Identification of pancreatic cancer risk factors from clinical notes using natural language processing.

OBJECTIVES: Screening for pancreatic ductal adenocarcinoma (PDAC) is considered in high-risk individuals (HRIs) with established PDAC risk factors, such as family history and germline mutations in PDAC susceptibility genes. Accurate assessment of risk factor status is provider knowledge-dependent and requires extensive manual chart review by experts. Natural Language Processing (NLP) has shown promise in automated data extraction from the electronic health record (EHR). We aimed to use NLP for automated extraction of PDAC risk factors from unstructured clinical notes in the EHR. METHODS: We first developed rule-based NLP algorithms to extract PDAC risk factors at the document-level, using an annotated corpus of 2091 clinical notes. Next, we further improved the NLP algorithms using a cohort of 1138 patients through patient-level training, validation, and testing, with comparison against a pre-specified reference standard. To minimize false-negative results we prioritized algorithm recall. RESULTS: In the test set (n = 807), the NLP algorithms achieved a recall of 0.933, precision of 0.790, and F1-score of 0.856 for family history of PDAC. For germline genetic mutations, the algorithm had a high recall of 0.851, while precision and F1-score were lower at 0.350 and 0.496 respectively. Most false positives for germline mutations resulted from erroneous recognition of tissue mutations. CONCLUSIONS: Rule-based NLP algorithms applied to unstructured clinical notes are highly sensitive for automated identification of PDAC risk factors. Further validation in a large primary-care patient population is warranted to assess real-world utility in identifying HRIs for pancreatic cancer screening.

Investigation of photoelectron elliptical dichroism for chiral analysis.

This paper describes a compact new instrument, conceived specifically for measurements of Photo Electron Elliptical Dichroism (PEELD) and designed for simplicity of use as a prototype for a practical analytical device. PEELD is an asymmetry in the electron angular distribution obtained from resonantly enhanced multi-photon ionisation of a chiral molecule, where there is also a non-linear dependence on the polarization ellipticity. Despite the fact that PEELD can provide a unique signature of molecular structure and dynamics it has only been investigated in a few molecules to date. This is addressed in the present study in a range of measurements of several terpenes and phenyl-alcohols. These show that the PEELD signatures in structural isomers can be dramatically different and can also be influenced by the intensity of the light. A systematic study in phenyl-alcohols containing the same chromophore and chiral centre configuration shows consistent PEELD behaviour across the molecules except that the magnitude reduces as the distance from the chromophore to the chiral centre increases. These achievements demonstrate that this relatively simple set up can be used for scientific studies as well as providing a blueprint for a practical chiral analysis instrument.

Velocity-map imaging of photoelectron circular dichroism in non-volatile molecules using a laser-based desorption source.

We present an initial demonstration of a velocity-map imaging (VMI) experiment using a back-irradiation laser-based desorption source directly integrated into the electrode assembly. This has the potential to greatly expand the utility of the popular VMI approach by permitting its use with high density plumes of non-volatile molecular samples. Photoelectron circular dichroism measurements on the phenylalanine molecule using 400 nm multiphoton ionization are used to illustrate this novel method, revealing forward-backward emission asymmetries on the order of 7%.

Using photoelectron elliptical dichroism (PEELD) to determine real-time variation of enantiomeric excess.

In this work, the photoionization of chiral molecules by an elliptically polarized, high repetition rate, femtosecond laser is probed. The resulting 3D photoelectron angular distribution shows a strong forward-backward asymmetry, which is highly dependent not only on the molecular structure but also on the ellipticity of the laser pulse. By continuously varying the laser ellipticity, we can observe molecular and enantiomer changes in real time at a previously unseen speed and precision. The technique allows enantiomeric excess of a pure compound to be measured with a 5% precision within 3 s, and a 10-min acquisition yields a precision of 0.4%. The isomers camphor and fenchone can be easily distinguished, unlike with conventional mass spectrometry. Preliminary results for the pharmaceutically interesting ibuprofen are also given, showing the capability of photoionization as a means of distinguishing larger molecular systems.

Dynamics of electronically excited states in the eumelanin building block 5,6-dihydroxyindole.

