BMAL1-Driven Tissue Clocks Respond Independently to Light to Maintain Homeostasis.

Circadian rhythms control organismal physiology throughout the day. At the cellular level, clock regulation is established by a self-sustained Bmal1-dependent transcriptional oscillator network. However, it is still unclear how different tissues achieve a synchronized rhythmic physiology. That is, do they respond independently to environmental signals, or require interactions with each other to do so? We show that unexpectedly, light synchronizes the Bmal1-dependent circadian machinery in single tissues in the absence of Bmal1 in all other tissues. Strikingly, light-driven tissue autonomous clocks occur without rhythmic feeding behavior and are lost in constant darkness. Importantly, tissue-autonomous Bmal1 partially sustains homeostasis in otherwise arrhythmic and prematurely aging animals. Our results therefore support a two-branched model for the daily synchronization of tissues: an autonomous response branch, whereby light entrains circadian clocks without any commitment of other Bmal1-dependent clocks, and a memory branch using other Bmal1-dependent clocks to "remember" time in the absence of external cues.

Identity Noise and Adipogenic Traits Characterize Dermal Fibroblast Aging.

During aging, stromal functions are thought to be impaired, but little is known whether this stems from changes of fibroblasts. Using population- and single-cell transcriptomics, as well as long-term lineage tracing, we studied whether murine dermal fibroblasts are altered during physiological aging under different dietary regimes that affect longevity. We show that the identity of old fibroblasts becomes undefined, with the fibroblast states present in young skin no longer clearly demarcated. In addition, old fibroblasts not only reduce the expression of genes involved in the formation of the extracellular matrix, but also gain adipogenic traits, paradoxically becoming more similar to neonatal pro-adipogenic fibroblasts. These alterations are sensitive to systemic metabolic changes: long-term caloric restriction reversibly prevents them, whereas a high-fat diet potentiates them. Our results therefore highlight loss of cell identity and the acquisition of adipogenic traits as a mechanism underlying cellular aging, which is influenced by systemic metabolism.

Aged Stem Cells Reprogram Their Daily Rhythmic Functions to Adapt to Stress.

Normal homeostatic functions of adult stem cells have rhythmic daily oscillations that are believed to become arrhythmic during aging. Unexpectedly, we find that aged mice remain behaviorally circadian and that their epidermal and muscle stem cells retain a robustly rhythmic core circadian machinery. However, the oscillating transcriptome is extensively reprogrammed in aged stem cells, switching from genes involved in homeostasis to those involved in tissue-specific stresses, such as DNA damage or inefficient autophagy. Importantly, deletion of circadian clock components did not reproduce the hallmarks of this reprogramming, underscoring that rewiring, rather than arrhythmia, is associated with physiological aging. While age-associated rewiring of the oscillatory diurnal transcriptome is not recapitulated by a high-fat diet in young adult mice, it is significantly prevented by long-term caloric restriction in aged mice. Thus, stem cells rewire their diurnal timed functions to adapt to metabolic cues and to tissue-specific age-related traits.

Exploring Adaptive Phenotypes for the Human Calcium-Sensing Receptor Polymorphism R990G.

Rainforest hunter-gatherers from Southeast Asia are characterized by specific morphological features including a particularly dark skin color (D), short stature (S), woolly hair (W), and the presence of steatopygia (S)-fat accumulation localized in the hips (DSWS phenotype). Based on previous evidence in the Andamanese population, we first characterized signatures of adaptive natural selection around the calcium-sensing receptor gene in Southeast Asian rainforest groups presenting the DSWS phenotype and identified the R990G substitution (rs1042636) as a putative adaptive variant for experimental follow-up. Although the calcium-sensing receptor has a critical role in calcium homeostasis by directly regulating the parathyroid hormone secretion, it is expressed in different tissues and has been described to be involved in many biological functions. Previous works have also characterized the R990G substitution as an activating polymorphism of the calcium-sensing receptor associated with hypocalcemia. Therefore, we generated a knock-in mouse for this substitution and investigated organismal phenotypes that could have become adaptive in rainforest hunter-gatherers from Southeast Asia. Interestingly, we found that mouse homozygous for the derived allele show not only lower serum calcium concentration but also greater body weight and fat accumulation, probably because of enhanced preadipocyte differentiation and lipolysis impairment resulting from the calcium-sensing receptor activation mediated by R990G. We speculate that such differential features in humans could have facilitated the survival of hunter-gatherer groups during periods of nutritional stress in the challenging conditions of the Southeast Asian tropical rainforests.

