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Jennifer M Hah,1 Heather Hilmoe,2 Peter Schmidt,2 Rebecca McCue,2 Jodie Trafton,3,4 Debra Clay,2 Yasamin Sharifzadeh,2 Gabriela Ruchelli,2 Tina Hernandez Boussard,5 Stuart Goodman,6 James Huddleston,7 William J Maloney,7 Frederick M Dirbas,8 Joseph Shrager,9 John G Costouros,7 Catherine Curtin,10 Sean C Mackey,1 Ian Carroll1 1Division of Pain Medicine, Department of Anesthesiology, Perioperative, and Pain Medicine, Stanford University, Stanford, CA, USA; 2Stanford Systems Neuroscience and Pain Lab, Stanford University, Stanford, CA, USA; 3Department of Psychiatry and Behavioral Sciences, Stanford University, Palo Alto, CA, USA; 4VA Program Evaluation and Resource Center, VHA Office of Mental Health Operations, Palo Alto, CA, USA; 5Department of Medicine, Department of Biomedical Data Science, Stanford University, Stanford, CA, USA; 6Department of Orthopaedic Surgery and (by Courtesy) Bioengineering, Department of Orthopaedic Surgery, Stanford University, Stanford, CA, USA; 7Department of Orthopaedic Surgery, Stanford University, Stanford, CA, USA; 8Department of General Surgery, Stanford University, Stanford, CA, USA; 9Division of Thoracic Surgery, Stanford University, Stanford, CA, USA; 10Division of Hand and Plastic Surgery, Department of Orthopaedic Surgery, Stanford University, Stanford, CA, USACorrespondence: Jennifer M HahDivision of Pain Medicine, Department of Anesthesiology, Perioperative, and Pain Medicine, Stanford University, 1070 Arastradero Road, Suite 200, Palo Alto, CA 94304, USATel +1 650-736-9415Fax +1 650-725-9642Email jhah@stanford.eduBackground: Preoperative patient-specific risk factors may elucidate the mechanisms leading to the persistence of pain and opioid use after surgery. This study aimed to determine whether similar or discordant preoperative factors were associated with the duration of postoperative pain and opioid use.Methods: In this post hoc analysis of a randomized, double-blind, placebo-controlled trial of perioperative gabapentin vs active placebo, 410 patients aged 18– 75 years, undergoing diverse operations underwent preoperative assessments of pain, opioid use, substance use, and psychosocial variables. After surgery, a modified Brief Pain Inventory was administered over the phone daily up to 3 months, weekly up to 6 months, and monthly up to 2 years after surgery. Pain and opioid cessation were defined as the first of 5 consecutive days of 0 out of 10 pain or no opioid use, respectively.Results: Overall, 36.1%, 19.8%, and 9.5% of patients continued to report pain, and 9.5%, 2.4%, and 1.7% reported continued opioid use at 3, 6, and 12 months after surgery. Preoperative pain at the future surgical site (every 1-point increase in the Numeric Pain Rating Scale; HR 0.93; 95% CI 0.87– 1.00; P=0.034), trait anxiety (every 10-point increase in the Trait Anxiety Inventory; HR 0.79; 95% CI 0.68– 0.92; P=0.002), and a history of delayed recovery after injury (HR 0.62; 95% CI 0.40– 0.96; P=0.034) were associated with delayed pain cessation. Preoperative opioid use (HR 0.60; 95% CI 0.39– 0.92; P=0.020), elevated depressive symptoms (every 5-point increase in the Beck Depression Inventory-II score; HR 0.88; 95% CI 0.80– 0.98; P=0.017), and preoperative pain outside of the surgical site (HR 0.94; 95% CI 0.89– 1.00; P=0.046) were associated with delayed opioid cessation, while perioperative gabapentin promoted opioid cessation (HR 1.37; 95% CI 1.06– 1.77; P=0.016).Conclusion: Separate risk factors for prolonged post-surgical pain and opioid use indicate that preoperative risk stratification for each outcome may identify patients needing personalized care to augment universal protocols for perioperative pain management and conservative opioid prescribing to improve long-term outcomes.Keywords: persistent postsurgical pain, persistent postoperative opioid use, chronic opioid use after surgery, chronic pain after surgery

