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When plants establish outside their native range, their ability to adapt to the new environment is influenced by both demography and dispersal. However, the relative importance of these two factors is poorly understood. To quantify the influence of demography and dispersal on patterns of genetic diversity underlying adaptation, we used data from a globally distributed demographic research network comprising 35 native and 18 nonnative populations of Plantago lanceolata Species-specific simulation experiments showed that dispersal would dilute demographic influences on genetic diversity at local scales. Populations in the native European range had strong spatial genetic structure associated with geographic distance and precipitation seasonality. In contrast, nonnative populations had weaker spatial genetic structure that was not associated with environmental gradients but with higher within-population genetic diversity. Our findings show that dispersal caused by repeated, long-distance, human-mediated introductions has allowed invasive plant populations to overcome environmental constraints on genetic diversity, even without strong demographic changes. The impact of invasive plants may, therefore, increase with repeated introductions, highlighting the need to constrain future introductions of species even if they already exist in an area.

Abstract Background Over one million yearly deaths are attributable to Streptococcus pneumoniae and people living with HIV are particularly vulnerable. Emerging penicillin non-susceptible Streptococcus pneumoniae (PNSP) challenges therapy of pneumococcal disease. The aim of this study was to determine the mechanisms of antibiotic resistance among PNSP isolates by next generation sequencing. Methods We assessed 26 PNSP isolates obtained from the nasopharynx from 537 healthy human immunodeficiency virus (HIV) infected adults in Dar es Salaam, Tanzania, participating in the randomized clinical trial CoTrimResist (ClinicalTrials.gov identifier: NCT03087890, registered on 23rd March, 2017). Next generation whole genome sequencing on the Illumina platform was used to identify mechanisms of resistance to antibiotics among PNSP. Results Fifty percent (13/26) of PNSP were resistant to erythromycin, of these 54% (7/13) and 46% (6/13) had MLSB phenotype and M phenotype respectively. All erythromycin resistant PNSP carried macrolide resistance genes; six isolates had mef(A)-msr(D), five isolates had both erm(B) and mef(A)-msr(D) while two isolates carried erm(B) alone. Isolates harboring the erm(B) gene had increased MIC (> 256 µg/mL) towards macrolides, compared to isolates without erm(B) gene (MIC 4-12 µg/mL) p

Abstract Background Anti-Müllerian hormone (AMH) is released by testicular Sertoli cells and of great importance during fetal male sexual development, but less is known about the role of circulating AMH during adulthood. In vitro studies have shown that vitamin D may induce AMH transcription, but a controlled trial investigating the possible effect of vitamin D on serum AMH has not been conducted in men. Methods A single-center, double-blinded, randomized placebo-controlled clinical trial (NCT01304927) conducted in Copenhagen, Denmark. A total of 307 infertile men were included and randomly assigned (1:1) to a single dose of 300,000 IU cholecalciferol followed by 1400 IU cholecalciferol + 500 mg of calcium daily (n = 151) or placebo (n = 156) for 150 days. Difference in serum AMH was a predefined secondary endpoint. Explorative outcomes were associations between serum AMH and gonadal function in infertile men. The primary endpoint was difference in semen quality and has previously been published. Results Infertile men in the lowest AMH tertile had significantly lower sperm concentration (∆T3-1 16 mill/mL (228%); P < 0.001), sperm count (∆T3-1 55 million (262%); P < 0.001), motile sperm count (∆T3-1 28 million (255%); P < 0.001), progressive motile sperm count (∆T3-1 18 million (300%); P < 0.001), testis size (∆T3-1 2.7 mL (16%); P < 0.001), serum inhibin B (∆T3-1 72 pg/mL (59%); P < 0.001), inhibin B/FSH ratio (∆T3-1 48 (145%); P < 0.001), and higher FSH (∆T3-1 2.6 (38%); P < 0.001) than the tertile of infertile men with highest serum AMH. Vitamin D supplementation had no effect on serum AMH compared with placebo treatment. Conclusions In infertile men, low serum AMH is associated with severely impaired gonadal function illustrated by poor semen quality and lower testosterone/LH ratio. Serum AMH in infertile men was not influenced by vitamin D supplementation.

