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Abstract The benefits of cancer early detection depend on various factors, including cancer type, screening method performance, stage at diagnosis, and subsequent treatment. Although numerous studies have evaluated the effectiveness of screening interventions for identifying cancer at earlier stages, there is no quantitative analysis that studies the optimal early detection time interval that results in the greatest mortality benefit; such data could serve as a target and benchmark for cancer early detection strategies. In this study, we focus on pancreatic ductal adenocarcinoma (PDAC), a cancer known for its lack of early symptoms. Consequently, it is most often detected at late stages when the 5-year survival rate is only 3%. We developed a PDAC population model that simulates an individual patient's age and stage at diagnosis, while replicating overall US cancer incidence and mortality rates. The model includes “cancer sojourn time,” serving as a proxy for the speed of cancer progression, with shorter times indicating rapid progression and longer times indicating slower progression. In our PDAC model, our hypothesis was that earlier cancer detection, potentially through a hypothetical screening intervention in the counterfactual analysis, would yield reduced mortality as compared to a no-screening group. We found that the benefits of early detection, such as increased life-years gained, are greater when the sojourn time is shorter, reaching their maximum when identification is made 4–6 years prior to clinical diagnosis (e.g., when a symptomatic diagnosis is made). However, when early detection occurs even earlier, for example 6–10 years prior to clinical diagnosis, the benefits significantly diminish for shorter sojourn time cancers, and level off for longer sojourn time cancers. Our study clarifies the potential benefits of PDAC early detection that explicitly incorporates individual patient heterogeneity in cancer progression and identifies quantitative benchmarks for future interventions.

Abstract Diffuse large B-cell lymphoma (DLBCL) represents the commonest subtype of non-Hodgkin lymphoma and encompasses a group of diverse disease entities, each harboring unique molecular and clinico-pathological features. The understanding of the molecular landscape of DLBCL has improved significantly over the past decade, highlighting unique genomic subtypes with implications on targeted therapy. At the same time, several new treatment modalities have been recently approved both in the frontline and relapsed settings, ending a dearth of negative clinical trials that plagued the past decade. Despite that, in the real-world setting, issues like drug accessibility, reimbursement policies, physician and patient preference, as well as questions regarding optimal sequencing of treatment options present difficulties and challenges in day-to-day oncology practice. Here, we review the recent advances in the therapeutic armamentarium of DLBCL and discuss implications on the practice landscape, with a particular emphasis on the context of the healthcare system in Singapore.

Abstract Background The 2020 National Comprehensive Cancer Network guidelines recommend neoadjuvant FOLFIRINOX or neoadjuvant gemcitabine plus nab‐paclitaxel (G‐nP) for borderline resectable/locally advanced pancreatic ductal adenocarcinoma (BR/LA PDAC). Aim The purpose of our study was to compare treatment outcomes, toxicity profiles, costs, and quality‐of‐life measures between these two treatments to further inform clinical decision‐making. Methods and Results We developed a decision‐analytic mathematical model to compare the total cost and health outcomes of neoadjuvant FOLFIRINOX against G‐nP over 12 years. The model inputs were estimated using clinical trial data and published literature. The primary endpoint was incremental cost‐effectiveness ratios (ICERs) with a willingness‐to‐pay threshold of $100 000 per quality‐adjusted‐life‐year (QALY). Secondary endpoints included overall (OS) and progression‐free survival (PFS), total cost of care, QALYs, PDAC resection rate, and monthly treatment‐related adverse events (TRAE) costs (USD). FOLFIRINOX was the cost‐effective strategy, with an ICER of $60856.47 per QALY when compared to G‐nP. G‐nP had an ICER of $44639.71 per QALY when compared to natural history. For clinical outcomes, more patients underwent an “R0” resection with FOLFIRINOX compared to G‐nP (84.9 vs. 81.0%), but FOLFIRINOX had higher TRAE costs than G‐nP ($10905.19 vs. $4894.11). A one‐way sensitivity analysis found that the ICER of FOLFIRINOX exceeded the threshold when TRAE costs were higher or PDAC recurrence rates were lower. Conclusion Our modeling analysis suggests that FOLFIRNOX is the cost‐effective treatment compared to G‐nP for BR/LA PDAC despite having a higher cost of total care due to TRAE costs. Trial data with sufficient follow‐up are needed to confirm our findings.