Distinct roles for PARP-1 and PARP-2 in c-Myc-driven B-cell lymphoma in mice.

Dysregulation of the c-Myc oncogene occurs in a wide variety of hematologic malignancies, and its overexpression has been linked with aggressive tumor progression. Here, we show that poly (ADP-ribose) polymerase 1 (PARP-1) and PARP-2 exert opposing influences on progression of c-Myc-driven B-cell lymphoma. PARP-1 and PARP-2 catalyze the synthesis and transfer of ADP-ribose units onto amino acid residues of acceptor proteins in response to DNA strand breaks, playing a central role in the response to DNA damage. Accordingly, PARP inhibitors have emerged as promising new cancer therapeutics. However, the inhibitors currently available for clinical use are not able to discriminate between individual PARP proteins. We found that genetic deletion of PARP-2 prevents c-Myc-driven B-cell lymphoma, whereas PARP-1 deficiency accelerates lymphomagenesis in the Eµ-Myc mouse model of aggressive B-cell lymphoma. Loss of PARP-2 aggravates replication stress in preleukemic Eµ-Myc B cells, resulting in accumulation of DNA damage and concomitant cell death that restricts the c-Myc-driven expansion of B cells, thereby providing protection against B-cell lymphoma. In contrast, PARP-1 deficiency induces a proinflammatory response and an increase in regulatory T cells, likely contributing to immune escape of B-cell lymphoma, resulting in an acceleration of lymphomagenesis. These findings pinpoint specific functions for PARP-1 and PARP-2 in c-Myc-driven lymphomagenesis with antagonistic consequences that may help inform the design of new PARP-centered therapeutic strategies, with selective PARP-2 inhibition potentially representing a new therapeutic approach for the treatment of c-Myc-driven tumors.

Evaluation of CHROMagar™ B. cepacia agar for the detection of Burkholderia cepacia complex species from sputum samples of patients with cystic fibrosis.

INTRODUCTION: Burkholderia cepacia complex (BCC) are non-fermenting Gram-negative bacteria that can chronically colonize the lungs of people with cystic fibrosis (pwCF), causing a severe and progressive respiratory failure, post-transplant complications and epidemic outbreaks. Therefore, rapid and accurate identification of these bacteria is relevant for pwCF, in order to facilitate early eradication and prevent chronic colonization. However, BCCs are often quite difficult to detect on culture media as they have a slow growth rate and can be hidden by other fast-growing microorganisms, including Pseudomonas aeruginosa and filamentous fungi. MATERIAL AND METHODS: We evaluated the sensitivity of CHROMagar™ B. cepacia agar using 11 isolates from a well-characterized BCC collection, using BCA agar (Oxoid, UK) as a gold standard. We also studied 180 clinical sputum samples to calculate positive (PPV) and negative (NPV) predictive values. Furthermore, we used three of the well-characterized BCC isolates to determine the limit of detection (LOD). RESULTS: Eleven isolates grew on CHROMagar™ B. cepacia at 37ºC after 48 h. The NPV and PPV of CHROMagar™ B. cepacia were 100% and 87.5%, respectively. The LOD of CHROMagar™ B. cepacia was around 1 × 103 CFU/ml, requiring a ten-fold dilution lower bacterial load than BCA for BCC detection. CONCLUSION: CHROMagar™ B. cepacia agar proved to have a very good sensitivity and specificity for the detection of clinical BCCs. Moreover, the chromogenic nature of the medium allowed us to clearly differentiate BCC from other Gram-negative species, filamentous fungi and yeasts, thereby facilitating the identification of contaminants.

Association between co-sleeping in the first year of life and preschoolers´ sleep patterns.

This study aimed to investigate the association between co-sleeping practiced during the first year of life and preschoolers' sleep patterns. A cross-sectional study including toddlers was designed to analyze their sleep patterns. The Brief Infant Sleep Questionnaire, validated in Spanish, was used to measure sleep quality. A latent class analysis was performed to identify qualitative subgroups in the sample and explore the effects of co-sleeping. The sleep patterns of 276 children were analyzed. A total of 181 (65%) parents reported having practiced co-sleeping with their children. The latent class analysis identified a two-class solution with two different sleep patterns. One of them showed a worse quality sleep pattern, which had a significant association with having practiced co-sleeping during the first year of life, and with the fact that they were still sleeping in the parents' room, among other characteristics related to co-sleeping and parental concerns. Breastfeeding also showed association with a worse quality sleep pattern.  Conclusion: Based on the present findings, co-sleeping during the first year of life appears to be associated with poor sleep patterns in young preschoolers. What is Known: • Co-sleeping shows benefits for infants and parents, mainly facilitating successful breastfeeding. • Literature on the effect of co-sleeping in lately sleep quality in children and their parents is very limited. What is New: • Co-sleeping practiced during the first year of life could be associated with a worse sleep pattern measured with BISQ-E tool. • A balance between the correct practice of co-sleeping and the achievement of a healthy sleep routine in preschool should probably be part of parents' health education.

