Auditory processing in mammals begins in the peripheral inner ear and extends to the auditory cortex. Sound is transduced from mechanical stimuli into electrochemical signals of hair cells, which relay auditory information via the primary auditory neurons to cochlear nuclei. Information is subsequently processed in the superior olivary complex, lateral lemniscus, and inferior colliculus and projects to the auditory cortex via the medial geniculate body in the thalamus. Recent advances have provided valuable insights into the development and functioning of auditory structures, complementing our understanding of the physiological mechanisms underlying auditory processing. This comprehensive review explores the genetic mechanisms required for auditory system development from the peripheral cochlea to the auditory cortex. We highlight transcription factors and other genes with key recurring and interacting roles in guiding auditory system development and organization. Understanding these gene regulatory networks holds promise for developing novel therapeutic strategies for hearing disorders, benefiting millions globally.

• MeSH
• Humans MeSH
• Brain metabolism   growth & development   MeSH
• Hearing * physiology   MeSH
• Auditory Pathways * physiology   MeSH
• Auditory Cortex metabolism   physiology   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

BACKGROUND: Despite concerns about worsening pregnancy outcomes resulting from healthcare restrictions, economic difficulties and increased stress during the COVID-19 pandemic, preterm birth (PTB) rates declined in some countries in 2020, while stillbirth rates appeared stable. Like other shocks, the pandemic may have exacerbated existing socioeconomic disparities in pregnancy, but this remains to be established. Our objective was to investigate changes in PTB and stillbirth by socioeconomic status (SES) in European countries. METHODS: The Euro-Peristat network implemented this study within the Population Health Information Research Infrastructure (PHIRI) project. A common data model was developed to collect aggregated tables from routine birth data for 2015-2020. SES was based on mother's educational level or area-level deprivation/maternal occupation if education was unavailable and harmonized into low, medium and high SES. Country-specific relative risks (RRs) of PTB and stillbirth for March to December 2020, adjusted for linear trends from 2015 to 2019, by SES group were pooled using random effects meta-analysis. RESULTS: Twenty-one countries provided data on perinatal outcomes by SES. PTB declined by an average 4% in 2020 {pooled RR: 0.96 [95% confidence intervals (CIs): 0.94-0.97]} with similar estimates across all SES groups. Stillbirths rose by 5% [RR: 1.05 (95% CI: 0.99-1.10)], with increases of between 3 and 6% across the three SES groups, with overlapping confidence limits. CONCLUSIONS: PTB decreases were similar regardless of SES group, while stillbirth rates rose without marked differences between groups.

• MeSH
• COVID-19 * epidemiology   MeSH
• Health Status Disparities MeSH
• Adult MeSH
• Humans MeSH
• Stillbirth * epidemiology   MeSH
• Infant, Newborn MeSH
• Pandemics MeSH
• Premature Birth * epidemiology   MeSH
• SARS-CoV-2 * MeSH
• Socioeconomic Factors MeSH
• Socioeconomic Disparities in Health MeSH
• Social Class MeSH
• Pregnancy MeSH
• Pregnancy Outcome epidemiology   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Infant, Newborn MeSH
• Pregnancy MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Europe MeSH

BACKGROUND: During the first epidemic wave, COVID-19 surveillance focused on quantifying the magnitude and the escalation of a growing global health crisis. The scientific community first assessed risk through basic indicators, such as the number of cases or rates of new cases and deaths, and later began using other direct impact indicators to conduct more detailed analyses. We aimed at synthesizing the scientific community's contribution to assessing the direct impact of the COVID-19 pandemic on population health through indicators reported in research papers. METHODS: We conducted a rapid scoping review to identify and describe health indicators included in articles published between January 2020 and June 2021, using one strategy to search PubMed, EMBASE and WHO COVID-19 databases. Sixteen experts from European public health institutions screened papers and retrieved indicator characteristics. We also asked in an online survey how the health indicators were added to and used in policy documents in Europe. RESULTS: After reviewing 3891 records, we selected a final sample of 67 articles and 233 indicators. We identified 52 (22.3%) morbidity indicators from 33 articles, 105 severity indicators (45.1%, 27 articles) and 68 mortality indicators (29.2%, 51). Respondents from 22 countries completed 31 questionnaires, and the majority reported morbidity indicators (29, 93.5%), followed by mortality indicators (26, 83.9%). CONCLUSIONS: The indicators collated here might be useful to assess the impact of future pandemics. Therefore, their measurement should be standardized to allow for comparisons between settings, countries and different populations.

