Lymph Node Yield is Associated with Improved Overall Survival and Increased Time to Recurrence in Node-Negative Pancreatic Ductal Adenocarcinoma Following Neoadjuvant Therapy.

OBJECTIVE: To determine if lymph node yield (LNY) is associated with improved overall survival (OS) and time to recurrence (TTR) in patients with node-negative pancreatic ductal adenocarcinoma (PDAC) treated with neoadjuvant therapy (NAT). BACKGROUND: Lymph node yield has been associated with survival in solid gastrointestinal cancers, including PDAC. METHODS: Patients with pathological T stage I-III, node-negative (N0), PDAC treated with NAT followed by pancreatoduodenectomy were identified in the Massachusetts General Hospital (MGH) pancreatectomy database and the National Cancer Database (NCDB). A cutoff point of 22 nodes was identified in the NCDB using the point with the optimal (log-rank test) split. Overall survival and TTR were evaluated using univariate and multivariable analyses. RESULTS: In the MGH cohort, 233 node-negative patients following NAT were included. A LNY ≥ 22 was associated with prolonged median OS (59 months vs. 25 months, P<0.001) and prolonged TTR (32 months vs. 14 months, P=0.019). On multivariable analysis, LNY was an independent predictor of survival (HR 0.97, 95% CI 0.95-0.99, P=0.034) per sampled node. In the NCDB, 2,029 node-negative patients following NAT were included. A LNY ≥ 22 was associated with prolonged median OS (49 months vs. 33 months, P<0.001). On multivariable analysis, LNY was an independent predictor of survival (HR 0.99, 95% CI 0.98-0.99, P<0.001) per sampled node. CONCLUSION: Lymph node yield was associated with improved oncologic outcomes in patients treated with NAT followed by pancreatoduodenectomy in two independent datasets. Responsible mechanisms by which LNY impacts the outcomes of node-negative patients following NAT warrant further exploration.

Rice proteins - Gum arabic coacervates: Effect of pH and polysaccharide concentration in oil-in-water emulsion stability.

In the context of replacing animal proteins in food matrices, rice proteins (RP) become promised because they come from an abundant plant source, are hypoallergenic, and have high digestibility and nutritional value. However, commercial protein isolates obtained by spray drying have low solubility and poor functionality, especially in their isoelectric point. One way to modify these properties is through interaction with polysaccharides, such as gum arabic (GA). Therefore, this work aims to evaluate the effects of pH and GA concentration on the interaction and emulsifying activity of RP:GA coacervates. First, the effects of pH (2.5 to 7.0) and GA concentrations (0.2 to 1.0 wt%, giving rise to RP:GA mass ratios of 1:0.2 to 1:1.0) in RP:GA blends were evaluated. The results demonstrated that biopolymers present opposite net charges at pH between 2.5 and 4.0. At pH 3.0, insoluble coacervates with complete charge neutralization were formed by electrostatic interactions, while at pH 5.0 it was observed that the presence of GA prevented the RP massive aggregation. Second, selected blends with 0.4 or 1.0 wt% of GA (RP:GA mass ratios of 1:0.4 or 1:1.0) at pH 3.0 or 5.0 were tested for their ability to stabilize oil-in-water emulsions. The emulsions were characterized for 21 days. It was observed that the GA increased the stability of RP emulsions, regardless of the pH and polysaccharide concentration. Taken together, our results show that it is possible to combine RP and GA to improve the emulsifying properties of these plant proteins at pH conditions close to their isoelectric point, expanding the possibility of implementation in food systems.

Unraveling dispersion and buoyancy dynamics around radial A + B → C reaction fronts: microgravity experiments and numerical simulations.

Radial Reaction-Diffusion-Advection (RDA) fronts for A + B → C reactions find wide applications in many natural and technological processes. In liquid solutions, their dynamics can be perturbed by buoyancy-driven convection due to concentration gradients across the front. In this context, we conducted microgravity experiments aboard a sounding rocket, in order to disentangle dispersion and buoyancy effects in such fronts. We studied experimentally the dynamics due to the radial injection of A in B at a constant flow rate, in absence of gravity. We compared the obtained results with numerical simulations using either radial one- (1D) or two-dimensional (2D) models. We showed that gravitational acceleration significantly distorts the RDA dynamics on ground, even if the vertical dimension of the reactor and density gradients are small. We further quantified the importance of such buoyant phenomena. Finally, we showed that 1D numerical models with radial symmetry fail to predict the dynamics of RDA fronts in thicker geometries, while 2D radial models are necessary to accurately describe RDA dynamics where Taylor-Aris dispersion is significant.

