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Data envelopment analysis (DEA) facilitates relative performance estimation of homogenous decision-making units (DMUs), whereas dynamic DEA pertains to intertemporal elements like carryovers for measuring DMUs’ efficiencies over time. To enhance DMU’s performance, there is a need to measure its efficiency with dynamic structure and further to determine input-output target points for making significant improvements in an inefficient DMU. Therefore, the present study proposes a relational dynamic DEA approach that comprises a dynamic structure in which periods are connected through good and bad links/carry-overs along with desirable and undesirable outputs and utilizes interval data. The system and period efficiency intervals are derived using a unique set of weights based on common weights methodology. Moreover, the relationship between the complement of the lower (upper) bound system and period efficiencies is established. Lastly, the input-output target points are suggested to improve DMUs in terms of upper-bound system efficiencies in a dynamic environment. To validate the usefulness of the proposed approach, a case study in Indian banks for the period 2017– 2021 is presented. This study investigates the impact of stressed assets (bad link/carryover) and loss due to non-performing assets (bad/undesirable output) on banks’ dynamic efficiency. The results are compared with the static structure. The findings, targets, and implications of the study can assist bank experts and policymakers in formulating policies/strategies for further improvements.

Earth-abundant transition metal phosphide (TMP) nanomaterials have gained significant attention as potential replacements for Pt-based electrocatalysts in green energy applications, such as the hydrogen evolution reaction (HER), oxygen evolution reaction (OER), and overall water splitting. In particular, FeP nanostructures exhibit superior electrical conductivity and high stability. Moreover, their diverse composition and unique crystal structures position FeP nanomaterials as emerging candidates for HER electrocatalysts. However, the synthesis or fabrication method employed for FeP nanostructures can significantly affect their overall electrocatalytic properties. For example, the solution synthesis of pure-phase FeP nanostructures remains challenging due to the formation of multiple binary phases and undesirable agglomeration. In this work, we use a simple approach to synthesizing FeP nanobundles by reacting β-FeOOH (iron oxyhydroxide) with trioctylphosphine (TOP). FeP nanobundles were evaluated as HER electrocatalysts in both acidic and basic conditions, demonstrating good HER activity with overpotential values of 170 and 338 mV at a current density of −10 mA cm–2in acidic and alkaline solutions, respectively. Additionally, they exhibited low values of Tafel slopes in both acidic and alkaline environments. In acidic media with a pH of 0.45, the nanobundles showed no signs of deterioration for up to 15 h (−50 mA cm−2). In basic media with a pH of 13.69, the nanobundles remain stable for up to 8 h (−50 mA cm−2). These results demonstrate a simple and effective method for producing highly efficient earth-abundant and cost-effective TMP-based electrocatalysts, which could play a vital role in the hydrogen economy of the future.

The understanding of the impact of tethered cord syndrome (TCS) on the physiology of the colorectal area is limited. Our aim was to describe anorectal and colonic motility in children with TCS and compare the findings to those of children with functional constipation (FC). We conducted a retrospective review of children with TCS who had an anorectal manometry (ARM) performed at our institution from January 2011 to September 2023. We recorded demographics, medical and surgical history, clinical symptoms, and treatment at time of ARM, ARM findings (resting pressure, push maneuver, rectal sensation, rectoanal inhibitory reflex [RAIR], and RAIR duration), and the final interpretation of colonic manometry (CM) if performed. We identified age and sex‐matched control groups of children with FC. We included 24 children with TCS (50% female) who had ARM testing (median age at ARM 6.0 years, interquartile range 4.0–11.8 years). All children had constipation at time of ARM. Nineteen children had detethering surgery before ARM was performed. No significant differences in ARM parameters were found between children who had detethering surgery before ARM and children with FC. Among the 24 children, 14 also had a CM performed (13/14 after detethering surgery). No significant differences in colonic motility were found between children with a history of TCS and children with FC. Anorectal physiology and colonic motility are similar between children with a history of TCS and children with FC, suggesting that the underlying pathophysiology of defecatory disorders in children with and without history of TCS is similar. The understanding of the impact of tethered cord syndrome (TCS) on the physiology of the colorectal area is limited.Even after detethering surgery, fecal incontinence and constipation are commonly seen in children with TCS. The understanding of the impact of tethered cord syndrome (TCS) on the physiology of the colorectal area is limited. Even after detethering surgery, fecal incontinence and constipation are commonly seen in children with TCS. No significant differences in anorectal manometry findings and colonic motility were found between children with a history of TCS and an age and sex‐matched cohort of children with functional constipation.The underlying pathophysiology of defecatory disorders in children with and without a history of TCS might be similar and not related to differences in colonic motor function. No significant differences in anorectal manometry findings and colonic motility were found between children with a history of TCS and an age and sex‐matched cohort of children with functional constipation. The underlying pathophysiology of defecatory disorders in children with and without a history of TCS might be similar and not related to differences in colonic motor function.