We report the first excited state dynamics study of gas-phase 5,6-dihydroxyindole (5,6-DHI), a key building block of eumelanin pigments that are found throughout nature and serve as important photo-protective compounds. Time-resolved ion-yield measurements over the 241-296 nm ultraviolet photoexcitation region revealed non-adiabatic processes occurring on up to three distinct timescales. These reflect ultrafast (i.e. sub-picosecond) internal conversion within the excited state singlet manifold, and much longer-lived processes ranging from 10 ps to in excess of 1 ns. Our investigation paves the way for precisely targeted future studies of 5,6-DHI that exploit more differential measurement techniques. The work was facilitated by the use of soft laser-based thermal desorption to introduce 5,6-DHI samples into the gas phase. This approach, based on low-cost, readily available diode lasers, is straightforward, easily controllable and potentially applicable to a wide range of non-volatile molecular species.

Ultraviolet relaxation dynamics in uracil: Time-resolved photoion yield studies using a laser-based thermal desorption source.

Wavelength-dependent measurements of the RNA base uracil, undertaken with nanosecond ultraviolet laser pulses, have previously identified a fragment at m/z = 84 (corresponding to the C3H4N2O+ ion) at excitation wavelengths ≤232 nm. This has been interpreted as a possible signature of a theoretically predicted ultrafast ring-opening occurring on a neutral excited state potential energy surface. To further investigate the dynamics of this mechanism, and also the non-adiabatic dynamics operating more generally in uracil, we have used a newly built ultra-high vacuum spectrometer incorporating a laser-based thermal desorption source to perform time-resolved ion-yield measurements at pump wavelengths of 267 nm, 220 nm, and 200 nm. We also report complementary data obtained for the related species 2-thiouracil following 267 nm excitation. Where direct comparisons can be made (267 nm), our findings are in good agreement with the previously reported measurements conducted on these systems using cold molecular beams, demonstrating that the role of initial internal energy on the excited state dynamics is negligible. Our 220 nm and 200 nm data also represent the first reported ultrafast study of uracil at pump wavelengths <250 nm, revealing extremely rapid (<200 fs) relaxation of the bright S3(1ππ*) state. These measurements do not, however, provide any evidence for the appearance of the m/z = 84 fragment within the first few hundred picoseconds following excitation. This key finding indicates that the detection of this specific species in previous nanosecond work is not directly related to an ultrafast ring-opening process. An alternative excited state process, operating on a more extended time scale, remains an open possibility.

Detection limits of organic compounds achievable with intense, short-pulse lasers.

Many organic molecules have strong absorption bands which can be accessed by ultraviolet short pulse lasers to produce efficient ionization. This resonant multiphoton ionization scheme has already been exploited as an ionization source in time-of-flight mass spectrometers used for environmental trace analysis. In the present work we quantify the ultimate potential of this technique by measuring absolute ion yields produced from the interaction of 267 nm femtosecond laser pulses with the organic molecules indole and toluene, and gases Xe, N2 and O2. Using multiphoton ionization cross sections extracted from these results, we show that the laser pulse parameters required for real-time detection of aromatic molecules at concentrations of one part per trillion in air and a limit of detection of a few attomoles are achievable with presently available commercial laser systems. The potential applications for the analysis of human breath, blood and tissue samples are discussed.

Proton irradiation of DNA nucleosides in the gas phase.

The four DNA nucleosides guanosine, adenosine, cytidine and thymidine have been produced in the gas phase by a laser thermal desorption source, and irradiated by a beam of protons with 5 keV kinetic energy. The molecular ions as well as energetic neutrals formed have been analyzed by mass spectrometry in order to shed light on the ionization and fragmentation processes triggered by proton collision. A range of 8-20 eV has been estimated for the binding energy of the electron captured by the proton. Glycosidic bond cleavage between the base and sugar has been observed with a high probability for all nucleosides, resulting in predominantly intact base ions for guanosine, adenosine, and cytidine but not for thymidine where intact sugar ions are dominant. This behavior is influenced by the ionization energies of the nucleobases (G < A < C < T), which seems to determine the localization of the charge following the initial ionization. This charge transfer process can also be inferred from the production of protonated base ions, which have a similar dependence on the base ionization potential, although the base proton affinity might also play a role. Other dissociation pathways have also been identified, including further fragmentation of the base and sugar moieties for thymidine and guanosine, respectively, and partial breakup of the sugar ring without glycosidic bond cleavage mainly for adenosine and cytidine. These results show that charge localization following ionization by proton irradiation is important in determining dissociation channels of isolated nucleosides, which could in turn influence direct radiation damage in DNA.