Acute graft-vs.-host (GVHD) disease remains a common complication of allogeneic stem cell transplantation with very poor outcomes once the disease becomes steroid refractory. Mesenchymal stem cells (MSCs) represent a promising therapeutic approach for the treatment of GVHD, but so far this strategy has had equivocal clinical efficacy. Therapies using MSCs require optimization taking advantage of the plasticity of these cells in response to different microenvironments. In this study, we aimed to optimize cord blood tissue derived MSCs (CBti MSCs) by priming them using a regimen of inflammatory cytokines. This approach led to their metabolic reprogramming with enhancement of their glycolytic capacity. Metabolically reprogrammed CBti MSCs displayed a boosted immunosuppressive potential, with superior immunomodulatory and homing properties, even after cryopreservation and thawing. Mechanistically, primed CBti MSCs significantly interfered with glycolytic switching and mTOR signaling in T cells, suppressing T cell proliferation and ensuing polarizing toward T regulatory cells. Based on these data, we generated a Good Manufacturing Process (GMP) Laboratory protocol for the production and cryopreservation of primed CBti MSCs for clinical use. Following thawing, these cryopreserved GMP-compliant primed CBti MSCs significantly improved outcomes in a xenogenic mouse model of GVHD. Our data support the concept that metabolic profiling of MSCs can be used as a surrogate for their suppressive potential in conjunction with conventional functional methods to support their therapeutic use in GVHD or other autoimmune disorders.

ObjectivesThe Coronavirus disease 2019 (COVID-19) pandemic disrupted medical student education, particularly in New York City (NYC). We aimed to assess the impact of the COVID-19 pandemic on medical students' residency choices.MethodsThe authors conducted a cross-sectional survey of medical students in all years of study at four NYC medical schools (Columbia, Cornell, NYU, and SUNY Downstate). The survey was fielded from 19 Aug 2020 to 21 Sep 2020. Survey questions included items assessing COVID-19 impact on residency choices, personal impact of COVID-19, residency/specialty choices, and factors influencing these choices.ResultsA total of 2310 students received the survey, with 547 (23.7%) providing partial responses and 212 (9.2%) providing valid responses for our primary analysis. 59.0% of participants thought that COVID-19 influenced their choice of residency/specialty, with 0.9% saying the influence was to a great extent, 22.2% to some extent, and 35.8% very little. On multivariable analysis, factors that were independently associated with COVID-19 impacting residency choice included low debt ($1 to $99,999: adjOR 2.23, 95%CI 1.02-5.03) compared with no debt and Other race/ethnicity (adjOR 0.26, 95%CI 0.10-0.63) compared with White race/ethnicity. On secondary analysis of all participants answering survey items for logistic regression regardless of survey completion, direct personal impact of COVID-19 was significantly associated with COVID-19 impacting specialty choice (adjOR 1.90, 95%CI 1.04-3.52). Moreover, 24 students (11.6%) reported a change in their top residency choice from before to during/after COVID-19, citing concerns about frontline work, work-life balance, and risk of harm.ConclusionsOur study found that 3 in 5 (59.0%) participants felt that COVID-19 impacted their residency choice, with 11.6% of respondents explicitly changing their top specialty choice. Investigating the impact of the pandemic on medical student residency considerations is crucial to understand how medical career outlooks may change in the future.

Down syndrome (DS) is the most common chromosomal disorder worldwide. Along with intellectual disability, endocrine disorders represent a remarkable share of the morbidities experienced by children, adolescents and young adults with DS. Auxological parameters are plotted on syndrome-specific charts, as growth rates are reduced compared to healthy age- and gender-matched peers. Furthermore, children with DS are at increased risk for thyroid dysfunctions, diabetes mellitus, osteopenia and obesity compared to general population. Additionally, male individuals with DS often show infertility, while women tend to experience menopause at an overall younger age than healthy controls. Given the recent outstanding improvements in the care of severe DS-related comorbidities, infant mortality has dramatically decreased, with a current average life expectancy exceeding 60 years. Accordingly, the awareness of the specificities of DS in this field is pivotal to timely detect endocrine dysfunctions and to undertake a prompt dedicated treatment. Notably, best practices for the screening and monitoring of pediatric endocrine disorders in DS are still controversial. In addition, specific guidelines for the management of metabolic issues along the challenging period of transitioning from pediatric to adult health care are lacking. By performing a review of published literature, we highlighted the issues specifically involving children and adolescent with DS, aiming at providing clinicians with a detailed up-to-date overview of the endocrine, metabolic and auxological disorders in this selected population, with an additional focus on the management of patients in the critical phase of the transitioning from childhood to adult care.

