Search

We present a detailed investigation of the coordination chemistry toward [ nat Cu/ 64 Cu]copper of a series of H 2 DEDPA derivatives (H 2 DEDPA = 6,6'-((ethane-1,2-diylbis(azanediyl))bis(methylene))dipicolinic acid) containing cyclohexyl (H 2 CHXDEDPA), cyclopentyl (H 2 CpDEDPA) or cyclobutyl (H 2 CBuDEDPA) spacers. Furthermore, we also developed a strategy that allowed the synthesis of a H 2 CBuDEDPA analogue containing an additional NHBoc group at the cyclobutyl ring, which can be used for conjugation to targeting units. The X-ray structures of the Cu(II) complexes evidence distorted octahedral coordination around the metal ion in all cases. Cyclic voltammetry experiments (0.15 M NaCl) evidence quasi-reversible reduction waves associated with the reduction of Cu(II) to Cu(I). The complexes show a high thermodynamic stability, with log K CuL values of 25.11(1), 22.18(1) and 20.19(1) for the complexes of CHXDEDPA 2- , CpDEDPA 2- and CBuDEDPA 2- , respectively (25 °C, 1 M NaCl). Dissociation kinetics experiments reveal that both the spontaneous- and proton-assisted pathways operate at physiological pH. Quantitative labeling with 64 CuCl 2 was observed at 0.1 nmol for CHXDEDPA 2- and CpDEDPA 2- , 0.025 nmol for CBuDEDPA 2- and 1 nmol for CBuDEDPA-NHBoc 2- , with no significant differences observed at 15, 30, and 60 min. The radio-complexes are stable in PBS over a period of 24 h.

We report a spectroscopic and computational study that investigates the absorption spectra of Bi(III) complexes, which often show an absorption band in the UV region (∼270-350 nm) due to 6sp ← 6s transitions. We investigated the spectra of three simple complexes, [BiCl 5 ] 2- , [BiCl 6 ] 3- and [Bi(DMSO) 8 ] 3+ , which show absorption maxima at 334, 326 and 279 nm due to 3 P 1 ← 1 S 0 transitions. Theoretical calculations based on quasi-degenerate N-electron valence perturbation theory to second order (QD-NEVPT2) provide an accurate description of the absorption spectra when employing CAS(2,9) wave functions. We next investigated the absorption spectra of the [Bi(NOTA)] complex (H 3 NOTA = 1,4,7-triazacyclononane-1,4,7-triacetic acid), which forms ternary complexes [Bi(NOTA)X] - (X = Cl, Br or I) in the presence of excess halide in aqueous solutions. Halide binding has an important impact on the position of the 3 P 1 ← 1 S 0 transition, which shifts progressively to longer wavelengths from 282 nm ([Bi(NOTA)]) to 298 nm (X = Cl), 305 nm (X = Br) and 325 nm (X = I). Subsequent QD-NEVPT2 calculations indicate that this effect is related to the progressive stabilization of the spin-orbit free states associated with the 6s 1 6p 1 configuration on increasing the covalent character of the metal-ligand(s) bonds, rather than with significant differences in spin-orbit coupling (SOC). These studies provide valuable insight into the coordination chemistry of Bi(III), an ion with increasing interest in targeted alpha therapy due to the possible application of bismuth isotopes bismuth-212 ( 212 Bi, t 1/2 = 60.6 min) and bismuth-213 ( 213 Bi, t 1/2 = 45.6 min).

Synthetic methodologies were developed to achieve the preparation of ligands L1 and L2 consisting of tacn- and pyclen-based chelators decorated with pyridinylphosphonic pendant arms combined with ethylpicolinamide or acetate coordinating functions, respectively. Phosphonate functions have been selected for their high affinity toward Ln 3+ ions compared to their carboxylated counterparts and for their steric hindrance that favors the formation of less-hydrated complexes. Thanks to regiospecific N -functionalization of the macrocyclic backbones, the two ligands were isolated with good yields and implicated in a comprehensive photophysical study for the complexation of Eu 3+ , Tb 3+ , and Yb 3+ . The coordination behavior of L1 and L2 with these cations has been first investigated by means of a combination of UV-vis absorption spectroscopy, steady-state and time-resolved luminescence spectroscopy, and 1 H and 31 P NMR titration experiments. Structural characterization in solution was assessed by NMR spectroscopy, corroborated by theoretical calculations. Spectroscopic characterization of the Ln 3+ complexes of L1 and L2 was done in water and D 2 O and showed the effective sensitization of the lanthanide metal-centered emission spectra, each exhibiting typical lanthanide emission bands. The results obtained for the phosphonated ligands were compared with those reported previously for the corresponding carboxylated analogues.