Ultrafast non-radiative decay of gas-phase nucleosides.

The ultrafast photo-physical properties of DNA are crucial in providing a stable basis for life. Although the DNA bases efficiently absorb ultraviolet (UV) radiation, this energy can be dissipated to the surrounding environment by the rapid conversion of electronic energy to vibrational energy within about a picosecond. The intrinsic nature of this internal conversion process has previously been demonstrated through gas phase experiments on the bases, supported by theoretical calculations. De-excitation rates appear to be accelerated when individual bases are hydrogen bonded to solvent molecules or their complementary Watson-Crick pair. In this paper, the first gas-phase measurements of electronic relaxation in DNA nucleosides following UV excitation are reported. Using a pump-probe ionization scheme, the lifetimes for internal conversion to the ground state following excitation at 267 nm are found to be reduced by around a factor of two for adenosine, cytidine and thymidine compared with the isolated bases. These results are discussed in terms of a recent proposition that a charge transfer state provides an additional internal conversion pathway mediated by proton transfer through a sugar to base hydrogen bond.

Continuity of Care: A Primer for Family Medicine Residencies.

Continuity of care has been an identifying characteristic of family medicine since its inception and is an essential ingredient for high-functioning health care teams. Many benefits, including the quadruple aim of enhancing patient experience, improving population health, reducing costs, and improving care team well-being, are ascribed to continuity of care. In 2023, the Accreditation Council for Graduate Medical Education (ACGME) added two new continuity requirements-annual patient-sided continuity and annual resident-sided continuity-in family medicine training programs. This article reviews continuity of care as it applies to family medicine training programs. We discuss the various types of continuity and issues surrounding the measurement of continuity. A generally agreed upon definition of patient-sided and resident-sided continuity is presented to allow programs to begin to collect the necessary data. Especially within resident training programs, intricacies associated with maintaining continuity of care, such as empanelment, resident turnover, and scheduling, are discussed. The importance of right-sizing resident panels is highlighted, and a mechanism for accomplishing this is presented. The recent ACGME requirements represent a cultural shift from measuring resident experience based on volume to measuring resident continuity. This cultural shift forces family medicine training programs to adapt their various systems, policies, and procedures to emphasize continuity. We hope this manuscript's review of several facets of contuinuity, some unique to training programs, helps programs ensure compliance with the ACGME requirements.

Detection and quantification of Babesia species intraerythrocytic parasites by flow cytometry.

OBJECTIVES: Recent work has demonstrated that automated fluorescence flow cytometry (FLC) is a potential alternative for the detection and quantification of Plasmodium parasites. The objective of this study was to apply this novel FLC method to detect and quantify Babesia parasites in venous blood and compare results to light microscopy and polymerase chain reaction methods. METHODS: An automated hematology/malaria analyzer (XN-31; Sysmex) was used to detect and quantify B microti-infected red blood cells from residual venous blood samples (n = 250: Babesia positive, n = 170; Babesia negative, n = 80). As no instrument software currently exists for Babesia, qualitative and quantitative machine learning (ML) algorithms were developed to facilitate analysis. RESULTS: Performance of the ML models was verified against the XN-31 software using P falciparum-infected samples. When applied to Babesia-infected samples, the qualitative ML model demonstrated an area under the curve (AUC) of 0.956 (sensitivity, 95.9%; specificity, 83.3%) relative to polymerase chain reaction. For valid scattergrams, the qualitive model achieved an AUC of 1.0 (sensitivity and specificity, 100%), while the quantitative model demonstrated an AUC of 0.986 (sensitivity, 94.4%; specificity, 100%). CONCLUSIONS: This investigation demonstrates that Babesia parasites can be detected and quantified directly from venous blood using FLC. Although promising, opportunities remain to improve the general applicability of the method.

The Role of Artificial Intelligence Model Documentation in Translational Science: Scoping Review.

