemodynamics in pediatric swine (n = 20). The chassis-based probe design comprises a detachable fiber housing which snaps into a 3D-printed, circumferential chassis piece that is secured to the skin. To validate its reproducibility, eight measurement repetitions of cerebral tissue blood flow index (BFI), oxygen saturation (StO2), and oxy-, deoxy- and total hemoglobin concentration were acquired at the same demarcated measurement location for each pig. The probe was detached after each measurement. Of the eight measurements, four were acquired by placing the probe into a secured chassis, and four were visually aligned and manually held. We compared the absolute value and intra-subject coefficient of variation (CV) of chassis versus manual measurements. No significant differences were observed in either absolute value or CV between chassis and manual measurements (p > 0.05). However, the CV for BFI (mean ± SD: manual, 19.5% ± 9.6; chassis, 19.0% ± 10.8) was significantly higher than StO2 (manual, 5.8% ± 6.7; chassis, 6.6% ± 7.1) regardless of measurement methodology (p<0.001). The chassis-based DOS/DCS probe design facilitated rapid probe attachment/re-attachment and demonstrated comparable accuracy and reproducibility to conventional, manual alignment. In the future, this design may be adapted for clinical applications to allow for non-invasive monitoring of cerebral health during pediatric critical care. [ABSTRACT FROM AUTHOR]

Introduction: Immune dysregulation with an excessive release of cytokines has been identified as a key driver in the development of severe COVID-19. The aim of this study was to evaluate the initial cytokine profile associated with 90-day mortality and respiratory failure in a cohort of patients hospitalized with COVID 19 that did not receive immunomodulatory therapy. Methods: Levels of 45 cytokines were measured in blood samples obtained at admission from patients with confirmed COVID-19. Logistic regression analysis was utilized to determine the association between cytokine levels and outcomes. The primary outcome was death within 90 days from admission and the secondary outcome was need for mechanical ventilation. Results: A total of 132 patients were included during the spring of 2020. We found that one anti-inflammatory cytokine, one pro-inflammatory cytokine, and five chemokines were associated with the odds of 90-day mortality, specifically: interleukin-1 receptor antagonist, interleukin-6, interleukin-8, monocyte chemoattractant protein-1, macrophage inflammatory protein-3α, macrophage inflammatory protein-3β, and fractalkine. All but fractalkine were also associated with the odds of respiratory failure during admission. Monocyte chemoattractant protein-1 showed the strongest estimate of association with both outcomes. Conclusion: We showed that one anti-inflammatory cytokine, one pro-inflammatory cytokine, and five chemokines were associated with 90-day mortality in patients hospitalized with COVID-19 that did not receive immunomodulatory therapy. [ABSTRACT FROM AUTHOR]

Recent research has elucidated the effects of strength training on climbing performance. Although local muscular endurance training of the upper-limbs and finger flexors is frequently suggested, there is currently insufficient evidence to support its impact on climbing performance and climbing-specific strength. Furthermore, there is no evidence on climbers' experiences related to training and the likelihood of consistent engagement. In addition, the effects of more climbing-specific strength training on walls with built in lights and adjustable angles have yet to be examined. The low percentage of studies involving female subjects, additionally, demonstrates a significant gap in understanding the specific effects of strength training on women in the context of climbing. The aim of this study was thus to assess the effects of five-week on-, and off-the-wall climbing training on climbing performance, climbing-specific strength, and training experience. Thirty-one female lower-grade to advanced climbers were randomly assigned to either a control group, an off-the-wall training or an on-the-wall training group. Apart from the training regimen, all groups followed their usual climbing and bouldering routine. Subjects trained at least twice a week. Bouldering performance, and maximum strength and muscular endurance of the finger flexors and upper-limbs were assessed before and after the intervention. Furthermore, rate of perceived exertion and discomfort, exercise enjoyment, and exercise pleasure were assessed during the first and last training session, as well as after two and a half weeks of training. Intrinsic training motivation was assessed after the last training session. The results showed trends towards positive effects of off-the-wall training on climbing-specific strength, and on-the-wall training on climbing technique. Furthermore, our finding revealed high exercise enjoyment and intrinsic training motivation for both on- and off-the-wall training. Hence, lower-grade to advanced female climbers should rely on personal training preferences. [ABSTRACT FROM AUTHOR]

