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Formålet med studien er å gi en oversikt over hva begrepet pedagogisk ledelse omhandler i fagfellevurderte artikler og fagbøker innenfor norsk barnehagefaglig forskningslitteratur. Studien er gjennomført som en scoping review, med undersøkelse i norske og internasjonale elektroniske databaser og forskningsbaserte fagbøker fra 2011 til 2021. Totalt 35 bidrag ble inkludert i samsvar med inklusjonskriteriene, og det ble gjennomført en tematisk innholdsanalyse. Litteraturstudien viser at pedagogisk ledelse er et vidt og lite utforsket begrep, spesielt i forståelsen av pedagogisk ledelse av barn. Denne litteraturgjennomgangen vil derfor kunne bidra til å tydeliggjøre innholdet i begrepet og eventuelt legge grunnlag for felles forståelse av begrepet innen barnehagefeltet. Studien peker på implikasjoner for barnehagefeltet og barnehagelærerutdanningen. ENGLISH ABSTRACT Pedagogical Leadership Within Norwegian Research Literature for Early Childhood Education and Care (ECEC) – A Scoping Review The purpose of the study is to summarize and provide an overview of what the concept of pedagogical leadership apply to in peer-reviewed articles and textbooks within the Norwegian early childhood education and care research literature (ECEC). The study was conducted as a scoping review as a method, with surveys in Norwegian and international electronic databases and research-based textbooks from 2011 to 2021. A total of 35 contributions were included in accordance with the inclusion criteria, and a thematic content analysis was conducted. The literature review shows that pedagogical leadership is a broad concept and little explored, especially in the understanding of pedagogical leadership of children. This literature review will therefore help to clarify the content of the term and possibly lay the foundation for a common understanding of the term in the ECEC field. The study points to implications for the field and ECEC teacher education.

Abstract Diet composition impacts metabolic health and is now recognized to shape the immune system, especially in the intestinal tract. Nutritional imbalance and increased caloric intake are induced by high-fat diet (HFD) in which lipids are enriched at the expense of dietary fibers. Such nutritional challenge alters glucose homeostasis as well as intestinal immunity. Here, we observed that short-term HFD induced dysbiosis, glucose intolerance and decreased intestinal RORγt+ CD4 T cells, including peripherally-induced Tregs and IL17-producing (Th17) T cells. However, supplementation of HFD-fed male mice with the fermentable dietary fiber fructooligosaccharides (FOS) was sufficient to maintain RORγt+ CD4 T cell subsets and microbial species known to induce them, alongside having a beneficial impact on glucose tolerance. FOS-mediated normalization of Th17 cells and amelioration of glucose handling required the cDC2 dendritic cell subset in HFD-fed animals, while IL-17 neutralization limited FOS impact on glucose tolerance. Overall, we uncover a pivotal role of cDC2 in the control of the immune and metabolic effects of FOS in the context of HFD feeding.

Abstract Background Oxaliplatin-induced peripheral neuropathy (OIPN) in general and painful OIPN in particular is a debilitating late effect that severely affects cancer survivors’ quality of life and causes premature cessation of potentially lifesaving treatment. No preventive treatments and no effective treatment for chronic OIPN exist despite many attempts. One of several suggested mechanisms includes neuroinflammation as a contributing factor to OIPN. Fish oil containing long-chain n-3 polyunsaturated fatty acids (n-3 LCPUFAs) are precursors to specialized proresolving mediators that mediate the resolution of inflammation. Our primary hypothesis is that a high supplementation of n-3 LCPUFAs will lower the prevalence and severity of OIPN. Methods The OxaNeuro project is an investigator-initiated, multicenter, double-blinded, randomized, placebo-controlled clinical study. We will include 120 patients eligible to receive adjuvant oxaliplatin after colorectal cancer surgery. Patients will receive fish oil capsules containing n-3 LCPUFAs or corn oil daily for 8 months. The primary endpoint is the prevalence of OIPN at 8 months defined as relevant symptoms, including one of the following: abnormal nerve conduction screening, abnormal vibration threshold test, abnormal skin biopsy, or abnormal pinprick test. Additional endpoints include the intensity and severity of OIPN-related neuropathic pain, patient-reported OIPN symptoms, quality of life, mental health symptoms, body composition, and cognitive evaluation. Furthermore, we will evaluate inflammatory biomarkers in blood samples and skin biopsies, including the potential OIPN biomarker neurofilament light protein (NfL) which will be measured before each cycle of chemotherapy. Discussion If readily available fish oil supplementation alleviates OIPN prevalence and severity, it will significantly improve the lives of both cancer survivors and palliative cancer patients receiving oxaliplatin; it will improve their quality of life, optimize chemotherapeutic treatment plans by lowering the need for dose reduction or premature cessation, and potentially increase survival. Trial registration ClinicalTrial.gov identifier: NCT05404230 Protocol version: 1.2, April 25th. 2023