Acute graft-vs.-host (GVHD) disease remains a common complication of allogeneic stem cell transplantation with very poor outcomes once the disease becomes steroid refractory. Mesenchymal stem cells (MSCs) represent a promising therapeutic approach for the treatment of GVHD, but so far this strategy has had equivocal clinical efficacy. Therapies using MSCs require optimization taking advantage of the plasticity of these cells in response to different microenvironments. In this study, we aimed to optimize cord blood tissue derived MSCs (CBti MSCs) by priming them using a regimen of inflammatory cytokines. This approach led to their metabolic reprogramming with enhancement of their glycolytic capacity. Metabolically reprogrammed CBti MSCs displayed a boosted immunosuppressive potential, with superior immunomodulatory and homing properties, even after cryopreservation and thawing. Mechanistically, primed CBti MSCs significantly interfered with glycolytic switching and mTOR signaling in T cells, suppressing T cell proliferation and ensuing polarizing toward T regulatory cells. Based on these data, we generated a Good Manufacturing Process (GMP) Laboratory protocol for the production and cryopreservation of primed CBti MSCs for clinical use. Following thawing, these cryopreserved GMP-compliant primed CBti MSCs significantly improved outcomes in a xenogenic mouse model of GVHD. Our data support the concept that metabolic profiling of MSCs can be used as a surrogate for their suppressive potential in conjunction with conventional functional methods to support their therapeutic use in GVHD or other autoimmune disorders. [ABSTRACT FROM AUTHOR]

Stimuli-responsive microgels have attracted great interest in recent years as building blocks for fabricating smart surfaces with many technological applications. In particular, PNIPAM microgels are promising candidates for creating thermo-responsive scaffolds to control cell growth and detachment via temperature stimuli. In this framework, understanding the influence of the solid substrate is critical for tailoring microgel coatings to specific applications. The surface modification of the substrate is a winning strategy used to manage microgel–substrate interactions. To control the spreading of microgel particles on a solid surface, glass substrates are coated with a PEI or an APTES layer to improve surface hydrophobicity and add positive charges on the interface. A systematic investigation of PNIPAM microgels spin-coated through a double-step deposition protocol on pristine glass and on functionalised glasses was performed by combining wettability measurements and Atomic Force Microscopy. The greater flattening of microgel particles on less hydrophilic substrates can be explained as a consequence of the reduced shielding of the water–substrate interactions that favors electrostatic interactions between microgels and the substrate. This approach allows the yielding of effective control on microgel coatings that will help to unlock new possibilities for their application in biomedical devices, sensors, or responsive surfaces.

In this study the adsorption and photodegradation capabilities of modified multi-walled carbon nanotubes (MWCNTs), using tartrazine as a model pollutant, is demonstrated. MWCNT-COOH/Fe3O4 and MWCNT-COOH/Fe3O4/NiO nanocomposites were prepared by precipitation of metal oxides in the presence of MWCNTs. Their properties were examined by X-ray diffraction in powder (XRD), Fourier-transform infrared spectroscopy (FT-IR), transmission electron microscopy (TEM), scanning electron microscopy (SEM), Raman spectroscopy, synchrotron-based Scanning PhotoElectron Microscopy (SPEM), and Brunauer-Emmett-Teller (BET) analysis. It was found that the optimal adsorption conditions were pH 4 for MWCNT-COOH/Fe3O4 and pH 3 for MWCNT-COOH/Fe3O4/NiO, temperature 25 °C, adsorbent dose 1 g L−1, initial concentration of tartrazine 5 mg L−1 for MWCNT-COOH/Fe3O4 and 10 mg L−1 for MWCNT-COOH/Fe3O4/NiO and contact time 5 min for MWCNT-COOH/Fe3O4/NiO and 15 min for MWCNT-COOH/Fe3O4. Moreover, the predominant degradation process was elucidated simultaneously, with and without simulated sunlight irradiation, using thermal lens spectrometry (TLS) and UV–Vis absorption spectrophotometry. The results indicated the prevalence of the photodegradation mechanism over adsorption from the beginning of the degradation process.