Digital Breast Tomosynthesis for Upgraded BIRADS Scoring towards the True Pathology of Lesions Detected by Contrast-Enhanced Mammography.

OBJECTIVE: To determine the added value of digital breast tomosynthesis (DBT) in the assessment of lesions detected by contrast-enhanced mammography (CEM). MATERIAL AND METHODS: A retrospective study was conducted in a tertiary university medical center. All CEM studies including DBT performed between January 2016 and December 2020 were included. Lesions were categorized and scored by four dedicated breast radiologists according to the recent CEM and DBT supplements to the Breast Imaging Reporting and Data System (BIRADS) lexicon. Changes in the BIRADS score of CEM-detected lesions with the addition of DBT were evaluated according to the pathology results and 1-year follow-up imaging study. RESULTS: BIRADS scores of CEM-detected lesions were upgraded toward the lesion's pathology with the addition of DBT (p > 0.0001), overall and for each reader. The difference in BIRADS scores before and after the addition of DBT was more significant for readers who were less experienced. The reason for changes in the BIRADS score was better lesion margin visibility. The main BIRADS descriptors applied in the malignant lesions were spiculations, calcifications, architectural distortion, and sharp or obscured margins. CONCLUSIONS: The addition of DBT to CEM provides valuable information on the enhancing lesion, leading to a more accurate BIRADS score.

Prognostic performance of microscopic size measurements in small invasive carcinomas arising in intraductal papillary mucinous neoplasms of the pancreas.

AIMS: Small invasive carcinomas arising in intraductal papillary mucinous neoplasms (IPMNs) of the pancreas can present as multiple, small foci. In such cases, there is no clear optimal measurement method for determining the invasive size for tumour staging and prognostication. METHODS: In all, 117 small invasive IPMNs (size of largest invasive component ≤2 cm) from seven institutions (2000-2016) were reviewed, and all individual foci of invasive carcinoma were measured. T stages (AJCC 8th edition) based on the largest single focus size (LS), average size of all foci (AS), and total sum of all foci (TS) were examined in association with clinicopathologic parameters and patient outcomes. RESULTS: The cohort comprised IPMNs with invasive tubular-type (n = 82, 70%) and colloid-type (n = 35, 30%) carcinomas. The mean LS, AS, and TS were 0.86, 0.71, and 1.32 cm, respectively. Based on the LS, AS, and TS, respectively, 48, 65, and 39 cases were classified as pT1a; 22, 18, and 11 cases as pT1b; and 47, 34, and 50 cases as pT1c. Higher pT stages based on all measurements were significantly associated with small vessel, large vessel, and perineural invasion (P < 0.05). LS-, AS-, and TS-based pT stages were not significantly associated with recurrence-free survival (RFS) or overall survival (OS) by univariate or multivariate analyses. However, among tubular-type carcinomas, higher LS-, AS-, and TS-based pT stages trended with lower RFS (based on 1-, 3-, and 5-year survival rates). All microscopic measurement methods were most predictive of RFS and OS using a 1.5-cm cutoff, with LS significantly associated with both RFS and OS by univariate and multivariate analysis. CONCLUSIONS: For invasive tubular-type carcinomas arising in IPMN, microscopic size-based AJCC pT stages were not significant predictors of patient outcomes. However, for LS, a size threshold of 1.5 cm was optimal for stratifying both RFS and OS. The AJCC 8th ed. may not be applicable for stratifying small invasive IPMNs with colloid-type histology that generally portend a more favourable prognosis.

Conservative non-pharmacological treatments for chemotherapy-induced peripheral neuropathies in women treated for breast cancer: a systematic review.

