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In this vein, the shape of the bladder necessitates consideration by physicians treating PF.

The use of a fasting-mimicking diet (FMD) combined with diverse antitumor agents is being evaluated across more than ten randomized clinical trials for its efficacy, effectiveness, and safety.
The process of UMI-mRNA sequencing, combined with cell-cycle analysis, label retention experiments, metabolomic profiling, multiple labeling techniques, and more. molecular oncology Mechanisms were analyzed by implementing the strategies embedded in these explorations. An animal model system, in combination with tandem mRFP-GFP-tagged LC3B, Annexin-V-FITC Apoptosis, TUNEL, H&E staining and Ki-67 immunostaining, was utilized to explore synergistic drug effects.
In our study, fasting or FMD was found to be more successful in slowing tumor growth, yet it did not increase the sensitivity of 5-fluorouracil/oxaliplatin (5-FU/OXA) to initiate apoptosis, in either laboratory or animal models. Through mechanistic means, we observed CRC cells changing from an active, proliferative state to a slow-cycling one during fasting. The metabolomic data indicated decreased cell proliferation in response to nutrient stress in vivo, characterized by lower levels of adenosine and deoxyadenosine monophosphate. CRC cells would decrease their proliferation rate to maximize survival and the likelihood of relapse after chemotherapy. Subsequently, fasting triggered quiescence in cells, which were then more susceptible to the formation of drug-tolerant persister (DTP) tumor cells, believed to be the driving force behind cancer recurrence and spread. UMI-mRNA sequencing revealed that the ferroptosis pathway showed the strongest response to the fasting conditions. By enhancing autophagy, fasting combined with ferroptosis inducers effectively inhibits tumor growth and eradicates quiescent cells.
Our study's results suggest that ferroptosis could augment the anti-tumor effect of FMD and chemotherapy, pointing towards a potential therapeutic avenue for preventing tumor relapse and treatment failure induced by DTP cells.
In the Acknowledgements section, you can find a complete listing of the funding bodies.
The Acknowledgements section contains a complete inventory of funding bodies.

Macrophages present at infection sites are viewed as promising therapeutic targets for the avoidance of sepsis. nocardia infections The antibacterial capacity of macrophages is subject to critical modulation by the Keap1-Nrf2 system. Recently, Keap1-Nrf2 protein-protein interaction inhibitors have been identified as more potent and safer Nrf2 activators, nevertheless, their effectiveness in sepsis is currently unknown. We introduce IR-61, a distinctive heptamethine dye, as an inhibitor of Keap1-Nrf2 protein-protein interactions, which selectively accumulates in macrophages at infection sites.
Employing a mouse model of acute lung bacterial infection, the biodistribution of IR-61 was explored. Investigation into the Keap1 binding behavior of IR-61 involved the application of SPR and CESTA approaches in both in vitro and cellular experiments. A study of IR-61's therapeutic effect on sepsis leveraged pre-established models in mice. Monocytes from human patients served as the basis for a preliminary study examining the relationship between Nrf2 levels and sepsis outcomes.
At sites of infection, IR-61 demonstrated a preferential accumulation in macrophages, a process linked, according to our data, to enhanced bacterial clearance and better outcomes for mice with sepsis. A mechanistic analysis of IR-61's effect indicated its ability to potentiate macrophage antibacterial function by activating Nrf2 via a direct inhibition of the Keap1-Nrf2 binding. In addition, the observation of IR-61's enhancement of phagocytosis in human macrophages is noteworthy, while Nrf2 monocyte expression levels might be predictive of the clinical course of sepsis.
Our findings show that the precise activation of Nrf2 in macrophages at infection sites is essential for the management and treatment of sepsis. IR-61's role as a Keap1-Nrf2 PPI inhibitor may contribute to the precise treatment of sepsis.
The National Natural Science Foundation of China (Major program 82192884), the Intramural Research Project (Grants 2018-JCJQ-ZQ-001 and 20QNPY018), and the Chongqing National Science Foundation (CSTB2022NSCQ-MSX1222) provided financial support to this undertaking.
Support for this work came from the National Natural Science Foundation of China (Major program 82192884), the Intramural Research Project (Grants 2018-JCJQ-ZQ-001 and 20QNPY018), and the Chongqing National Science Foundation (CSTB2022NSCQ-MSX1222).

