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    Disciplines / Research questions

    Medicine

    55 research topics · 216 questions

    The Emergence of the 'Cell Map' Will Benefit Humanity5 questions

    1. Completing the total cell-number calculation for the human body: a cell-type-resolved census of all anatomical compartments

    2. A unified human cell perturbation atlas across cell types and perturbation modalities for deterministic cell state engineering

    3. Open methodological obstacles to a high-fidelity cell-centric human cell atlas (hECA): general-purpose preprocessing, sampling-bias-robust portraiture, and automated re-annotation

    4. Single-cell-resolution cell atlas approximations and real-time natural-language exploration of user datasets

    5. A complete single-cell reference basis for cell-type-resolved deconvolution of the human plasma cell-free transcriptome

    Mechanisms and Treatment of Scar Formation2 questions

    1. Durability, safety, and optimal regimen of intralesional corticosteroid plus botulinum toxin type A versus corticosteroid alone for keloid and hypertrophic scars

    2. Making oral asiaticoside an effective systemic therapy for hypertrophic scars: overcoming very low bioavailability

    Early Protection of Intestinal Barrier Function4 questions

    1. Which milk fat globule membrane components causally drive SCFA-producer enrichment and intestinal barrier enhancement in the neonatal intestine, and is the effect microbiota-mediated?

    2. Molecular mechanism of lactadherin-mediated restoration of intestinal tight-junction and adherens-junction organization in neonatal necrotizing enterocolitis, and the maturation-versus-compensatory-repair question

    3. Which microbiota-derived metabolites drive intestinal barrier maturation at the suckling-to-weaning transition, by what cellular and epigenetic mechanisms, and which effects are epithelial-autonomous?

    4. Pioneer settlers and microbial mediators of preterm-infant-microbiota-induced ileal epithelial maturation in gnotobiotic mice

    The Unsolved Mystery of Kashin-Beck Disease Etiology4 questions

    1. Mechanistic etiology of endemic Kashin–Beck disease: whether and how combined grain-mycotoxin (T-2 toxin), selenium-deficiency, and protein-deficiency exposures produce the characteristic cartilage lesions

    2. Establishing whether low-mineralization drinking-water chemistry is a causal contributor to Kashin-Beck disease risk, and through what mechanism

    3. Molecular mechanism of selenium's suppression of deoxynivalenol-induced Wnt/β-catenin activation in chondrocytes in the context of Kashin-Beck disease

    4. Causal status and prospective replication of essential trace-element disturbances in Kashin-Beck disease

    Development of Vaccines for Herpes Simplex Virus, HIV, and Hepatitis C Virus3 questions

    1. Mechanistic basis of the type-specific efficacy of the HSV-2 glycoprotein D subunit vaccine (Herpevac Trial for Women): protection against HSV-1 but not HSV-2

    2. Differential regulation of CD4, CD8, CD80, and CD86 promoter activity by HSV-1 glycoproteins: the host factors responsible and the in vivo efficacy of a stimulator-only vaccine cocktail

    3. Vaccine elicitation of PGT-like glycan-dependent broadly neutralizing antibodies against HIV-1 in uninfected humans

    Application of Qualitative Research in Clinical Epidemiology2 questions

    1. Systematic and transparent integration of qualitative research into WHO guideline development: standard procedures, evidence-to-decision transparency, contextualisation, certainty appraisal, and panel expertise

    2. Closing the clinician-side gatekeeping gap: causal mechanisms of non-invitation and effective targeted interventions to increase older adults' participation in cancer clinical trials

    Silica, Pneumoconiosis, and Lung Cancer3 questions

    1. Does ambient-level crystalline silica exposure cause excess mortality? Quantifying risk at concentrations far below occupational limits

    2. Completing the risk characterization of respirable crystalline silica and lung cancer: risk in women, time since last exposure, and non-quartz polymorphs (cristobalite and tridymite)

    3. Quantitative exposure–response relationship between respirable crystalline silica and lung cancer: high-dose attenuation, joint action with smoking, cross-industry generalizability, and risk-based exposure limits

