Immunogenicity of mRNA vs. BBV152 vaccine boosters against Omicron subvariants: Final results from Phase B of the PRIBIVAC study, a randomized clinical trial.

BACKGROUND: BBV152 (Covaxin™) is a whole-virion inactivated SARS-CoV-2 vaccine mixed with an immune adjuvant. We aimed to compare immune responses after booster vaccination with heterologous BBV152 versus homologous mRNA vaccine. METHODS: We conducted a randomized, participant-blinded, controlled trial. Fifty mRNA-vaccinated participants were enrolled and randomized to receive an mRNA booster (n = 26) or BBV152 (n = 24). Blood samples were collected pre-vaccination, and at Day 7, 28, 180 and 360 post-booster for analysis of humoral and cellular immune responses. Primary end point was the SARS-CoV-2 anti-spike antibody titer at day 28. RESULTS: Recruitment began in January 2022 and was terminated early due to the BBV152 group meeting pre-specified criteria for futility. At Day 28 post-boost, mean SARS-CoV-2 spike antibody titers were lower with BBV152 (2004 IU/mL; 95 % confidence interval [CI], 1132-3548) vs mRNA (26,669 IU/mL; 95 % CI, 21,330-33,266; p < 0.0001), but comparable levels of spike-specific CD4 and cytotoxic T-cells were observed. Anti-spike antibody titers remained significantly different at Day 180: BBV152 4467 IU/mL (95 % CI, 1959-10,186) vs mRNA 20,749 IU/mL (95 % CI, 12,303-35,075; p = 0.0017). Levels of surrogate virus neutralizing antibodies against ancestral and Omicron subvariants BA.1 and BA.2 were significantly higher among mRNA recipients at Day 180, including after adjusting for intercurrent infection. By Day 360, anti-spike antibody titers and neutralizing antibody levels against Omicron subvariants became similar between vaccine groups. By the end of the study, 16 in each arm (mRNA 64 % and BBV152 69.6 %) had breakthrough infections and time to COVID-19 infection between vaccine groups were similar (p = 0.63). CONCLUSIONS: Wild-type SARS-CoV-2 anti-spike antibody titer and surrogate virus neutralizing test levels against wild-type SARS-CoV-2 and Omicron subvariants BA.1/BA.2/BA.5 were significantly higher at Day 28 and 180 in individuals who received booster vaccination with an mRNA vaccine compared with BBV152. CLINICAL TRIAL REGISTRATION NUMBER: NCT05142319.

Direct observation of arene⋯sulphur dioxide interaction: role of metal ions in electronic modulation for binding and activation.

In the quest to understand biologically relevant interactions of environmentally detrimental SO2 with host molecules to modulate the electronic properties of the binding sites, we have directly observed the lone pair⋯π interaction between the aromatic ring and nucleophilic O of SO2 (3.11 Å), for the first time to the best of our knowledge, in addition to the interaction between electrophilic S of SO2 and metal-bound thiolate (2.63 Å).

First SARS-CoV-2 Omicron infection as an effective immune booster among mRNA vaccinated individuals: final results from the first phase of the PRIBIVAC randomised clinical trial.

BACKGROUND: Understanding how SARS-CoV-2 breakthrough infections impacts the breadth of immune responses against existing and pre-emergent SARS-CoV-2 strains is needed to develop an evidence-based long-term immunisation strategy. METHODS: We performed a randomised, controlled trial to assess the immunogenicity of homologous (BNT162b2) versus heterologous (mRNA-1273) booster vaccination in 100 BNT162b2-vaccinated infection-naïve individuals enrolled from October 2021. Post hoc analysis was performed to assess the impact of SARS-CoV-2 infection on humoral and cellular immune responses against wild-type SARS-CoV-2 and/or Omicron subvariants. FINDINGS: 93 participants completed the study at day 360. 71% (66/93) of participants reported first SARS-CoV-2 Omicron infection by the end of the study with similar proportions of infections between homologous and heterologous booster groups (72.3% [34/47] vs 69.6% [32/46]; p = 0.82). Mean wildtype SARS-CoV-2 anti-S-RBD antibody level was significantly higher in heterologous booster group compared with homologous group at day 180 (14,588 IU/mL; 95% CI, 10,186-20,893 vs 7447 IU/mL; 4646-11,912; p = 0.025). Participants who experienced breakthrough infections during the Omicron BA.1/2 wave had significantly higher anti-S-RBD antibody levels against wildtype SARS-CoV-2 and antibody neutralisation against BA.1 and pre-emergent BA.5 compared with infection-naïve participants. Regardless of hybrid immunity status, wildtype SARS-CoV-2 anti-S-RBD antibody level declined significantly after six months post-booster or post-SARS-CoV-2 infection. INTERPRETATION: Booster vaccination with mRNA-1273 was associated with significantly higher antibody levels compared with BNT162b2. Antibody responses are narrower and decline faster among uninfected, vaccinated individuals. Boosters may be more effective if administered shortly before infection outbreaks and at least six months after last infection or booster. FUNDING: Singapore NMRC, USFDA, MRC.

