Autoimmune Hepatitis Induced by Hepatitis Delta Virus: A Conundrum.

Introduction: The association of hepatitis delta virus (HDV) infection with positive autoantibodies and autoimmune features has been known for decades. However, to date, very few cases of clinical autoimmune hepatitis (AIH) have been reported in association with HDV infection, most of them being in the context of treatment with peginterferon. Case Report: This case refers to a 46-year-old woman born in Guinea-Bissau who moved to Portugal in 2018 to investigate complaints of diffuse abdominal discomfort and nausea. Her initial work-up, including laboratory and liver histology, was consistent with type 1 AIH. She had HBe antigen-negative chronic hepatitis B virus infection with negative DNA and also a positive total anti-HDV antibody, with negative IgM and undetectable RNA. Therefore, after initiating prophylactic tenofovir difumarate, she was started on prednisolone followed by azathioprine, which was later stopped due to presumed hepatotoxicity. Repeated histology showed signs of viral superinfection, and she was treated with acyclovir due to a positive herpes simplex IgM, with HDV RNA remaining negative. A third flare in transaminases prompted the introduction of mycophenolate mofetil (MMF) after a thorough exclusion of additional causes of liver disease. About 6 months later, during another bout of hepatitis, HDV RNA was finally positive and classified as genotype 5. MMF was stopped, and, considering a contraindication to interferon, the patient was offered therapy with bulevirtide, which she refused for personal reasons as she is currently living in her home country. Discussion: This is a challenging case of autoimmune or "autoimmune-like" hepatitis, probably induced by chronic HDV infection. High suspicion of HDV was essential because, had the case been interpreted as refractory AIH, with escalation of immunosuppression, a more severe course of the viral infection might have ensued. Recently, HDV suppression with bulevirtide was shown to reverse autoimmune liver disease. We hypothesize that the same could have happened to our patient, had she accepted this treatment.

Introdução: A associação da infeção pelo vírus da hepatite delta (VHD) com a presença de autoanticorpos e outros aspetos de autoimunidade é conhecida desde há várias décadas. Contudo, até à data, muito poucos casos de hepatite autoimune (HAI) clínica foram reportados em relação com a infeção VHD, sendo a maioria destes no contexto de terapêutica com interferão peguilado. Caso clínico: O caso refere-se a uma mulher de 46 anos natural da Guiné-Bissau, que se mudou para Portugal em 2018 para investigação de queixas de desconforto abdominal difuso e náuseas. A avaliação laboratorial inicial e a histologia hepática foram compatíveis com HAI tipo 1. A doente apresentava também infeção crónica a VHB (vírus da hepatite B) antigénio HBe negativa, com DNA negativo, e anti-VHD (vírus da hepatite delta) total positivo, com IgM negativo e RNA indetetável. Assim, após início de tenofovir difumarato profilático, foi iniciada terapêutica com prednisolona seguida de azatioprina, que posteriormente se interrompeu por presumível hepatotoxicidade. Uma segunda biópsia mostrou aspetos de superinfeção viral e como tal a doente foi tratada com aciclovir, tendo em conta IgM positivo para Herpes Simplex, mantendo-se o RNA VHD negativo. Um terceiro flare de transaminases motivou o início de micofenolato de mofetil, após extensa investigação e exclusão de outras causas de doença hepática. Cerca de 6 meses mais tarde, durante novo episódio de hepatite, o RNA VHD revelou-se finalmente positivo e este foi classificado como genotipo 5. O MMF foi suspenso e, considerando a contra-indicação para interferão, foi proposto à doente tratamento com bulevirtide, que esta recusou, alegando motivos pessoais, visto estar atualmente a residir no seu país de origem. Discussão: Este é um caso desafiante de hepatite autoimune, ou autoimune-like, provavelmente induzida pela infeção crónica pelo VHD. Um elevado índice de suspeição para VHD foi essencial porque, se o caso tivesse sido interpretado como HAI refratária, com incremento de imunossupressão, poderia ter-se verificado um agravamento da hepatite viral. Recentemente, foi reportado que a supressão do VHD pelo bulevirtide pode reverter a doença hepática autoimune. Questionamo-nos se o mesmo poderia ter sucedido com a nossa doente, caso esta tivesse aceite este tratamento.

Public perception of psychiatry, psychology and mental health professionals: a 15-year analysis.