    Pulmonary Hypertension Intervention2 questions

    1. Repeat inhaled nitric oxide vasoreactivity testing in pulmonary arterial hypertension: determinants of longitudinal change and clinical value for prognosis and treatment selection

    2. Consensus definitions of proximal versus distal chronic thromboembolic pulmonary hypertension and generalizable operability criteria for pulmonary endarterectomy

    Mechanisms of Immune Tolerance in Liver Transplantation3 questions

    1. Mechanisms by which donor-resident invariant natural killer T cells induce and maintain spontaneous liver allograft tolerance

    2. Cellular mechanisms of the liver tolerizing effect in nonhuman-primate liver transplantation: functional mediators of intrahepatic suppression, memory T-cell recruitment, and reproducible tolerance induction

    3. Donor-reactive CD8+ T-cell fate and the alloantigen exposure window underlying spontaneous liver-allograft tolerance: deletion, exhaustion, or reversible anergy?

    Biological Treatment Strategies for Sensorineural Hearing Loss2 questions

    1. Mechanism, supporting-cell pool fate, and functional completeness of 5-azacytidine-driven supporting-cell-to-hair-cell conversion in the deafened adult cochlea

    2. Functional maturation, mechanisms, and therapeutic conditions of in vivo cochlear glial-to-spiral-ganglion-neuron reprogramming by Neurog1 (Ngn1) and Neurod1

    Osteoporosis and Osteoporotic Fractures: Ancient and Current Challenges2 questions

    1. Molecular mechanisms by which SIRT6 deficiency produces the bone-loss phenotype of senile osteoporosis: chromatin-metabolic integration in bone-lineage cells and the osteoclast fusion/maturation abnormality

    2. Bone fragility despite high bone mineral density in type 2 diabetes: the mechanistic basis of hyperglycemia-impaired bone material quality and whether improving glycemic control can prevent or reverse it

    How Nucleic Acid Drugs Can Be Effectively Administered3 questions

    1. Mechanism of lipid-nanoparticle-mediated nucleic acid endosomal escape: the molecular events at the endosomal membrane, the identity of the escape-permissive compartment, and how LNPs alter endosomal maturation

    2. Generalizing the structural criteria of degradable branched lipidoids for mRNA delivery and resolving their in vitro–in vivo potency discrepancy

    3. Mechanism and in-vivo exploitability of late-endosomal residence as a candidate route to functional RISC delivery of lipid-nanoparticle siRNA: why does blocking endocytic recycling enhance gene silencing?

    How the Body Negatively Regulates Immune Responses8 questions

    1. Causal direction of immune-neuroendocrine (HPA-axis) feedback dysregulation in dementia of the Alzheimer's type

    2. Initiation and maintenance of the late IL-10-centered anti-inflammatory negative feedback in double-hit burn and sepsis, and experimental validation of the inferred transcription factor-cytokine regulatory links

    3. In vivo necessity and quantitative contribution of regulatory T cell–mediated cytokine deprivation and deprivation-induced apoptosis of effector T cells to immune suppression and tolerance

    4. Mechanism by which Banf1/BAF prevents basal cytosolic self-DNA accumulation and constrains the cGAS-STING-IRF3 axis

    5. Molecular mechanisms by which resolution of acute inflammation establishes prolonged immune suppression and 'adapted homeostasis' of tissue macrophages

    6. Molecular mechanism of MHC class II-dependent, contact-mediated suppression by activated human regulatory T cells

    7. In vivo contribution of parenchymal regulatory T cell-mediated suppression of CD8+ T cell cytotoxicity to the course and severity of autoimmune CNS inflammation, and its dependence on antigen load

    8. The molecular mechanism by which interleukin-7 represses Socs3 in T cells during chronic viral infection

    How the Body Recognizes Transplant Antigens and Triggers Organ Transplant Rejection4 questions

    1. Causal role of preexisting donor-reactive memory T cells in loss of mixed hematopoietic chimerism and failure of kidney allograft tolerance induction in primates

    2. Dominant indirect-pathway alloantigen specificities in human graft rejection and targeted antigen-specific regulatory T cell therapy

    3. In vivo route and molecular machinery of host CD8α+/CD103+ dendritic-cell cross-dressing with donor MHC in priming allo-specific CD8+ T cells after transplantation

    4. Causal link from ischemia-reperfusion injury and innate danger sensing to CXCL13-driven B-cell recruitment and humoral alloimmunity in kidney transplantation

    Why the Body Attacks Its Own Tissues Causing Autoimmune Diseases8 questions

    1. What initiates the loss of self-tolerance before clinical autoimmune disease, and why does immune regulation fail to arrest it?