Structural basis for CCR6 modulation by allosteric antagonists.

The CC chemokine receptor 6 (CCR6) is a potential target for chronic inflammatory diseases. Previously, we reported an active CCR6 structure in complex with its cognate chemokine CCL20, revealing the molecular basis of CCR6 activation. Here, we present two inactive CCR6 structures in ternary complexes with different allosteric antagonists, CCR6/SQA1/OXM1 and CCR6/SQA1/OXM2. The oxomorpholine analogues, OXM1 and OXM2 are highly selective CCR6 antagonists which bind to an extracellular pocket and disrupt the receptor activation network. An energetically favoured U-shaped conformation in solution that resembles the bound form is observed for the active analogues. SQA1 is a squaramide derivative with close-in analogues reported as antagonists of chemokine receptors including CCR6. SQA1 binds to an intracellular pocket which overlaps with the G protein site, stabilizing a closed pocket that is a hallmark of inactive GPCRs. Minimal communication between the two allosteric pockets is observed, in contrast to the prevalent allosteric cooperativity model of GPCRs. This work highlights the versatility of GPCR antagonism by small molecules, complementing previous knowledge of CCR6 activation, and sheds light on drug discovery targeting CCR6.

Expedient, regioselective C-H chalcogenation of 3,4-dihydro-1,4-benzoxazines using a palladium-copper catalyst.

The palladium-catalysed regioselective C-H chalcogenation of benzoxazines with disulfides and diselenides in air has been described. In this protocol, palladium acetate serves as the catalyst in conjunction with copper as an oxidizing agent. Through this approach, a wide array of sulfenylation and selenylation reactions of benzomorpholines have been effected, yielding results ranging from good to excellent. Thus, the established procedure demonstrates superb regioselectivity and a strong tolerance towards various functional groups and is suitable for gram-scale synthesis. Additionally, this synthetic approach offers a practical and convenient pathway for late-stage functionalization leading to the Rosenmund-von Braun reaction.

Pharmacokinetics of a topical application of moxidectin in bare-nosed wombats (Vombatus ursinus).

Sarcoptic mange is a debilitating disease that affects bare-nosed wombats (Vombatus ursinus). One of the drugs currently used for treatment is moxidectin, as it has a relatively high efficacy against endo and ectoparasites and side effects are uncommon in domestic species, thus it is considered a relatively safe drug to use at the recommended doses. Developing further understanding of the pharmacokinetics of moxidectin will aid in developing treatment regimens for sarcoptic mange in wombats. Here we analyzed the pharmacokinetic parameters of using 100 ml of moxidectin (5 g/l) applied topically. We found that mean peak plasma concentration was 0.50 ng/ml and half-life was 8 days. Moxidectin was excreted in scats with the mean peak concentration of 2461.43 ng/g (on a dry matter basis). Our study has provided the pharmacokinetic parameters of a commonly used treatment for sarcoptic mange in wombats. There were no adverse side effects recorded in the wombats after applying moxidectin topically. This study replicated real-world conditions using topical application on free-living wombats. The relatively low plasma concentration suggests the drug is not accumulating in the blood stream and is excreted via scats.

Synthesis and characterization of organoselenium based BODIPY and its application in living cells.

Phenylselenide based BODIPY probe was successfully synthesized and characterized by NMR spectroscopic techniques (1H, 13C and 77Se NMR), mass spectrometry and single crystal XRD. Surprisingly, crystal packing diagram of the probe showed formation of 1-D strip through intermolecular F---H interaction. The probe was screened with various Reactive Oxygen Species (ROS) and found to be selective for superoxide ion over other ROS via "turn-on" fluorescence response. The probe selectively and sensitively detects superoxide with a lower detection limit (43.34 nM) without interfering with other ROS. The quantum yield of the probe was found to increase from 0.091 % to 30.4 % (334-fold) after oxidation. Theoretical calculations (DFT and TD-DFT) were also performed to understand the sensing mechanism of the probe. The probe was able to effectively detect superoxide inside living cells without any toxic effect.