Abstract Movement is a key behaviour to better understand how individuals respond to their environment. Movement behaviours are affected by both extrinsic factors that individuals face, such as weather conditions, and intrinsic factors, such as sex and experience. Because of the energy costs it entails, movement behaviours can have direct consequences on an individual's demographic parameters—and ultimately on population dynamics. However, the relationship between extrinsic factors, intrinsic factors, daily movement behaviour and demographic parameters such as breeding performance is poorly known, in particular for central place forager territorial species. We investigated here the link between movement behaviours and breeding performance of the French population of Bonelli's eagle (Aquila fasciata), a territorial and sedentary long‐lived raptor, and how this link may depend on extrinsic and intrinsic factors. By using data from annual monitoring of breeding performance for the population and GPS tracking of 48 individuals (26 males and 22 females), we found that the breeding performance of this population was mainly driven by whether a new individual was recruited into the territory, and only slightly by weather conditions. Movement behaviours (proportion of time in flight, range of movement and straightness of trajectories) showed large between‐individual variation. Those behaviours were related with weather conditions (wind and rainfall) at a daily scale, as well as with individual's experience. We found only one significant correlation between movements and breeding performance: male Bonelli's eagles spending more time flying during chick‐rearing phase had lower productivity. Movement behaviours and breeding performance were also indirectly linked through individual's experience, with more experienced birds having better breeding success and a shorter range of movement and spent less time in flight. This suggests that experienced individuals progressively acquire knowledge of their breeding territory, are more efficient in finding prey, and adapt their foraging strategies to weather conditions to minimise energy costs, allowing them higher breeding performance.

A travers une analyse systémique de l’édition scientifique en France – et plus particulièrement via une étude des contextes historiques, socio-économiques et politique – cet article soulève les problématiques éthiques qui ont jalonné la construction de l’écosystème scientifique et l’exploitation des produits de la recherche, et livre une réflexion sur les défis éthiques liés à la mise en place depuis 2018 de la politique de la Science Ouverte mais aussi des conséquences directes que cela va avoir sur les pratiques des chercheurs.

Background The REDO trial (REtreatment with Rituximab in RhEmatoid arthritis: Disease Outcome after Dose Optimisation) showed similar disease activity for retreatment with ultralow doses (200 mg and 500 mg per 6 months) compared with standard low-dose rituximab (RTX, 1000 mg per 6 months). We performed an observational extension study of the REDO trial to assess long-term effectiveness.Methods Patients from the REDO trial were followed from start of the trial to censoring in April 2021. RTX use was at the discretion of patient and rheumatologist using treat to target. The primary outcome was disease activity (disease activity score in 28 joints C-reactive protein (DAS28-CRP)), analysed using a longitudinal mixed model by original randomisation and time-varying RTX dose. The original DAS28-CRP non-inferiority (NI) margin of 0.6 was used. RTX dose and persistence, safety and radiological outcomes were also assessed.Findings Data from 126 of 142 REDO patients was collected from 15 December 2016, up to 30 April 2021. Drop-outs continued treatment elsewhere (n=3) or did not consent (n=13).Disease activity did not differ by original randomisation group: 1000 mg mean DAS28-CRP (95% CI) of 2.2 (2.0 to 2.5), 500 mg 2.3 (2.1 to 2.4) and 200 mg 2.4 (2.2 to 2.5). Lower time-varying RTX dose was associated with higher DAS28-CRP (0.22 (95% CI 0.05 to 0.40) higher for 200 mg/6 months compared with 1000 mg/6 months), but remained within the NI-margin. RTX persistence was 93%. Median RTX dose was 978 mg (IQR 684–1413) per year, and no association was found between RTX dose and adverse events or radiological damage.Interpretation Long-term use of ultralow doses of RTX is effective in patients with rheumatoid arthritis responding to standard dose RTX.