Cyanobacteria dominate the world's oceans where iron is often barely detectable. One manifestation of low iron adaptation in the oligotrophic marine environment is a decrease in levels of iron-rich photosynthetic components, including the reaction center of photosystem I and the cytochrome b6f complex [R.F. Strzepek and P.J. Harrison, Photosynthetic architecture differs in coastal and oceanic diatoms, Nature 431 (2004) 689-692.]. These thylakoid membrane components have well characterised roles in linear and cyclic photosynthetic electron transport and their low abundance creates potential impediments to photosynthetic function. Here we show that the marine cyanobacterium Synechococcus WH8102 exhibits significant alternative electron flow to O2, a potential adaptation to the low iron environment in oligotrophic oceans. This alternative electron flow appears to extract electrons from the intersystem electron transport chain, prior to photosystem I. Inhibitor studies demonstrate that a propyl gallate-sensitive oxidase mediates this flow of electrons to oxygen, which in turn alleviates excessive photosystem II excitation pressure that can often occur even at relatively low irradiance. These findings are also discussed in the context of satisfying the energetic requirements of the cell when photosystem I abundance is low. © 2008 Elsevier B.V. All rights reserved.

In this experiment, Sprague-Dawley rats with elastase-induced emphysema were imaged using hyperpolarized 3He MRI. Regional fractional ventilation r, the fraction of gas replaced with a single tidal breath, was calculated from a series of images in a wash-in study of hyperpolarized gas. We compared the regional fractional ventilation in these emphysematous rats to the regional fractional ventilations we calculated from a previous baseline study in healthy Sprague-Dawley rats. We found that there were differences in the maps of fractional ventilation and its associated frequency distribution between the healthy and emphysematous rat lungs. Fractional ventilation tended to be much lower in emphysematous rats than in normal rats. With this information, we can use data on fractional ventilation to regionally distinguish between healthy and emphysematous portions of the lung. The successful implementation of such a technique on a rat model could lead to work toward the future implementation of this technique in human patients. Magn Reson Med 53:1341-1346, 2005. © 2005 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Discusses the entry of women into the field of medicine in the U.S., particularly at the Johns Hopkins University in Baltimore, Maryland, in the 1890s. Medical education offered at the university; Implications of the participation of women in medicine for the industry; Issue of sexism in medical schools.

Presents a theory and model to account for two phenomena of learning: the power law of practice and the problem-solving fan effect. Definition; Data; Theory; Models.

Abstract Background Several physiological adaptations occur in the respiratory muscles in rodent models of elastase-induced emphysema. Although the contractile properties of the diaphragm are altered in a way that suggests expression of slower isoforms of myosin heavy chain (MHC), it has been difficult to demonstrate a shift in MHCs in an animal model that corresponds to the shift toward slower MHCs seen in human emphysema. Methods We sought to identify MHC and corresponding physiological changes in the diaphragms of rats with elastase-induced emphysema. Nine rats with emphysema and 11 control rats were studied 10 months after instillation with elastase. MHC isoform composition was determined by both reverse transcriptase polymerase chain reaction (RT-PCR) and immunocytochemistry by using specific probes able to identify all known adult isoforms. Physiological adaptation was studied on diaphragm strips stimulated in vitro. Results In addition to confirming that emphysematous diaphragm has a decreased fatigability, we identified a significantly longer time-to-peak-tension (63.9 ± 2.7 ms versus 53.9 ± 2.4 ms). At both the RNA (RT-PCR) and protein (immunocytochemistry) levels, we found a significant decrease in the fastest, MHC isoform (IIb) in emphysema. Conclusion This is the first demonstration of MHC shifts and corresponding physiological changes in the diaphragm in an animal model of emphysema. It is established that rodent emphysema, like human emphysema, does result in a physiologically significant shift toward slower diaphragmatic MHC isoforms. In the rat, this occurs at the faster end of the MHC spectrum than in humans.

The Linac Coherent Light Source (LCLS) is the world's first x-ray free electron laser. It is a scientific user facility operated by the SLAC National Accelerator Laboratory, at Stanford, for the U.S. Department of Energy. As beam time at LCLS is extremely valuable and limited, experimental efficiency-getting the most high quality data in the least time-is critical. Our overall project employs cognitive engineering methodologies with the goal of improving experimental efficiency and increasing scientific productivity at LCLS by refining experimental interfaces and workflows, simplifying tasks, reducing errors, and improving operator safety and stress. Here, we describe a multi-agent, multi-scale computational cognitive interaction model of instrument operations at LCLS. Our model simulates the aspects of human cognition at multiple cognitive and temporal scales, ranging from seconds to hours, and among agents playing multiple roles, including instrument operator, real time data analyst, and experiment manager. The model can roughly predict impacts stemming from proposed changes to operational interfaces and workflows. Example results demonstrate the model's potential in guiding modifications to improve operational efficiency. We discuss the implications of our effort for cognitive engineering in complex experimental settings and outline future directions for research. The model is open source, and the videos of the supplementary material provide extensive detail., (© 2025 Author(s). Published under an exclusive license by AIP Publishing.)