In the first-ever Undiagnosed Hackathon, nearly 100 experts from 28 countries combined advanced phenotyping and genomic techniques for 48 hours, ultimately providing diagnoses to 40% of the previously undiagnosed families. This inspiring model demonstrates the power of multidisciplinary collaboration and patient partnership in precision diagnostics.

Stable isotopic labeling is a powerful tool for determining the biosynthetic origin of metabolites and for discovering natural products that incorporate precursors of interest. When isotopically substituted precursors are not available commercially or synthetically, inverse stable isotopic labeling (InverSIL) is a useful alternative. With InverSIL, an organism is grown on an isotopically substituted medium and then fed precursors of natural isotopic abundance which can be tracked by mass spectrometry, thereby bypassing issues with precursor availability. Currently, there is no automated way to identify precursor incorporation in untargeted metabolomic data using InverSIL without specifying an expected change in the mass-to-charge ratio of metabolites that have incorporated the precursor. This makes it difficult to identify unknown natural products that may incorporate portions of precursors of interest using new biochemistry or to rapidly identify incorporation of multiple precursors into different metabolites simultaneously. To address this, we developed a new, robust workflow for the automated identification of inverse labeling in untargeted metabolomic data. We then use this method to identify metabolites that incorporate para-aminobenzoic acid and different portions of l-methionine, including in the same sample, and in the process discover the likely biosynthetic origin for the C-7 and C-9 methyl groups of the pterin portion of dephosphotetrahydromethanopterin, a C1 transfer coenzyme used by methylotrophic bacteria. This workflow can be applied in the future to streamline the use of the versatile InverSIL approach for natural product and metabolism research.

Rumination syndrome (RS) is challenging to diagnose, which can lead to diagnostic delays. Our objective was to evaluate the length of time from RS symptom onset to diagnosis in patients referred to our institution and to examine whether this duration predicts treatment outcomes. We conducted a review of patients with RS evaluated at our institution. Data were collected from chart review and patient/family reported questionnaires. We evaluated the time from symptom onset to diagnosis over time and whether it was associated with symptom resolution. We included 247 patients with RS (60% female, median age of 14 years, interquartile range [IQR]: 9–16 years). The median age at symptom onset was 11 years (IQR: 5–14 years) and median age at diagnosis was 13 years (IQR: 9–15 years) for a median duration of 1 year (IQR: 0–3 years) between symptom onset and diagnosis. Length of time between symptom onset and diagnosis did not change significantly at our institution from 2016 to 2022. Among the 164 children with outcome data, 47 (29%) met criteria for symptom resolution after treatment. A longer time to diagnosis was associated with a lower likelihood of symptom resolution after treatment (p= 0.01). In our experience, the time to RS diagnosis after symptom onset is shorter than previously described. A longer delay in diagnosis is associated with lower likelihood of symptom resolution after treatment, emphasizing the importance of a prompt recognition of rumination symptoms and a timely diagnosis. Rumination syndrome can be challenging to diagnose, due to overlapping features with more common disorders, which often leads to a delay in diagnosis.Data on the length of time between symptom onset and diagnosis are limited, especially in pediatric populations. Previous studies showed an average number of years to diagnosis of 8 years in adults and 2–3 years in children and adolescents. Rumination syndrome can be challenging to diagnose, due to overlapping features with more common disorders, which often leads to a delay in diagnosis. Data on the length of time between symptom onset and diagnosis are limited, especially in pediatric populations. Previous studies showed an average number of years to diagnosis of 8 years in adults and 2–3 years in children and adolescents. Our institution's experience shows a shorter length of time to diagnosis than was previously reported.We found that patients who experience a longer delay in diagnosis are less likely to have symptom resolution after treatment. Our institution's experience shows a shorter length of time to diagnosis than was previously reported. We found that patients who experience a longer delay in diagnosis are less likely to have symptom resolution after treatment.