Abstract Background According to current evidence, the best treatment for fit patients with non-resectable pancreatic cancer (PC) is combination chemotherapy, whereas frail patients are recommended gemcitabine (Gem) monotherapy. Randomized controlled trials in colorectal cancer and a post-hoc analysis of gemcitabine and nab-paclitaxel (GemNab) in PC suggest, however, that reduced dose of combination chemotherapy may be feasible and more efficient compared to monotherapy in frail patients. The aim of this study is to investigate whether reduced dose GemNab is superior to full dose Gem in patients with resectable PC, who are not candidates for full dose combination chemotherapy in first line. Methods The Danish Pancreas Cancer Group (DPCG)-01 trial is a national multicenter prospective randomized phase II trial. A total of 100 patients in ECOG performance status 0–2 with non-resectable PC, not candidate for full dose combination chemotherapy in first line, but eligible for full dose Gem, will be included. Patients are randomized 1:1 to either full dose Gem or GemNab in 80% of recommended dose. The primary endpoint is progression-free survival. Secondary endpoints are overall survival, overall response rate, quality of life, toxicity and rate of hospitalizations during treatment. The correlation between blood inflammatory markers, including YKL-40 and IL-6, circulating tumor DNA, and tissue biomarkers of resistance to chemotherapy and outcome will be explored. Finally, the study will include measures of frailty (G8, modified G8, and chair-stand-test) to assess whether scoring would enable a personalized allocation to different treatments or indicates a possibility for interventions. Discussion Single-drug treatment with Gem has for frail patients with non-resectable PC been the main treatment option for more than thirty years, but the impact on outcome is modest. If improved results and sustained tolerability with reduced dose combination chemotherapy can be shown, this could change the future practice for this increasing group of patients. Trial registration ClinicalTrials.gov Identifier: NCT05841420. Secondary Identifying No: N-20210068. EudraCT No: 2021–005067-52. Protocol version: 1.5, 16-MAY-2023.

Abstract Western redcedar (WRC; Thuja plicata) is a conifer of the Pacific Northwest of North America prized for its durable and rot‐resistant wood. WRC has naturally low outcrossing rates and readily self‐fertilizes in nature. Challenges faced in WRC breeding and propagation involve selecting trees for accelerated growth while also ensuring enhanced heartwood rot resistance and resistance to ungulate browsing, as well as mitigating potential effects of inbreeding depression. Terpenes, a large and diverse class of specialized metabolites, confer both rot and browse resistance in the wood and foliage of WRC, respectively. Using a Bayesian modelling approach, we isolated single nucleotide polymorphism (SNP) markers estimated to be associated with three different foliar terpene traits and four different heartwood terpene traits, as well as two growth traits. We found that all traits were complex, being associated with between 1700 and 3600 SNPs linked with putatively causal loci, with significant polygenic components. Growth traits tended to have a larger polygenic component while terpene traits had larger major gene components; SNPs with small or polygenic effect were spread across the genome, while larger‐effect SNPs tended to be localized to specific linkage groups. To determine whether there was inbreeding depression for terpene chemistry or growth traits, we used mixed linear models for a genomic selection training population to estimate the effect of the inbreeding coefficient F on foliar terpenes, heartwood terpenes and several growth and dendrochronological traits. We did not find significant inbreeding depression for any assessed trait. We further assessed inbreeding depression across four generations of complete selfing and found that not only was inbreeding depression not significant but that selection for height growth was the only significant predictor for growth during selfing, suggesting that inbreeding depression due to selfing during operational breeding can be mitigated by increased selection intensity.