We present a detailed analysis of the 1 H NMR chemical shifts and transverse relaxation rates of three small Dy(III) complexes having different symmetries ( C 3 , D 2 F C 2 ). The complexes show sizeable emission in the visible region due to 4 F 9/2 → 6 F J transitions ( J = 15/2 to 11/2). Additionally, NIR emission is observed at ca. 850 ( 4 F 9/2 F 6 H 7/2 ), 930 ( 4 F 9/2 F 6 H 5/2 F 4 F 9/2 F 6 F 9/2 F 4 F 9/2 → 6 F 7/2 ). Emission quantum yields of 1-2% were determined in aqueous solutions. The emission lifetimes indicate that no water molecules are present in the inner coordination sphere of Dy(III), which in the case of [Dy(CB-TE2PA)] + was confirmed through the X-ray crystal structure. The 1 H NMR paramagnetic shifts induced by Dy(III) were found to be dominated by the pseudocontact mechanism, though, for some protons, contact shifts are not negligible. The analysis of the pseudocontact shifts provided the magnetic susceptibility tensors of the three complexes, which were also investigated using CASSCF calculations. The transverse 1 H relaxation data follow a good linear correlation with 1/ r 6 , where r is the distance between the Dy(III) ion and the observed proton. This indicates that magnetic anisotropy is not significantly affecting the relaxation of 1 H nuclei in the family of complexes investigated here.

Octadentate ligands containing ethyl (H 4 OCTAPA), cyclohexyl (H 4 CHX OCTAPA) or cyclopentyl (H 4 Cp OCTAPA) spacers were assessed as chelators for Bi(III)-based radiopharmaceuticals. The H 4 CHX OCTAPA chelator displays excellent properties, including 205/206 Bi-nuclide radiolabelling under mild conditions, excellent stability in serum and in the presence of competing cations or H 5 DTPA. The poor performance of H 4 Cp OCTAPA appears to be related to the stereochemical activity of the Bi(III) lone pair.

This account reports the synthesis and structural characterization of the first cyclometallated platinum(II) complex that coordinates a potassium cation in a sandwich arrangement via two 15-crown-5 ether rings within the same molecule. The cooperation of the two small crown ether moieties allows the entrapment of the non-ideal potassium ion. The reaction of the parent thiosemicarbazone ligand 3,4-(C 8 H 16 O 5 )C 6 H 3 C(Me)=NN-(H)C(=S)NHMe, 1 , containing the crown ether ring, with K 2 [PtCl 4 ], or alternatively with PtCl 2 (DMSO) 2 , and subsequent treatment with the diphosphanes Ph 2 PCH 2 PPh 2 (dppm) and Ph 2 PC(=CH 2 )PPh 2 (vdpp) produced the double nuclear platinacycles 3a , 3b , and 4 , probably via formation of the 2a and 2b intermediates. Complex 3a with the K + cation in a sandwich coordination was slightly mixed with 3b lacking any K + . Alternatively, reaction of 1 with K 2 [PtCl 4 ] or with PtCl 2 (DMSO) 2 followed by the diphosphane Ph 2 PC(=CH 2 )PPh 2 (vdpp) only gave the dinuclear phosphane-bridged compound 4 ; this highlights the importance of choosing the right diphosphane ligand. Density functional theory calculations (B3LYP-D3/LANL2DZ-ECP-6.311++G**) revealed similar affinities for both dppm and vdpp derivatives to coordinate potassium cations. Crystal structure analysis was performed for compounds 3a and 4 ., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