Abstract The Centre for Marine Evolutionary Biology (CeMEB) at the University of Gothenburg, Sweden, was established in 2008 through a 10‐year research grant of 8.7 m€ to a team of senior researchers. Today, CeMEB members have contributed >500 scientific publications, 30 PhD theses and have organised 75 meetings and courses, including 18 three‐day meetings and four conferences. What are the footprints of CeMEB, and how will the centre continue to play a national and international role as an important node of marine evolutionary research? In this perspective article, we first look back over the 10 years of CeMEB activities and briefly survey some of the many achievements of CeMEB. We furthermore compare the initial goals, as formulated in the grant application, with what has been achieved, and discuss challenges and milestones along the way. Finally, we bring forward some general lessons that can be learnt from a research funding of this type, and we also look ahead, discussing how CeMEB’s achievements and lessons can be used as a springboard to the future of marine evolutionary biology.

Abstract Aim To describe and compare the clinical learning environment in community‐based home care and primary health care in postgraduate district nursing students' education. Design Cross‐sectional study design. Methods A convenience sample of postgraduate district nursing students was derived from five Swedish universities in 2016 and 2017. Results The postgraduate district nursing students were generally satisfied with the clinical learning environment in their clinical placement. In clinical placement, several factors affected the students' opportunities to learn, such as sufficiently meaningful learning situations with multidimensional content. A working environment that imposed psychosocial strain and high levels of stress among the staff negatively affected the students' learning. To further improve their learning from clinical practices, the students need preceptors who have the skills and competence required to support more advanced reflections and critical thinking on caring situations.

Abstract Background The primary aim was to evaluate the association between gestational diabetes and blood glucose levels and vulvovaginal yeast infections in pregnancy. Secondly, we clarified the possible associations between maternal and prenatal factors, and birth outcomes and yeast infections. Methods Three thousand nine hundred sixty-five pregnant women of the Kuopio Birth Cohort Study (KuBiCo) reported vulvovaginal yeast infections during pregnancy, via electronic questionnaires. Maternal and prenatal data, as well as clinical obstetric and early neonatal outcomes were registered during and after birth. The oral glucose tolerance test was performed on 3,079 women during pregnancy. Logistic regression analysis evaluated the possible multivariable associations between yeast infections, gestational diabetes and other prenatal and maternal factors. Results No association was detected between gestational diabetes or blood glucose levels and vulvovaginal yeast infections during pregnancy. In multivariable analysis, women with yeast infections were more often multiparous, with higher education and had used more often antibiotics during pregnancy compared to others. No significant associations were detected in multivariable analysis between infections, the mode of delivery, preterm birth, birth weight or Apgar scores. Conclusions Women with reported vulvovaginal yeast infections managed generally well during pregnancy. They had no more gestational diabetes or higher blood glucose levels and their newborns managed equally well during early neonatal period.

Abstract Background Myocardial infarction (MI) patients presenting without chest pain are a diagnostic challenge. They receive suboptimal prehospital management and have high mortality. To elucidate potential benefits of improved management, we analysed expected outcome among non-chest pain MI patients if hypothetically they (1) received emergency ambulances/acetylsalicylic acid (ASA) as often as observed for chest pain patients, and (2) all received emergency ambulance/ASA. Methods We sampled calls to emergency and non-emergency medical services for patients hospitalized with MI within 24 h and categorized calls as chest pain/non-chest pain. Outcomes were 30-day mortality and a 1-year combined outcome of re-infarction, heart failure admission, and mortality. Targeted minimum loss-based estimation was used for all statistical analyses. Results Among 5418 calls regarding MI patients, 24% (1309) were recorded with non-chest pain. In total, 90% (3689/4109) of chest pain and 40% (525/1309) of non-chest pain patients received an emergency ambulance, and 73% (2668/3632) and 37% (192/518) of chest pain and non-chest pain patients received prehospital ASA. Providing ambulances to all non-chest pain patients was not associated with improved survival. Prehospital administration of ASA to all emergency ambulance transports of non-chest pain MI patients was expected to reduce 30-day mortality by 5.3% (CI 95%: [1.7%;9%]) from 12.8% to 7.4%. No significant reduction was found for the 1-year combined outcome (2.6% CI 95% [− 2.9%;8.1%]). In comparison, the observed 30-day mortality was 3% among ambulance-transported chest pain MI patients. Conclusions Our study found large differences in the prehospital management of MI patients with and without chest pain. Improved prehospital ASA administration to non-chest pain MI patients could possibly reduce 30-day mortality, but long-term effects appear limited. Non-chest pain MI patients are difficult to identify prehospital and possible unintended effects of ASA might outweigh the potential benefits of improving the prehospital management. Future research should investigate ways to improve the prehospital recognition of MI in the absence of chest pain.