INTRODUCTION: Over the last few decades, the use of neo/adjuvant therapies has significantly increased the number of breast cancer survivors who experience chemotherapy-induced peripheral neuropathy (CIPN). To date, few, low-efficacy, pharmacological remedies exist to manage this side effect. For this reason, alternative treatments are increasingly being investigated as possible strategies to prevent or promote faster recovery from CIPN. In this review we aimed to provide an overview of the literature evidence regarding all the non-pharmacological and rehabilitative interventions for patients affected by CIPN secondary to breast cancer care. EVIDENCE ACQUISITION: A comprehensive literature search was conducted on PubMed, Scopus and Web of Science and included a total of 1895 patients (1528 with breast cancer) with a wide range of CIPN (motor, sensory and autonomic neuropathies) and chemotherapy treatments (e.g., Taxanes, Platins, Vinca alkaloids or monoclonal antibody drugs). EVIDENCE SYNTHESIS: Of the initial 1108 hits, only 25 studies - describing different treatment modalities for peripheral neuropathies - were finally included in the qualitative synthesis. Most studies focused on acupuncture, physiotherapy, cryotherapy, and yoga. CONCLUSIONS: There is still controversial evidence on conservative non-pharmacological interventions for the management of CIPN symptoms. We believe however that moderate exercise, as well as all types of stress reducing activities like sport, yoga and mindfulness, should be encouraged in cancer patients for their positive effect on global physical and psychological health. Further studies of higher methodological quality are needed to determine the best conservative approach to CIPN.

Promoting Longitudinal and Developmental Computer-Based Assessments of Clinical Reasoning: Validity Evidence for a Clinical Reasoning Mapping Exercise.

PURPOSE: Clinical reasoning is vitally important for practitioners across the health professions. However, the assessment of clinical reasoning remains a significant challenge. Combined with other assessment methods, non-workplace-based assessment can increase opportunities to address multiple components of clinical reasoning, evaluate growth, and foster learning, but tools with validity evidence to assess clinical reasoning outside the workplace are scare. This study examined validity evidence for a novel clinical reasoning mapping exercise (CResME). METHOD: Data include CResME performance scores from 120 third-year medical students at the University of Central Florida for 3 topics in May 2022. Each CResME was scored by 2 physician raters based on a scoring rubric that included a combined diagnosis and sequence score. Descriptive statistics were used to examine trends in scores. The authors gathered validity evidence for response process, internal structure, and relations to other variables. RESULTS: The overall mean (SD) score across cases was 66 (29). Internal consistency reliability of cases (Cronbach α) ranged from 0.75 to 0.91. The Phi and G coefficients were 0.45 and 0.56, respectively. Students accounted for 10% of the total variance, indicating the ability to differentiate high and low clinical reasoning skills; the interaction between learner and case accounted for 8.1% of the variance, demonstrating case specificity. There was a moderate correlation between the overall CResME scores and the mean overall score of patient encounter notes from an objective structured clinical examination performed at the end of the third year (0.46; P = .001). Significant associations were also found between the CResME scores and subject exam scores. CONCLUSIONS: The CResME can be used to facilitate the assessment of clinical reasoning, supporting the developmental progress of learners throughout the curriculum. Future research is needed to gather validity evidence for CResMEs with different learners across different settings and formats.

Tumor Size Reduction and Serum Carbohydrate Antigen 19-9 Kinetics After Neoadjuvant FOLFIRINOX in Patients With Pancreatic Ductal Adenocarcinoma.

BACKGROUND: Changes in tumor size and serum carbohydrate antigen 19-9 are commonly reported markers used to assess response to neoadjuvant therapy in pancreatic ductal adenocarcinoma. We evaluated the impact of the percentual tumor size reduction and carbohydrate antigen 19-9 kinetics on resectability and response to neoadjuvant FOLFIRINOX. METHODS: This was an institutional analysis of patients with non-metastatic (upfront resectable, borderline resectable, and locally advanced) pancreatic ductal adenocarcinoma who underwent neoadjuvant FOLFIRINOX. Resectability, pathologic response, disease recurrence, and overall survival were evaluated. RESULTS: Among 193 patients who completed FOLFIRINOX, 60% underwent resection, and 91% were R0. Pathologically, complete, and near-complete responses were achieved in 4% and 40% of patients, respectively. Tumor size reduction (odds ratio 1.02 per 1%, P = .024) and normalization of carbohydrate antigen 19-9 (odds ratio 2.61, P = .035) were associated with increased odds of resectability. Concerning pathologic response, tumor size reduction (odds ratio 1.03 per 1%, P = .018) was associated with increased odds of a complete and near-complete response. Lastly, in resected patients, a postoperative increase in carbohydrate antigen 19-9 after prior normalization after neoadjuvant therapy were at an increased risk of recurrence (hazard ratio 9.58, P < .001) and worse survival (hazard ratio 10.4, P < .001) compared to patients who maintained normalization. CONCLUSION: In patients with non-metastatic pancreatic ductal adenocarcinoma who underwent neoadjuvant therapy, tumor size reduction was a significant predictor of resectability and pathologic response, including complete and near complete responses, whereas serum carbohydrate antigen 19-9 normalization predicted resectability, disease recurrence, and survival. Patients with a postoperative carbohydrate antigen 19-9 rise after prior normalization after administration of neoadjuvant therapy were at an increased risk of recurrence and worse overall survival.