Ototoxic and nephrotoxic drugs in neonatal intensive care units: results of a Spanish and Italian survey.

Neonates face heightened susceptibility to drug toxicity, often exposed to off-label medications with dosages extrapolated from adult or pediatric studies. Premature infants in Neonatal Intensive Care Units (NICUs) are particularly at risk due to underdeveloped pharmacokinetics and exposure to multiple drugs. The study aimed to survey commonly used medications with a higher risk of ototoxicity and nephrotoxicity in Spanish and Italian neonatal units. A prospective cross-sectional study was conducted in Italian and Spanish neonatal units using a web-based survey with 43 questions. A modified Delphi method involved experts refining the survey through online consensus. Ethical approval was obtained, and responses were collected from January to July 2023. The survey covered various aspects, including drug-related ototoxic and nephrotoxic management, hearing screening, and therapeutic drug monitoring. Responses from 131 participants (35.9% from Spain and 64.1% from Italy) revealed awareness of drug toxicity risks. Varied practices were observed in hearing screening protocols, and a high prevalence of ototoxic and nephrotoxic drug use, including aminoglycosides (100%), vancomycin (70.2%), loop diuretics (63.4%), and ibuprofen (62.6%). Discrepancies existed in guideline availability and adherence, with differences between Italy and Spain in therapeutic drug monitoring practices. CONCLUSIONS: The study underscores the need for clinical guidelines and uniform practices in managing ototoxic and nephrotoxic drugs in neonatal units. Awareness is high, but inconsistencies in practices indicate a necessity for standardization, including the implementation of therapeutic drug monitoring and the involvement of clinical pharmacologists. Addressing these issues is crucial for optimizing neonatal care in Southern Europe. WHAT IS KNOWN: • Neonates in intensive care face a high risk of nephrotoxicity and ototoxicity from drugs like aminoglycosides, vancomycin, loop diuretics, and ibuprofen. • Therapeutic drug monitoring is key for managing these risks, optimizing dosing for efficacy and minimizing side effects. WHAT IS NEW: • NICUs in Spain and Italy show high drug toxicity awareness but differ in ototoxic/nephrotoxic drug management. • Urgent need for standard guidelines and practices to address nephrotoxic risks from aminoglycosides, vancomycin, loop diuretics, and ibuprofen.

Sex differences in patient-reported outcome measure of psychotic symptoms in schizophrenia.

PURPOSE: to study sex differences in self-reported symptoms measured with the Scale of Patient-Reported Impact of Symptoms in Schizophrenia (PRISS), to investigated sex differences in the degree of agreements between self-reported symptoms and clinical symptoms assessed by professionals, and to identify which clinical and sociodemographic variables predicted a greater presence of self-reported symptoms split by sex. METHODS: 161 patients (37 females; 124 males), aged between 18 and 65 years, with a diagnosis of schizophrenia assisted in non-acute mental health services at four mental health catchment areas in Andalucia and Catalonia were included. The PRISS scale was administered to asses self-reported symptoms. RESULTS: males reported higher presence of excitement, grandiosity, motor retardation and poor attention) than women. There was less agreement in the presence of psychotic symptoms in men than in women when comparing self-reported symptoms and clinical symptoms assessed by professionals. Finally, in men the predictors variables for the greater presence of self-perceived symptoms were greater psychotic symptomatology and more disability, while in women were greater presence of alogia and higher doses of chlorpromazine. CONCLUSIONS: Assessing and being aware of the self-perceived symptoms of patients with schizophrenia should be considered in the clinic, especially in men, as there appears to be a lack of agreement on certain items. This would allow treatments to be more focused on patients' need by sex, and would make them feel part of the therapeutic process, improving their therapeutic adherence, evolution and quality of life.

Automatic Discrimination of Species within the Enterobacter cloacae Complex Using Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry and Supervised Algorithms.