Background: Giant cell tumor of bone (GCTB) is the most common primary tumor of proximal fibula. Because of its close proximity to vascular structures, common peroneal nerve (CPN) and attachment of lateral collateral ligament (LCL), proximal fibulectomy poses unique challenges. We analyzed oncological and functional outcome of patients who underwent proximal fibulectomy for GCTB of proximal fibula. Material and methods: Between January 2006 and December 2020, 23 patients underwent proximal fibulectomy for GCTB of proximal fibula, four were recurrent tumors. Mean resection length was 9 cm (5 to 15 cm). The LCL and biceps tendon were not reconstructed in 22 cases. The common peroneal nerve was sacrificed in seven patients including three recurrent cases. Functional status was assessed using the Musculoskeletal Tumour Society (MSTS) scoring system. Results: There were two vascular complications and one infection. With 4 patients lost to follow up, mean follow up was 90 months (12 to 197). No patient had local or distant recurrence. Mean MSTS score was 26 (21 to 30). Eleven of 23 patients (48%) had loss of common peroneal nerve function with poorer functional outcome. No patient had symptoms suggestive of knee instability. Conclusion: Proximal fibulectomy is oncologically safe. Reconstruction of the LCL attachment is not mandatory and patients do not have symptomatic knee instability. Functional outcomes are compromised after sacrifice of common peroneal nerve and may be potentially improved with tendon transfers at index surgery.

Resistance to genotoxic therapies and tumor recurrence are hallmarks of glioblastoma (GBM), an aggressive brain tumor. In this study, we investigated functional drivers of post-treatment recurrent GBM through integrative genomic analyses, genome-wide genetic perturbation screens in patient-derived GBM models and independent lines of validation. Specific genetic dependencies were found consistent across recurrent tumor models, accompanied by increased mutational burden and differential transcript and protein expression compared to its primary GBM predecessor. Our observations suggest a multi-layered genetic response to drive tumor recurrence and implicate PTP4A2(protein tyrosine phosphatase 4A2) as a modulator of self-renewal, proliferation and tumorigenicity in recurrent GBM. Genetic perturbation or small-molecule inhibition of PTP4A2 acts through a dephosphorylation axis with roundabout guidance receptor 1 (ROBO1) and its downstream molecular players, exploiting a functional dependency on ROBO signaling. Because a pan-PTP4A inhibitor was limited by poor penetrance across the blood–brain barrier in vivo, we engineered a second-generation chimeric antigen receptor (CAR) T cell therapy against ROBO1, a cell surface receptor enriched across recurrent GBM specimens. A single dose of ROBO1-targeted CAR T cells doubled median survival in cell-line-derived xenograft (CDX) models of recurrent GBM. Moreover, in CDX models of adult lung-to-brain metastases and pediatric relapsed medulloblastoma, ROBO1 CAR T cells eradicated tumors in 50–100% of mice. Our study identifies a promising multi-targetable PTP4A–ROBO1 signaling axis that drives tumorigenicity in recurrent GBM, with potential in other malignant brain tumors.