BACKGROUND: Despite the touted potential of artificial intelligence (AI) and machine learning (ML) to revolutionize health care, clinical decision support tools, herein referred to as medical modeling software (MMS), have yet to realize the anticipated benefits. One proposed obstacle is the acknowledged gaps in AI translation. These gaps stem partly from the fragmentation of processes and resources to support MMS transparent documentation. Consequently, the absence of transparent reporting hinders the provision of evidence to support the implementation of MMS in clinical practice, thereby serving as a substantial barrier to the successful translation of software from research settings to clinical practice. OBJECTIVE: This study aimed to scope the current landscape of AI- and ML-based MMS documentation practices and elucidate the function of documentation in facilitating the translation of ethical and explainable MMS into clinical workflows. METHODS: A scoping review was conducted in accordance with PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines. PubMed was searched using Medical Subject Headings key concepts of AI, ML, ethical considerations, and explainability to identify publications detailing AI- and ML-based MMS documentation, in addition to snowball sampling of selected reference lists. To include the possibility of implicit documentation practices not explicitly labeled as such, we did not use documentation as a key concept but as an inclusion criterion. A 2-stage screening process (title and abstract screening and full-text review) was conducted by 1 author. A data extraction template was used to record publication-related information; barriers to developing ethical and explainable MMS; available standards, regulations, frameworks, or governance strategies related to documentation; and recommendations for documentation for papers that met the inclusion criteria. RESULTS: Of the 115 papers retrieved, 21 (18.3%) papers met the requirements for inclusion. Ethics and explainability were investigated in the context of AI- and ML-based MMS documentation and translation. Data detailing the current state and challenges and recommendations for future studies were synthesized. Notable themes defining the current state and challenges that required thorough review included bias, accountability, governance, and explainability. Recommendations identified in the literature to address present barriers call for a proactive evaluation of MMS, multidisciplinary collaboration, adherence to investigation and validation protocols, transparency and traceability requirements, and guiding standards and frameworks that enhance documentation efforts and support the translation of AI- and ML-based MMS. CONCLUSIONS: Resolving barriers to translation is critical for MMS to deliver on expectations, including those barriers identified in this scoping review related to bias, accountability, governance, and explainability. Our findings suggest that transparent strategic documentation, aligning translational science and regulatory science, will support the translation of MMS by coordinating communication and reporting and reducing translational barriers, thereby furthering the adoption of MMS.

Evaluation of tumour motion and internal/external correlation in lung SABR.

OBJECTIVE: This study aims to analyse lung tumour motion and to investigate the correlation between the internal tumour motion acquired from four-dimensional computed tomography (4DCT) and the motion of an external surrogate. METHODS: A data set of 363 4DCT images was analysed. Tumours were classified based on their anatomical lobes. The recorded gross tumour volume (GTV) information included the centroid GTV motion in the superior-inferior, anteroposterior and left-right directions, and in three-dimensions (3D). For the internal/external correlation, the RPM surrogate breathing signals of 260 patients were analysed via an in-house script. The external motion was correlated with the 3D centroid motion, and the maximum tumour motion via Spearman's correlation. The effect of tumour volume on the amount of motion was evaluated. RESULTS: The greatest 3D tumour amplitude was found for tumours located in the lower part of the lung, with a maximum of 26.7 mm. The Spearman's correlation of the internal 3D motion was weak in the upper (r = 0.21) and moderate in the middle (r = 0.51) and the lower (r = 0.52) lobes. There was no obvious difference in the correlation coefficients between the maximum tumour displacement and the centroid motion. No correlation was found between the tumour volume and the magnitude of motion. CONCLUSION: Our results suggest that tumour location can be a good predictor of its motion. However, tumour size is a poor predictor of the motion. ADVANCES IN KNOWLEDGE: This knowledge of the distribution of tumour motion throughout the thoracic regions will be valuable to research groups investigating the refinement of motion management strategies.

Focal-occult placenta accreta: a clandestine source of maternal morbidity.