Direct laser patterning is a potential and powerful technique to localize nanomaterials within a host matrix. The main goal of this study is to demonstrate that by tuning some parameters of a laser source, like power and laser pulse frequency, it is possible to modify and tune the optical properties of the generated quantum dots (QDs) within a host matrix of a specific chemical composition. The study is realized by using cadmium telluride (CdTe) QD precursors, embedded in polymethylmethacrylate (PMMA) host matrix, as starting materials. The patterning of the CdTe QDs is carried out by using a UV nanosecond laser source at 355. Fluorescence microscopy and photoluminescence spectroscopy, associated with transmission electron microscopy, indicate that it is possible to obtain desired patterns of QDs emitting from green to red of the visible spectrum, due to the formed CdTe QDs. Preliminary highlights of the CdTe QDs’ formation mechanism are given in terms of laser power and laser pulse frequency (repetition rate).

In the present study, we successfully synthesized N-doped carbon quantum dots (N-CQDs) using a top-down approach, i.e., hydroxyl radical opening of fullerene with hydrogen peroxide, in basic ambient using ammonia for two different reaction times. The ensuing characterization via dynamic light scattering, SEM, and IR spectroscopy revealed a size control that was dependent on the reaction time, as well as a more pronounced -NH2 functionalization. The N-CQDs were probed for metal ion detection in aqueous solutions and during bioimaging and displayed a Cr3+ and Cu2+ selectivity shift at a higher degree of -NH2 functionalization, as well as HEK-293 cell nuclei marking.

This study focuses on the investigation of a CdTe quantum dots (QDs) formation from a cadmium-carboxylate precursor, such as cadmium isostearate (Cd(ISA)2), to produce CdTe QDs with tunable photoluminescent (PL) properties. The CdTe QDs are obtained by the thermal decomposition of precursors directly in the polymer matrix (in situ method) or in solution and then encapsulated in the polymer matrix (ex situ method). In both approaches, the time course of the CdTe QDs formation is followed by means of optical absorption and PL spectroscopies focusing on viable emission in the spectral interval between 520 and 630 nm. In the polymeric matrix, the QDs formation is slower than in solution and the PL bands have a higher full width at half maximum (FWHM). These results can be explained on the basis of the limited mobility of atoms and QDs in a solid matrix with respect to the solution, inducing an inhomogeneous growth and the presence of surface defects. These achievements open the way to the exploitation of Cd(ISA)2 as suitable precursor for direct laser patterning (DPL) for the manufacturing of optoelectronic devices.

In this research, two 4-styrylpyridines carrying an acceptor –NO2 (L1) or a donor –NMe2 group (L2) were axially coordinated to A4 ZnII porphyrins displaying in 5,10,15,20 meso position aryl moieties with remarkable electron withdrawing properties (pentafluorophenyl (TFP)), and with moderate to strong electron donor properties (phenyl (TPP) < 3,5-di-tert-butylphenyl (TBP) < bis(4-tert-butylphenyl)aniline) (TNP)). The second order nonlinear optical (NLO) properties of the resulting complexes were measured in CHCl3 solution by the Electric-Field-Induced Second Harmonic generation technique, and the quadratic hyperpolarizabilities βλ were compared to the Density Functional Theory (DFT)-calculated scalar quantities β||. Our combined experimental and theoretical approach shows that different interactions are involved in the NLO response of L1- and L2-substituted A4 ZnII porphyrins, suggesting a role of backdonation-type mechanisms in the determination of the negative sign of Electric-Field-Induced Second Harmonic generation (EFISH) βλ, and a not negligible third order contribution for L1-carrying complexes.