Background: Currently, nanoliposomal irinotecan (nal-IRI) + 5-fluorouracil/folinic acid (5-FU/LV) is the only approved second-line treatment for patients suffering from metastatic pancreatic ductal adenocarcinoma (mPDAC). However, also other chemotherapeutic regimens are used in this setting and due to the lack of clear real-world data on the efficacy of the different regimens, there is no consensus on the optimal treatment sequence for mPDAC patients. Objectives: To provide information on the safe and efficacious use of nal-IRI + 5-FU/LV in clinical practice in Belgium, which is needed for healthcare professionals to estimate the risk–benefit ratio of the intervention. Methods: Medical data of adult patients with mPDAC who were treated with nal-IRI + 5-FU/LV in one of the participating Belgian hospitals were retrospectively collected. Kaplan–Meier analysis was performed to obtain survival curves to estimate the median overall survival (OS) and progression-free survival (PFS). All other results were presented descriptively. Results: A total of 56 patients [median age at diagnosis: 69 years (range 43 years), 57.1% male] were included. Patients received a median of 5 (range 49 cycles) nal-IRI + 5-FU/LV cycles, extended over 10 weeks (range 130.8 weeks). The median start dose for nal-IRI was 70 mg/m² (range 49.24 mg/m²) and chemotherapy dose reduction and delay occurred in, respectively, 42.8% and 37.5% of the patients. The median OS was 6.8 months (95% CI: 5.6–8.4 months) with a 6-month survival rate of 57.4% and a 1-year survival rate of 27.8% in the overall study population. The median OS for patients treated with nal-IRI as second-line therapy or as later-line treatment was, respectively, 6.8 months (95% CI: 5.9–7.0 months) and 5.6 months (95% CI: 4.2– no upper limit ). In the overall study population, a median PFS of 3.1 months (95% CI: 2.4–4.6 months) and a disease control rate of 48.3%, comprising 30.4% stable disease, 16.1% partial and 1.8% complete response, was observed. The median PFS for patients treated with nal-IRI as second-line therapy was 3.9 months (95% CI: 2.8–4.8 months) while this was 2.4 months (95% CI: 1.9–9.1 months) for those that received nal-IRI in a later-line treatment. In terms of safety, gastrointestinal problems occurred most (64.3% of the patients) and from all reported treatment emergent adverse events, 39.2% were grade 3 or 4. Conclusion: Nal-IRI + 5-FU/LV is a valuable, effective, and safe sequential treatment option following gemcitabine-based therapy in patients with mPDAC. Trial details: Retrospective study on the efficacy and tolerability of liposomal irinotecan (NALIRI); ClinicalTrials.gov Identifier: NCT0509506 ( https://clinicaltrials.gov/ct2/show/NCT05095064?term=naliri&draw=2&rank=2 ).

Abstract Western redcedar (WRC) is an ecologically and economically important forest tree species characterized by low genetic diversity with high self‐compatibility and high heartwood durability. Using sequence capture genotyping of target genic and non‐genic regions, we genotyped 44 parent trees and 1520 offspring trees representing 26 polycross (PX) families collected from three progeny test sites using 45,378 SNPs. Trees were phenotyped for eight traits related to growth, heartwood and foliar chemistry associated with wood durability and deer browse resistance. We used the genomic realized relationship matrix for paternity assignment, maternal pedigree correction, and to estimate genetic parameters. We compared genomics‐based (GBLUP) and two pedigree‐based (ABLUP: polycross and reconstructed full‐sib [FS] pedigrees) models. Models were extended to estimate dominance genetic effects. Pedigree reconstruction revealed significant unequal male contribution and separated the 26 PX families into 438 FS families. Traditional maternal PX pedigree analysis resulted in up to 51% overestimation in genetic gain and 44% in diversity. Genomic analysis resulted in up to 22% improvement in offspring breeding value (BV) theoretical accuracy, 35% increase in expected genetic gain for forward selection, and doubled selection intensity for backward selection. Overall, all traits showed low to moderate heritability (0.09–0.28), moderate genotype by environment interaction (type‐B genetic correlation: 0.51–0.80), low to high expected genetic gain (6.01%–55%), and no significant negative genetic correlation reflecting no large trade‐offs for multi‐trait selection. Only three traits showed a significant dominance effect. GBLUP resulted in smaller but more accurate heritability estimates for five traits, but larger estimates for the wood traits. Comparison between all, genic‐coding, genic‐non‐coding and intergenic SNPs showed little difference in genetic estimates. In summary, we show that GBLUP overcomes the PX limitations, successfully captures expected historical and hidden relatedness as well as linkage disequilibrium (LD), and results in increased breeding efficiency in WRC.