Abstract Background Urinary tract infection (UTI) is particularly common in young women and the elderly. The Emergency Medical Services (EMS) in Copenhagen, Denmark can be reached by calling either of two dedicated telephone lines: 1–1-2 in case of an emergency and 1813 during general practitioner’s (GP) out-of-office hours (OOH). This study investigated characteristics of patients with symptoms of UTI calling the Copenhagen EMS and the response they received. Methods A retrospective observational cohort study was conducted in which 7.5 years of telephone data on UTI from the EMS in Copenhagen were analyzed. Descriptive statistics and multinomial logistic regression were used to analyze patient characteristics, the timing of the incident and response. Patients’ age and gender were assessed and the use of urinary catheters, the timing of the incident, and the impact on the response were evaluated. Results A total of 278.961 calls were included (78% female, mean age 47), with an average of 120 patients with UTI symptoms calling each day. Most people contacted the 1813-medical helpline (98%) and of those, the majority were referred to the emergency department (ED)(37%). Patients were more likely to be referred to the ED during the weekend compared to a weekday and less likely during OOH compared to in-office hours (IH). Patients with a urinary catheter were more likely to receive specialized care referred to as ‘other’. For the smaller proportion of patients calling 1–1-2, most people got a B (urgent) response (1.5%). The most likely response to be given was an A (emergency) or F (non-emergency) response during OOH compared to IH and on weekends compared to weekdays. Patients with a urinary catheter were more likely to receive a D (unmonitored transport) response. Conclusions Since 2015, there was a decrease in 1813 antibiotic prescription rates and a subsequent increase in referral to the ED of UTI patients. Patients were referred less to the ED during OOH as they were likely to be sent to their GP the next day. During the weekend, patients were referred more to the ED for the likely reason that their GP is closed.

Abstract Background Every year an emergency medical technician or paramedic treats and transports up to several hundred patients. Only some patients are acutely seriously ill, and a few of these show only discrete signs and symptoms of their condition. This study aims to describe patients who died within 48 h of being admitted non-emergently to hospital by ambulance, examine the extent to which critically ill patients are recognized prehospitally, and identify clinical warning signs that might be frequently overlooked. Method Registry based follow-up study on patients receiving an ambulance from the Copenhagen EMS in 2018. Data was included regarding the dispatch of the ambulance from the emergency services disposition system, ICD-10 hospital admission diagnoses from the National Patient Register, 48-h mortality from the Central Person Register and assessment and treatment in the ambulance by reviewing the electronic pre-hospital patient record. Results In 2018 2279 patients died within 48 h after contact with the EMS, 435 cases met inclusion criteria. The patients’ median age was 83 years (IQR 75–90), and 374 (86.0%) had one or more underlying serious medical conditions. A triage category based on vitals and presentation was not assigned by the EMS in 286 (68.9%) cases, of which 38 (13.3%) would meet red and 126 (44.1%) orange criteria. For 409 (94.0%) patients, it was estimated that death within 48 h could not have been avoided prehospitally, and for 26 (6.0%) patients it was uncertain. We found 27 patients with acute aortic syndrome as admission diagnosis, of these nine (33.3%) had not been admitted urgently to a hospital with vascular surgery specialty. Conclusions It was estimated that death within 48 h could generally not be avoided prehospitally. The patients’ median age was 83 years, and they often had serious comorbidity. Patients whose vital parameters met red or orange triage criteria were to a lesser degree triaged prehospitally, compared to patients in the yellow or green categories. Patients with acute aortic syndrome were not recognized by EMS 33.3% of the time.