Syntheses, characterizations, crystal structures and Hirshfeld surface analyses of methyl 4-[4-(di-fluorometh-oxy)phen-yl]-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexa-hydro-quinoline-3-carboxyl-ate, isopropyl 4-[4-(di-fluoro-meth-oxy)phen-yl]-2,6,6-trimethyl-5-oxo-1,4,5,6,7,8-hexa-hydro-quinoline-3-carboxyl-ate and tert-butyl 4-[4-(di-fluoro-meth-oxy)phen-yl]-2,6,6-trimethyl-5-oxo-1,4,5,6,7,8-hexa-hydro-quinoline-3-carboxyl-ate.

The crystal structures and Hirshfeld surface analyses of three similar compounds are reported. Methyl 4-[4-(di-fluoro-meth-oxy)phen-yl]-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexa-hydro-quinoline-3-carboxyl-ate, (C21H23F2NO4), (I), crystallizes in the monoclinic space group C2/c with Z = 8, while isopropyl 4-[4-(di-fluoro-meth-oxy)phen-yl]-2,6,6-trimethyl-5-oxo-1,4,5,6,7,8-hexa-hydro-quinoline-3-carb-oxyl-ate, (C23H27F2NO4), (II) and tert-butyl 4-[4-(di-fluoro-meth-oxy)phen-yl]-2,6,6-trimethyl-5-oxo-1,4,5,6,7,8-hexa-hydro-quinoline-3-carboxyl-ate, (C24H29F2NO4), (III) crystallize in the ortho-rhom-bic space group Pbca with Z = 8. In the crystal structure of (I), mol-ecules are linked by N-H⋯O and C-H⋯O inter-actions, forming a tri-periodic network, while mol-ecules of (II) and (III) are linked by N-H⋯O, C-H⋯F and C-H⋯π inter-actions, forming layers parallel to (002). The cohesion of the mol-ecular packing is ensured by van der Waals forces between these layers. In (I), the atoms of the 4-di-fluoro-meth-oxy-phenyl group are disordered over two sets of sites in a 0.647 (3): 0.353 (3) ratio. In (III), the atoms of the dimethyl group attached to the cyclo-hexane ring, and the two carbon atoms of the cyclo-hexane ring are disordered over two sets of sites in a 0.646 (3):0.354 (3) ratio.

Differences in maternal-newborn ABO blood groups and risk of serious infant infection.

BACKGROUND: During pregnancy, various maternal IgG antibodies are transferred to the developing fetus, some of which may protect the newborn against infection. If a mother and her fetus have different A, B or O (ABO) blood groups, then transferred maternal antibodies may plausibly protect the infant against infection. AIM: To determine if maternal-newborn ABO blood group incongruence vs. congruence is associated with a lower risk of serious infection in the infant. DESIGN: Retrospective population-based cohort. METHODS: We used linked patient-level datasets for all singleton hospital livebirths from 2008 to 2022 in Ontario, Canada, with known maternal and newborn ABO blood groups. We used a dichotomous exposure state, either ABO blood group congruent (N = 114 507) or incongruent (N = 43 074). The main outcome of interest was the risk of serious infant infection within 27 days, and from 28 to 365 days, after birth. Cox proportional hazard models generated hazard ratios and 95% confidence intervals, and were adjusted for maternal age, world region of origin, residential income quintile and gestational age at birth. RESULTS: Relative to maternal-newborn congruency, incongruent ABO blood group was associated with an adjusted hazard ratio of 0.88 (95% CI: 0.80-0.97) for serious neonatal infection within 27 days of birth, and 0.93 (95% CI: 0.90-0.96) for serious infection between 28 and 365 days after birth. CONCLUSIONS: Maternal-newborn ABO incongruence may be associated with a lower relative risk of a serious infant infection within 27 days, and from 28 to 365 days, after birth.

Synthesis, characterization, and cancer cell-selective cytotoxicity of mixed-ligand cobalt(III) complexes of 8-hydroxyquinolines and phenanthroline bases.