Multidisciplinary pulmonary embolism response teams (PERTs) have shown that timely triage expedites treatment. The use of artificial intelligence (AI) may help improve pulmonary embolism (PE) management with early CT pulmonary angiogram (CTPA) screening and accelerate PERT coordination. This study aimed to test the clinical validity of an FDA-approved PE AI algorithm. CTPA scan data of 200 patients referred due to automated AI detection of suspected PE were retrospectively reviewed. In our institution, all patients suspected of PE received a CTPA. The AI app was then used to analyze CTPA for the presence of PE and calculate the right-ventricle/left-ventricle (RV/LV) ratio. We compared the AI’s output with the radiologists’ report. Inclusion criteria included segmental PE with and without RV dysfunction and high-risk PE. The primary endpoint was false positive rate. Secondary end points included clinical outcomes according to the therapy selected, including catheter-directed interventions, systemic thrombolytics, and anticoagulation. Fifty-seven of 200 exams (28.5%) were correctly identified as positive for PE by the algorithm. A total of 143 exams (71.5%) were incorrectly reported as positive. In 8% of cases, PERT was consulted. Four patients (7%) received systemic thrombolytics without any complications. There were six patients (10.5%) who developed high-risk PE and underwent thrombectomy, one of whom died. Among 46 patients with acute PE without right heart strain, 44 (95%) survived. The false positive rate of our AI algorithm was 71.5%, higher than what was reported in the AI’s prior clinical validity study (91% sensitivity, 100% specificity). A high rate of discordant AI auto-detection of suspected PE raises concerns about its diagnostic accuracy. This can lead to increased workloads for PERT consultants, alarm/notification fatigue, and automation bias. The AI direct notification process to the PERT team did not improve PERT triage efficacy.

Oculocutaneous albinism is an inherited disorder of melanin biosynthesis, characterized by absent or reduced pigmentation of the skin, hair, and eyes. Molecular alterations of genes that cause non-syndromic albinism in Asian Indians are poorly characterized. This information would be useful for developing therapies for this disorder. We analyzed 164 persons with non-syndromic albinism, belonging to unrelated families from all parts of India, for molecular changes in the causative genes. Subjects with white hair, white skin, and red iris had their tyrosinase gene sequenced and were also tested by MLPA for deletions/duplications. Subjects with negative results or with darker skin, golden/brown or darker hair had sequencing of TYR, P, TYRP1, SLC45A2and GPR143genes. Pathogenic variants in TYR(OCA1) were observed in 139 (84.7%) patients, in the P gene(OCA2) in 20 (12.2%), in TYRP1(OCA3) in two (1.2%), in SLC45A2(OCA 4) in one (0.61%), and in GPR143(X-linked ocular albinism) in two (1.2%) patients. Of 278 alleles with variants in TYR, 179 (64.3%) alleles had (p.R278*) alteration, suggesting the possibility of therapy with a stop codon readthrough molecule. We report 20 patients with 13 disease associated variants in the Pgene and 18 novel pathogenic variants in TYR, P, TYRP1, SLC45A2and GPR143genes. The data are compared with those reported from India, Pakistan and rest of the world. The therapeutic options in albinism are briefly described, opening this field for future therapies.

Diffuse large B-cell lymphomas (DLBCLs) are heterogeneous cancers that still require better and less toxic treatments. SIRT3, a member of the sirtuin family of NAD+-dependent protein deacylase, is critical for DLBCL growth and survival. A mitochondria-targeted SIRT3 small-molecule inhibitor, YC8-02, exhibits promising activity against DLBCL. However, YC8-02 has several limitations including poor solubility. Here, we report our medicinal chemistry efforts that led to an improved mitochondria-targeted SIRT3 inhibitor, SJ-106C, achieved by using a triethylammonium group, which helps to increase both solubility and SIRT3 inhibition potency. SJ-106C, while still inhibiting SIRT1 and SIRT2, is enriched in the mitochondria to help with SIRT3 inhibition. It is more active against DLBCL than other solid tumor cells and effectively inhibits DLBCL xenograft tumor growth. The findings provide useful insights for the development of SIRT3 inhibitors and mitochondrial targeting agents and further support the notion that SIRT3 is a promising druggable target for DLBCL.