Abstract Background Pediatric out-of-hospital cardiac arrest (POHCA) has received limited attention. All causes of POHCA and outcomes were examined during a 4-year period in a Danish nationwide register and prehospital medical records. The aim was to describe the incidence, reversible causes, and survival rates for POHCA in Denmark. Methods This is a registry-based follow-up cohort study. All POHCA for a 4-year period (2016–2019) in Denmark were included. All prehospital medical records for the included subjects were reviewed manually by five independent raters establishing whether a presumed reversible cause could be assigned. Results We identified 173 cases within the study period. The median incidence of POHCA in the population below 17 years of age was 4.2 per 100,000 persons at risk. We found a presumed reversible cause in 48.6% of cases, with hypoxia being the predominant cause of POHCA (42.2%). The thirty-day survival was 40%. Variations were seen across age groups, with the lowest survival rate in cases below 1 year of age. Defibrillators were used more frequently among survivors, with 16% of survivors defibrillated bystanders as opposed to 1.9% in non-survivors and 24% by EMS personnel as opposed to 7.8% in non-survivors. The differences in initial rhythm being shockable was 34% for survivors and 16% for non-survivors. Conclusion We found pediatric out-of-hospital cardiac arrests was a rare event, with higher incidence and mortality in infants compared to other age groups of children. Use of defibrillators was disproportionally higher among survivors. Hypoxia was the most common presumed cause among all age groups.

Abstract Background Environmental exposures to industrial chemicals, including perfluoroalkyl substances (PFAS), may play a role in bone development and future risk of osteoporosis. However, as prospective evidence is limited, the role of developmental PFAS exposures in bone density changes in childhood is unclear. The objective of this study was to estimate associations between serum-PFAS concentrations measured in infancy and early childhood and areal bone mineral density (aBMD) measured at age 9 years in a birth cohort of children from the Faroe Islands. Methods We prospectively measured concentrations of five PFAS in cord serum and serum collected at 18 months, 5 years and 9 years, and conducted whole-body DXA scans at the 9-year clinical visit. Our study included 366 mother-child pairs with DXA scans and at least one PFAS measurement. We estimated covariate-adjusted associations of individual PFAS concentrations with age-, sex- and height-adjusted aBMD z-scores using multivariable regression models and applied formal mediation analysis to estimate the possible impact of by several measures of body composition. We also evaluated whether associations were modified by child sex. Results We found PFAS exposures in childhood to be negatively associated with aBMD z-scores, with the strongest association seen for perfluorononanoic acid (PFNA) at age 5 years. A doubling in age-5 PFNA was associated with a 0.15 decrease in aBMD z-score (95% CI: − 0.26, − 0.039). The PFNA-aBMD association was significantly stronger in males than females, although effect modification by sex was not significant for other PFAS exposures. Results from the mediation analysis suggested that any potential associations between aBMD and 18-month PFAS concentrations may be mediated by total body fat and BMI, although most estimated total effects for PFAS exposures at age 18 months were non-significant. PFAS exposures at age 9 were not associated with age-9 aBMD z-scores. Conclusions The PFAS-aBMD associations identified in this and previous studies suggest that bone may be a target tissue for PFAS. Pediatric bone density has been demonstrated to strongly track through young adulthood and possibly beyond; therefore, these prospective results may have important public health implications.

Tetraspanin CD37 deficiency has been reported as a prognostic marker for aggressive B-cell lymphoma. Here, the authors show that CD37 interacts with the fatty acid transporter 1 to inhibit palmitate uptake and its deficiency leads to increased fatty acid metabolism which promotes tumorigenesis in B-cell lymphoma.

Objectives: Gastrointestinal colonization of extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-PE) is of concern because prior colonization increases risk for subsequent infections. To date, the link between ESBL-PE faecal carriage and the risk of subsequent ESBL-PE infection has not been well established, and information on carriage of such pathogens among children with invasive infections such as bloodstream infections (BSI) remains to be explored worldwide. Methods: This cross-sectional study was conducted among children under the age of 5 years admitted for febrile illness in Dar es Salaam, Tanzania, between March 2017 and July 2018. We used rectal swabs to screen for ESBL-PE using selective media, ChromID ESBL. Bacterial isolates were identified by MALDI-TOF. Blood cultures were drawn from all children. Antimicrobial susceptibility testing was done using a disk diffusion method. ESBL alleles were identified by real-time PCR and sequencing. Results: The overall prevalence of ESBL-PE carriage was 56% (112/200) and was highest among children 4 to 6 months old (17/21, 81%) (P = 0.05). Children with BSI had high ESBL-PE carriage (78.4%) compared to those without BSI (53.1%) (P = 0.02; aOR 3.4, 95% confidence interval 1.20–9.58). The most common isolate was E. coli (64/112, 45%). Sixteen pairs of ESBL-PE isolates (from the gut and from blood) had a similar antimicrobial susceptibility profile. We detected blaCTX-M gene in 97% of all phenotypically detected ESBL-PE; among those, blaCTX-M-15 was dominant (99%). Conclusion: We report a high prevalence of ESBL-PE faecal carriage among children with BSI in Tanzania. Colonization of ESBL-PE was a risk factor for ESBL-BSI.