COVID-19 revealed and magnified the preexisting health inequities faced by many vulnerable groups. The Latinx community is one of these groups and has borne the brunt of disparate rates of infection, hospitalization, and mortality associated with COVID-19. These disparities are rooted in social inequities, such as poverty and lack of access to health care, as well as health inequities associated with disparate disease and condition burdens. Moreover, the lack of an adequate Latinx physician workforce contributes to and exacerbates these inequities. The COVID-19 pandemic has intersected with the U.S. Supreme Court's decision in the Department of Homeland Security v. Regents of the University of California case. The court's decision in this case struck down the attempted ending of the Deferred Action for Childhood Arrivals (DACA) program, although it was settled that the government could end the program if it was done lawfully. Even though this constitutes a win for DACA recipients, the decision is a stopgap as the future of DACA recipients remains vulnerable and subject to other legal challenges and political vagaries. In a time when the need to ameliorate health inequities for the Latinx community is so pronounced, DACA recipient medical trainees could provide much-needed relief. Since the implementation of DACA, some medical schools have decided to accept DACA recipient students, but many do not. This access-limiting practice stymies a group of potential trainees who could help to increase the Latinx physician workforce, as the majority of DACA recipients are Latinx. This article argues that all medical schools should take steps to consider accepting DACA recipient applicants in line with the principles of health equity and suggests 5 recommendations for medical school admissions, support, and advocacy practices., (Copyright © 2022 by the Association of American Medical Colleges.)

Treatment of the imines a-c with palladium(II) acetate in acetic acid yielded the μ-acetate dinuclear complexes 1a-c , which readily reacted with sodium chloride or bromide to provide μ-halide analogues. The reaction of the latter with nitrogen, phosphorus and oxygen donor nucleophiles yielded new imine palladacycles following the cleavage of the Pd 2 X 2 unit. The complexes were fully characterized by microanalysis, 1 H, 13 C and 31 P NMR spectroscopies, as appropriate. The compounds were applied as catalysts in the Suzuki-Miyaura coupling reaction in aqueous and semi-aqueous media.

The stability constants of lanthanide complexes with the potentially octadentate ligand CHX OCTAPA 4- , which contains a rigid 1,2-diaminocyclohexane scaffold functionalized with two acetate and two picolinate pendant arms, reveal the formation of stable complexes [log K LaL = 17.82(1) and log K YbL = 19.65(1)]. Luminescence studies on the Eu 3+ and Tb 3+ analogues evidenced rather high emission quantum yields of 3.4 and 11%, respectively. The emission lifetimes recorded in H 2 O and D 2 O solutions indicate the presence of a water molecule coordinated to the metal ion. 1 H nuclear magnetic relaxation dispersion profiles and 17 O NMR chemical shift and relaxation measurements point to a rather low water exchange rate of the coordinated water molecule ( k ex 298 = 1.58 × 10 6 s -1 ) and relatively high relaxivities of 5.6 and 4.5 mM -1 s -1 at 20 MHz and 25 and 37 °C, respectively. Density functional theory calculations and analysis of the paramagnetic shifts induced by Yb 3+ indicate that the complexes adopt an unprecedented cis geometry with the two picolinate groups situated on the same side of the coordination sphere. Dissociation kinetics experiments were conducted by investigating the exchange reactions of LuL occurring with Cu 2+ . The results confirmed the beneficial effect of the rigid cyclohexyl group on the inertness of the Lu 3+ complex. Complex dissociation occurs following proton- and metal-assisted pathways. The latter is relatively efficient at neutral pH, thanks to the formation of a heterodinuclear hydroxo complex.

Introduction: Although the diversity in orthopaedic residency programs has been studied, the diversity within academic orthopaedics has not., Methods: The board of specialty societies, five leading journals and the National Institutes of Health RePORTER tool, and three accreditation organizations were explored., Results: The board of directors comprised 220 (72%) Caucasians, 36 (12%) Asians, 4 (1%) Hispanic/Latinos, 29 (9%) African Americans, and 18 (6%) Other individuals; 250 (81%) were men, and 57 (19%) were women. The editorial boards comprised 288 (77%) Caucasians, 62 (16%) Asians, 14 (4%) Hispanic/Latinos, 8 (2%) African Americans, and 4 (1%) Other individuals; 341 (91%) were men, and 35 (9%) were women. The National Institutes of Health grant recipients comprised 117 (64%) Caucasians, 58 (32%) Asians, 4 (2%) Hispanic/Latinos, and 3 (2%) African Americans; 128 (70%) were men, and 54 (30%) were women. On average, Caucasians, Asians, Hispanic/Latinos, and African Americans received $776,543, $439,600, $420,182, and $494,049, respectively. On average, men and women received $759,426 and $419,518, respectively. The accreditation boards comprised 45 (82%) Caucasians, 6 (11%) Asians, and 4 (7%) African Americans; 45 (82%) were men, and 10 (18%) were women., Conclusions: Academic orthopaedic surgery does not resemble the United States. Residency, fellowship committees, and professional organization boards need to become aware of these disparities., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Orthopaedic Surgeons.)