Objective: Presentation with multiple ground-glass opacities (GGOs) is an increasingly common occurrence, and the optimal management of these lesions is unclear. Active surveillance has been increasingly adopted as a management strategy for other low-grade malignancies. We hypothesized that active surveillance could be a feasible and safe option for patients with multiple GGOs., Methods: Patients with ≥2 GGOs (ground-glass predominant, <50% solid, ≤3 cm) were enrolled in a multi-institutional registry and prospectively followed up on active surveillance with computed tomography scans every 6 to 12 months. Each GGO was catalogued and measured individually at each follow-up visit., Results: Target accrual was met, with 337 patients from 23 institutions. The mean age was 70 years (interquartile range, 65-77 years), and 74% were women. Most were former (70%) or current (9%) smokers, with a mean exposure of 30 pack-years (interquartile range [IQR], 15-44 pack-years). One half of the patients (51%) had a previous lung cancer, and the majority (86%) were already under surveillance at the time of study entry. The median number of GGOs per patient was 3 (IQR, 2-5), with a total of 1467 GGOs under surveillance. The median GGO size was 0.9 cm (IQR, 0.7-1.3 cm). Most GGOs were 0.5 to 1 cm in size., Conclusions: Active surveillance, rather than immediate intervention, was an acceptable option to patients, and accrual to this registry trial was feasible. Safety end points and long-term outcomes will be assessed in the planned 5-year follow-up in accordance with the protocol., Competing Interests: Conflict of Interest Statement The authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2024 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Tissue-resident immunity underlies essential host defenses against pathogens, but analysis in humans has lacked in vitro model systems where epithelial infection and accompanying resident immune cell responses can be observed en bloc . Indeed, human primary epithelial organoid cultures typically omit immune cells, and human tissue resident-memory lymphocytes are conventionally assayed without an epithelial infection component, for instance from peripheral blood, or after extraction from organs. Further, the study of resident immunity in animals can be complicated by interchange between tissue and peripheral immune compartments. To study human tissue-resident infectious immune responses in isolation from secondary lymphoid organs, we generated adult human lung three-dimensional air-liquid interface (ALI) lung organoids from intact tissue fragments that co-preserve epithelial and stromal architecture alongside endogenous lung-resident immune subsets. These included T, B, NK and myeloid cells, with CD69 + CD103 + tissue-resident and CCR7 - and/or CD45RA - T RM and conservation of T cell receptor repertoires, all corresponding to matched fresh tissue. SARS-CoV-2 vigorously infected organoid lung epithelium, alongside secondary induction of innate cytokine production that was inhibited by antiviral agents. Notably, SARS-CoV-2-infected organoids manifested adaptive virus-specific T cell activation that was specific for seropositive and/or previously infected donor individuals. This holistic non-reconstitutive organoid system demonstrates the sufficiency of lung to autonomously mount adaptive T cell memory responses without a peripheral lymphoid component, and represents an enabling method for the study of human tissue-resident immunity., Competing Interests: Additional Declarations: Yes there is potential Competing Interest. C.J.K. and S.S.C. are listed as inventors on provisional patent PCT/US2022/029869 describing the methods in this paper. C.J.K. is a founder of Surrozen Inc. C.J.K. and M.M.D. are founders of Mozart Therapeutics and NextVivo, Inc. All other authors declare no competing interests. COMPETING INTERESTS C.J.K. and S.S.C. are listed as inventors on provisional patent PCT/US2022/029869 describing the methods in this paper. C.J.K. is a founder of Surrozen, Inc. C.J.K. and M.M.D. are founders of Mozart Therapeutics and NextVivo, Inc. All other authors declare no competing interests.