AI applications are being explored to improve breast screening programs by decreasing false positive results, boosting cancer detection, and mitigating resource limitations. A study comparing the accuracy of AI with radiologists in the practical setting of breast cancer screening assessed the likely effects on cancer detection rate, the number of cases requiring further examination, and the workload for collaborative AI-radiologist reading.
External validation of a commercially-available AI algorithm was undertaken in a retrospective cohort of 108,970 consecutive mammograms from a population-based screening program. Outcomes, including interval cancers, were determined using registry linkages. The area under the ROC curve (AUC), sensitivity, and specificity of the AI were evaluated in relation to the practical interpretations of the images provided by radiologists. Program metrics were compared against estimations of CDR and recall derived from simulated AI-radiologist readings (with arbitration).
An AI's AUC of 0.83 was observed, in comparison to the 0.93 AUC of radiologists. At a predicted limit, the sensitivity of AI (0.67; 95% confidence interval 0.64-0.70) was similar to that of radiologists (0.68; 95% confidence interval 0.66-0.71), but with a lower specificity (0.81 [95% confidence interval 0.81-0.81] compared to 0.97 [95% confidence interval 0.97-0.97]). The recall rate for AI-radiologists (314%) proved significantly lower compared to the BSWA program's rate (338%), with a difference of -0.25% (95% CI -0.31 to -0.18); this difference is statistically significant (P<0.0001). CDR's performance, quantified as 637 per 1000, was lower than that of the radiologists, with a rate of 697 per 1000 (-0.61; 95% CI -0.77 to -0.44; P<0.0001). This lower CDR rate, however, did not negate the fact that the AI identified interval cancers (0.72 per 1000; 95% CI 0.57-0.90) which were not found by the radiologists. AI-radiologists, though increasing arbitration, concurrently diminished overall screen-reading volume by a substantial 414% (95% CI 412-416).
The replacement of a radiologist by AI, accompanied by arbitration, produced a drop in recall rates and overall screen-reading volume. A reduction, though small, was observed in CDR scores when utilizing AI for radiologist interpretation. The AI system detected intermittent cases missed by radiologists, implying a possible increased CDR score if radiologists' assessments were influenced by the AI's findings. AI's application in mammogram review suggests potential benefits, but substantial prospective trials are required to establish if computer-aided detection (CAD) accuracy improves by implementing an AI-powered double-reading process with arbitration.
Among the leading organizations in health and research, the National Breast Cancer Foundation (NBCF) and the National Health and Medical Research Council (NHMRC) are especially noteworthy.
National Breast Cancer Foundation (NBCF), alongside the National Health and Medical Research Council (NHMRC), serve important purposes.

This study sought to investigate the temporal accumulation of functional components in the longissimus muscle of growing goats, examining the dynamic regulatory metabolic pathways involved. The longissimus muscle's characteristics, including intermuscular fat content, cross-sectional area, and the fast-to-slow fiber switch proportion, demonstrated a synchronous increase between day 1 and day 90, as highlighted in the results. Animal development in the longissimus muscle involved two distinct phases that were observable in the dynamic profiles of its functional components and transcriptomic pathways. The expression of genes facilitating de novo lipogenesis escalated from birth to weaning, resulting in palmitic acid accumulation in the early stages of development. After weaning, the second phase witnessed a substantial increase in oleic, linoleic, and linolenic acid levels, predominantly due to the heightened expression of genes involved in fatty acid elongation and desaturation. Following weaning, a change in production from serine to glycine was noted, correlated with the gene expression patterns controlling their conversion. this website The key window and pivotal targets of the chevon's functional components' accumulation process are systematically outlined in our findings.

As the global meat market expands and intensive livestock farming methods proliferate, the consequences of livestock production are increasingly recognized by consumers, consequently affecting their meat choices. Thus, deciphering consumer viewpoints on livestock production is paramount. Consumer views on the ethical and environmental effects of livestock farming were investigated through a survey of 16,803 individuals in France, Brazil, China, Cameroon, and South Africa, categorized by their sociodemographic characteristics. Generally, current respondents in Brazil and China, often characterized by low meat consumption, who are female, not associated with the meat sector, and/or with a higher level of education, are more likely to view livestock meat production as causing serious ethical and environmental issues; on the other hand, respondents from China, France, and Cameroon, typically exhibiting low meat consumption, who are women, younger, outside the meat sector, and/or with higher levels of education, frequently agree that reducing meat consumption could help resolve these problems. The current study's respondents identify affordable pricing and the sensory experience as crucial factors in their food purchasing decisions.