* Context.--Perinatal death is an increasingly important problem as the coronavirus disease 2019 (COVID-19) pandemic continues, but the mechanism of death has been unclear. Objective.--To evaluate the role of the placenta in causing stillbirth and neonatal death following maternal infection with COVID-19 and confirmed placental positivity for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Design.--Case-based retrospective clinicopathologic analysis by a multinational group of 44 perinatal specialists from 12 countries of placental and autopsy pathology findings from 64 stillborns and 4 neonatal deaths having placentas testing positive for SARS-CoV-2 following delivery to mothers with COVID-19. Results.--Of the 3 findings constituting SARS-CoV-2 placentitis, all 68 placentas had increased fibrin deposition and villous trophoblast necrosis and 66 had chronic histiocytic intervillositis. Sixty-three placentas had massive perivillous fibrin deposition. Severe destructive placental disease from SARS-CoV-2 placentitis averaged 77.7% tissue involvement. Other findings included multiple intervillous thrombi (37%; 25 of 68) and chronic villitis (32%; 22 of 68). The majority (19; 63%) of the 30 autopsies revealed no significant fetal abnormalities except for intrauterine hypoxia and asphyxia. Among all 68 cases, SARS-CoV-2 was detected from a body specimen in 16 of 28 cases tested, most frequently from nasopharyngeal swabs. Four autopsied stillborns had SARS-CoV-2 identified in internal organs. Conclusions.--The pathology abnormalities composing SARS-CoV-2 placentitis cause widespread and severe placental destruction resulting in placental malperfusion and insufficiency. In these cases, intrauterine and perinatal death likely results directly from placental insufficiency and fetal hypoxic-ischemic injury. There was no evidence that SARS-CoV-2 involvement of the fetus had a role in causing these deaths., The emergence of new viral diseases has always created anxiety among persons at risk for infection, but perhaps this is most true for pregnant women, who fear not only for [...]

Agriculture is an important link to many issues that challenge society today, including adaptation to and mitigation of climate change, food security, and communicable and non-communicable diseases in animals and humans. Transformation of agriculture and food systems has become a priority for a range of federal agencies and global organizations. It is imperative that food and agricultural researchers effectively harness the global convergence of priorities to overcome research “silos” through deep and sustained systemic change. Herein, we identify intersections in federal and global initiatives encompassing climate adaptation and mitigation; human health and nutrition; animal health and welfare; food safety and security; and equity and inclusion. Many agencies and organizations share these priorities, but efforts to address them remain uncoordinated and opportunities for collaboration untapped. Based on the interconnectedness of the identified priority areas, we present a research framework to catalyze agricultural transformation, beginning with the research enterprise. We propose that transformation in agricultural research should incorporate (1) innovation, (2) integration, (3) implementation, and (4) evaluation. This framework provides approaches for food and agricultural research to contribute to sustainable, flexible, and coordinated transformation in the agricultural sector.

Worldwide, fetal growth restriction (FGR) affects 7%–10% of pregnancies, or roughly 20.5 million infants, each year. FGR increases not only neonatal mortality and morbidity but also the risk of obesity in later life. Currently, the molecular mechanisms by which FGR “programs” an obese phenotype are not well understood. Studies demonstrate that FGR females are more prone to obesity compared to males; however, the molecular mechanisms that lead to the sexually dimorphic programming of FGR are not known. Thus, we hypothesized that FGR leads to the sexually dimorphic programming of preadipocytes and reduces their ability to differentiate into mature adipocytes. To test the hypothesis, we utilized a maternal hyperthermia-induced placental insufficiency to restrict fetal growth in sheep. We collected perirenal adipose tissue from near-term (∼140 days gestation) male and female FGR and normal-weight fetal lambs (N = 4 to 5 in each group), examined the preadipocytes’ differentiation potential, and identified differential mRNA transcript expression in perirenal adipose tissue. Male FGR fetuses have a lower cellular density (nuclei number/unit area) compared to control male fetuses. However, no difference was observed in female FGR fetuses compared to control female fetuses. In addition, the ability of preadipocytes to differentiate into mature adipocytes with fat accumulation was impaired in male FGR fetuses, but this was not observed in female FGR fetuses. Finally, we examined the genes and pathways involved in the sexually dimorphic programming of obesity by FGR. On enrichment of differentially expressed genes in males compared to females, the Thermogenesis KEGG Pathway was downregulated, and the Metabolic and Steroid Biosynthesis KEGG pathways were upregulated. On enrichment of differentially expressed genes in male FGR compared to male control, the Steroid Biosynthesis KEGG Pathway was downregulated, and the PPAR Signaling KEGG pathway was upregulated. No pathways were altered in females in response to growth restriction in perirenal adipose tissue. Thus, the present study demonstrates a sexually dimorphic program in response to growth restriction in sheep fetal perirenal adipose tissue.