Randomized controlled trials (RCTs) offer a clear causal interpretation of treatment effects, but are inefficient in terms of information gain per patient. Moreover, because they are intended to test cohort-level effects, RCTs rarely provide information to support precision medicine, which strives to choose the best treatment for an individual patient. If causal information could be efficiently extracted from widely available real-world data, the rapidity of treatment validation could be increased, and its costs reduced. Moreover, inferences could be made across larger, more diverse patient populations. We created a "virtual trial" by fitting a multilevel Bayesian survival model to treatment and outcome records self-reported by 451 brain cancer patients. The model recovers group-level treatment effects comparable to RCTs representing over 3200 patients. The model additionally discovers the feature-treatment interactions needed to make individual-level predictions for precision medicine. By learning from heterogeneous real-world data, virtual trials can generate more causal estimates with fewer patients than RCTs, and they can do so without artificially limiting the patient population. This demonstrates the value of virtual trials as a complement to large randomized controlled trials, especially in highly heterogeneous or rare diseases., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Portions of the material described here are included in a patent application describing a computer-implemented system., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Both primary lung adenocarcinoma and benign processes can have a ground-glass opacity (GGO) appearance on imaging. This study evaluated the incidence of and risk factors for malignancy in a diverse cohort of patients who underwent resection of a GGO suspicious for lung cancer., Methods: All patients who underwent resection of a pulmonary nodule with a GGO component and suspected to be primary lung cancer at a single institution from 2001-2017 were retrospectively reviewed. Risk factors for malignancy were evaluated using multivariable logistic regression analysis that included nodule size, age, sex, and race as potential predictors., Results: The incidence of pulmonary adenocarcinoma in the 243 patients who met inclusion criteria was 86% (n=208). The most common pathologic findings in 35 patients with a benign pathology was granulomatous inflammation (n=14, 40%). Risk factors for adenocarcinoma in multivariable logistic regression were age [odds ratio (OR) 1.06, P=0.003], GGO size (OR 2.76, P<0.001), female sex (OR 4.47, P=0.002), and Asian race (OR 8.35, P=0.002). In this cohort, adenocarcinoma was found in 100% (44/44) of Asian females, 86% (25/29) of Asian males, 84% (98/117) of non-Asian females, and 77% (41/53) of non-Asian males., Conclusions: The likelihood of adenocarcinoma in lung nodules with a ground-glass component is influenced by sex and race. Asian females with a GGO have a much higher likelihood of having adenocarcinoma than men and non-Asians. This data can be used when deciding whether to pursue nodule resection or surveillance in a patient with a GGO., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-22-583/coif). NL reports grants from the Intuitive Foundation and Auspex Diagnostics. She serves as an unpaid editorial board member of Journal of Thoracic Disease from September 2021 to August 2023. LB reports grants from the Department of Veterans Affairs, National Institutes of Health, Chan Zuckerberg Institute, consulting fees from Bristol Squibb Myers, Genentech, and Johnson & Johnson, speaker honoraria from International Lung Cancer Congress, and support for attending meeting from national lung cancer roundtable. MFB serves as an unpaid editorial board member of Journal of Thoracic Disease from September 2020 to August 2022. The other authors have no conflicts of interest to declare., (2022 Journal of Thoracic Disease. All rights reserved.)

Background: Despite demonstration of its clear benefits relative to open approaches, a video-assisted thoracic surgery technique for pulmonary lobectomy has not been universally adopted. This study aims to overcome potential barriers by establishing the essential components of the operation and determining which steps are most useful for simulation training., Methods: After randomly selecting experienced thoracic surgeons to participate, an initial list of components to a lower lobectomy was distributed. Feedback was provided by the participants, and modifications were made based on anonymous responses in a Delphi process. Components were declared essential once at least 80% of participants came to an agreement. The steps were then rated based on cognitive and technical difficulty followed by listing the components most appropriate for simulation., Results: After 3 rounds of voting 18 components were identified as essential to performance of a video-assisted thoracic surgery for lower lobectomy. The components deemed the most difficult were isolation and division of the basilar and superior segmental branches of the pulmonary artery, isolation and division of the lower lobe bronchus, and dissection of lymphovascular tissue to expose the target bronchus. The steps determined to be most amenable for simulation were isolation and division of the branches of the pulmonary artery, the lower lobe bronchus, and the inferior pulmonary vein., Conclusions: Using a Delphi process a list of essential components for a video-assisted thoracic surgery for lower lobectomy was established. Furthermore 3 components were identified as most appropriate for simulation-based training, providing insights for future simulation development., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)