PurposeThis study aimed to translate and cross-culturally adapt the work rehabilitation questionnaire (WORQ) into Danish to examine the internal consistency and test-retest reliability of the Danish WORQ and, second, to test the feasibility of WORQ in the Danish context of vocational rehabilitation.MethodsThe translation was performed in a dual-panel approach. The panel consisted of a bilingual physician, a university student in psychology, a layperson, a specialist in social work and rehabilitation, and a professor in social medicine. The international classification of functioning, disability, and health (ICF) codes were cross-evaluated to secure that there was a high level of agreement of ICF codes for each specific WORQ item in the Danish and English version. The content validity was evaluated by the clinical physicians at an outpatient clinic in social medicine and by the case managers at a municipality job center. Data for the examination of the internal consistency and test-retest reliability were collected at the Holbæk municipality from citizens in the working age. The test-retest took place 14 days apart. The internal consistency and test-retest reliability were tested conducting Cronbach's alpha, intraclass correlation, and Spearman’s correlation analyses.ResultsThe panel experienced only minor challenges in the translation process, leading to minor modifications. The cross-evaluation of coding in the Danish WORQ compared with the initial English version only found small deviations, while the remaining coding agreed between the initial English and the Danish items. The panel argued to add sub-codes to culturally adapt to the transportation forms generally used in Denmark. The general perception among the participating patients and citizens at the job center as well as the clinical physicians and case managers was that the WORQ was easy, understandable, and meaningful.ConclusionsThis study showed that the Danish WORQ have a high content validity and usability. Nonetheless, the Danish WORQ needs to be validated against well-acknowledged tools for assessing functional ability specific to work and in general.

Objectives To develop evidence-based points to consider for cost-effective use of biological and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) in the treatment of inflammatory rheumatic diseases, specifically rheumatoid arthritis, psoriatic arthritis and axial spondyloarthritis.Methods Following EULAR procedures, an international task force was formed, consisting of 13 experts in rheumatology, epidemiology and pharmacology from seven European countries. Twelve strategies for cost-effective use of b/tsDMARDs were identified through individual and group discussion. For each strategy, PubMed and Embase were systematically searched for relevant English-language systematic reviews and, for six strategies, additionally for randomised controlled trials (RCTs). Thirty systematic reviews and 21 RCTs were included. Based on the evidence, a set of overarching principles and points to consider was formulated by the task force using a Delphi procedure. Level of evidence (1a–5) and grade (A–D) were determined for each point to consider. Individual voting on the level of agreement (LoA; between 0 (completely disagree) and 10 (completely agree)) was performed anonymously.Results The task force agreed on five overarching principles. For 10 of 12 strategies, the evidence was sufficient to formulate one or more points to consider, leading to 20 in total, regarding response prediction, drug formulary use, biosimilars, loading doses, low-dose initial therapy, concomitant conventional synthetic DMARD use, route of administration, medication adherence, disease activity–guided dose optimisation and non-medical drug switching. Ten points to consider (50%) were supported by level 1 or 2 evidence. The mean LoA (SD) varied between 7.9 (1.2) and 9.8 (0.4).Conclusion These points to consider can be used in rheumatology practices and complement inflammatory rheumatic disease treatment guidelines to incorporate cost-effectiveness in b/tsDMARD treatment.

Abstract Very high‐resolution satellite (VHR) imagery is a promising tool for estimating the abundance of wildlife populations, especially in remote regions where traditional surveys are limited by logistical challenges. Emperor penguins Aptenodytes forsteri were the first species to have a circumpolar population estimate derived via VHR imagery. Here we address an untested assumption from Fretwell et al. (2012) that a single image of an emperor penguin colony is a reasonable representation of the colony for the year the image was taken. We evaluated satellite‐related and environmental variables that might influence the calculated area of penguin pixels to reduce uncertainties in satellite‐based estimates of emperor penguin populations in the future. We focused our analysis on multiple VHR images from three representative colonies: Atka Bay, Stancomb‐Wills (Weddell Sea sector) and Coulman Island (Ross Sea sector) between September and December during 2011. We replicated methods in Fretwell et al. (2012), which included using supervised classification tools in ArcGIS 10.7 software to calculate area occupied by penguins (hereafter referred to as ‘population indices’) in each image. We found that population indices varied from 2 to nearly 6‐fold, suggesting that penguin pixel areas calculated from a single image may not provide a complete understanding of colony size for that year. Thus, we further highlight the important roles of: (i) sun azimuth and elevation through image resolution and (ii) penguin patchiness (aggregated vs. distributed) on the calculated areas. We found an effect of wind and temperature on penguin patchiness. Despite intra‐seasonal variability in population indices, simulations indicate that reliable, robust population trends are possible by including satellite‐related and environmental covariates and aggregating indices across time and space. Our work provides additional parameters that should be included in future models of population size for emperor penguins.