Background: X (previously known as "Twitter") serves as a platform for open discussions on mental health, providing an avenue for scrutinizing public perspectives regarding psychiatry, psychology and their associated professionals. Objective: To analyze the conversations happening on X about psychiatrists, psychologists, and their respective disciplines to understand how the public perception of these professionals and specialties has evolved over the last 15 years. Methods: We collected and analyzed all tweets posted in English or Spanish between 2007 and 2023 referring to psychiatry, psychology, neurology, mental health, psychiatrist, psychologist, or neurologist using advance topic modelling and sentiment analysis. Results: A total of 403,767 tweets were analyzed, 155,217 (38%) were in English and 248,550 (62%) in Spanish. Tweets about mental health and mental health professionals and disciplines showed a consistent volume between 2011 and 2016, followed by a gradual increase from 2016 through 2022. The proportion of tweets discussing mental health doubled from 2016 to 2022, increasing from 20% to 67% in Spanish and from 15% to 45% in English. Several differences were observed on the volume of tweets overtime depending on the language they were written. Users associated each term with varied topics, such as seeking for help and recommendation for therapy, self-help resources, medication and side effects, suicide prevention, mental health in times of crisis, among others. The number of tweets mentioning these topics increased by 5-10% from 2016 to 2022, indicating a growing interest among the population. Emotional analysis showed most of the topics were associated with fear and anger. Conclusion: The increasing trend in discussions about mental health and the related professionals and disciplines over time may signify an elevated collective awareness of mental health. Gaining insights into the topics around these matters and user's corresponding emotions towards them presents an opportunity to combat the stigma surrounding mental health more effectively.

Comparison of intranasal dexmedetomidine versus oral midazolam for premedication in pediatric patients: an updated meta-analysis with trial-sequential analysis.

BACKGROUND: Midazolam is routinely used as preanesthetic medication in pediatric patients. Recently, dexmedetomidine has emerged as an alternative as a premedicant. We aimed to add more evidence about the efficacy and safety of two common routes of administration for pediatric premedication: oral midazolam versus intranasal dexmedetomidine. METHODS: We systematically searched Randomized Controlled Trials (RCTs) involving patients ≤ 18 years old undergoing preanesthetic medication and comparing intranasal dexmedetomidine with oral midazolam. Risk Ratio (RR) and Mean Difference (MD) with 95% Confidence Intervals (95% CI) were computed using a random effects model. Trial-sequential analyses were performed to assess inconsistency. RESULTS: Sixteen RCTs (1,239 patients) were included. Mean age was 5.5 years old, and most procedures were elective. There was no difference in satisfactory induction or mask acceptance (RR = 1.15, 95% CI 0.97-1.37; p = 0.11). There was a higher incidence of satisfactory separation from parents in the dexmedetomidine group (RR = 1.40; 95% CI 1.13-1.74; p = 0.002). Dexmedetomidine was also associated with a reduction in the incidence of emergence agitation (RR=0.35; 95% CI 0.14-0.88; p = 0.02). Heart rate and mean arterial pressure were marginally lower in the dexmedetomidine group but without clinical repercussions. CONCLUSION: Compared with oral midazolam, intranasal dexmedetomidine demonstrated better separation from parents and lower incidence of emergence agitation in pediatric premedication, without a difference in satisfactory induction. Intranasal dexmedetomidine may be a safe and effective alternative to oral midazolam for premedication in pediatric patients.

Converting cell death into senescence by PARP1 inhibition improves recovery from acute oxidative injury.

Excessive amounts of reactive oxygen species (ROS) lead to macromolecular damage and high levels of cell death with consequent pathological sequelae. We hypothesized that switching cell death to a tissue regenerative state could potentially improve the short-term and long-term detrimental effects of ROS-associated acute tissue injury, although the mechanisms regulating oxidative stress-induced cell fate decisions and their manipulation for improving repair are poorly understood. Here, we show that cells exposed to high oxidative stress enter a poly (ADP-ribose) polymerase 1 (PARP1)-mediated regulated cell death, and that blocking PARP1 activation promotes conversion of cell death into senescence (CODIS). We demonstrate that this conversion depends on reducing mitochondrial Ca2+ overload as a consequence of retaining the hexokinase II on mitochondria. In a mouse model of kidney ischemia-reperfusion damage, PARP inhibition reduces necrosis and increases transient senescence at the injury site, alongside improved recovery from damage. Together, these data provide evidence that converting cell death into transient senescence can therapeutically benefit tissue regeneration.