The Enterobacter cloacae complex (ECC) encompasses heterogeneous clusters of species that have been associated with nosocomial outbreaks. These species may have different acquired antimicrobial resistance and virulence mechanisms, and their identification is challenging. This study aims to develop predictive models based on matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) profiles and machine learning for species-level identification. A total of 219 ECC and 118 Klebsiella aerogenes clinical isolates from three hospitals were included. The capability of the proposed method to differentiate the most common ECC species (Enterobacter asburiae, Enterobacter kobei, Enterobacter hormaechei, Enterobacter roggenkampii, Enterobacter ludwigii, and Enterobacter bugandensis) and K. aerogenes was demonstrated by applying unsupervised hierarchical clustering with principal-component analysis (PCA) preprocessing. We observed a distinctive clustering of E. hormaechei and K. aerogenes and a clear trend for the rest of the ECC species to be differentiated over the development data set. Thus, we developed supervised, nonlinear predictive models (support vector machine with radial basis function and random forest). The external validation of these models with protein spectra from two participating hospitals yielded 100% correct species-level assignment for E. asburiae, E. kobei, and E. roggenkampii and between 91.2% and 98.0% for the remaining ECC species; with data analyzed in the three participating centers, the accuracy was close to 100%. Similar results were obtained with the Mass Spectrometric Identification (MSI) database developed recently (https://msi.happy-dev.fr) except in the case of E. hormaechei, which was more accurately identified with the random forest algorithm. In short, MALDI-TOF MS combined with machine learning was demonstrated to be a rapid and accurate method for the differentiation of ECC species.

An interactive video increasing French students' mental health literacy: a mixed-methods randomized controlled pilot study.

Mental health literacy (MHL) is a determinant of psychological well-being in young people. A randomized controlled design was used to evaluate the appreciation and effectiveness of an interactive video on French University students' MHL (knowledge about depression and suicidal behavior, mental health help-seeking behaviors, stigma and misconceptions about mental health). At the baseline, all participants (n = 101) completed a questionnaire including several scales on MHL. One month after, participants were randomly assigned to two homogeneous groups (intervention, n = 50 or control, n = 51) and again completed the questionnaire on MHL. Through a mixed-methods approach, semi-structured interviews were also conducted with the intervention group to collect information on the appreciation of the interactive video. Quantitative data indicated that MHL scores increased or remained stable in the intervention group. Comparison with the control group and multivariate logistic regression models did not show statistically significant differences, due to the small sample of the study. According to qualitative data, users appreciated the content and the format of the intervention. It was suggested that the video could be disseminated in other University campuses in France and internationally to promote MHL among students.

Hemophagocytic Lymphohistiocytosis Secondary to Hodgkin's Lymphoma with Isolated Bone Marrow Involvement in a Newly Diagnosed HIV Patient.

Human immunodeficiency virus (HIV) infection is known to be associated with the development of Hodgkin's lymphoma (HL). Exclusive extranodal bone marrow involvement is less common. Co-infection by other viruses, such as the Epstein-Barr virus (EBV), increases the incidence of a frequent complication denominated by hemophagocytic lymphohistocytosis (HLH). We present the case of a 50-year-old patient with the above clinical spectrum who develops several serious complications during treatment.

Primary Effusion Lymphoma, Multicentric Castleman's Disease, and Kaposi's Sarcoma in an HHV-8 and HIV-Positive Patient: A Case Report.

Primary effusion lymphoma (PEL), Kaposi's sarcoma (KS), and multicentric Castleman's disease (MCD) is an uncommon group of diseases included in the same spectrum with related characteristics. The coexistence of all of them in the same individual is a rare occurrence. We present the case of a 25-year-old patient diagnosed with human immunodeficiency virus (HIV) and the development of all these related pathologies. Despite the use of intensive treatment according to the latest recommendations, the evolution was unfavorable. This case reflects the need for new therapies and research in this field.

Patient-reported impact of symptoms in schizophrenia scale (PRISS): Development and validation.

