Introduction
Although previous studies have consistently demonstrated that physicians are more likely than non‐physicians to experience work‐related stressors prior to suicide, the specific nature of ...these stressors remains unknown. The current study aimed to better characterize job‐related problems prior to physician suicide.
Methods
The study utilized a mixed methods approach combining thematic analysis and natural language processing to develop themes representing death investigation narratives of 200 physician suicides with implicated job problems in the National Violent Death Reporting System database between 2003 and 2018.
Results
Through thematic analysis, six overarching themes were identified: incapacity to work due to deterioration of physical health, substance use jeopardizing employment, interaction between mental health and work‐related issues, relationship conflict affecting work, legal problems leading to work‐related stress, and increased financial stress. Natural language processing analysis confirmed five of these themes and elucidated important subthemes.
Conclusions
This is the first known study that integrated thematic analysis and natural language processing to characterize work‐related stressors preceding physician suicide. The findings highlight the importance of bolstering systemic support for physicians experiencing job problems associated with their physical and mental health, substance use, relationships, legal matters, and finances in suicide prevention efforts.
Lung carcinoid tumours are neuroendocrine neoplasms originating from the bronchopulmonary tract's neuroendocrine cells, accounting for only 1%–3% of all lung cancers but 30% of all neuroendocrine ...tumours. The incidence of lung carcinoids, both typical and atypical, has been increasing over the years due to improved diagnostic methods and increased awareness among clinicians and pathologists. The most recent WHO classification includes a subgroup of lung carcinoids with atypical morphology and higher mitotic count and/or Ki67 labelling index. Despite appropriate surgery, the 5‐year survival rate for atypical carcinoids barely exceeds 50%–70%. The role of adjuvant therapy in lung carcinoids is not well‐defined, and clinical decisions are generally based on the presence of high‐risk features. Long‐term follow‐up is essential to monitor for recurrence, although the optimal follow‐up protocol remains unclear. To address the lack of consensus in clinical management decisions, the European Neuroendocrine Tumor Society (ENETS) initiated a survey among 20 expert centres. The survey identified varied opinions on approaches to imaging, surgery, use of adjuvant therapy, and follow‐up protocols. Notably, the absence of dedicated multidisciplinary lung neuroendocrine tumour boards in some centres was evident. Experts agreed on the need for a prospective adjuvant trial in high‐risk patients, emphasizing the feasibility of such a study. In conclusion, the study highlights the need for a more uniform adoption of existing guidelines in the management of lung carcinoid tumours and emphasizes the importance of international collaboration to advance research and patient care. Close collaboration between healthcare providers and patients is vital for effective long‐term surveillance and management of these rare tumours.
The manuscript describes the result of a survey in relation to current practices in relation to typical and atypical carcinoids tumors of the lung. The survey indicates a variability in opinions among experts in relation to therapeutic strategies and follow‐up and points out to a great need for further research in high risk disease.
Somatostatin receptor (SST) PET/CT is the gold standard for well‐differentiated neuroendocrine tumours (NET) imaging. Higher grades of neuroendocrine neoplasms (NEN) show preferential 18FFDG (FDG) ...uptake, and even low‐grade NET may de‐differentiate over time. FDG PET/CT's prognostic role is widely accepted; however, its impact on clinical decision‐making remains controversial and its use varies widely. A questionnaire‐based survey on FDG PET/CT use and perceived decision‐making utility in NEN was submitted to the ENETS Advisory Board Meeting attendees (November 2022, response rate = 70%). In 3/15 statements, agreement was higher than 75%: (i) FDG was considered useful in NET, irrespective of grade, in case of mis‐matched lesions (detectable on diagnostic CT but negative/faintly positive on SST PET/CT), especially if PRRT is contemplated (80%); (ii) in NET G3 if curative surgery is considered (82%); and (iii) in NEC prior to surgery with curative intent (98%). FDG use in NET G3, even in the presence of matched lesions, as a baseline for response assessment was favoured by 74%. Four statements obtained more than 60% consensus: (i) FDG use in NET G3 if locoregional therapy is considered (65%); (ii) in neuroendocrine carcinoma before initiating active therapy as a baseline for response assessment (61%); (iii) biopsy to re‐assess tumour grade prior to a change in therapeutic management (68%) upon detection of FDG‐positivity on the background of a prior G1‐2 NET; (iv) 67% were in favour to reconsider PRRT to treat residual SST‐positive lesions after achieving complete remission on FDG of the SST‐negative disease component. Multidisciplinary opinion broadly supports the use of FDG PET/CT for characterisation of disease biology and to guide treatment selection across a range of indications, despite the lack of full consensus in many situations. This may reflect existing clinical access due to lack of reimbursement or experience with this investigation, which should be addressed by further research.
FDG PET/CT use and perceived decision‐making utility in NEN assessed through a questionnaire‐based survey submitted to the ENETS Advisory Board Meeting attendees.
The cytokine-induced SH2-containing protein CIS belongs to the suppressor of cytokine signaling (SOCS) protein family. Here, we show the critical role of CIS in suppressing natural killer (NK) cell ...control of tumor initiation and metastasis. Cish-deficient mice were highly resistant to methylcholanthrene-induced sarcoma formation and protected from lung metastasis of B16F10 melanoma and RM-1 prostate carcinoma cells. In contrast, the growth of primary subcutaneous tumors, including those expressing the foreign antigen OVA, was unchanged in Cish-deficient mice. The combination of Cish deficiency and relevant targeted and immuno-therapies such as combined BRAF and MEK inhibitors, immune checkpoint blockade antibodies, IL-2 and type I interferon revealed further improved control of metastasis. The data clearly indicate that targeting CIS promotes NK cell antitumor functions and CIS holds great promise as a novel target in NK cell immunotherapy.