Background: Diversity and inclusion are critical to providing the best possible health care. Previous studies have shown that diversity among physicians increases cultural competency, which in turn enhances the quality of care provided and increases minoritized patients' participation in decisions regarding their health care. However, physician diversity in both race and sex is lacking in orthopaedic surgery. This study seeks to determine the sex and racial diversity in the membership and leadership of the Pediatric Orthopaedic Society of North America (POSNA)., Methods: POSNA membership and leadership were reviewed for the years 2010, 2015, and 2020. This data was gathered from membership directories and committee reference books. All North American Active Members' race/ethnicity and sex were recorded for each year. The categories for race/ethnicity are Caucasian, East/South/Middle Eastern Asian American (Asian), Hispanic/Latin/South American (HLSA), and African American., Results: From 2010 to 2020, Active Members of POSNA increased from 608 to 818, and the percentage of female (14.6% to 23.7%), Asian (7.4% to 11.2%), HLSA (2.5% to 2.9%), and African American membership (1.6% to 1.8%) increased. Male (85.4% to 76.3%) and Caucasian (88.5% to 84.0%) membership decreased. From 2010 to 2020, male leadership decreased on both the Board of Directors and Committee Chairs (89.5% to 81.8% and 86.4% to 64.7%, respectively), as did Caucasians (94.7% to 81.8% and 90.9% to 88.2%, respectively). The number of Asian members holding positions on both the Board of Directors and Committee Chairs increased (0% to 18.2% and 4.5% to 11.8%, respectively) as did the number of females (10.5% to 18.2% and 13.6% to 35.3%, respectively). HLSA and African American members were proportionally represented in leadership for the years 2010 and 2015., Conclusions: Membership in POSNA has increased between 2010 to 2020 for every diversity category examined and POSNA membership exhibits significantly more diversity than the orthopaedic specialty as a whole. Leadership as a whole is more diverse in 2020 than it was in 2010., Level of Evidence: Level II-retrospective., Competing Interests: S.C.P. reports grants from Pediatric Orthopaedic Society of North America, personal fees from Medtronic Inc., personal fees from Stryker Inc., grants from Orthopaedic Research and Education Foundation, all outside and unrelated to the submitted work. The remaining authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Stereotactic body radiation therapy is increasingly used in the treatment of early-stage lung cancers. Guidelines provide indications regarding the constraints to the organs at risk (OARs) and the minimum coverage of the planning target volume but do not suggest optimal dose distribution. Data on dose distribution from the different published series are not comparable due to different prescription modalities and reported dose parameters., Methods: We conducted a review of the published data on dose prescription, focusing on the role of homogeneity on local tumor control, and present suggestions on how to specify and report the prescriptions to permit comparisons between studies or between cases from different centers., Conclusions: To identify the dose-prescription modality that better correlates with oncologic outcomes, future studies should guarantee a close uniformity of dose distribution between cases and complete dose parameters reporting for treatment volumes and OARs.