Transition metal complexes exhibiting selective toxicity towards a broad range of cancer types are highly desirable as potential anticancer agents. Herein, we report the synthesis, characterization, and cytotoxicity studies of six new mixed-ligand cobalt(III) complexes of general formula [Co(B)2(L)](ClO4)2 (1-6), where B is a N,N-donor phenanthroline base, namely, 1,10-phenanthroline (phen in 1, 2), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq in 3, 4), and dipyrido[3,2-a:2',3'-c]phenazine (dppz in 5, 6), and L is the monoanion of 8-hydroxyquinoline (HQ in 1, 3, 5) and 5-chloro-7-iodo-8-hydroxyquinoline (CQ in 2, 4, 6). The X-ray single crystal structures of complexes 1 and 2 as PF6- salts revealed a distorted octahedral CoN5O coordination environment. Complexes demonstrated good stability in an aqueous buffer medium and in the presence of ascorbic acid as a reductant. Cytotoxicity studies using a panel of nine cancer cell lines showed that complex 6, with the dppz and CQ ligands, was significantly toxic against most cancer cell types, yielding IC50 values in the range of 2 to 14 µM. Complexes 1, 3, and 5, containing the HQ ligand, displayed lower toxicity compared to their CQ counterparts. The phenanthroline complexes demonstrated marginal toxicity towards the tested cell lines, while the dpq complexes exhibited moderate toxicity. Interestingly, all complexes demonstrated negligible toxicity towards normal HEK-293 kidney cells (IC50 > 100 µM). The observed cytotoxicity of the complexes correlated well with their lipophilicities (dppz > dpq > phen). The cytotoxicity of complex 6 was comparable to that of the clinical drug cisplatin under similar conditions. Notably, neither the HQ nor the CQ ligands alone demonstrated noticeable toxicity against any of the tested cell lines. The Annexin-V-FITC and DCFDA assays revealed that the cell death mechanism induced by the complexes involved apoptosis, which could be attributed to the metal-assisted generation of reactive oxygen species. Overall, the dppz complex 6, with its remarkable cytotoxicity against a broad range of cancer cells and negligible toxicity toward normal cells, holds significant potential for cancer chemotherapeutic applications.

Hydrogen-bonding interactions in 5-fluorocytosine-urea (2/1), 5-fluorocytosine-5-fluorocytosinium 3,5-dinitrosalicylate-water (2/1/1) and 2-amino-4-chloro-6-methylpyrimidine-6-chloronicotinic acid (1/1).

Three new compounds, namely, 5-fluorocytosine-urea (2/1), 2C4H4FN3O·CH4N2O, (I), 5-fluorocytosine-5-fluorocytosinium 3,5-dinitrosalicylate-water (2/1/1), 2C4H4FN3O·C4H5FN3O+·C7H2N2O7-·H2O, (II), and 2-amino-4-chloro-6-methylpyrimidine-6-chloronicotinic acid (1/1), C6H4ClNO2·C5H6ClN3, (III), have been synthesized and characterized by single-crystal X-ray diffraction. In compound (I), 5-fluorocytosine (5FC) molecules A and B form two different homosynthons [R22(8) ring motif], one formed via N-H...O hydrogen bonds and the second via N-H...N hydrogen bonds. In addition to this interaction, a sequence of fused-ring motifs [R21(6), R33(8), R22(8), R43(10) and R22(8)] are formed, generating a supramolecular ladder-like hydrogen-bonded pattern. In compound (II), 5FC and 5-fluorocytosinium are linked by triple hydrogen bonds, generating two fused-ring motifs [R22(8)]. The neutral 5FC and protonated 5-fluorocytosinum cation form a dimeric synthon [R22(8) ring motif] via N-H...O and N-H...N hydrogen bonds. On either side of the dimeric synthon, the neutral 5FC, 5-fluorocytosinium cation, 3,5-dinitrosalicylate anion and water molecule are hydrogen bonded through N-H...O, N-H...N, N-H...OW and OW-HW...O hydrogen bonds, forming a large ring motif [R1010(56)], leading to a three-dimensional supramolecular network. In compound (III), 2-amino-4-chloro-6-methylpyrimidine (ACP) interacts with the carboxylic acid group of 6-chloronicotinic acid via N-H...O and O-H...O hydrogen bonds, generating an R22(8) primary ring motif. Furthermore, the ACP molecules form a base pair via N-H...N hydrogen bonds. The primary motif and base pair combine to form tetrameric units, which are further connected by Cl...Cl interactions. In addition to this hydrogen-bonding interaction, compounds (I) and (III) are further enriched by π-π stacking interactions.

Chemistry of a series of heterobimetallic complexes MnIII2(CaII/SrII)X2 (X = Cl-, Br-).