BACKGROUND: We report the psychometric properties of the Patient-Reported Impact of Symptoms in Schizophrenia Scale (PRISS), which assesses the impact of subjective experiences or qualia in outpatients with this condition. METHODS: A cross-sectional study was carried out in 162 patients diagnosed with schizophrenia in Spain. The PRISS measures the presence, frequency, concern and interference with daily life of self-reported experiences related to the main symptoms observed in these patients. The psychometric analysis included test-retest reliability, internal consistency and structural and convergent validity. RESULTS: The 28-item PRISS showed good test-retest reliability as 64.3% of the intraclass correlation coefficient values were between 0.40 and 0.79, which were statistically significant (p < 0.01). Analysis of the structural validity revealed a three-factor structure, (1) productive subjective experiences, (2) affective-negative subjective experiences and (3) excitation, which accounted for 56.11% of the variance. Of the Pearson's correlation coefficients analysed between the PRISS and the Positive and Negative Syndrome Scale (PANSS), Scale for Assessment of Negative Symptoms (SANS) and World Health Organization Disability Assessment Schedule (WHO-DAS), 72.2% were statistically significant (p < 0.05) and ranged from 0.38-0.42, 0.32-0.42 and 0.40-0.42, respectively. CONCLUSION: Our results indicate that the PRISS appears to be a brief, reliable and valid scale to measure subjective experiences in schizophrenia and provides valuable information complementary to clinical evaluation.

Measuring Digital Vaccine Literacy: Development and Psychometric Assessment of the Digital Vaccine Literacy Scale.

BACKGROUND: The use of the internet to look for information about vaccines has skyrocketed in the last years, especially with the COVID-19 pandemic. Digital vaccine literacy (DVL) refers to understanding, trust, appraisal, and application of vaccine-related information online. OBJECTIVE: This study aims to develop a tool measuring DVL and assess its psychometric properties. METHODS: A 7-item online questionnaire was administered to 848 French adults. Different psychometric analyses were performed, including descriptive statistics, exploratory factor analysis, confirmatory factor analysis, and convergent and discriminant validity. RESULTS: We developed the 7-item DVL scale composed of 3 factors (understanding and trust official information; understanding and trust information in social media; and appraisal of vaccine information online in terms of evaluation of the information and its application for decision making). The mean DVL score of the baseline sample of 848 participants was 19.5 (SD 2.8) with a range of 7-28. The median score was 20. Scores were significantly different by gender (P=.24), age (P=.03), studying or working in the field of health (P=.01), and receiving regular seasonal flu shots (P=.01). CONCLUSIONS: The DVL tool showed good psychometric proprieties, resulting in a promising measure of DVL.

Clinical, biological, and prognostic implications of SF3B1 co-occurrence mutations in very low/low- and intermediate-risk MDS patients.

SF3B1 is a highly mutated gene in myelodysplastic syndrome (MDS) patients, related to a specific subtype and parameters of good prognosis in MDS without excess blasts. More than 40% of MDS patients carry at least two myeloid-related gene mutations but little is known about the impact of concurrent mutations on the outcome of MDS patients. In applying next-generation sequencing (NGS) with a 117 myeloid gene custom panel, we analyzed the co-occurrence of SF3B1 with other mutations to reveal their clinical, biological, and prognostic implications in very low/low- and intermediate-risk MDS patients. Mutations in addition to those of SF3B1 were present in 80.4% of patients (median of 2 additional mutations/patient, range 0-5). The most frequently mutated genes were as follows: TET2 (39.2%), DNMT3A (25.5%), SRSF2 (10.8%), CDH23 (5.9%), and ASXL1, CUX1, and KMT2D (4.9% each). The presence of at least two mutations concomitant with that of SF3B1 had an adverse impact on survival compared with those with the SF3B1 mutation and fewer than two additional mutations (median of 54 vs. 87 months, respectively: p = 0.007). The co-occurrence of SF3B1 mutations with specific genes is also linked to a dismal prognosis: SRSF2 mutations were associated with shorter overall survival (OS) than SRSF2wt (median, 27 vs. 75 months, respectively; p = 0.001), concomitant IDH2 mutations (median OS, 11 [mut] vs. 75 [wt] months; p = 0.001), BCOR mutations (median OS, 11 [mut] vs. 71 [wt] months; p = 0.036), and NUP98 and STAG2 mutations (median OS, 27 and 11 vs. 71 months, respectively; p = 0.008 and p = 0.002). Mutations in CHIP genes (TET2, DNMT3A) did not significantly affect the clinical features or outcome. Our results suggest that a more comprehensive NGS study in low-risk MDS SF3B1mut patients is essential for a better prognostic evaluation.

Dual effects of entomopathogenic fungi on control of the pest Lobesia botrana and the pathogenic fungus Eutypella microtheca on grapevine.