Phasing is the process of inferring haplotypes from genotype data. Efficient algorithms and associated software for accurate phasing in pedigrees are needed, especially for populations lacking ...reference panels of sequenced individuals. We present a novel method for phasing genotypes from whole-genome sequence data in pedigrees, called PULSAR (Phasing Using Lineage Specific Alleles/Rare variants). The method is based on the property that alleles specific to a single founding chromosome within a pedigree are highly informative for identifying haplotypes that are shared identical by descent. Simulation studies are used to assess the performance of PULSAR with various pedigree sizes and structures, and the effect of genotyping errors and the presence of nonsequenced individuals is investigated. In pedigrees with complete sequencing and realistic genotyping error rates, PULSAR correctly phases >99.9% of heterozygous genotypes, excluding sites at which all individuals are heterozygous, and does so with a switch error rate frequently below 10
. PULSAR is highly accurate, capable of genotype error correction and imputation, and computationally competitive with alternative phasing software applicable to pedigrees. Our method has the significant advantage of not requiring reference panels that are essential for other population-based phasing algorithms. A software implementation of PULSAR is freely available.
ABSTRACT
Stellar mergers and accretion events have been crucial in shaping the evolution of the Milky Way (MW). These events have been dynamically identified and chemically characterized using red ...giants and main-sequence stars. RR Lyrae (RRL) variables can play a crucial role in tracing the early formation of the MW since they are ubiquitous, old (t ≥ 10 Gyr) low-mass stars and accurate distance indicators. We exploited Data Release 3 of the GALAH survey to identify 78 field RRLs suitable for chemical analysis. Using synthetic spectra calculations, we determined atmospheric parameters and abundances of Fe, Mg, Ca, Y, and Ba. Most of our stars exhibit halo-like chemical compositions, with an iron peak around Fe/H ≈ −1.40, and enhanced Ca and Mg content. Notably, we discovered a metal-rich tail, with Fe/H values ranging from −1 to approximately solar metallicity. This sub-group includes almost 1/4 of the sample, it is characterized by thin disc kinematics and displays sub-solar α-element abundances, marginally consistent with the majority of the MW stars. Surprisingly, they differ distinctly from typical MW disc stars in terms of the s-process elements Y and Ba. We took advantage of similar data available in the literature and built a total sample of 535 field RRLs for which we estimated kinematical and dynamical properties. We found that metal-rich RRLs (1/3 of the sample) likely represent an old component of the MW thin disc. We also detected RRLs with retrograde orbits and provided preliminary associations with the Gaia–Sausage–Enceladus, Helmi, Sequoia, Sagittarius, and Thamnos stellar streams.
Pathologic response (PathR) by histopathologic assessment of resected specimens may be an early clinical end point associated with long-term outcomes with neoadjuvant therapy. Digital pathology may ...improve the efficiency and precision of PathR assessment. LCMC3 (NCT02927301) evaluated neoadjuvant atezolizumab in patients with resectable NSCLC and reported a 20% major PathR rate.
We determined PathR in primary tumor resection specimens using guidelines-based visual techniques and developed a convolutional neural network model using the same criteria to digitally measure the percent viable tumor on whole-slide images. Concordance was evaluated between visual determination of percent viable tumor (n = 151) performed by one of the 47 local pathologists and three central pathologists.
For concordance among visual determination of percent viable tumor, the interclass correlation coefficient was 0.87 (95% confidence interval CI: 0.84–0.90). Agreement for visually assessed 10% or less viable tumor (major PathR MPR) in the primary tumor was 92.1% (Fleiss kappa = 0.83). Digitally assessed percent viable tumor (n = 136) correlated with visual assessment (Pearson r = 0.73; digital/visual slope = 0.28). Digitally assessed MPR predicted visually assessed MPR with outstanding discrimination (area under receiver operating characteristic curve, 0.98) and was associated with longer disease-free survival (hazard ratio HR = 0.30; 95% CI: 0.09–0.97, p = 0.033) and overall survival (HR = 0.14, 95% CI: 0.02–1.06, p = 0.027) versus no MPR. Digitally assessed PathR strongly correlated with visual measurements.
Artificial intelligence–powered digital pathology exhibits promise in assisting pathologic assessments in neoadjuvant NSCLC clinical trials. The development of artificial intelligence–powered approaches in clinical settings may aid pathologists in clinical operations, including routine PathR assessments, and subsequently support improved patient care and long-term outcomes.
Appendiceal neuroendocrine neoplasms (ANEN) are mostly discovered coincidentally during appendicectomy and usually have a benign clinical course; thus, appendicectomy alone is considered curative. ...However, in some cases, a malignant potential is suspected, and therefore additional operations such as completion right hemicolectomy are considered. The existing European Neuroendocrine Tumour Society (ENETS) guidelines provide useful data about epidemiology and prognosis, as well as practical recommendations with regards to the risk factors for a more aggressive disease course and the indications for a secondary operation. However, these guidelines are based on heterogeneous and retrospective studies. Therefore, the evidence does not seem to be robust, and there are still unmet needs in terms of accurate epidemiology and overall prognosis, optimal diagnostic and follow-up strategy, as well as identified risk factors that would indicate a more aggressive surgical approach at the beginning and a more intense follow-up. In this review, we are adopting a critical approach of the ENETS guidelines and published series for ANEN, focusing on the above-noted "grey areas".
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