Ineffective esophageal motility (IEM) on high‐resolution manometry (HRM) is not consistently associated with specific clinical syndromes or outcomes. We evaluated the prevalence, clinical features, management, and outcomes of pediatric IEM patients across the United States. Clinical and manometric characteristics of children undergoing esophageal HRM during 2021−2022 were collected from 12 pediatric motility centers. Clinical presentation, test results, management strategies, and outcomes were compared between children with IEM and normal HRM. Of 236 children (median age 15 years, 63.6% female, 79.2% Caucasian), 62 (23.6%) patients had IEM, and 174 (73.7%) patients had normal HRM, with similar demographics, medical history, clinical presentation, and median symptom duration. Reflux monitoring was performed more often for IEM patients (25.8% vs. 8.6%, p= 0.002), but other adjunctive testing was similar. Among 101 patients with follow‐up, symptomatic cohorts declined in both groups in relation to the initial presentation (p> 0.107 for each comparison) with management targeting symptoms, particularly acid suppression. Though prokinetics were used more often and behavioral therapy less often in IEM (p≤ 0.015 for each comparison), symptom outcomes were similar between IEM and normal HRM. Despite a higher proportion with residual dysphagia on follow‐up in IEM (64.0% vs. 39.1%, p= 0.043), an alternate mechanism for dysphagia was identified more often in IEM (68.8%) compared to normal HRM (27.8%, p= 0.017). IEM is a descriptive manometric pattern rather than a clinical diagnosis requiring specific intervention in children. Management based on clinical presentation provides consistent symptom outcomes. Ineffective esophageal motility (IEM) is a manometric pattern identified on esophageal high‐resolution manometry (HRM).There is no clear directive regarding when IEM needs specific management and what treatment is optimal.Clinical outcomes in IEM are understudied, with no available pediatric‐specific literature. Ineffective esophageal motility (IEM) is a manometric pattern identified on esophageal high‐resolution manometry (HRM). There is no clear directive regarding when IEM needs specific management and what treatment is optimal. Clinical outcomes in IEM are understudied, with no available pediatric‐specific literature. Symptom outcomes were similar between IEM and normal HRM despite a higher use of prokinetic agents in patients with IEM.An alternate mechanism for residual dysphagia was identified more often in IEM compared to normal HRM.Management strategies based on clinical presentation provided consistent symptomatic improvement. Symptom outcomes were similar between IEM and normal HRM despite a higher use of prokinetic agents in patients with IEM. An alternate mechanism for residual dysphagia was identified more often in IEM compared to normal HRM. Management strategies based on clinical presentation provided consistent symptomatic improvement.

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The concept of circular bioeconomy is embraced now-a-days as an integrated approach for sustainable production of renewable materials having minimum energy demand, maximum utility, and recycling capacity, minimizing the production waste with complete degradation. This bio-circularity needs cutting-edge technologies that have the potential to promote economic growth and are responsible for solving various environmental complications. Among various technologies, metagenomics is proving its mettle that can lead to sustainability. The identification and characterization of diverse microbial communities present in various environments such as water, soil, and waste streams help in sustainable resource utilization. The power of the unseen majority is enormous and unfolds the genetic information and functions of the microbes that can be applied in various avenues of combating societal problems. The discovery of novel catalysts and genes responsible for waste utilization and their valorization leads to the closed-loop system in which biological resources are reused and recycled. The production of biofuels, bioplastics, and other value-added biobased chemicals from various waste materials is aligning with the principles of circular bioeconomy. Moreover, optimization of microbial consortia for specific applications by understanding the interactions between different microorganisms and their metabolic functions by metagenomics is facilitating the efficient utilization of bioresources for the production of desired bioproducts. Therefore, the present review highlighted the synergy between the development of metagenomics and circular bioeconomy transforming the role of metagenomics in the development of circular bioeconomy by facilitating various paradigms of societal needs such as bioenergy, health, agriculture, and environment and has the potential to fulfill sustainable development goals.

A critical challenge in developing scalable quantum systems is correcting the accumulation of errors while performing operations and measurements. It is known that systems where dominant errors can be detected and converted into erasures have relaxed requirements for quantum error correction. Recently, it has been proposed that this can be achieved using a dual-rail encoding of quantum information in the microwave photon states of two superconducting cavities. One necessary step to realize this erasure qubit is to demonstrate a measurement and to flag errors as erasures. In this work, we demonstrate a projective logical measurement of a dual-rail cavity qubit with integrated erasure detection and measure the qubit idling errors. We measure the logical state preparation and measurement errors at the 0.01% level and detect over 99% of the cavity decay events as erasures. We use the precision of this measurement protocol to distinguish different types of error in this system, finding that although decay errors occur with a probability of approximately 0.2% per microsecond, phase errors occur 6 times less frequently and bit flips occur at least 150 times less frequently. These findings represent a confirmation of the expected error hierarchy necessary to concatenate dual-rail cavity qubits into a highly efficient erasure code.