BackgroundPreventing infection in healthcare workers (HCWs) is crucial for protecting healthcare systems during the COVID-19 pandemic. Here, we investigated the seroepidemiology of SARS-CoV-2 in HCWs in Norway with low-transmission settings.MethodsFrom March 2020, we recruited HCWs at four medical centres. We determined infection by SARS-CoV-2 RT-PCR and serological testing and evaluated the association between infection and exposure variables, comparing our findings with global data in a meta-analysis. Anti-spike IgG antibodies were measured after infection and/or vaccination in a longitudinal cohort until June 2021.ResultsWe identified a prevalence of 10.5% (95% confidence interval, CI: 8.8–12.3) in 2020 and an incidence rate of 15.0 cases per 100 person-years (95% CI: 12.5–17.8) among 1,214 HCWs with 848 person-years of follow-up time. Following infection, HCWs (n = 63) mounted durable anti-spike IgG antibodies with a half-life of 4.3 months since their seropositivity. HCWs infected with SARS-CoV-2 in 2020 (n = 46) had higher anti-spike IgG titres than naive HCWs (n = 186) throughout the 5 months after vaccination with BNT162b2 and/or ChAdOx1-S COVID-19 vaccines in 2021. In a meta-analysis including 20 studies, the odds ratio (OR) for SARS-CoV-2 seropositivity was significantly higher with household contact (OR 12.6; 95% CI: 4.5–35.1) and occupational exposure (OR 2.2; 95% CI: 1.4–3.2).ConclusionWe found high and modest risks of SARS-CoV-2 infection with household and occupational exposure, respectively, in HCWs, suggesting the need to strengthen infection prevention strategies within households and medical centres. Infection generated long-lasting antibodies in most HCWs; therefore, we support delaying COVID-19 vaccination in primed HCWs, prioritising the non-infected high-risk HCWs amid vaccine shortage.

Objectives To explore health problems and the recovery process after being deployed in a major incident.Design Qualitative, explorative design.Setting Ambulance services in Sweden.Participants and methods Semistructured, individual two-session interviews with 15 ambulance nurses with the experience of being deployed to major incidents were conducted. Data were analysed with thematic analysis.Results Being deployed in major incidents was perceived to be straining and led to both physical health problems and distress. To recover, the ambulance nurses strived to use strategies to distance themselves from the situation and created supportive conditions for their recovery, and if successful, the experiences led to both professional and personal growth and self-awareness. However, being deployed in major incidents without significant preparedness or experience could harm individuals and, in the worst case, end their career.Conclusions A successful recovery from the physical and mental exhaustion experienced after being deployed in a major incident required both individual abilities and self-care strategies as well as a supportive working environment. Supporting individual recovery strategies and following up on physical and mental well-being over time should be part of all ambulance services procedures after major incidents.