Individuals with substantial tooth loss had a higher likelihood of death (73 cases in a group of 276 individuals) relative to those with less severe tooth loss (78 cases in a group of 657 individuals), this difference remaining significant even after adjusting for other relevant factors (hazard ratio 145 [95% CI 102–204]).
Remote communities experience a higher risk of death when substantial tooth loss is present.
The prevalence of significant tooth loss correlates with elevated death rates in remote communities.

Osteocytes, the mature and specifically differentiated bone cells, are created as a direct result of bone formation. Two distinct processes, intramembranous and endochondral ossification, form calvarial and long bones, but the precise manner in which these disparate pathways affect the distinctions between osteocytes from calvarial and femoral cortical bone remains unclear. Our current research utilized confocal structured illumination microscopy, coupled with mRNA sequencing, to analyze the morphological and transcriptomic expression of osteocytes isolated from murine calvaria and mid-shaft femoral cortical bone. Through the use of structured illumination microscopy and geometric modeling, a difference in shape and distribution was noted between calvarial and cortical osteocytes, the former appearing round and irregularly scattered, and the latter displaying a spindle shape and orderly alignment. mRNA sequencing analysis exposed disparities in the transcriptomes of calvarial and cortical osteocytes, implicating mechanical responses of osteocytes in explaining the observed variations in their geometrical aspects. Additionally, a transcriptomic examination demonstrated that the two osteocyte groups originated from distinct developmental routes, exhibiting differential expression of 121 genes associated with ossification. A comparative analysis of the correlation between ossification and osteocyte geometries, presented via a Venn diagram, showcased differential expression of certain genes associated with ossification, cytoskeletal organization, and dendrite growth between calvarial and cortical osteocytes. Flow Cytometers In the end, our experiments showed that advancing age caused a disturbance in the arrangement of dendrites and cortical osteocytes, with no impact on the organization of calvarial osteocytes. We jointly determine the dissimilarities in the properties of calvarial and cortical osteocytes, probably attributable to differing ossification processes.

The bodies of most swimming fishes are exceptionally adaptable, their deformations being a product of external fluid dynamic stresses and internal musculoskeletal forces. Body motion of the fish will be affected if forces of fluid changes unless the fish is able to sense these variations and adjusts its muscular operations. Mechanosensory cells, situated within the spinal cords of lampreys and other fish species, facilitate the detection of body flexion. The lamprey (Petromyzon marinus) was hypothesized to actively manage its body curvature, ensuring a largely consistent swimming wave pattern despite fluctuating swimming velocities and fluid dynamic pressures. To evaluate this hypothesis, we quantified the consistent swimming movements of lampreys navigating normal water and water with viscosity enhanced tenfold or twofold by incorporating methylcellulose. Viscosity augmentation within this range correlates with a surge in drag coefficient, possibly leading to a 40% rise in fluid forces. Computational results from earlier studies indicated that without lamprey compensation for these forces, a decrease in swimming speed of approximately 52%, a reduction in amplitude of movement by 39%, and an increase in posterior body curvature by about 31% would occur, while tail beat frequency would remain consistent. Epigenetics chemical Standard techniques were used to digitize the midlines of five juvenile sea lampreys, which were filmed swimming within the undisturbed water. The swimming speed reduction of 44%, when viscosity transitioned from 1 to 10, was not mirrored by an equivalent reduction in amplitude, which only decreased by 4%, and a surprising 7% increase in curvature, a finding which contrasts greatly with our estimates in a hypothetical scenario with no compensation. A detailed orthogonal decomposition of the entire swimming waveform revealed the primary swimming pattern (first mode) to be largely unchanged, even at a viscosity of 20. Consequently, lampreys seem to be offsetting, to some extent, the variations in viscosity; this, in turn, implies that sensory input plays a role in controlling the body's wave pattern.

Aesthetic interventions leveraging botulinum toxin type A (BoNT-A) may sometimes produce unwanted consequences, including the paralysis of unintended muscle groups. Beyond that, the effects of BoNT-A may last for several months, and no medical strategy presently exists to accelerate the recuperation of muscle function. A female patient with a movement disorder of the mimic muscles, a result of BoNT-A injections, received daily sessions of photobiomodulation therapy (PBMT). Within just a few weeks, noticeable improvements were witnessed in both facial asymmetry and muscle function. Following nine weeks of treatment, nearly total recovery was observed. In light of this case study, PMBT appears to be an effective intervention for expediting muscle function restoration after BoNT-A treatment.