Exploring CDKN1A Upregulation Mechanisms: Insights into Cell Cycle Arrest Induced by NC2603 Curcumin Analog in MCF-7 Breast Cancer Cells.

Breast cancer stands out as one of the most prevalent malignancies worldwide, necessitating a nuanced understanding of its molecular underpinnings for effective treatment. Hormone receptors in breast cancer cells substantially influence treatment strategies, dictating therapeutic approaches in clinical settings, serving as a guide for drug development, and aiming to enhance treatment specificity and efficacy. Natural compounds, such as curcumin, offer a diverse array of chemical structures with promising therapeutic potential. Despite curcumin's benefits, challenges like poor solubility and rapid metabolism have spurred the exploration of analogs. Here, we evaluated the efficacy of the curcumin analog NC2603 to induce cell cycle arrest in MCF-7 breast cancer cells and explored its molecular mechanisms. Our findings reveal potent inhibition of cell viability (IC50 = 5.6 µM) and greater specificity than doxorubicin toward MCF-7 vs. non-cancer HaCaT cells. Transcriptome analysis identified 12,055 modulated genes, most notably upregulation of GADD45A and downregulation of ESR1, implicating CDKN1A-mediated regulation of proliferation and cell cycle genes. We hypothesize that the curcumin analog by inducing GADD45A expression and repressing ESR1, triggers the expression of CDKN1A, which in turn downregulates the expression of many important genes of proliferation and the cell cycle. These insights advance our understanding of curcumin analogs' therapeutic potential, highlighting not just their role in treatment, but also the molecular pathways involved in their activity toward breast cancer cells.

Enhancing Lung Cancer Care in Portugal: Bridging Gaps for Improved Patient Outcomes.

Lung cancer has the highest incidence and cancer-related mortality worldwide. In Portugal, it ranks as the fourth most common cancer, with nearly 6000 new cases being diagnosed every year. Lung cancer is the main cause of cancer-related death among males and the third cause of cancer-related death in females. Despite the globally accepted guidelines and recommendations for what would be the ideal path for a lung cancer patient, several challenges occur in real clinical management across the world. The recommendations emphasize the importance of adequate screening of high-risk individuals, a precise tumour biopsy, and an accurate final diagnosis to confirm the neoplastic nature of the nodule. A detailed histological classification of the lung tumour type and a comprehensive molecular characterization are of utmost importance for the selection of an efficacious and patient-directed therapeutic approach. However, in the context of the Portuguese clinical organization and the national healthcare system, there are still several gaps in the ideal pathway for a lung cancer patient, involving aspects ranging from the absence of a national lung cancer screening programme through difficulties in histological diagnosis and molecular characterization to challenges in therapeutic approaches. In this manuscript, we address the most relevant weaknesses, presenting several proposals for potential solutions to improve the management of lung cancer patients, helping to decisively improve their overall survival and quality of life.

Adherence to the Mediterranean Diet, Sodium and Potassium Intake in People at a High Risk of Dementia.

Adequate sodium and potassium intake, along with adherence to the Mediterranean diet (MedDiet), are key factors for preventing hypertension and cerebrovascular diseases. However, data on the consumption of these nutrients within the MedDiet are scarce. This cross-sectional study aims to assess the association between MedDiet adherence and sodium/potassium intake in the MIND-Matosinhos randomized controlled trial, targeting Portuguese adults at a high risk of dementia. Good adherence to the MedDiet was defined using the Portuguese Mediterranean Diet Adherence Screener questionnaire (≥10 points), and both sodium/potassium intakes were estimated from 24-hour urine collections. The association between MedDiet adherence and these nutrients' intake (dichotomized by the median) was quantified by calculating odds ratios (OR) and respective 95% confidence intervals (95% CI) using a logistic regression. A total of 169 individuals (60.9% female; median age: 70 years; range: 36-85 years) were included. Good adherence to the MedDiet was observed among 18.3% of the sample. After adjusting for sex, age, education and using antihypertensive drugs, good MedDiet adherence was associated with higher sodium (OR = 3.11; 95% CI: 1.27-7.65) and potassium intake (OR = 9.74; 95% CI: 3.14-30.26). Increased adherence to the MedDiet may contribute to a higher potassium intake but seems to have limited effects on the adequacy of sodium levels.

Workforce migration and brain drain - A nationwide cross-sectional survey of early career psychiatrists in Nigeria.