    2. Immune-intrinsic or tissue-intrinsic initiation: adjudicating where autoimmune disease begins, without presupposing broken self-tolerance

    3. Validating the holoimmunity/holoautoimmunity hypothesis: are disease-specific T-cell-receptor mimicry signatures of microbial antigens robust and predictive, and do the predicted microbial combinations induce autoimmune disease in animals?

    4. Antigen-driven activation-induced cell death of self-reactive regulatory T cells: scope, molecular determinants, thymic-lineage origins, and consequences for Treg-directed therapy in autoimmunity

    5. Cellular origin, differentiation pathway, and maintenance of kidney-resident autoreactive CD8 tissue-resident memory T cells in immune-mediated nephritis

    6. Mechanism of liver-specific deletional tolerance and differential pancreas-versus-liver/gut susceptibility to immune-mediated destruction in the co-drained upper digestive system

    7. Dynamical quorum-threshold model of infection-triggered T cell autoimmunity with explicit regulatory T cells and peptide-dependent quorum thresholds

    8. Direct experimental validation of autoimmune surveillance of hyper-secreting mutants (ASHM) in endocrine tissues

    Treatment of Hormone-Refractory Prostate Cancer3 questions

    1. Regulation and causal role of the CCM1–DDX5–YAP/TAZ–AR axis in metastatic castration-resistant prostate cancer

    2. Mechanistic and clinical validation of bipolar androgen therapy in castration-resistant prostate cancer exposed to androgen receptor pathway inhibitors

    3. Optimal sequencing, resistance mechanisms, and rechallenge with second-generation androgen receptor pathway inhibitors in metastatic castration-resistant prostate cancer

    Performance Management and Incentive Mechanisms in Public Healthcare Institutions2 questions

    1. Unexplained heterogeneity in physician responses to performance-based pay: the roles of social preferences, attitudes, and self-selection into payment systems

    2. Sustainable effectiveness, cost-effectiveness, and credible measurement of pay-for-performance in Iranian public hospitals

    How antigens achieve cross-presentation9 questions

    1. The molecular mechanism of endosome-to-cytosol antigen export in dendritic-cell cross-presentation: identity, recruitment, and mode of action of the translocation machinery

    2. Unresolved steps of GILT-dependent cytosolic cross-presentation: the phagosomal antigen-export machinery, the MHC-I peptide-loading compartment, and the in vivo balance of cross-priming versus direct priming for disulfide-rich viral antigens

    3. Molecular mechanism and subset-specific contribution of Rab39a-dependent delivery of ER cargo and peptide-empty MHC-I to cross-presenting phagosomes in dendritic cells

    4. Molecular mechanism and in vivo contribution of the intraphagosomal proteasome-dependent, TAP-independent route of antigen cross-presentation

    5. Unresolved mechanism and in vivo contribution of Sec22b-dependent ER/ERGIC delivery to phagosomes in dendritic-cell antigen cross-presentation

    6. Molecular control and in vivo contribution of dendritic cell cross-dressing with live tumor cell antigens in anti-tumor cross-priming

    7. Molecular substrates and mechanism of UCH-L1-controlled MHC class I recycling in dendritic cell cross-presentation

    8. Biogenesis, HSP70-sequestration chemistry, and therapeutic reversal of oxidatively truncated lipid bodies that block dendritic-cell cross-presentation in cancer

    9. How apoptosis-induced p62-dependent protein aggregates form in donor cells and are recognized, de-aggregated, and processed by dendritic cells into MHC class I cross-presented peptides