Even with tattoos' ancient origins and immense appeal to young people, a desire to remove them remains prevalent due to regret. Laser removal, as a treatment option, consistently produces the most successful results, exhibiting the highest level of pigment removal and the lowest likelihood of complications. This study on three patients with tattoos involved the precise removal of black pigments only. No patient participating in this study had previously experienced skin allergies, skin cancer, or the development of keloids. Case 1's right calf tattoo was eliminated by a professional tattoo removal specialist in two appointment sessions. In Case 2, a removal process, consisting of three sessions, was needed for the amateur scalp tattoo. In Case 3, two professional tattoos graced the face, requiring eleven sessions for their complete removal. The Spectra XT Q-Switched Nd:YAG 1064 nm laser, possessing a 5-nanosecond pulse width, along with the Pico Ultra 300 Nd:YAG 1064 nm laser, featuring a 300-picosecond pulse width, and the SoftLight Q-Switched Nd:YAG 1064 nm laser, with its 17-nanosecond pulse width, were the equipment employed. phage biocontrol Generally, pleasing results were obtained, despite the presence of hypopigmentation in cases one and three. The likely culprits behind the outcome were sun exposure at the laser removal site, the brief interval between sessions, and/or a higher radiant exposure combined with a smaller spot size. Achieving successful tattoo removal in higher phototypes hinges upon professionals' knowledge of the best parameters, coupled with a thorough understanding of each patient's individual characteristics and the unique aspects of the tattoo. Furthermore, the patient's active participation in pre and post-laser treatment care, and a well-defined interval between sessions, is indispensable for preventing any unwanted complications.

The COVID-19 pandemic significantly altered the course of research progress. Employing video-reflexive ethnography (VRE), a methodology founded on exnovation, collaboration, reflexivity, and care, this article investigates how a group of researchers responded to the pandemic's impact on practices, exploring both the advantages and the disadvantages. Through two focus groups, each composed of 12 members of the International Association of Video-Reflexive Ethnographers, we explored the pandemic's influence on VRE research methodologies. While the pandemic intensified pre-existing methodological difficulties, it also presented a valuable window into revisiting our research strategies, including site access, developing rapport, enabling reflective moments, and promoting a compassionate environment. Due to the implementation of public health measures, researchers leveraged internal connections to access specific locations. Insiders shouldering additional burdens, this alteration may have strengthened participant involvement, highlighted the project's significance, and facilitated entry to rural sites. Limited access to sites and a dependence on insiders proved a barrier to researchers' ability to cultivate relationships with participants, thereby impeding the emergence of the rich ethnographic insights typically associated with sustained engagement. Researchers faced the complex interplay of technological, logistical, and methodological difficulties while conducting reflexive sessions in remote settings, affecting both themselves and their participants. Finally, participants recognized that while the shift to more digital approaches may have broadened the project's scope, it was imperative to cultivate mindful care practices within the digital realm to protect participant data and ensure psychological safety. Opportunities and challenges encountered by a group of researchers using VRE during the pandemic are demonstrated by these findings, which are valuable for future methodological dialogue.

The recent COVID-19 outbreak has made public health a priority once again. The sealed environment and inadequate ventilation systems in elevator cabins put passengers at risk of respiratory tract infections. Nonetheless, the dispersal and distribution of droplet aerosols within the enclosed spaces of elevator cabins are still enigmatic. Employing three ventilation methods, this study investigated the transmission dynamics of droplet aerosols, originating from a source patient. Computational fluid dynamics (CFD) simulations were employed to analyze the dispersal of droplet aerosols generated by nasal breathing and oral coughing. To simulate the flow field, we selected the verified renormalization group (RNG) k- turbulence model, and to track the droplet aerosols, the Lagrangian method was chosen. A further analysis considered the ventilation method's role in droplet transmission. In the elevator cabin, droplet aerosols clustered and proved stubborn to remove under the mixed and displacement ventilation designs and their related starting conditions.