BACKGROUND: Focal-occult placenta accreta spectrum is known to cause adverse obstetrical morbidity outcomes, however, direct comparisons with previa-associated placenta accreta spectrum morbidity are lacking. OBJECTIVE: We sought to compare the baseline characteristics, surgical and obstetrical morbidity, and subsequent pregnancy outcomes of patients with focal-occult placenta accreta spectrum with those of patients with previa-associated accreta. STUDY DESIGN: A retrospective review was conducted of all pathologically confirmed placenta accreta spectrum cases from 2018 to 2022 at a tertiary care center. The baseline characteristics, surgical, obstetrical, and subsequent pregnancy outcomes were recorded. Cases of focal-occult placenta accreta spectrum was compared with cases of previa-associated placenta accreta spectrum across a range of morbidity characteristics including hemorrhagic factors, interventions, postdelivery reoperations, infections, and intensive care unit admission. Statistical comparison was performed using Kruskal-Wallis or chi-square tests, and a P value of <.05 was considered significant. RESULTS: A total of 74 cases were identified with 43 focal-occult and 31 previa-associated placenta accreta spectrum cases. Of those, 25.6% of the patients with focal-occult placenta accreta spectrum and 100% of the patients with previa-associated placenta accreta spectrum underwent a hysterectomy. One case of focal-occult placenta accreta spectrum and 29 cases of previa-associated placenta accreta spectrum were diagnosed antenatally. Patients with focal-occult placenta accreta spectrum did not differ from those with previa-associated placenta accreta spectrum in mean maternal age (33.0 vs 33.1 years), body mass index, or the incidence of previous dilation and curettage procedures (16.3% vs 25.8%). Patients with focal-occult placenta accreta spectrum were significantly more likely to have a lower mean parity (1.5 vs 3.6 gestations), higher gestational age at delivery (36.1 vs 33.9 weeks' gestation), and were less likely to have had a previous cesarean delivery (12/43, 27.9% vs 30/31, 96.8%). In addition, patients with focal-occult placenta accreta spectrum had less previous cesarean deliveries (mean, 0.5 vs 2.3), were more likely to have undergone in vitro fertilization (20.9% vs 3.2%), and less likely to have anterior placentation. When contrasting the clinical outcomes of patients with focal-occult placenta accreta spectrum with those with previa-associated placenta accreta spectrum, the postpartum hemorrhage rates (71.0% vs 67.4%), mean quantitative blood loss (2099 mL; range, 500-9516 mL vs 2119 mL; range 350-12,220 mL), mean units of red blood cells transfused (1.4 vs 1.7), massive transfusion rate (9.3% vs 3.2%), and intensive care unit admission rates (11.6% vs 6.5%) were not significantly different, but there was a nonsignificant trend toward higher morbidity among patients with focal-occult accreta. Patients with focal-occult accreta had a higher incidence of reoperations or return to the operating room (30.2 vs 6.5%; P=.01). When comparing focal-occult with previa-associated placenta accreta spectrum, the composite outcomes, including hemorrhagic morbidity (77.4% vs 74.4%), any maternal morbidity (83.9% vs 76.7%), and severe maternal morbidity (64.5% vs 65.1%), were not significantly different between the groups. Nine focal-occult placenta accreta spectrum patients had a subsequent pregnancy, and 3 of those had recurrent placenta accreta spectrum. CONCLUSION: Focal-occult placenta accreta spectrum presents with fewer identifiable risk factors than placenta previa-associated placenta accreta spectrum but may be associated with an in vitro fertilization pregnancy. Patients with focal-occult placenta accreta spectrum was observed to have a higher incidence of reoperation when compared with patients previa-associated placenta accreta spectrum, and no other statistically significant differences in morbidity outcomes were observed. The absence of differences in morbidity outcomes may be attributable to a lack of antenatal detection of focal-occult accreta and merits further investigation.

Femtosecond lasers for mass spectrometry: proposed application to catalytic hydrogenation of butadiene.

Mass spectra from the interaction of intense, femtosecond laser pulses with 1,3-butadiene, 1-butene, and n-butane have been obtained. The proportion of the fragment ions produced as a function of intensity, pulse length, and wavelength was investigated. Potential mass spectrometry applications, for example in the analysis of catalytic reaction products, are discussed.

Effects of charge location on the absorptions and lifetimes of protonated tyrosine peptides in vacuo.

Nearby charges affect the electronic energy levels of chromophores, with the extent of the effect being determined by the magnitude of the charge and degree of charge-chromophore separation. The molecular configuration dictates the charge-chromophore distance. Hence, in this study, we aim to assess how the location of the charge influences the absorption of a set of model protonated and diprotonated peptide ions, and whether spectral differences are large enough to be identified. The studied ions were the dipeptide YK, the tripeptide KYK (Y = tyrosine; K = lysine) and their complexes with 18-crown-6-ether (CE). The CE targets the ammonium group by forming internal ionic hydrogen bonds and limits the folding of the peptide. In the tripeptide, the distance between the chromophore and the backbone ammonium is enlarged relative to that in the dipeptide. Experiments were performed in an electrostatic ion storage ring using a tunable laser system, and action spectra based on lifetime measurements were obtained in the range from 210 to 310 nm. The spectra are all quite similar though there seems to be some changes in the absorption band between 210 and 250 nm, while in the lower energy band all ions had a maximum absorption at ~275 nm. Lifetimes after photoexcitation were found to shorten upon protonation and lengthen upon CE complexation, in accordance with the increased number of degrees of freedom and an increase in activation energies for dissociation as the mobile proton model is no longer operative.