    Challenges in antiviral treatment of chronic hepatitis B1 questions

    1. Safe discontinuation of nucleos(t)ide analogue therapy in chronic hepatitis B: validated predictors of off-therapy outcome, monitoring and re-treatment rules, and standardized cccDNA/HBV RNA assays

    How immune memory is formed8 questions

    1. In vivo operation and tunability of cytokine positive-feedback circuits that maintain antigen-agnostic immune memory durability

    2. Immunological memory maintenance: long-lived cells versus self-organized idiotypic-network maintenance

    3. The mechanistic basis of 'memory of danger': mediator contributions, cellular reservoirs, tissue danger sensing, danger-signal hierarchy, and nonspecific protection against allergic disease

    4. Mechanisms that program and maintain the local versus circulating subdivision of memory T follicular helper cells, and their exploitation for vaccine design

    5. Mechanisms specifying which effector CD4 T cells seed long-lived memory

    6. The consolidation phase of immunological memory: what cellular and molecular mechanism does a day-15 booster disrupt, and what is the scope of the phase?

    7. Fate-specification signals and long-term maintenance mechanisms of the terminally differentiated effector-memory (terminal-TEMT_{EM}) CD8 T cell population

    8. Mechanistic basis of P2RX7-dependent memory-fate imprinting in early effector CD8+ T cells

    Mechanisms of immune tolerance formation and research value8 questions

    1. Effector pathway of autoimmune arthritis in adaptively tolerant lymphopenic hosts and the division between T cell-intrinsic adaptation and extrinsic regulation of tolerance to persistent antigen

    2. Maintenance mechanisms of Treg-facilitated mixed chimerism transplant tolerance: donor-derived Treg origin, lineage chimerism dynamics, protocol timing, and human donor-specific Treg translation

    3. Generality and disease relevance of epithelial endogenous-retroelement–cGAS/STING sensing in the control of oral tolerance to dietary antigens

    4. Molecular basis of effector CD8 T-cell conditioning to regulatory T-cell-mediated suppression in oral tolerance, and the role of environmental IL-10

    5. Causal Mechanisms of Chromatin-Primed Low-Threshold Activation of Tolerance-Associated Genes in Tolerized CD4+ T Cells

    6. Mechanistic basis of the B7-H1 (PD-L1)/CD80 tolerogenic axis: additional receptors, cellular sources of PD-L1, and CD80 inhibitory signaling in peripheral T-cell tolerance

    7. Mechanistic basis of anti-CD3 antibody–induced immune tolerance: in vivo activation and deployment of phagocyte-derived TGF-β from apoptotic T-cell clearance

    8. Mechanism of infectious tolerance: antigen specificity and cellular checkpoints of regulatory T-cell suppression in lymphopenic versus lymphoreplete settings

    Regulatory mechanisms of immune cell development and differentiation4 questions

    1. Upstream inputs to the NFIL3-initiated innate lymphoid cell and NK cell specification cascade in bone marrow progenitors

    2. Quantitative decoding of IL-7 and Notch signals into lineage-specifying transcription-factor programs in developing lymphoid cells: physiological signal sources, dose-duration-to-fate mapping, and the fetal-versus-adult Notch requirement in RORγt+ innate lymphoid cell development

    3. Mechanistic basis of Tcf1-enforced T-lineage commitment and fidelity in the Notch→Tcf1→(Gata3, Bcl11b) hierarchy: dedifferentiation in vivo, dual activator/repressor activity, alternative-lineage derepression, hierarchy extension, and the leukemogenesis link

    4. Mechanistic basis of the microbiota–cholic acid–TGR5–TET1–DNA hydroxymethylation crosstalk in innate lymphoid cell differentiation

    How immune cells sense danger signals6 questions

    1. Mechanism of Clec2d-dependent activation of endosomal TLR9 by histone–DNA complexes and the ligand scope of Clec2d among polybasic DAMPs

    2. Determinants of death-mode execution and IL-1α release in HMGB1–bacterial lipid activation of the TLR4–TRIF–RIPK3 inflammatory cell death pathway, and its species generality and in vivo function

    3. Biological basis of rapidness-sensitive discrimination between harmful and harmless antigens: implementation and experimental validation of the predictive immune memory model