Purpose: To investigate the performance of various algorithms for deformable image registration (DIR) for propagating regions of interest (ROIs) using multiple commercial platforms, from computed tomography to cone beam computed tomography (CBCT) and megavoltage computed tomography., Methods and Materials: Fourteen institutions participated in the study using 5 commercial platforms: RayStation (RaySearch Laboratories, Stockholm, Sweden), MIM (Cleveland, OH), VelocityAI and SmartAdapt (Varian Medical Systems, Palo Alto, CA), and ABAS (Elekta AB, Stockholm, Sweden). Algorithms were tested on synthetic images generated with the ImSimQA (Oncology Systems Limited, Shrewsbury, UK) package by applying 2 specific deformation vector fields (DVF) to real head and neck patient datasets. On-board images from 3 systems were used: megavoltage computed tomography from Tomotherapy and 2 kinds of CBCT from a clinical linear accelerator. Image quality of the system was evaluated. The algorithms' accuracy was assessed by comparing the DIR-mapped ROIs returned by each center with those of the reference, using the Dice similarity coefficient and mean distance to conformity metrics. Statistical inference on the validation results was carried out to identify the prognostic factors of DIR performance., Results: Analyzing 840 DIR-mapped ROIs returned by the centers, it was demonstrated that DVF intensity and image quality were significant prognostic factors of DIR performance. The accuracy of the propagated contours was generally high, and acceptable DIR performance can be obtained with lower-dose CBCT image protocols., Conclusions: The performance of the systems proved to be image quality specific, depending on the DVF type and only partially on the platforms. All systems proved to be robust against image artifacts and noise, except the demon-based software., (Copyright © 2019 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

The chronic mild stress (CMS) paradigm is the most frequently investigated animal model for major depression. The hypothalamic-pituitary-adrenal (HPA) axis participates in the generation of depressive symptomatology. We examined whether the depression-like state induced by CMS is associated with immediate changes in HPA axis activation in response to a novel acute stress and whether this response could be modified by hormonal status. Adult female Wistar rats were ovariectomized and received estrogen or vehicle pellets. After 2 weeks, rats were subjected to CMS (or control) conditions for 2.5 or 4.5 weeks. Rats were subsequently subjected to restraint stress for 1 h, and plasma corticosterone (CT) levels were determined before (2:00 p.m.) and after acute stress induction (3:00 and 4:00 p.m.). CT levels and FOS expression were measured in the medial parvocellular subdivision of the PVN (PaMP), central (CeA) and medial amygdala (MeA) and ventral subiculum of the hippocampus (vSub). Plasma CT levels in animals treated with 6.5 weeks of estrogen were elevated before and 1 h after restraint stress induction. Results indicate that the estrogen chronicity and CMS exposure impacted CT secretion. Neuronal PaMP, CeA, MeA and vSub activity decreased after 4.5 weeks of CMS in all groups. No differences were detected between CMS and non-CMS groups. These data suggest that the HPA central hyporesponsiveness observed in the experimental groups subjected to a longer protocol period was independent to CMS paradigm and estrogen treatment restored partially its activity. These data suggest that additional stressors could be responsible for the observed alterations of the HPA axis., (Copyright © 2019. Published by Elsevier B.V.)

Vasopressinergic neurones of the supraoptic (SON) and paraventricular (PVN) nuclei express oestrogen receptor (ER)β and receive afferent projections from osmosensitive neurones that express ERα. However, which subtype of these receptors mediates the effects of oestradiol on vasopressin (AVP) secretion induced by hydromineral challenge has not yet been demonstrated in vivo. Moreover, AVP secretion induced by hyperosmolality is known to involve activation of TRPV1 (transient receptor potential vanilloid, member 1) in magnocellular neurones, although whether oestradiol modulates expression of this receptor is unknown. Thus, the present study aimed to clarify the mechanisms involved in the modulation exerted by oestradiol on AVP secretion, specifically investigating the involvement of ERβ, ERα and TRPV1 receptors in response to water deprivation (WD). We observed that treatment with an ERβ agonist potentiated AVP secretion and vasopressinergic neuronal activation induced by WD. This increase in AVP secretion induced by WD was reversed by an ERβ antagonist. By contrast to ERβ, the ERα agonist did not alter plasma AVP concentrations or activation of AVP neurones in the SON and PVN. Additionally, Fos expression in the subfornical organ was not altered by the ERα agonist. TRPV1 mRNA expression was increased by WD in the SON, although this response was not altered by any treatment. The results of the present study suggest that ERβ mediates the effects of oestradiol on AVP secretion in response to WD, indicating that the effects of oestradiol occur directly in AVP neurones without affecting TRPV1., (© 2019 British Society for Neuroendocrinology.)