• MeSH
• COVID-19 * mortality   epidemiology   MeSH
• Humans MeSH
• Morbidity MeSH
• Mortality trends   MeSH
• Pandemics MeSH
• Severity of Illness Index MeSH
• Health Status Indicators MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Geographicals
• Europe MeSH

• MeSH
• Genome-Wide Association Study MeSH
• Mental Disorders * genetics   MeSH
• Phenotype * MeSH
• Genetic Predisposition to Disease genetics   MeSH
• Humans MeSH
• Multifactorial Inheritance * genetics   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Editorial MeSH

OBJECTIVES: To characterize the genetic basis of azithromycin resistance in Escherichia coli and Salmonella collected within the EU harmonized antimicrobial resistance (AMR) surveillance programme in 2014-18 and the Danish AMR surveillance programme in 2016-19. METHODS: WGS data of 1007 E. coli [165 azithromycin resistant (MIC > 16 mg/L)] and 269 Salmonella [29 azithromycin resistant (MIC > 16 mg/L)] were screened for acquired macrolide resistance genes and mutations in rplDV, 23S rRNA and acrB genes using ResFinder v4.0, AMRFinder Plus and custom scripts. Genotype-phenotype concordance was determined for all isolates. Transferability of mef(C)-mph(G)-carrying plasmids was assessed by conjugation experiments. RESULTS: mph(A), mph(B), mef(B), erm(B) and mef(C)-mph(G) were detected in E. coli and Salmonella, whereas erm(C), erm(42), ere(A) and mph(E)-msr(E) were detected in E. coli only. The presence of macrolide resistance genes, alone or in combination, was concordant with the azithromycin-resistant phenotype in 69% of isolates. Distinct mph(A) operon structures were observed in azithromycin-susceptible (n = 50) and -resistant (n = 136) isolates. mef(C)-mph(G) were detected in porcine and bovine E. coli and in porcine Salmonella enterica serovar Derby and Salmonella enterica 1,4, [5],12:i:-, flanked downstream by ISCR2 or TnAs1 and associated with IncIγ and IncFII plasmids. CONCLUSIONS: Diverse azithromycin resistance genes were detected in E. coli and Salmonella from food-producing animals and meat in Europe. Azithromycin resistance genes mef(C)-mph(G) and erm(42) appear to be emerging primarily in porcine E. coli isolates. The identification of distinct mph(A) operon structures in susceptible and resistant isolates increases the predictive power of WGS-based methods for in silico detection of azithromycin resistance in Enterobacterales.

• MeSH
• Anti-Bacterial Agents * pharmacology   MeSH
• Azithromycin * pharmacology   MeSH
• Genes, Bacterial MeSH
• Drug Resistance, Bacterial * genetics   MeSH
• Epidemiological Monitoring MeSH
• Escherichia coli * drug effects   genetics   MeSH
• Genotype MeSH
• Escherichia coli Infections microbiology   MeSH
• Macrolides pharmacology   MeSH
• Meat * microbiology   MeSH
• Microbial Sensitivity Tests * MeSH
• Plasmids genetics   MeSH
• Swine MeSH
• Salmonella * drug effects   genetics   isolation & purification   MeSH
• Whole Genome Sequencing MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Europe MeSH

OBJECTIVE: Ankylosing Spondylitis Disease Activity Score based on C-reactive protein (ASDAS-CRP) is recommended over ASDAS based on erythrocyte sedimentation rate (ASDAS-ESR) to assess disease activity in axial spondyloarthritis (axSpA). Although ASDAS-CRP and ASDAS-ESR are not interchangeable, the same disease activity cut-offs are used for both. We aimed to estimate optimal ASDAS-ESR values corresponding to the established ASDAS-CRP cut-offs (1.3, 2.1, and 3.5) and investigate the potential improvement of level of agreement between ASDAS-ESR and ASDAS-CRP disease activity states when applying these estimated cut-offs. METHODS: We used data from patients with axSpA from 9 European registries initiating a tumor necrosis factor inhibitor. ASDAS-ESR cut-offs were estimated using the Youden index. The level of agreement between ASDAS-ESR and ASDAS-CRP disease activity states was compared against each other. RESULTS: In 3664 patients, mean ASDAS-CRP was higher than ASDAS-ESR at both baseline (3.6 and 3.4, respectively) and aggregated follow-up at 6, 12, or 24 months (1.9 and 1.8, respectively). The estimated ASDAS-ESR values corresponding to the established ASDAS-CRP cut-offs were 1.4, 1.9, and 3.3. By applying these cut-offs, the proportion of discordance between disease activity states according to ASDAS-ESR and ASDAS-CRP decreased from 22.93% to 19.81% in baseline data but increased from 27.17% to 28.94% in follow-up data. CONCLUSION: We estimated the optimal ASDAS-ESR values corresponding to the established ASDAS-CRP cut-off values. However, applying the estimated cut-offs did not increase the level of agreement between ASDAS-ESR and ASDAS-CRP disease activity states to a relevant degree. Our findings did not provide evidence to reject the established cut-off values for ASDAS-ESR.