    4. Molecular mechanism by which oxidized phospholipids (oxPAPC) engage caspase-11 to drive catalysis-independent NLRP3 inflammasome activation and interleukin-1 release from living dendritic cells

    5. Molecular mechanisms of S100B-mediated RAGE-TLR cross-talk: TRIF-biased TLR9 signalling by S100B-DNA complexes and RAGE-associated inhibition of TLR2

    6. Ligand-source decoding by formyl peptide receptor 1: higher-order FPR assemblies and the native phagocyte context

    How immune cells migrate9 questions

    1. In vivo regulation of T cell infiltration by extracellular matrix shear strength and the molecular basis of breaststroke-like matrix tearing

    2. Molecular mechanism and coordination of the DOCK8-dependent mechanosensitive central actin pool in confined leukocyte migration

    3. Generality of haptotactic leukocyte guidance by immobilized chemokine gradients in vivo (beyond CCL21/CCR7-driven dendritic cell migration in skin)

    4. Molecular mechanism and quantitative role of load-induced WASp activation in amoeboid leukocyte migration through dense 3D tissues

    5. Mechanisms and functional roles of focal adhesion-mediated migration of T cells in confined environments

    6. Molecular mechanism of microtubule-dependent torque-based chemotaxis in dendritic cells

    7. Mechanism and physiological validity of boundary-restricted neutrophil and monocyte migration along endothelial cell-cell boundaries

    8. Mechanism and regulation of the steric-hindrance-induced switch to integrin-mediated contractile migration in immune cells within 3D biopolymer matrices

    9. Molecular control circuit of neutrophil swarming: initiation, relay amplification, termination, and scaling of swarm size to the insult

    Occupational safety in nanotechnology3 questions

    1. Baseline exposure measurement and engineering-control effectiveness for nanomaterial work in Tehran's nanotechnology research laboratories

    2. Validation of control banding tools for engineered nanomaterials: does their use reduce worker exposure to safe levels, and do their comparative performance and divergence patterns hold across materials, sectors, and missing hazard data?

    3. Whether long-term occupational exposure to engineered nanomaterials causes chronic adverse health effects in workers: the open longitudinal-evidence question left by the Wu et al. (2019) four-year panel study

    Genetic mechanisms of ankylosing spondylitis4 questions

    1. Causal resolution of the Han Chinese ankylosing spondylitis GWAS loci: causal variants and genes at 5q14.3 (EDIL3–HAPLN1) and 12q12 (ANO6), the status of 6q21, cross-ancestry effect heterogeneity, and functional links to new bone formation

    2. Causal variants and molecular mechanisms underlying the ankylosing spondylitis risk loci identified by the IGAS 2013 Immunochip study

    3. Genetic basis of axial spondyloarthritis risk: the HLA-B27 mechanism, causal variants at associated loci, and the genetic relationship between non-radiographic disease and ankylosing spondylitis

    4. Molecular mechanism of the ERAP1-HLA-B27 interaction in ankylosing spondylitis: how peptide handling mediates HLA-B27-driven disease susceptibility

    Infection and embolism in artificial hearts3 questions

    1. The thrombus–infection complex in total artificial hearts: bacterial–thrombus–surface mechanisms, host immune and gut-barrier contributions, prevention, and eradication

    2. Thromboembolic safety of the venous-side (right) pump in continuous-flow total artificial hearts: speed-modulation control and blood-path design for unfiltered venous blood

    3. Comparative effectiveness of antithrombotic strategies and their monitoring in SynCardia total artificial heart recipients

    Folding mechanisms of human chromosomes4 questions

    1. Generality and mechanistic basis of the co-existence of loop extrusion and polymer phase separation in chromatin folding

    2. In vivo architecture of the vertebrate mitotic chromosome loop array: condensin encounter rules, loop overlap, and helical versus aperiodic ordering

    3. Mechanistic basis of human genome folding principles: the molecular and biophysical origins of A/B compartment segregation and megabase-scale chromatin organization

    4. Mechanistic origin of few-kilobase chromatin nanodomains in situ and their relationship to topologically associated domains

