{ "inputs_sha256": "acffc16a75bfdbf2164db8641f816713c3a09d6cbd4250fe32837ab9fd3dc89f", "hash_convention": "UTF-8 text after universal-newline normalization to LF", "analysis_status": "Descriptive source reanalysis, no new significance/equivalence tests or reproductive-risk model", "PC3_cell_selectivity": { "rapamycin": { "C1_ic50_pM": { "n": 4, "mean": 63.30875, "sample_sd": 18.539744161755127, "sem": 9.269872080877564 }, "C2_ic50_pM": { "n": 4, "mean": 534.8955, "sample_sd": 257.4247456772561, "sem": 128.71237283862806 }, "paired_replicate_C2_C1_selectivity": [ 11.138165864518875, 16.67567071411712, 1.8753832100804584, 9.088419859381116 ], "mean_of_paired_ratios": { "n": 4, "mean": 9.694409912024392, "sample_sd": 6.119009618852125, "sem": 3.0595048094260626 }, "ratio_of_mean_ic50s": 8.448997966315872 }, "DL001": { "C1_ic50_pM": { "n": 4, "mean": 74.93599999999999, "sample_sd": 24.883770118961746, "sem": 12.441885059480873 }, "C2_ic50_pM": { "n": 4, "mean": 26245.41275, "sample_sd": 14227.642744789488, "sem": 7113.821372394744 }, "paired_replicate_C2_C1_selectivity": [ 829.2318040543676, 587.6838400281579, 94.54376231254774, 222.04815010511405 ], "mean_of_paired_ratios": { "n": 4, "mean": 433.37688912504683, "sample_sd": 336.6400018476735, "sem": 168.32000092383674 }, "ratio_of_mean_ic50s": 350.2377061759368 }, "relative_DL001_vs_rapamycin": { "ratio_of_compound_mean_paired_selectivities": 44.70379250082162, "ratio_of_compound_ratios_of_mean_ic50s": 41.45316492822587, "cross_compound_replicate_pairing_assumed": false, "new_p_value": null, "interpretation": "Different descriptive estimands, not conflicting experiments. No reproductive or tissue selectivity follows from PC3 ratios." } }, "tissue_pathway_series": 18, "tissue_pathway_interpretation": "Different tissues and source sex/context; zeros retained as normalized readouts, not proof of absent kinase activity. No parent tissue exposure is measured by these values.", "reported_whole_blood_compound_concentration_ng_per_mL": { "DL001": { "n": 9, "mean": 186.27777777777777, "sample_sd": 34.14135241088795, "sem": 11.380450803629316 }, "rapamycin": { "n": 18, "mean": 257.2055555555556, "sample_sd": 174.50345512245082, "sem": 41.13085881918912 } }, "whole_blood_DL001_to_rapamycin_mean_ratio": 0.7242369915977276, "blood_parent_exposure_qualification": "Single reported post-administration whole-blood time point, not AUC, oral F, unbound or testis concentration. Assay validation/specificity not established from the retrieved main-text methods. Cannot match to female Figure3d animals or infer cause of pathway selectivity.", "adult_mouse_testis_mass": { "rapamycin_to_control_reported_mean_ratio": 0.4609740670461733, "reported_mean_difference_mg_per_pair": -85.22, "control_n_animals": 5, "rapamycin_n_animals": 4, "individual_observations_or_new_confidence_interval": null, "human_testicular_volume_inference": null, "mechanistic_attribution_to_C2_alone": null }, "human_transplant_descriptive_contrasts": { "total_sperm_count_mean_difference_million": -263.59999999999997, "motile_sperm_mean_difference_percentage_points": -18.8, "n_semen_by_regimen": null, "adjusted_causal_effect": null, "probability_of_infertility_or_recovery": null, "comparison_to_DL001": null, "interpretation": "Unadjusted differences of reported abstract means in transplant recipients. Respondents are not the established semen sample size; no healthy-person effect or testicular-volume estimate follows." }, "candidate_joint_evidence_gates": { "DL001": { "joint_human_reproductive_protection_comparison_eligible": false, "missing": [ "testis_cell_native_parent_exposure", "testis_cell_C1_C2_time_context", "direct_reproductive_endpoints", "matched_specified_intended_function", "same_relevant_population_for_joint_comparison", "human_reproductive_candidate_comparison" ], "human_reproductive_risk_reduction_estimate": null }, "rapamycin": { "joint_human_reproductive_protection_comparison_eligible": false, "missing": [ "testis_cell_native_parent_exposure", "testis_cell_C1_C2_time_context", "matched_specified_intended_function", "same_relevant_population_for_joint_comparison", "human_reproductive_candidate_comparison" ], "human_reproductive_risk_reduction_estimate": null } }, "human_safe_analogue_or_equivalent_benefit_identified": false, "recovery_qualification": { "source_location": "Figure 7 and results/abstract", "n_animals_per_group": 3, "followup_months": 2, "reported_outcomes": "testis mass and motility described as restored; sperm counts increased; abstract qualifies the effect as partially reversible", "raw_individual_count_or_motility_values": null, "numeric_recovery_probability": null, "human_recovery_guarantee": false, "qualification": "Do not reinterpret non-significant testis mass as demonstrated equivalence or recovery of every reproductive outcome. No figure digitization is substituted for raw data." } }