Lysozymes are universal components of the innate immune system of animals that kill bacteria by hydrolyzing their main cell wall polymer, peptidoglycan. Three main families of lysozyme have been identified, designated as chicken (c)-, goose (g)- and invertebrate (i)-type. In response, bacteria have evolved specific protein inhibitors against each of the three lysozyme families. In this study, we developed a serial array of three affinity matrices functionalized with a c-, g-, and i-type inhibitors for lysozyme typing, i.e., to detect and differentiate lysozymes in fluids or extracts from animals. The tool was validated on the blue mussel (Mytilus edulis), whose genome carries multiple putative i-, g-, and c-type lysozyme genes. Hemolymph plasma of the animals was found to contain both i- and g-type, but not c-type lysozyme. Furthermore, hemolymph survival of Aeromonas hydrophila and E. coli strains lacking or overproducing the i- type or g-type lysozyme inhibitor, respectively, was analyzed to study the role of the two lysozymes in innate immunity. The results demonstrated an active role for the g-type lysozyme in the innate immunity of the blue mussel, but failed to show a contribution by the i-type lysozyme. Lysozyme profiling using inhibitor-based affinity chromatography will be a useful novel tool for studying animal innate immunity.

Anthropogenic climate change and ecological crisis are affecting people's mental health. One such manifestation, eco-anxiety, is anxiety in the form of negative, troublesome, and automatic physiological, cognitive, emotional, and behavioral reactions to climate change and ecological degradation. The speed, scale, and severity of unfolding environmental crises will continue to exacerbate experiences of eco-anxiety. Scholars and practitioners are still in the early stages of understanding and addressing the phenomenon. To help prioritize future endeavors, we advocate for an interdisciplinary approach to address the urgency and complexity of eco-anxiety, which can be understood in the context of a larger problem facing humanity. We provide an eco-anxiety primer based on recent scoping reviews and seminal empirical research. Additionally, we recommend four opportunities for collective learning and strategic communication: (1) motivational and actionable message framing, (2) storytelling for social and behavior change, (3) knowledge sharing and linked resources, and (4) positive deviance for complex problem-solving. We hope this article will benefit health practitioners, media professionals, academic researchers, policy makers, community leaders, climate activists, and other stakeholders.

We conducted an experiment with translation students to assess the influence of two different post-editing (PE) strategies (reading the source segment or the target segment first) on three aspects: PE time, ratio of corrected errors and number of optional modifications per word. Our results showed that the strategy that is adopted has no influence on the PE time or ratio of corrected errors. However, it does have an influence on the number of optional modifications per word. Two other thought-provoking observations emerged from this study: first, the ratio of corrected errors showed that, on average, students correct only half of the MT errors, which underlines the need for PE practice. Second, the time logs of the experiment showed that when students are not forced to read the source segment first, they tend to neglect the source segment and almost do monolingual PE. This experiment provides new insight relevant to PE teaching as well as the designing of PE environments.

BackgroundPatients with cancer, especially hematological cancer, are at increased risk for breakthrough COVID-19 infection. So far, a predictive biomarker that can assess compromised vaccine-induced anti-SARS-CoV-2 immunity in cancer patients has not been proposed.MethodsWe employed machine learning approaches to identify a biomarker signature based on blood cytokines, chemokines, and immune- and non-immune-related growth factors linked to vaccine immunogenicity in 199 cancer patients receiving the BNT162b2 vaccine.ResultsC-reactive protein (general marker of inflammation), interleukin (IL)-15 (a pro-inflammatory cytokine), IL-18 (interferon-gamma inducing factor), and placental growth factor (an angiogenic cytokine) correctly classified patients with a diminished vaccine response assessed at day 49 with >80% accuracy. Amongst these, CRP showed the highest predictive value for poor response to vaccine administration. Importantly, this unique signature of vaccine response was present at different studied timepoints both before and after vaccination and was not majorly affected by different anti-cancer treatments.ConclusionWe propose a blood-based signature of cytokines and growth factors that can be employed in identifying cancer patients at persistent high risk of COVID-19 despite vaccination with BNT162b2. Our data also suggest that such a signature may reflect the inherent immunological constitution of some cancer patients who are refractive to immunotherapy.