Background: Danish women—who were HPV-vaccinated as girls—are now reaching an age where they are invited to cervical cancer screening. Because of their expected lower cervical cancer risk, we must reassess our screening strategies. We analyzed Danish HPV-vaccinated women's outcomes after the first screening test at age 23. Methods and findings: Our study was embedded in Danish routine cytology-based screening. We conducted an observational study and included women born in 1994, offered the 4-valent HPV vaccine at age 14, and subsequently invited to screening at age 23. Cervical cytology was used for diagnostics and clinical management. Residual material was HPV tested with Cobas® 4800/6800. The most severe histology diagnosis within 795 days of screening was found through linkage with the Danish National Pathology Register. We calculated the number of women undergoing follow-up (repeated testing and/or colposcopy) per detected cervical intraepithelial neoplasia (CIN2+). A total of 6021 women were screened; 92% were HPV-vaccinated; 12% had abnormal cytology; 35% were high-risk HPV-positive, including 0.9% HPV16/18 positive, and 20% had follow-up. In women that were cytology-abnormal and HPV-positive (Cyt+/HPV+), 610 (98.5%) had been followed up, and 138 CIN2+ cases were diagnosed, resulting in 4.4 (95% CI 3.9–5.2) women undergoing follow-up per detected CIN2+. In contrast to recommendations, 182 (12.2%) cytology-normal and HPV-positive (Cyt-/HPV+) women were followed up within 795 days, and 8 CIN2+ cases were found, resulting in 22.8 (95% CI 13.3–59.3) women undergoing follow-up per detected CIN2+. Conclusion: Overall, HPV prevalence was high in HPV-vaccinated women, but HPV16/18 had largely disappeared. In the large group of cytology-normal and HPV-positive women, 23 had been followed up per detected CIN2+ case. Our data indicated that primary HPV screening of young HPV-vaccinated women would require very effective triage methods to avoid an excessive follow-up burden. Trial registration: Trial registration number:NCT0304955. [ABSTRACT FROM AUTHOR]

Background: Neck pain remains a persistent challenge in modern society and is frequently encountered across a wide range of occupations, particularly those involving repetitive and monotonous tasks. It might be expected that patterns of trapezius muscle activity at work, characterized by few breaks and prolonged periods of sustained muscle activity, are linked to neck pain. However, previous cross-sectional studies have generally failed to establish a definitive association. While some longitudinal studies have suggested that extended periods of heightened muscle activity could be a risk factor for neck pain, these findings often relied on limited participant numbers or specific professional groups. This study aimed to investigate the relationship between trapezius muscle activity and neck pain by pooling data from seven Scandinavian research institutes encompassing a diverse range of occupational backgrounds. Methods: Electromyographic (EMG) data for the upper trapezius muscle, collected during working hours, were coupled with questionnaire responses pertaining to neck pain, individual characteristics, and potential confounding variables for a total of 731 subjects. Additionally, longitudinal data from 258 subjects were available. The various EMG datasets were consolidated into a standardized format, and efforts were made to harmonize inquiries about neck pain. Regression analyses, adjusting for sex and height, were conducted to explore the associations between muscle activity variables and neck pain. An exposure index was devised to quantify the cumulative neck load experienced during working hours and to differentiate between various occupational categories. Results: The cross-sectional data displayed a distinct pattern characterized by positive associations for brief periods of sustained muscle activity (SUMA) and negative associations for prolonged SUMA-periods and neck pain. The longitudinal data exhibited a contrasting trend, although it was not as pronounced as the cross-sectional findings. When employing the exposure index, notable differences in cumulative muscle load emerged among occupational groups, and positive associations with longitudinal neck pain were identified. Discussion: The results suggest that individuals with neck pain experience higher cumulative workloads and extended periods of muscle activity over the long term. In the short term, they appear to compensate by taking frequent short breaks, resulting in a lower cumulative workload. Regardless of their occupation, it is crucial to distribute work breaks throughout the workday to ensure that the cumulative load remains manageable. [ABSTRACT FROM AUTHOR]