• MeSH
• Spondylitis, Ankylosing * blood   diagnosis   MeSH
• Axial Spondyloarthritis * blood   diagnosis   MeSH
• C-Reactive Protein * analysis   MeSH
• Adult MeSH
• Blood Sedimentation * MeSH
• Middle Aged MeSH
• Humans MeSH
• Registries MeSH
• Severity of Illness Index * MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

• MeSH
• Cell Differentiation MeSH
• Cell Lineage MeSH
• Hematopoietic Stem Cells * cytology   metabolism   MeSH
• Hematopoiesis MeSH
• Humans MeSH
• Phosphoprotein Phosphatases metabolism   genetics   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Comment MeSH
• Editorial MeSH

• MeSH
• Precursor Cell Lymphoblastic Leukemia-Lymphoma * therapy   epidemiology   mortality   MeSH
• Leukemia, Myeloid, Acute * therapy   MeSH
• Adult MeSH
• Incidence MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Central Nervous System Neoplasms * therapy   MeSH
• Recurrence MeSH
• Aged MeSH
• Hematopoietic Stem Cell Transplantation * methods   MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Letter MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Europe MeSH

• MeSH
• Drug Resistance, Neoplasm MeSH
• Dexamethasone * therapeutic use   administration & dosage   MeSH
• Phenylalanine therapeutic use   analogs & derivatives   MeSH
• Quality of Life * MeSH
• Middle Aged MeSH
• Humans MeSH
• Neoplasm Recurrence, Local drug therapy   MeSH
• Multiple Myeloma * drug therapy   MeSH
• Antineoplastic Combined Chemotherapy Protocols * therapeutic use   adverse effects   MeSH
• Recurrence MeSH
• Aged MeSH
• Treatment Outcome MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Clinical Trial, Phase III MeSH
• Multicenter Study MeSH
• Research Support, Non-U.S. Gov't MeSH

The primary and prespecified updated analyses of ICARIA-MM (clinicaltrial gov. Identifier: NCT02990338) demonstrated improved progression-free survival (PFS) and a benefit in overall survival (OS) was reported with the addition of isatuximab, an anti-CD38 monoclonal antibody, to pomalidomide-dexamethasone (Pd) in patients with relapsed/refractory multiple myeloma. Here, we report the final OS analysis. This multicenter, randomized, open-label, phase III study included patients who had received and failed ≥2 previous therapies, including lenalidomide and a proteasome inhibitor. Between January 10, 2017, and February 2, 2018, 307 patients were randomized (1:1) to isatuximab-pomalidomide-dexamethasone (Isa-Pd; N=154) or Pd (N=153), stratified based on age (<75 vs. ≥75 years) and number of previous lines of therapy (2-3 vs. >3). At data cutoff for the final OS analysis after 220 OS events (January 27, 2022), median follow-up duration was 52.4 months. Median OS was 24.6 months (95% confidence interval [CI]: 20.3-31.3) with Isa-Pd and 17.7 months (95% CI: 14.4- 26.2) with Pd (hazard ratio=0.78; 95% CI: 0.59-1.02; 1-sided P=0.0319). Despite subsequent daratumumab use in the Pd group and its potential benefit on PFS in the first subsequent therapy line, median PFS2 was significantly longer with Isa-Pd versus Pd (17.5 vs. 12.9 months; log-rank 1-sided P=0.0091). In this analysis, Isa-Pd continued to be efficacious and well tolerated after follow-up of approximately 52 months, contributing to a clinically meaningful, 6.9-month improvement in median OS in patients with relapsed/refractory multiple myeloma.

• MeSH
• Survival Analysis MeSH
• Drug Resistance, Neoplasm MeSH
• Dexamethasone * administration & dosage   MeSH
• Adult MeSH
• Antibodies, Monoclonal, Humanized * administration & dosage   therapeutic use   MeSH
• Middle Aged MeSH
• Humans MeSH
• Multiple Myeloma * drug therapy   mortality   pathology   MeSH
• Antineoplastic Combined Chemotherapy Protocols * therapeutic use   adverse effects   MeSH
• Recurrence MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Thalidomide * analogs & derivatives   administration & dosage   MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial, Phase III MeSH
• Multicenter Study MeSH
• Research Support, Non-U.S. Gov't MeSH
• Randomized Controlled Trial MeSH