Background: Nigeria's shortage of psychiatrists is exacerbated due to health worker migration. Aim: This study explores migration experiences and tendencies among early-career psychiatrists in Nigeria. Methods: We conducted a cross-sectional survey covering Nigeria's six geopolitical zones, using a 61-item online questionnaire assessing short-term mobility, long-term migration experiences and migration attitudes. Data was analysed using IBM SPSS version 29. Results: Of 228 early-career psychiatrists surveyed, 9.7% had short-term mobility and 8.0% had long-term migration experiences. However, 85.8% had 'ever' considered migration, 69.2% were planning to leave 'now', and 52.9% had taken 'practical migration steps'. Over half (52.7%) said they would be working abroad in 5 years, with 25.2% indicating they would migrate within a year. The top reasons to leave were financial and academic, while personal and cultural factors were the key reasons to stay. Income dissatisfaction (OR = 2.27, 95%, CI = 1.05-4.88) predicted planning to leave 'now', while being in a relationship (OR = 3.46, 95%CI = 1.06-11.30) predicted taking 'practical migration steps'. Attractive job features were good welfare (85.4%) and high salaries (80.3%). Improvements in finances (90.8%) and work conditions (86.8%) were requested. Conclusions: Systemic changes to address psychiatrists' migration from Nigeria are needed.

Barriers and facilitators of the reporting by family doctors of cases of domestic violence - a qualitative study across Portugal.

BACKGROUND: Domestic violence (DV) is a serious and prevalent public health problem with devastating consequences for the victims and their families. Whilst the number of cases reported to the authorities has risen in recent years, many victims still chose not to present a complaint. In Portugal, to address this, DV became a public crime. As victims of DV present multiple health problems and frequently seek professional help, family doctors are in a privileged position to detect and report cases of DV to the authorities. However, little is known about what motivates these professionals to report or not the DV cases they encounter in their practice to the authorities. METHODS: We conducted semi-structured interviews with family doctors from all regional health administrations of continental Portugal. Interviews occurred between July 2020 and September 2022, were conducted in person or remotely, audio recorded, transcribed, and analysed using thematic analysis. Content analysis was conducted to assess the agreement or disagreement regarding mandatory reporting in each of the themes and subthemes. RESULTS: Fifty-four family doctors took part in this study (n = 39 women, n = 15 men). The main themes that arose from the analysis were: "Barriers related to the physician's activity," "Barriers related to the victim or aggressor," "Facilitators related to the physician's activity," "Facilitators related to the victim or aggressor." Although different barriers were described, most doctors agreed with the mandatory reporting of DV cases. CONCLUSIONS: Family doctors encounter multiple barriers and facilitators when considering reporting a DV case to the authorities. The results of this study can help develop new interventions to address the barriers described by the doctors, increasing their compliance with mandatory reporting, the protection of victims and the just persecution of the aggressor.

Breaking down barriers: promoting journals beyond the page with open access journal clubs.

In 2020, during the early days of the COVID-19 pandemic, the British Journal of Psychiatry (BJPsych) established a series of free online teaching sessions called BJPsych Journal Clubs. Their educational purpose is two-fold: (a) to provide junior psychiatrists with a friendly but large-scale platform to evaluate and critically appraise recent articles published in the BJPsych and (b) to present new research findings in an open and accessible manner. In this paper, we discuss our framework, the challenges we encountered, how the original model is evolving based on feedback from trainees, and tips for success when delivering international online journal clubs.

Psychotherapy training in postgraduate psychiatry training in Nigeria - Are we doing enough?

Introduction: Nigeria, with an estimated 40 million people living with mental disorders, faces a critical shortage of psychiatrists to address the significant burden. Despite psychotherapy being integral to psychiatric training, it lacks structure, consistency and adequate supervision. This is alarming, particularly given the substantial demand for specialized psychotherapeutic support among those with mental illness. Methodology: A cross-sectional study utilised an online survey targeting early career psychiatrists recruited from the Early Career Psychiatrists section of the Association of Psychiatrists in Nigeria. Results: The questionnaire was distributed to 252 early career psychiatrists across Nigeria, with a 42.9% response rate, of which 50% were male, with 73.2% trainees and 26.8% early career psychiatrists. While 52.8% had received some psychotherapy training, only 2.8% were qualified psychotherapists. Notably, only 27.6% of those with psychotherapy training had over 100 hours of training. Factors such as receiving psychotherapy training during postgraduate training and having supervised psychotherapy training were found significant for having independent psychotherapy training. Conclusions: There is little emphasis on psychotherapy training in the postgraduate training in Nigeria. Those who had full training in psychotherapy were self-sponsored. Structured, supervised and mandatory psychotherapy within psychiatry training curriculum is recommended.