This article is an attempt to design and develop a metamaterial-based microwave absorber with a low profile, broad incidence angle and compactness in the microwave frequency range. Further, equivalent circuit model of the proposed structure is discussed based on circuit theory. The unit cell focuses on achieving maximum absorption at C-, X-, and K-band. The dimensions of the proposed design are ultrathin and compact, having an overall size of 8 mm × 8 mm × 0.8 mm. The dimensions are optimized in such a fashion to achieve three different peaks at three various bands (C, X and K), thereby making the triple-band behaviour of the metamaterial absorber possible. The structure provides absorption of 98.26 % absorption at 7.76 GHz (C-band) while absorption of 96.74 % is achieved at 10.26 GHz (X-band) and 99.92 % absorption at 19.32 GHz (K-band) of microwave regime. The experimental verification of design conform that the measured results are found to be in close agreement to simulated ones.

Graphical abstract:

AlxYB2O3[(6-x–Y)P2O5]TeO3(x= 3, 2, 1, andY=2.5, 1.5, and 0.5) was synthesised by the sol–gel autocombustion method and calcinated at 800 °C for 2 h. The ultraviolet–visible study shows maximum absorbance at ~ 264 nm with optical band gaps ranging from 4.21 to 4.24 eV. The X-ray diffraction pattern confirmed the body-centred cubic (BCC) structure, with an average particle size of 21.63–25.77 nm. The glass nanomaterials have a total composition appearance; their granular morphological shape was confirmed by field emission scanning electron microscopy and energy-dispersive X-ray spectroscopy (FE-SEM and EDS); and their porous nanorods were exhibited by high-resolution transmission electron microscopy (HR-TEM). The incorporation of TeO3units into the glass network is associated with the depolymerisation of borophosphate chains influenced by aluminium, as revealed by the Raman spectra. The glass nanomaterial acts as a conducting material because of its dielectric loss. As well, the application of the various antimicrobial and anticancer activities for compound concentrations (x= 1 andY= 0.5) is strongly inhibiting the growth of the human cervical cancer cell line HeLa.

Current therapies for pulmonary vein stenosis (PVS) or pulmonary vein total occlusion (PVTO) involving angioplasty and stenting are hindered by high rates of restenosis.

For children with intractable functional constipation (FC), there are no evidence‐based guidelines for subsequent evaluation and treatment. Our objective was to assess the practice patterns of a large, international cohort of pediatric gastroenterologists. We administered a survey to physicians who attended the 2nd World Congress of Pediatric Neurogastroenterology and Motility held in Columbus, Ohio (USA) in September 2023. The survey included 29 questions on diagnostic testing, nonpharmacological and pharmacological treatment, and surgical options for children with intractable FC. Ninety physicians from 18 countries completed the survey. For children with intractable FC, anorectal manometry was the most commonly used diagnostic test. North American responders were more likely than Europeans to use stimulant laxatives (97% vs.77%, p= 0.032), prosecretory medications (69% vs.8%, p< 0.001), and antegrade continence enemas (ACE; 83% vs.46%, p= 0.009) for management. Europeans were more likely than North Americans to require colonic transit testing before surgery (85% vs.30%, p< 0.001). We found major differences in management practices between Americans and the rest of the world, including use of prosecretory drugs (73% vs.7%, p< 0.001), anal botulinum toxin injections (81% vs.58%, p= 0.018), ACE (81% vs.58% p= 0.018), diverting ileostomies (56% vs.26%, p= 0.006), and colonic resections (42% vs.16%, p= 0.012). No differences were found when respondents were compared by years of experience. Practice patterns in the evaluation and treatment of children with intractable FC differ widely among pediatric gastroenterologists from around the world. A clinical guideline regarding diagnostic testing and surgical decision‐making is needed. For children with intractable functional constipation (FC), there are no evidence‐based guidelines for subsequent evaluation and treatment.The diagnostic and therapeutic approach toward children with intractable FC differs considerably, even among physicians with interest and expertise in the fields of pediatric gastroenterology and pediatric surgery. For children with intractable functional constipation (FC), there are no evidence‐based guidelines for subsequent evaluation and treatment. The diagnostic and therapeutic approach toward children with intractable FC differs considerably, even among physicians with interest and expertise in the fields of pediatric gastroenterology and pediatric surgery. The persisting diversity in approaches emphasizes the complex nature of managing children with intractable FC.The use of anorectal and colonic manometry to guide surgical‐decision making is increasing.A clinical guideline regarding diagnostic testing and surgical decision‐making for children with intractable FC is needed. The persisting diversity in approaches emphasizes the complex nature of managing children with intractable FC. The use of anorectal and colonic manometry to guide surgical‐decision making is increasing. A clinical guideline regarding diagnostic testing and surgical decision‐making for children with intractable FC is needed.