Skin Biopsy Techniques.

Because many skin lesions and disorders can appear similar, primary care clinicians often struggle to diagnose them definitively without histopathologic information obtained from a biopsy. This review article explains how to decide whether a lesion should be biopsied and what type of biopsy technique to use and then outlines the stepwise approach to each of the most common skin biopsy techniques: shave, saucerization, punch, fusiform, and subcutaneous nodule biopsies. Finally, potential pitfalls and complications are discussed so the clinician can avoid those and can provide a cosmetically acceptable result from these common outpatient procedures.

Association of a housing based individual socioeconomic status measure with diabetic control in primary care practices.

AIMS: Socioeconomic status (SES) is an important variable that impacts healthcare outcomes. However, grouped SES data is not always representative of all members and it is difficult to obtain individual level data. A validated individual housing-based measure termed HOUSES is available, but has not been studied in diabetes. We hypothesize that patients in the lowest HOUSES quartile are associated with worse diabetic control as measured by the D5. METHODS: A retrospective cohort study of 5463 patients with diabetes in 5 patient centered medical home practices in southeast Minnesota was conducted. HOUSES is a validated, standardized housing-based SES measure constructed from publicly available county assessor's office data. Diabetic control was assessed by the D5 (HgbA1c < 8, BP < 140/90, statin use, nonsmoking status, and antiplatelet therapy). RESULTS: In the lowest HOUSES quartile, more patients had an uncontrolled D5 (56.4%) than any of the other quartiles (49.2%, 49.8%, 49.6% respectively, p < 0.001). A multivariate analysis shows the adjusted odds of D5 control for patients in the 2nd, 3rd or 4th HOUSES quartiles as opposed to the 1st quartile are 1.28, 1.21, and 1.20, respectively. CONCLUSION: Lower SES as represented by the first quartile of HOUSES index, is associated with lower odds of D5 control and thus worse diabetic outcomes. Using the HOUSES index to identify these individuals in a patient centered medical home might prove useful in deciding where to focus diabetic control efforts.

Patient on Immunomodulatory Therapy Experiencing Joint Pain and Skin Lesions: A Case Report.

A woman in her late fifties was admitted to the Family Medicine Inpatient Service directly from Rheumatology clinic for polyarticular pain and erythema with concern for infection. She was taking immunosuppressant medications for a history of multiple autoimmune diseases. Examination showed increasing erythema and tenderness on the upper and lower extremity joints. Histologic evaluation, surgical evaluation, and cultures were consistent with mycobacterium haemophilum infection. Mycobacterium haemophilum is an uncommon opportunistic infection that usually affects immunocompromised patients. The patient was treated with a multi-drug antibiotic regimen for several months due to drug resistance. Although this opportunistic infection is not common it should be considered in the differential of immunocompromised patients with skin and articular symptoms. Treatment outcomes are usually favorable if it caught earlier in the course.

Real-time observation of a correlation-driven sub 3 fs charge migration in ionised adenine.

Sudden ionisation of a relatively large molecule can initiate a correlation-driven process dubbed charge migration, where the electron density distribution is expected to rapidly move along the molecular backbone. Capturing this few-femtosecond or attosecond charge redistribution would represent the real-time observation of electron correlation in a molecule with the enticing prospect of following the energy flow from a single excited electron to the other coupled electrons in the system. Here, we report a time-resolved study of the correlation-driven charge migration process occurring in the nucleic-acid base adenine after ionisation with a 15-35 eV attosecond pulse. We find that the production of intact doubly charged adenine - via a shortly-delayed laser-induced second ionisation event - represents the signature of a charge inflation mechanism resulting from many-body excitation. This conclusion is supported by first-principles time-dependent simulations. These findings may contribute to the control of molecular reactivity at the electronic, few-femtosecond time scale.