Organoid models: the future companions of personalized drug development.

High failure rates of the current drug development process are driving exemplary changes toward methodologies centered on human disease in-vitro modeling. Organoids are self-organized tissue sub-units resembling their organ of origin and are widely acknowledged for their unique potential in recapitulating human physio-pathological mechanisms. They are transformative for human health by becoming the platform of choice to probe disease mechanisms and advance new therapies. Furthermore, the compounds' validation as therapeutics represents another point of the drug development pipeline where organoids may provide key understandings and help pharma organizations replace or reduce animal research. In this review, we focus on gastrointestinal organoid models, which are currently the most advanced organoid models in drug development. We focus on experimental validations of their value, and we propose avenues to enhance their use in drug discovery and development, as well as precision medicine and diagnostics.

Vitamin D regulates microbiome-dependent cancer immunity.

A role for vitamin D in immune modulation and in cancer has been suggested. In this work, we report that mice with increased availability of vitamin D display greater immune-dependent resistance to transplantable cancers and augmented responses to checkpoint blockade immunotherapies. Similarly, in humans, vitamin D-induced genes correlate with improved responses to immune checkpoint inhibitor treatment as well as with immunity to cancer and increased overall survival. In mice, resistance is attributable to the activity of vitamin D on intestinal epithelial cells, which alters microbiome composition in favor of Bacteroides fragilis, which positively regulates cancer immunity. Our findings indicate a previously unappreciated connection between vitamin D, microbial commensal communities, and immune responses to cancer. Collectively, they highlight vitamin D levels as a potential determinant of cancer immunity and immunotherapy success.

Sinonasal Adenocarcinoma: Clinicopathological Characterization and Prognostic Factors.

Sinonasal (SN) malignancies are rare. Within SN adenocarcinomas, the most frequent are intestinal-type adenocarcinomas (ITACs). ITAC has been associated with wood and leather dust occupational exposure and TP53 mutations. Not much information is available regarding its characterization and treatment. The aim of this study is to characterize the clinicopathologic and prognostic factors of patients with sinonasal adenocarcinomas (SNACs) treated in our tertiary-level hospital. A retrospective, consecutive study including SNAC patients diagnosed between 2004-2023 was conducted. Clinicopathological data was collected, and p53 status was assessed in the tumor specimens. The association between p53 status and clinicopathological variables, as well as their impact on survival, was evaluated. In total, 35 were included, most of them having ITAC (91.4%) with papillary subtype (37.5%); the majority were subjected to occupational risk exposure (82.9%). Overexpression of p53 was identified in 48.6% of the tumors. Papillary and colonic subtypes were associated with higher median progression-free survival (mPFS) than mucinous and solid subtypes (mPFS 37 months, 95% CI, 20.0-54.0, vs. 9 months, 95% CI, 7.15-10.85, p=0.01); the former was also associated with higher median overall survival (mOS) (mOS 64 months, 95% CI, 37.18-90.81 vs. 14 months, 95% CI, 0-41.58, p=0.02). Histologic grade 1-2 and macroscopic complete resection were associated with higher PFS (PFS of five months of 90.9% vs. 33.3%, p=0.01; mPFS of 37 months, 95% CI, 4.93-69.07 vs. 10 months, 95% CI, 6.43-13.57, p=0.04, respectively). Disease recurrence with distant metastases was associated with lower OS (11 months, 95% CI, 6.1-15.9 vs. 53 months, 95% CI, 22.70-83.30, p=0.04). This study reinforces the importance of protective occupational measures. Future studies will be important to validate the best treatment strategy in the advanced stages of this disease and also to identify new prognostic and/or therapeutic target biomarkers in SNAC.

New Approaches to the Prevention of Visceral Leishmaniasis: A Review of Recent Patents of Potential Candidates for a Chimeric Protein Vaccine.

The development of prophylactic vaccines is important in preventing and controlling diseases such as visceral leishmaniasis (VL), in addition to being an economic measure for public health. Despite the efforts to develop a vaccine against human VL caused by Leishmania infantum, none is available, and the focus has shifted to developing vaccines against canine visceral leishmaniasis (CVL). Currently, commercially available vaccines are targeted at CVL but are not effective. Different strategies have been applied in developing and improving vaccines, such as using chimeric proteins to expand vaccine coverage. The search for patents can be a way of tracking vaccines that have the potential to be marketed. In this context, the present work presents a summary of immunological aspects relevant to VL vaccine development with a focus on the composition of chimeric protein vaccines for CVL deposited in patent banks as an important approach for biotechnological development. The resulting data could facilitate the screening and selection of antigens to compose vaccine candidates with high performance against VL.