Herein we report on the synthesis, characterization and the ensuing chemistry of iminophosphorane palladacycles. Treatment of Ph3P[double bond, length as m-dash]N-(2-OHC6H4), 1, with sodium tetrachloropalladate gives 2 with the ligand as terdentate [C,N,O] allowing for only one μ-Cl ligand bonding the metal centers, resulting in a dinuclear complex. Treatment of 2 with PPh3 gives the mononuclear complex 3, whereas the reaction of 2 with diphosphanes Ph2P(CH2)nPPh2 in 1 : 2 ratio gives mixtures of 4 and 5 (n = 2) and 6 and 7 (n = 3). From them, the mononuclear complexes 4 and 6, and the dinuclear compounds, 5 and 7, were obtained with the parent ligand as bidentate [C,N]. The former two are of zwitterionic nature void of any counterion, with the phosphane ligand in the chelating mode. In a remarkable case of chemical serendipity, a solution of 2 left to stand produced crystals of complex 8: this is the missing link in the series of triphenylphosphane chalcogenide metallacycles. The experiment is repeatable; however, direct metallation of triphenylphosphane oxide was not possible.

In the world of science, in particular the section concerning the field of chemistry, when the results encountered during the experiment do not meet our expectations, our shrewdness may play an important role to open up new unexplored fields that could be much more interesting than what we were seeking. In those cases, our research undergoes an unforeseen shift, delivering novel and challenging results that may altogether alter our point of view and our future work. We have then struck serendipity. Specifically, in our investigation linked to palladacycles we have found that the new trends in their reactivity, as well as in their structure, have been, in many cases, related to this experience, broadening our research scope within this field. Herein, we describe our most relevant findings, which have shed new light upon the reactivity of palladacycles, thus opening new routes that lead to novel unexpected structures.

Introduction: VATS wedge resection can require conversion to thoracotomy when pulmonary lesions cannot be identified. Hybrid operating rooms (HORs) provide real-time image acquisition capabilities allowing the intraoperative placement of markers to facilitate the removal of non-palpable nodules during VATS., Objectives: To present our workflow based on the alternative use of two different markers according to the location of the lung lesion and report our initial results., Methods: All consecutive patients with non-palpable lesions requiring VATS wedge resection underwent localization of the targets in HOR. Lesions were considered non-palpable if they were small (<1 cm), deep (>1 cm from surface), subsolid, or located within a dystrophic area. Anesthetized patients were placed in lateral decubitus. Cone-beam CT (CBCT) was performed, and the needle trajectory was planned using Syngo iGuide Needle Guidance. Metal hook-wire or coil was placed, according to our workflow, close to the lesion and their position was verified by CBCT or fluoroscopy., Results: Eleven VATS wedge resections were performed in 10 patients with 12 non-palpable lesions. The localization was performed with seven hook-wires and four coils in 30 minutes (range 17-56 minutes). The median estimated total effective dose was 11.6 mSv (range 1.9-24.7 mSv). Eleven lesions were removed by VATS, and one deep nodule required a thoracotomy. No complications were observed., Conclusions: Our experience confirms that HOR is suitable for simultaneous localization and VATS resection of 'difficult' pulmonary lesions. A versatile approach, using different devices, seems advisable for the removal of targets in every clinical scenario, reducing the VATS conversion rate., (© 2017 John Wiley & Sons Ltd.)

Palladacycles of the type [Pd 2 (Ph 2 PCH 2 PPh 2 -P,P) 2 (C,N:C,N)] (C,N:C,N = bis(N-2,3,4-trimethoxybenzylidene)-4,4'-sulfonyldianiline or -4,4'-oxydianiline) can undergo a spontaneous slow chelate-to-bridging diphosphane coordination shift in solution. Following this strategy a tailor-made synthetic procedure was devised that culminates in isolation of double A-frame tetranuclear palladium complexes.