Six treatments of 5-fluorouracil, dosed at 500 mg/m², were prescribed for high-risk patients.
The patient received 100 mg/m² of epirubicin.
The patient was given a dose of cyclophosphamide, 500 milligrams per square meter, for treatment.
The treatment approach can be FEC or a sequence of three FEC courses, then three docetaxel courses at 100 mg per square meter.
The schema requests, a list of sentences, returned. Disease-free survival (DFS) served as the principal metric for evaluating the efficacy of the intervention.
For the intent-to-treat cohort, 1286 patients were administered FEC-Doc, whereas 1255 patients received FEC. After a median follow-up duration of 45 months, the data was analyzed. An equitable distribution of tumor characteristics was found; 906% of the examined tumors displayed elevated uPA/PAI-1 levels. Planned courses were facilitated, with 844% completion rate (FEC-Doc) and 915% completion rate (FEC). Five-year DFS, analyzed with the FEC-Doc methodology, achieved a rate of 932% (95% Confidence Interval 911-948). microbiome stability Overall survival rates for five years following FEC-Doc treatment were remarkably high, at 970% (954-980). Comparatively, five-year overall survival associated with FEC therapy was 966% (949-978).
With suitable supplementary chemotherapy, even high-risk node-negative breast cancer patients are anticipated to have a favorable outcome. Early recurrence rates were not affected by docetaxel, and there was a substantial rise in the number of patients who stopped treatment.
High-risk node-negative breast cancer patients stand to gain an excellent prognosis with the use of sufficient adjuvant chemotherapy. Docetaxel's application did not translate into reduced early recurrence rates, but instead prompted a considerable escalation in the cessation of treatment.

A substantial portion of lung cancer diagnoses, 85%, are classified as non-small-cell lung cancer (NSCLC). For the past two decades, the evolution of treatment for patients diagnosed with non-small cell lung cancer (NSCLC) has been marked by a departure from general chemotherapy to targeted therapies, specifically those designed for individuals with an epidermal growth factor receptor (EGFR) mutation. The REFLECT multinational study assessed treatment methodologies, patient outcomes, and diagnostic procedures for EGFR-mutated advanced non-small cell lung cancer (NSCLC) patients receiving initial EGFR tyrosine kinase inhibitor (TKI) therapy across Europe and Israel. Describing Polish REFLECT study patients, this analysis centers on treatment patterns and their T790M mutation testing implementations. A medical record-based, descriptive, retrospective, and non-interventional analysis was conducted on the Polish cohort in the REFLECT study (NCT04031898) for patients with locally advanced or metastatic NSCLC and EGFR mutations. A medical chart review, encompassing data collection, was undertaken from May to December of 2019. As the first-line EGFR-TKI therapy, 45 patients (409%) were treated with afatinib, 41 patients (373%) with erlotinib, and 24 patients (218%) with gefitinib. Ninety (81.8%) patients discontinued their first-line EGFR-TKI therapy. The median duration of progression-free survival (PFS) observed in the initial EGFR-TKI treatment group was 129 months, with a 95% confidence interval spanning from 103 to 154 months. A total of 54 patients began second-line therapy, and 31 of these patients (57.4%) received osimertinib. From the 85 patients who experienced treatment progression following their first-line EGFR-TKI therapy, 58 were subjected to testing for the T790M mutation. genetic homogeneity A total of 31 patients (534% of those tested) showing the T790M mutation benefited from osimertinib treatment, which was initiated as a later therapy option. Beginning with the first-line administration of EGFR-TKI, the median overall survival (OS) was estimated at 262 months (95% confidence interval 180-297). Selleck Resigratinib The median overall survival duration for individuals with brain metastases, starting from the initial brain metastasis diagnosis, was 155 months (confidence interval 99-180). The REFLECT study, examining the Polish population, reveals a critical need for the development and implementation of effective treatments for individuals suffering from advanced EGFR-mutated non-small cell lung cancer. A significant percentage, almost one-third, of patients whose disease progressed following initial EGFR-TKI therapy were not evaluated for the presence of the T790M mutation, rendering them ineligible for potentially effective treatment options. A diagnosis of brain metastases served as an unfavorable predictor of survival.