The impact of the COVID-19 pandemic on the well-being, work conditions, and education of early career psychiatrists in the WHO Eastern Mediterranean Region: study protocol.

Background: The COVID-19 pandemic placed great strain on healthcare professionals, leading to a substantial impact and a redistribution of the workforce. Despite the active involvement of the Eastern Mediterranean Region Office (EMRO) and the World Health Organization in managing mental health crises, there is a knowledge gap concerning the working conditions and training opportunities available for early career psychiatrists (ECPs) during the pandemic period. Objectives: This study aims to investigate the impact of the COVID-19 pandemic on ECPs and how it affected their well-being, employment, and educational opportunities. Methods: A mixed methods study has been conducted in Iran, Egypt, and Tunisia, three EMRO member countries. It includes a cross-sectional survey with self-reported questions, and a qualitative study with individual in-depth interviews. Discussion: The findings of this study will raise awareness to the working conditions of ECPs within the EMRO region and its member societies, both during the COVID-19 pandemic and beyond. The results will serve as a basis for encouraging supervisors and policymakers to mitigate the pandemic's impact on psychiatric training, strengthen healthcare systems' preparedness, and equip early career psychiatrists with the necessary skills to deal with the mental health consequences of the COVID-19 pandemic.

Analysis of the hikikomori phenomenon - an international infodemiology study of Twitter data in Portuguese.

BACKGROUND: Hikikomori refers to the extreme isolation of individuals in their own homes, lasting at least six months. In recent years social isolation has become an important clinical, social, and public health problem, with increased awareness of hikikomori around the globe. Portuguese is one of the six most spoken languages in the world, but no studies have analysed the content regarding this phenomenon expressed in Portuguese. OBJECTIVE: To explore the hikikomori phenomenon on Twitter in Portuguese, utilising a mixed-methods approach encompassing content analysis, emotional analysis, and correlation analysis. METHODS: A mixed methods analysis of all publicly available tweets in the Portuguese language using a specific keyword (hikikomori) between 1st January 2008 and 19th October 2022. The content analysis involved categorising tweets based on tone, content, and user types, while correlation analysis was used to investigate user engagement and geographical distribution. Statistical analysis and artificial intelligence were employed to classify and interpret the tweet data. RESULTS: Among the total of 13,915 tweets generated, in terms of tone 10,731 were classified as "negative", and 3184 as "positive". Regarding content, "curiosities" was the most posted, as well as the most retweeted and liked topic. Worldwide, most of the hikikomori related tweets in Portuguese were posted in Europe, while "individuals with hikikomori" were the users most active posting. Regarding emotion analysis, the majority of tweets were "neutral". CONCLUSIONS: These findings show the global prevalence of the discourse on hikikomori phenomenon among Portuguese speakers. It also indicates an increase in the number of tweets on this topic in certain continents over the years. These findings can contribute to developing specific interventions, support networks, and awareness-raising campaigns for affected individuals.

Distinct ontogenetic lineages dictate cDC2 heterogeneity.

Conventional dendritic cells (cDCs) include functionally and phenotypically diverse populations, such as cDC1s and cDC2s. The latter population has been variously subdivided into Notch-dependent cDC2s, KLF4-dependent cDC2s, T-bet+ cDC2As and T-bet- cDC2Bs, but it is unclear how all these subtypes are interrelated and to what degree they represent cell states or cell subsets. All cDCs are derived from bone marrow progenitors called pre-cDCs, which circulate through the blood to colonize peripheral tissues. Here, we identified distinct mouse pre-cDC2 subsets biased to give rise to cDC2As or cDC2Bs. We showed that a Siglec-H+ pre-cDC2A population in the bone marrow preferentially gave rise to Siglec-H- CD8α+ pre-cDC2As in tissues, which differentiated into T-bet+ cDC2As. In contrast, a Siglec-H- fraction of pre-cDCs in the bone marrow and periphery mostly generated T-bet- cDC2Bs, a lineage marked by the expression of LysM. Our results showed that cDC2A versus cDC2B fate specification starts in the bone marrow and suggest that cDC2 subsets are ontogenetically determined lineages, rather than cell states imposed by the peripheral tissue environment.