Roux-en-Y gastric bypass (RYGB) is efficient at inducing drastic albeit variable weight loss and type-2 diabetes (T2D) improvements in patients with severe obesity and T2D. We hypothesized a causal implication of the gut microbiota (GM) in these metabolic benefits, as RYGB is known to deeply impact its composition. In a cohort of 100 patients with baseline T2D who underwent RYGB and were followed for 5-years, we used a hierarchical clustering approach to stratify subjects based on the severity of their T2D (Severe vs Mild) throughout the follow-up. We identified via nanopore-based GM sequencing that the more severe cases of unresolved T2D were associated with a major increase of the class Bacteroidia, including 12 species comprising Phocaeicola dorei, Bacteroides fragilis, and Bacteroides caecimuris. A key observation is that patients who underwent major metabolic improvements do not harbor this enrichment in Bacteroidia, as those who presented mild cases of T2D at all times. In a separate group of 36 patients with similar baseline clinical characteristics and preoperative GM sequencing, we showed that this increase in Bacteroidia was already present at baseline in the most severe cases of T2D. To explore the causal relationship linking this enrichment in Bacteroidia and metabolic alterations, we selected 13 patients across T2D severity clusters at 5-years and performed fecal matter transplants in mice. Our results show that 14 weeks after the transplantations, mice colonized with the GM of Severe donors have impaired glucose tolerance and insulin sensitivity as compared to Mild-recipients, all in the absence of any difference in body weight and composition. GM sequencing of the recipient animals revealed that the hallmark T2D-severity associated bacterial features were transferred and were associated with the animals’ metabolic alterations. Therefore, our results further establish the GM as a key contributor to long-term glucose metabolism improvements (or lack thereof) after RYGB.

Abstract Background Chiropractic care is commonly used to treat infantile colic. However large trials with parental blinding are missing. Therefore, the purpose of this study is to evaluate the effect of chiropractic care on infantile colic. Method This is a multicenter, single-blind randomized controlled trial conducted in four Danish chiropractic clinics, 2015–2019. Information was distributed in the maternity wards and by maternal and child health nurses. Children aged 2–14 weeks with unexplained excessive crying were recruited through home visits and randomized (1:1) to either chiropractic care or control group. Both groups attended the chiropractic clinic twice a week for 2 weeks. The intervention group received chiropractic care, while the control group was not treated. The parents were not present in the treatment room and unaware of their child’s allocation. The primary outcome was change in daily hours of crying before and after treatment. Secondary outcomes were changes in hours of sleep, hours being awake and content, gastrointestinal symptoms, colic status and satisfaction. All outcomes were based on parental diaries and a final questionnaire. Results Of 200 recruited children, 185 completed the trial (treatment group n = 96; control group n = 89). Duration of crying in the treatment group was reduced by 1.5 h compared with 1 h in the control group (mean difference − 0.6, 95% CI − 1.1 to − 0.1; P = 0.026), but when adjusted for baseline hours of crying, age and chiropractic clinic, the difference was not significant (P = 0.066). The proportion obtaining a clinically important reduction of 1 h of crying was 63% in the treatment group and 47% in the control group (p = 0.037), and NNT was 6.5. We found no effect on any of the secondary outcomes. Conclusion Excessive crying was reduced by half an hour in favor of the group receiving chiropractic care compared with the control group, but not at a statistically significant level after adjustments. From a clinical perspective, the mean difference between the groups was small, but there were large individual differences, which emphasizes the need to investigate if subgroups of children, e.g. those with musculoskeletal problems, benefit more than others from chiropractic care. Trial registration Clinical Trials NCT02595515 , registered 2 November 2015