Purpose: To investigate the performance of various algorithms for deformable image registration (DIR) to propagate regions of interest (ROIs) using multiple commercial platforms., Methods and Materials: Thirteen institutions participated in the study with six commercial platforms: RayStation (RaySearch Laboratories, Stockholm, Sweden), MIM (Cleveland, OH, USA), VelocityAI and Smart Adapt (Varian Medical Systems, Palo Alto, CA, USA), Mirada XD (Mirada Medical Ltd, Oxford, UK), and ABAS (Elekta AB, Stockholm, Sweden). The DIR algorithms were tested on synthetic images generated with the ImSimQA package (Oncology Systems Limited, Shrewsbury, UK) by applying two specific Deformation Vector Fields (DVF) to real patient data-sets. Head-and-neck (HN), thorax, and pelvis sites were included. The accuracy of the algorithms was assessed by comparing the DIR-mapped ROIs from each center with those of reference, using the Dice Similarity Coefficient (DSC) and Mean Distance to Conformity (MDC) metrics. Statistical inference on validation results was carried out in order to identify the prognostic factors of DIR performances., Results: DVF intensity, anatomic site and participating center were significant prognostic factors of DIR performances. Sub-voxel accuracy was obtained in the HN by all algorithms. Large errors, with MDC ranging up to 6 mm, were observed in low-contrast regions that underwent significant deformation, such as in the pelvis, or large DVF with strong contrast, such as the clinical tumor volume (CTV) in the lung. Under these conditions, the hybrid DIR algorithms performed significantly better than the free-form intensity based algorithms and resulted robust against intercenter variability., Conclusions: The performances of the systems proved to be site specific, depending on the DVF type and the platforms and the procedures used at the various centers. The pelvis was the most challenging site for most of the algorithms, which failed to achieve sub-voxel accuracy. Improved reproducibility was observed among the centers using the same hybrid registration algorithm., (© 2017 American Association of Physicists in Medicine.)

The potential of 15-crown-5 ethers to link large cations, such as potassium, is limited by the quasi-parallel arrangement of two oxygen donor moieties upon appropriate orientation of the corresponding ether-ring-containing molecules. Substrates bearing the two crown ethers that are capable of achieving such coordination are hitherto unknown. The synthesis and isolation of a tailor-made dinuclear palladacycle bearing 15-crown-5 ether rings on the metallated phenyls offers such a possibility, providing the adequate environment for the formation of the sandwiched [K(metallacycle-15-crown-5) 2 ] moiety. This synthetic strategy also culminates in the isolation of the first palladacycle able to entrap a potassium cation through bonding to two 15-crown-5 ether rings in a single molecule., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Herein we report a Suzuki-Miyaura type cross-coupling between an aryl halide and a functionalized boronic acid palladacycle in the absence of an external catalyst. This reaction is an unprecedented case of catalysis in palladium metallacycle chemistry.

Aim: To investigate the prognostic role of invariant natural killer T (iNKT) cells and antibody-dependent cell-mediated cytotoxicity (ADCC) in wild type KRAS metastatic colorectal cancer (mCRC) patients treated with cetuximab., Methods: Forty-one KRAS wt mCRC patients, treated with cetuximab and irinotecan-based chemotherapy in II and III lines were analyzed. Genotyping of single nucleotide polymorphism (SNP)s in the FCGR2A, FCGR3A and in the 3' untranslated regions of KRAS and mutational analysis for KRAS, BRAF and NRAS genes was determined either by sequencing or allelic discrimination assays. Enriched NK cells were obtained from lymphoprep-peripheral blood mononuclear cell and iNKT cells were defined by co-expression of CD3, TCRVα24, TCRVβ11. ADCC was evaluated as ex vivo NK-dependent activity, measuring lactate dehydrogenase release., Results: At basal, mCRC patients performing ADCC activity above the median level (71%) showed an improved overall survival (OS) compared to patients with ADCC below (median 16 vs 8 mo; P = 0.026). We did not find any significant correlation of iNKT cells with OS (P = 0.19), albeit we observed a trend to a longer survival after 10 mo in patients with iNKT above median basal level (0.382 cells/microliter). Correlation of OS and progression-free survival (PFS) with interesting SNPs involved in ADCC ability revealed not to be significant. Patients carrying alleles both with A in FCGR2A and TT in FCGR3A presented a trend of longer PFS (median 9 vs 5 mo; P = 0.064). Chemotherapy impacted both iNKT cells and ADCC activity. Their prognostic values get lost when we analysed them after 2 and 4 mo of treatment., Conclusion: Our results suggest a link between iNKT cells, basal ADCC activity, genotypes in FCGR2A and FCGR3A, and efficacy of cetuximab in KRAS wt mCRC patients.