The Promise of Cancer Health Justice: How Stakeholders and the Community Can Build a Sustained and Equitable System of Cancer Care Through the Lens of Colorectal Cancer Interventions.

ABSTRACT: Disparities in outcomes and persistent barriers to adequate care in colorectal cancer are reflective of a system that has failed to achieve the ideals of health equity and health justice. In this review, we discuss that although much research has been done to improve upon gaps in screening, treatment, and supportive care in colorectal cancer, a concerted effort across multiple research, regulatory, and funding stakeholders with community-level organizations is essential in building a self-sustained system that effectively achieves health equity outcomes. We also highlight several examples of novel community-based interventions along the continuum of cancer care that demonstrate the potential of what can be accomplished when we invest in scaling up small-scale solutions to the state and national levels and offer ways in which stakeholders and the community may mutually benefit through a system of incentives, self-assessment tools, and attainable metrics.

Guanidyl-Rich Poly(ß Amino Ester)s for Universal Functional Cytosolic Protein Delivery and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) Cas9 Ribonucleoprotein Based Gene Editing.

Protein therapeutics are highly promising for complex disease treatment. However, the lack of ideal delivery vectors impedes their clinical use, especially the carriers for in vivo delivery of functional cytosolic protein. In this study, we modified poly(ß amino ester)s (PAEs) with a phenyl guanidine (PG) group to enhance their suitability for cytosolic protein delivery. The effects of the PG group on protein binding, cell internalization, protein function protection, and endo/lysosomal escape were systematically evaluated. Compared to the unmodified PAEs (L3), guanidyl rich PAEs (L3PG) presented superior efficiency of protein binding and protein internalization, mainly via clathrin-mediated endocytosis. In addition, both PAEs showed robust capabilities to deliver cytosolic proteins with different molecular weight (ranging from 30 to 464 kDa) and isoelectric points (ranging from 4.3 to 9), which were significantly improved in comparison with the commercial reagents of PULsin and Pierce Protein Transection Reagent. Moreover, L3PG successfully delivered Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) Cas9 ribonucleoprotein (RNP) into HeLa cells expressing green fluorescent protein (GFP) and achieved more than 80% GFP expression knockout. These results demonstrated that guanidyl modification on PAEs can enhance its capabilities for intracellular delivery of cytosolic functional proteins and CRISPR/Cas9 ribonucleoprotein. The guanidyl-rich PAEs are promising nonviral vectors for functional protein delivery and potential use in protein and nuclease-based gene editing therapies.

Different Tendencies in Muscle Ultrasound Characteristic in Amyotrophic Lateral Sclerosis and Chronic Inflammatory Demyelinating Polyradiculoneuropathy.