Small-cell lung cancer (SCLC) has traditionally been considered a recalcitrant cancer with a dismal prognosis, with only modest advances in therapeutic strategies over the past several decades. Comprehensive genomic assessments of SCLC have revealed that most of these tumours harbour deletions of the tumour-suppressor genes TP53and RB1but, in contrast to non-small-cell lung cancer, have failed to identify targetable alterations. The expression status of four transcription factors with key roles in SCLC pathogenesis defines distinct molecular subtypes of the disease, potentially enabling specific therapeutic approaches. Overexpression and amplification of MYCparalogues also affect the biology and therapeutic vulnerabilities of SCLC. Several other attractive targets have emerged in the past few years, including inhibitors of DNA-damage-response pathways, epigenetic modifiers, antibody–drug conjugates and chimeric antigen receptor T cells. However, the rapid development of therapeutic resistance and lack of biomarkers for effective selection of patients with SCLC are ongoing challenges. Emerging single-cell RNA sequencing data are providing insights into the plasticity and intratumoural and intertumoural heterogeneity of SCLC that might be associated with therapeutic resistance. In this Review, we provide a comprehensive overview of the latest advances in genomic and transcriptomic characterization of SCLC with a particular focus on opportunities for translation into new therapeutic approaches to improve patient outcomes.

Conjugated polymer nanoparticles (CPNs or Pdots) have become increasingly popular fluorophores for multimodal applications that combine imaging with phototherapeutic effects. Reports of CPNs in photodynamic therapy applications typically focus on their ability to generate singlet oxygen. Alternatively, CPN excited states can interact with oxygen to form superoxide radical anion and a CPN-based hole polaron, both of which can have deleterious effects on fluorescence properties. Here, we demonstrate that CPNs prepared from the common conjugated polymer poly[(9,9-dioctylfluorenyl-2,7-diyl)-alt-co-(1,4-benzo-{2,1′,3}-thiadiazole)] (PFBT, also known as F8BT) generate superoxide upon irradiation. We use the same CPNs to detect superoxide by doping them with a superoxide-responsive hydrocyanine dye developed by Murthy and co-workers. Superoxide induces off-to-on fluorescence switching by converting quenching hydrocyanine dyes to fluorescent cyanine dyes that act as fluorescence resonance energy transfer (FRET) acceptors for PFBT chromophores. Amplified FRET from the multichromophoric CPNs yields fluorescence signal intensities that are nearly 50 times greater than when the dye is excited directly or over 100 times greater when signal readout is from the CPN channel. The dye loading level governs the maximum amount of superoxide that induces a change in fluorescence properties and also influences the rate of superoxide generation by furnishing competitive excited state deactivation pathways. These results suggest that CPNs can be used to deliver superoxide in applications in which it is desirable and provide a caution for fluorescence-based CPN applications in which superoxide can damage fluorophores.

Directed hydrogen atom transfer to alkenes is described. The process is catalyzed by iron complexes and allows for the site-selective hydrofunctionalization of polyenols. Experimental data suggest that coordination of the hydroxy group to the iron hydride intermediate plays an important role in preferential engagement of the allylic alcohol motif and provides a new basis for selectivity in radical hydrofunctionalization events. As a proof of concept, β- and γ-amino alcohols are prepared from the corresponding polyenols in a selective manner.