The presence of tumor hypoxia poses a serious impediment to the success of photodynamic therapy (PDT). In order to resolve this concern, two approaches, in situ oxygen generation and oxygen delivery, were formulated. Catalysts, such as catalase, are integral to the in situ oxygen generation approach, which decomposes the excess hydrogen peroxide produced by tumors. Although it demonstrates precision in targeting tumors, its potency is constrained by the habitually low hydrogen peroxide concentration encountered within cancerous growths. Perfluorocarbon's high oxygen solubility is a key component of the oxygen delivery strategy, enabling oxygen transport. While the treatment shows efficacy, its selectivity for tumors is inadequate. A multifunctional nanoemulsion system, CCIPN, was engineered to incorporate the positive features of two distinct methods. Its preparation employed a multi-step process comprising sonication, phase inversion, composition adjustment, and further sonication, optimized using orthogonal methods. The CCIPN formulation contained the following: catalase, the methyl ester of 2-cyano-312-dioxooleana-19(11)-dien-28-oic acid (CDDO-Me), photosensitizer IR780, and perfluoropolyether. Perfluoropolyether nanostructures might retain oxygen produced by catalase, a process beneficial for photodynamic therapy (PDT). CCIPN demonstrated cytocompatibility and contained spherical droplets, each measuring below 100 nanometers. The sample, with its catalase and perfluoropolyether components intact, demonstrated a superior capacity to produce cytotoxic reactive oxygen species, culminating in tumor cell annihilation under light stimulation, compared to its control counterpart lacking these components. This research supports the development and preparation processes for oxygen-supplementing PDT nanomaterials.

Amongst the leading causes of death worldwide is cancer. For superior patient outcomes, early diagnosis and prognosis are essential. Tissue biopsy, the gold standard for characterizing tumors, provides the necessary information for accurate diagnosis and prognosis. Sampling frequency and the incomplete representation of the entire tumor mass are among the limitations of tissue biopsy collection. Circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), circulating microRNAs (miRNAs), and tumor-derived extracellular vesicles (EVs), as well as tumor-derived protein profiles present in the bloodstream from primary and metastatic sites, provide a promising and more potent tool for both initial and ongoing patient diagnostic and surveillance needs. Real-time monitoring of therapeutic response in cancer patients is achievable via the frequent sample collection afforded by the minimally invasive technique of liquid biopsies, consequently allowing for the development of novel therapeutic approaches. In this examination, we shall detail the recent developments in liquid biopsy markers, highlighting both their benefits and drawbacks.

A healthful diet, regular physical activity, and weight management are integral to the prevention and control of cancer. While adherence is crucial, it unfortunately remains subpar in cancer survivors and others, highlighting the need for innovative interventions. Daughters, dudes, mothers, and others, united in their fight against cancer (DUET), offer a six-month, online, diet and exercise program for weight loss to improve health habits and outcomes for cancer survivor-partner pairs. DUET's performance was examined across 56 dyads of partnered individuals (survivors of obesity-related cancers and their partners; n = 112). All participants experienced the combined effects of overweight/obesity, sedentary lifestyle, and inadequate dietary habits. Dyads underwent a baseline assessment, after which they were randomly assigned to either the DUET intervention or a waitlist control group; data were collected at three and six months, and analyzed using chi-square tests, t-tests, and mixed linear models with a significance level of less than 0.005. Results were retained at 89% in the waitlisted group, in comparison to the intervention group's 100% retention. The primary outcome, dyad weight loss, exhibited a mean decrease of -11 kg in the waitlist group, in contrast to a mean decrease of -28 kg in the intervention group, demonstrating a statistically significant difference (p = 0.0044/time-by-arm interaction p = 0.0033). A statistically significant (p = 0.0027) decrease in caloric intake was found in DUET survivors when compared to the control group. Physical activity and function, blood glucose, and C-reactive protein demonstrated benefits, as evidenced. Partner-based elements, represented by dyadic terms, were significant across outcomes, suggesting that the intervention's positive effects were facilitated by this collaborative approach. DUET, a pioneering initiative in scalable, multi-behavior weight management interventions for cancer prevention and control, points to the necessity of larger-scale studies with extended durations and greater scope.

Over the past two decades, targeted molecular therapies have profoundly transformed the landscape of treatment for numerous malignancies. Non-small cell lung cancer (NSCLC) and other lethal malignancies are cases in point for how precision-matched immune- and gene-targeted therapies are revolutionizing treatment. Now recognized are various small NSCLC subgroups characterized by their genomic aberrations; a remarkable consequence is that approximately 70% exhibit a druggable mutation. Unfortunately, the rare tumor cholangiocarcinoma is characterized by a poor prognosis. Molecular alterations, novel to CCA patients, have been recently identified, and this bodes well for the potential of targeted therapy.