INTRODUCTION: The difference in muscle ultrasound (MUS) characteristics in primary axonal degeneration and demyelination has not been well established. The authors aimed to investigate the subject based on the correlation between MUS findings (echo intensity and muscle thickness) and compound muscle action potential (CMAP) amplitude in amyotrophic lateral sclerosis (ALS) and chronic inflammatory demyelinating polyradiculoneuropathy. METHODS: Fifteen patients with ALS and 16 patients with chronic inflammatory demyelinating polyradiculoneuropathy were examined. For each patient, echo intensity and muscle thickness of the abductor pollicis brevis, abductor digiti minimi, and first dorsal interosseous muscles were investigated. Compound muscle action potential amplitudes were measured by median and ulnar nerve conduction studies. RESULTS: In total, 45 muscles were evaluated in each group. The ALS group showed a linear correlation between the MUS finding and CMAP amplitude (rs = -0.70 and 0.59 for echo intensity and muscle thickness, respectively), whereas the chronic inflammatory demyelinating polyradiculoneuropathy group showed a weaker correlation than the ALS group (rs = -0.32 for echo intensity and rs = 0.34 for muscle thickness). CONCLUSIONS: The relationship between MUS abnormalities and CMAP amplitude showed different tendencies in ALS and chronic inflammatory demyelinating polyradiculoneuropathy. The results suggested that MUS abnormalities substantially reflect the muscle function in primary axonal degeneration, whereas a discrepancy between MUS findings and muscle function can be frequently seen in demyelination; specifically, MUS findings tend to be normal even though CMAP showed a reduction. These tendencies originating from underlying pathophysiology should be considered when MUS findings are used as biomarkers of disease severity.

Sequential chiral induction between organic and inorganic supramolecular helical assemblies for the in situ formation of chiral carbon dots.

Self-organised helical bilayers of dicationic gemini surfactants confined in helical silica nanospace were transformed in situ to carbon dots (CDots) via pyrolysis. These water-dispersible CDots exhibit electronic absorption spanning the UV and visible range and possess symmetrical circular dichroism (CD) signals, the sign of which depends on the handedness of the helices.

Redox-active ions unlock substitutional doping in halide perovskites.

Electrical doping of metal halide perovskites (MPHs) is a key step towards the use of this efficient and cost-effective semiconductor class in modern electronics. In this work, we demonstrate n-type doping of methylammonium lead iodide (CH3NH3PbI3) by the post-fabrication introduction of Sm2+. The ionic radius of the latter is similar to that of Pb2+ and can replace it without altering the perovskite crystal lattice. It is demonstrated that once incorporated, Sm2+ can act as a dopant by undergoing oxidation to Sm3+. This results in the release of a negative charge that n-dopes the material, resulting in an increase of conductivity of almost 3 orders of magnitude. Unlike substitution doping with heterovalent ions, furtive dopants do not require counterions to maintain charge neutrality with respect to the ions they replace and are thus more likely to be incorporated into the crystalline structure. The incorporation of the dopant throughout the material is evidenced by XPS and ToF-SIMS, while the XRD pattern shows no phase separation at low and medium doping concentrations. A shift of the Fermi level towards a conduction energy of 0.52 eV confirms the doping to be n-type with a charge carrier density, calculated using the Mott-Schottky method, estimated to be nearly 1017 cm-3 for the most conductive samples. Variable-temperature conductivity experiments show that the dopant is only partially ionized at room temperature due to dopant freeze-out.

Strong circularly polarized luminescence via intramolecular excited-state symmetry-breaking charge separation.

Trans-1,2-di(1-pyrenylamino)cycloxexane was found to display circularly polarized excimer emission (glum = 0.016) both in polar and non-polar solvents that is assigned to charge separation symmetry breaking on the basis of its large transition state dipole moment (12.1 D).

PEP mask therapy for the rehabilitation of a pre-term infant with respiratory distress syndrome: a case report.

BACKGROUND: Preterm infants can develop many complications related to organs underdevelopment. Respiratory distress syndrome (RDS) is considered the most important cause of morbidity and mortality in these patients. Traditional therapies for severe RDS, such as mechanical ventilation, come with a potential risk for pneumothorax and bronchopulmonary dysplasia while evidence on chest physiotherapy in preterm infants are controversial in terms of feasibility, tolerability and safety. The use of the positive expiratory pressure (PEP) mask is known in the pediatric field especially in cystic fibrosis for the removal of secretions and lung re-expansion. However, no literature exists on the application and effectiveness of this treatment modality for the respiratory rehabilitation of preterm infants. In this study, we aimed to assess the efficacy of a respiratory rehabilitation protocol based on PEP mask in a preterm infant with respiratory distress syndrome. CASE REPORT: A Caucasian girl born at 26 + 5 weeks of gestational age with respiratory distress syndrome was treated with mechanical ventilation, oxygen therapy and PEP-mask. CLINICAL REHABILITATION IMPACT: Three weeks of PEP mask led to a significant clinical and radiological improvement of the lung's function with progressive reduction of the oxygen supplement and mechanical ventilation until complete weaning off. Given the absence of literature on this subject, further studies should be conducted to confirm these preliminary observations.