BACKGROUND: Entomopathogenic fungi (EPF) are the natural enemies of insect pests. Nevertheless, research on the use of EPF for simultaneous prevention of pest and disease agents on the same crop is limited. In this study, we explored the potential dual effects of three strains of the EPF Metarhizium anisopliae on the control of detrimental agents of Vitis vinifera L., including different developmental stages (larvae, pupae, and adult) of the insect pest Lobesia botrana and the phytopathogenic fungus Eutypella microtheca. METHODS: Laboratory pathogenicity trials were performed to examine the effects of the three M. anisopliae strains on the mortality rate of L. botrana. In addition, field trials were conducted to assess the biocontrol potential of one selected M. anisopliae strain on the larval stage of L. botrana. Moreover, inhibitory effects of the three EPF strains on E. microtheca growth were examined in vitro. RESULTS: All the M. anisopliae strains were highly effective, killing all stages of L. botrana as well as inhibiting the growth of E. microtheca. The in vitro mortality of larvae treated with the strains was over 75%, whereas that of treated pupae and adults was over 85%. The three EPF strains showed similar efficacy against larvae and adult stages; nevertheless, pupal mortality was observed to be strain dependent. Mortality of L. botrana larvae ranged from 64 to 91% at field conditions. Inhibition of E. microtheca growth reached 50% in comparison to the control. CONCLUSIONS: Our study showed that M. anisopliae strains were highly effective in ensuring control of two different detrimental agents of V. vinifera L., providing new evidence to support the dual effects of entomopathogenic fungi.

A Semiautomated Classification System for Producing Service Directories in Social and Health Care (DESDE-AND): Maturity Assessment Study.

BACKGROUND: DESDE-LTC (Description and Evaluation of Services and DirectoriEs for Long-Term Care) is an international classification system that allows standardized coding and comparisons between different territories and care sectors, such as health and social care, in defined geographic areas. We adapted DESDE-LTC into a computer tool (DESDE-AND) for compiling a directory of care services in Andalucia, Spain. OBJECTIVE: The aim of this study was to evaluate the maturity of DESDE-AND. A secondary objective of this study is to show the practicality of a new combined set of standard evaluation tools for measuring the maturity of health technology products. METHODS: A system for semiautomated coding of service provision has been co-designed. A panel of 23 domain experts and a group of 68 end users participated in its maturity assessment that included its technology readiness level (TRL), usability, validity, adoption (Adoption Impact Ladder [AIL]), and overall degree of maturity [implementation maturity model [IMM]). We piloted the prototype in an urban environment (Seville, Spain). RESULTS: The prototype was demonstrated in an operational environment (TRL 7). Sixty-eight different care services were coded, generating fact sheets for each service and its geolocation map. The observed agreement was 90%, with moderate reliability. The tool was partially adopted by the regional government of Andalucia (Spain), reaching a level 5 in adoption (AIL) and a level 4 in maturity (IMM) and is ready for full implementation. CONCLUSIONS: DESDE-AND is a usable and manageable system for coding and compiling service directories and it can be used as a core module of decision support systems to guide planning in complex cross-sectoral areas such as combined social and health care.

Measurement of Organ-Specific and Acute-Phase Blood Protein Levels in Early Lyme Disease.

Lyme disease results from infection of humans with the spirochete Borrelia burgdorferi. The first and most common clinical manifestation is the circular, inflamed skin lesion referred to as erythema migrans; later manifestations result from infections of other body sites. Laboratory diagnosis of Lyme disease can be challenging in patients with erythema migrans because of the time delay in the development of specific diagnostic antibodies against Borrelia. Reliable blood biomarkers for the early diagnosis of Lyme disease in patients with erythema migrans are needed. Here, we performed selected reaction monitoring, a targeted mass spectrometry-based approach, to measure selected proteins that (1) are known to be predominantly expressed in one organ (i.e., organ-specific blood proteins) and whose blood concentrations may change as a result of Lyme disease, or (2) are involved in acute immune responses. In a longitudinal cohort of 40 Lyme disease patients and 20 healthy controls, we identified 10 proteins with significantly altered serum levels in patients at the time of diagnosis, and we also developed a 10-protein panel identified through multivariate analysis. In an independent cohort of patients with erythema migrans, six of these proteins, APOA4, C9, CRP, CST6, PGLYRP2, and S100A9, were confirmed to show significantly altered serum levels in patients at time of presentation. Nine of the 10 proteins from the multivariate panel were also verified in the second cohort. These proteins, primarily innate immune response proteins or proteins specific to liver, skin, or white blood cells, may serve as candidate blood biomarkers requiring further validation to aid in the laboratory diagnosis of early Lyme disease.