Formic acid is one of the main weak acids in lignocellulosic hydrolysates that is known to be inhibitory to yeast growth even at low concentrations. In this study, we employed a CRISPR interference (CRISPRi) strain library comprising >9000 strains encompassing >98% of all essential and respiratory growth-essential genes, to study formic acid tolerance in Saccharomyces cerevisiae. To provide quantitative growth estimates on formic acid tolerance, the strains were screened individually on solid medium supplemented with 140 mM formic acid using the Scan-o-Matic platform. Selected resistant and sensitive strains were characterized in liquid medium supplemented with formic acid and in synthetic hydrolysate medium containing a combination of inhibitors. Strains with gRNAs targeting genes associated with chromatin remodeling were significantly enriched for strains showing formic acid tolerance. In line with earlier findings on acetic acid tolerance, we found genes encoding proteins involved in intracellular vesicle transport enriched among formic acid sensitive strains. The growth of the strains in synthetic hydrolysate medium followed the same trend as when screened in medium supplemented with formic acid. Strains sensitive to formic acid had decreased growth in the synthetic hydrolysate and all strains that had improved growth in the presence of formic acid also grew better in the hydrolysate medium. Systematic analysis of CRISPRi strains allowed identification of genes involved in tolerance mechanisms and provided novel engineering targets for bioengineering strains with increased resistance to inhibitors in lignocellulosic hydrolysates.

Summary: Background: The burden of COVID-19 in children and adolescents has increased during the delta and omicron waves, necessitating studies of long-term symptoms such as fatigue, dyspnoea and cognitive problems. Furthermore, immune responses in relation to persisting symptoms in younger people have not been well characterised. In this cohort study, we investigated the role of antibodies, vaccination and omicron reinfection upon persisting and long-term symptoms up to 8 months post-delta infection. Methods: SARS-CoV-2 RT-PCR positive participants (n = 276, aged 10–20 years) were prospectively recruited in August 2021. We recorded the major symptoms of post COVID-19 condition and collected serum samples 3- and 8-months post delta infection. Binding antibodies were measured by spike IgG ELISA, and surrogate neutralising antibodies against Wuhan and delta variants by the hemagglutination test (HAT). Findings: After delta infection, persisting symptoms at 3 months were significantly associated with higher delta antibody titres (OR 2.97, 95% CI 1.57–6.04, p = 0.001). Asymptomatic acute infection compared to symptomatic infection lowered the risk of persisting (OR 0.13, 95% CI 0.02–0.55, p = 0.013) and long-term (OR 0.28 95% CI 0.11–0.66, p = 0.005) symptoms at 3 and 8 months, respectively. Adolescents (16–20 years) were more likely to have long-term symptoms compared to children (10–15 years) (OR 2.44, 95% CI 1.37–4.41, p = 0.003). Interpretation: This clinical and serological study compares long-term symptoms after delta infection between children and adolescents. The association between high antibody titres and persisting symptoms suggest the involvement of an immune mechanism. Similarly to adults, the dominant long-term symptoms in children are fatigue, dyspnoea and cognitive problems. Funding: This work was funded by the Ministry of Health and Care Services, Norway, the University of Bergen, Norway and Helse Vest, Norway (F-12621).

Type 2 diabetes mellitus (T2DM) poses a higher risk for complications in South Asian individuals compared to other ethnic groups. To shed light on potential mediating factors, we investigated lipidomic changes in plasma of Dutch South Asians (DSA) and Dutch white Caucasians (DwC) with and without T2DM and explore their associations with clinical features. Using a targeted quantitative lipidomics platform, monitoring over 1000 lipids across 17 classes, along with 1H NMR based lipoprotein analysis, we studied 51 healthy participants (21 DSA, 30 DwC) and 92 T2DM patients (47 DSA, 45 DwC) from the MAGNetic resonance Assessment of VICTOza efficacy in the Regression of cardiovascular dysfunction in type 2 dIAbetes mellitus (MAGNA VICTORIA) study. This comprehensive mapping of the circulating lipidome allowed us to identify relevant lipid modules through unbiased weighted correlation network analysis, as well as disease and ethnicity related key mediatory lipids. Significant differences in lipidomic profiles, encompassing various lipid classes and species, were observed between T2DM patients and healthy controls in both the DSA and DwC populations. Our analyses revealed that healthy DSA, but not DwC, controls already exhibited a lipid profile prone to develop T2DM. Particularly, in DSA-T2DM patients, specific lipid changes correlated with clinical features, particularly diacylglycerols (DGs), showing significant associations with glycemic control and renal function. Our findings highlight an ethnic distinction in lipid modules influencing clinical outcomes in renal health. We discover distinctive ethnic disparities of the circulating lipidome and identify ethnicity-specific lipid markers. Jointly, our discoveries show great potential as personalized biomarkers for the assessment of glycemic control and renal function in DSA-T2DM individuals.