    Biological limitations of human physical capacity1 questions

    1. Integrating individual thermoregulatory factors into projections of heat-related occupational work-capacity loss under climate change

    How the human body adapts to high-altitude hypoxic environments2 questions

    1. Causal nucleotide variants and molecular mechanisms of Tibetan high-altitude adaptation at EPAS1, EGLN1 and PPARA, and whether low hemoglobin concentration is the direct target of natural selection

    2. Erythrocyte hypoxic purinergic memory: generalization of ADORA2B-PKA-ubiquitin-proteasome ENT1 downregulation, human memory kinetics, and therapeutic manipulation to speed altitude acclimatization

    How the maternal immune system 'tolerates' the fetus during pregnancy9 questions

    1. Mechanisms of antigen-specific maternal T cell tolerance to the allogeneic fetus and the effectors of allospecific early pregnancy loss

    2. In-vivo mechanism, dynamics, and causal role of the decidual NK–CD14+ myelomonocytic crosstalk that induces regulatory T cells at the human maternal–fetal interface

    3. Durability, maintenance mechanism, and therapeutic exploitation of pregnancy-imprinted fetal-antigen-specific regulatory T cell memory

    4. Mechanisms and provenance of fetus-specific regulatory T cells at the human maternal-fetal interface

    5. Fate and functional consequences of fetal antigen uptake by maternal circulating neutrophils and monocytes

    6. Antigen specificity and causal role of clonally expanded decidual effector regulatory T cells in human pregnancy and preeclampsia

    7. Regulatory NK cells at the human maternal-fetal interface: in vivo existence, defining marker, and tolerogenic role of CD56brightCD25+ decidual NK cells versus regulatory T cells

    8. Causal role of soluble HLA-G in the induction and functional enhancement of CD4+CD25+FOXP3+ regulatory T cells during healthy human pregnancy

    9. Antigen-specific maternal T-cell tolerance to fetal alloantigens: clonal dynamics in human pregnancy and the interplay with antigen-independent immune programs

    Monitoring human brain networks during unconstrained behavior4 questions

    1. A common validated standard for removing systemic physiological noise from wearable/mobile fNIRS signals

    2. Ecological and clinical validity of frontal-theta and beta-rebound markers of proactive and reactive control during real-world ambulatory obstacle avoidance

    3. Validation and clinical utility of ultra-long-term subcutaneous EEG for objective seizure counting in epilepsy: gold-standard detection limits, controlled outcome trials, and artifact bias

    4. Mechanisms and generality of hippocampal spatial coding during real-world human navigation

    How to repair human organ defects3 questions

    1. Functional validation of cell-free decellularized xenogenic cartilage extracellular matrix scaffolds for osteochondral defect repair: quantitative, mechanically verified, zonally organized restoration at load-bearing scale

    2. Molecular mechanisms of epithelium–mesenchyme–enteric nervous system crosstalk in human pluripotent stem cell-derived gastric organoids

    3. Reliable, functionally stable stem-cell-mediated bio-root regeneration for tooth replacement

    How epithelial-mesenchymal transition affects tumor progression2 questions

    1. Molecular mechanism by which APOBEC3A deaminase activity induces epithelial–mesenchymal transition programs in high-grade serous ovarian cancer

    2. Hybrid epithelial/mesenchymal states in breast cancer brain metastases: defining the E/M-state spectrum and its contributions to invasion, post-surgical relapse, and therapy resistance

    Non-human primate transgenic animal models of neurological diseases2 questions

    1. Causal mechanisms linking SHANK3 haploinsufficiency to circuit and behavioural phenotypes in the SHANK3-mutant macaque model of Phelan–McDermid syndrome

    2. Determinants of phenotypic variability and long-term disease course in the second-generation transgenic SCA3 (ATXN3-120Q) marmoset model

    Integrated mathematical models for personalized medicine2 questions

    1. Prospective validation of endoxifen exposure–response and clinical utility of model-informed precision dosing of tamoxifen in ER-positive breast cancer

    2. Restoring practical identifiability for individualized oncolytic-virus plus dendritic-cell immunotherapy models

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