Chiral Binaphthalene Building Blocks for Self-Assembled Nanoscale CPL Emitters.

The introduction of biuret hydrogen-bonding sites onto chiral binaphthalene-based chromophores was investigated as a route to sub-micron-sized, vesicle-like aggregates endowed with chiroptical properties. The synthesis was conducted from the corresponding chiral 4,4'-dibromo-1,1'-bis(2-naphthol) via Suzuki-Miyaura coupling to afford luminescent chromophores whose emission spectrum could be tuned from blue to yellow-green through extension of the conjugation. For all compounds, the spontaneous formation of hollow spheres with a diameter of ca. 200-800 nm was evidenced by scanning electron microscopy, along with strong asymmetry in the circularly polarized absorption spectra. For some compounds, the emission also displayed circular polarization with values of glum = ca. 10-3 which could be increased upon aggregation.

A facile strategy for reclaiming discarded graphite and harnessing the rate capabilities of graphite anodes.

Graphite negative electrodes are unbeaten hitherto in lithium-ion batteries (LiBs) due to their unique chemical and physical properties. Thus, the increasing scarcity of graphite resources makes smart recycling or repurposing of discarded graphite particularly imperative. However, the current recycling techniques still need to be improved upon with urgency. Herein a facile and efficient hydrometallurgical process is reported to effectively regenerate aged (39.5 %, 75 % state-of-health, SOH) scrapped graphite (SG) from end-of-life lithium-ion batteries. Ultimately, the first cycle reversible capacity of SG1 (SOH = 39.5 %) improved from 266 mAh/g to 337 mAh/g while 330 mAh/g (98 %) remain after 100 cycles at 0.5 C. The reversible capacity for the first cycle of SG2 (SOH = 75 %) boosted from 335 mAh/g to 366 mAh/g with the capacity retention of 99.3 % after 100 cycles at 0.5 C, which is comparable with the benchmark commercial graphite. The regenerated graphites RG1 and RG2 exhibit excellent output characteristics even increasing the rate up to 4 C. This is the best rate level reported in the literature to date. Finally, the diffusion coefficient of Li ions during deintercalation and intercalation in the regenerated graphites have been measured by galvanostatic intermittent titration technique (GITT), determining values 2 orders-of-magnitude higher than that of the spent counterparts. Taking advantage of the synergistic effect of acid leaching and heat treatment, this strategy provides a simple and up-scalable method to recycle graphitic anodes.

Advance Care Planning With Black Women with Breast Cancer: A Community Health Worker Model.

BACKGROUND: Despite the importance of advance care planning (ACP), a process that optimizes future medical treatment and end-of-life care, for at-risk populations, rates of patient-provider ACP conversations are extremely low among Black women with breast cancer. Community health workers (CHWs) are well-positioned to support patients in engaging in ACP conversations with their providers; yet research on integrating CHWs to promote ACP is scant. The current study examined multilevel facilitators and barriers to successful ACP conversations among Black women from the perspective of providers and CHWs who serve this community. METHODS: Providers and CHWs were recruited from an academic medical center in a large urban city. Retrospective qualitative data on barriers and facilitators to ACP conversations, as well as CHWs' training needs, were collected from two focus groups (N = 5 providers, N = 5 CHWs) and one individual interview (N = 1 provider), and transcribed and coded for themes. RESULTS: All providers reported working primarily with Black patients, and identified stigma and time constraints as major barriers to ACP discussions; they also identified the structural barriers and injustices that their patients face during medical care. CHWs reported having a trusted relationship with their patients and flexibility in their care that would allow for ongoing ACP conversations, discussing their ability to serve as a bridge between the patient and provider. However, CHWs discussed that they lacked the tools and skills to have ACP conversations, largely because existing formal trainings in ACP are cost prohibitive. DISCUSSION: Competing priorities of the provider to discuss/treat the patient's disease and medical mistrust were major barriers to successful ACP conversations among Black women with breast cancer, leading to ACP completion occurring late in treatment. CHWs are uniquely qualified to overcome multilevel barriers to ACP and establish trusting relationships with patients in order to facilitate earlier and ongoing communication between patients and providers.