This manuscript describes the syntheses, structures and magnetism of MnIII-CaII/SrII complexes which are compositionally relevant in the context of the oxygen evolving complex (OEC) of photosystem II (PS II). A series of trimetallic tetraoxo complexes containing redox-inactive metal ions CaII or SrII were synthesized using a tetranucleating ligand framework. The structural characteristics of these complexes, with the oxido ligands bridging the redox-inactive metals and the manganese centres, make them particularly relevant to biological and heterogeneous metal-oxido clusters. Electrochemical studies of these compounds show that the reduction potentials are highly dependent upon the Lewis acidity of the redox-inactive metal, identifying the chemical basis for the observed differences in electrochemistry. This correlation provides insights into the role of the CaII/SrII ion in modulating the redox potential of the OEC and of other redox-inactive ions in tuning the redox potentials of other metal-oxide electrocatalysts. Temperature dependent magnetic measurements have also been performed for the complexes.

Neuromodulation for Craniofacial Pain and Headaches.

Headaches and facial pain are highly prevalent diseases but are often difficult to treat. Though there have been significant advances in medical management, many continue to suffer from refractory pain. Neuromodulation has been gaining interest for its therapeutic purposes in many chronic pain conditions, including headaches and facial pain. There are many potential targets of neuromodulation for headache and facial pain, and some have more robust evidence in favor of their use than others. Despite the need for more high-quality research, the available evidence for the use of neuromodulation in treating headaches and facial pain is promising. Considering the suffering that afflicts patients with intractable headache, neuromodulation may be an appropriate tool to improve not only pain but also disability and quality of life.

Disentangling the trajectories of maternal depressive symptoms and partnership problems in the transition to parenthood and their impact on child adjustment difficulties.

Maternal perinatal depression (PND) and partnership problems have been identified to influence the development of later child adjustment difficulties. However, PND and partnership problems are closely linked which makes it difficult to draw conclusions about the exact transmission pathways. The aim of the present study was to investigate to what extent PND symptoms and partnership problems influence each other longitudinally and to examine the influence of their trajectories on child adjustment difficulties at the age of three. Analyses were based on publicly available data from the German family panel "pairfam". N = 354 mothers were surveyed on depressive symptoms and partnership problems annually from pregnancy (T0) until child age three (T4). Child adjustment difficulties were assessed at age three. Results of latent change score modeling showed that partnership problems predicted change in PND symptoms at T0 and T3 while PND symptoms did not predict change in partnership problems. Child adjustment difficulties at age three were predicted by PND symptoms, but not by partnership problems. Partnership problems predicted externalizing, but not internalizing symptoms. Results underline the effects of family factors for the development of child adjustment difficulties and emphasize the importance of early interventions from pregnancy onwards.

Synthesis, crystal structure, Hirshfeld surface analysis, DFT and NBO study of ethyl 1-(4-fluoro-phen-yl)-4-[(4-fluoro-phen-yl)amino]-2,6-diphenyl-1,2,5,6-tetra-hydro-pyridine-3-carboxyl-ate.

The title com-pound, C32H28F2N2O2, a highly functionalized tetra-hydro-pyridine, was synthesized by a one-pot multi-com-ponent reaction of 4-fluoro-aniline, ethyl aceto-acetate and benzaldehyde at room temperature using sodium lauryl sulfate as a catalyst. The com-pound crystallizes with two mol-ecules in the asymmetric unit. The tetra-hydro-pyridine ring adopts a distorted boat conformation in both mol-ecules and the dihedral angles between the planes of the fluoro-substituted rings are 77.1 (6) and 77.3 (6)°. The amino group and carbonyl O atom are involved in an intra-molecular N-H⋯O hydrogen bond, thereby generating an S(6) ring motif. In the crystal, mol-ecules are linked by C-H⋯F hydrogen bonds forming a three-dimensional network and C-H⋯π inter-actions. A Hirshfeld surface analysis of the crystal structure indicates that the most important contributions to the crystal packing are from H⋯H (47.9%), C⋯H/H⋯C (30.7%) and F⋯H/H⋯F (12.4%) contacts. The optimized structure calculated using density functional theory (DFT) at the B3LYP/6-311+G(2d,p) level is compared with the experimentally determined molecular structure in the solid state. The HOMO-LUMO behaviour was used to determine the energy gap and the Natural Bond Orbital (NBO) analysis was done to study donor-acceptor interconnections.

Securing maize reproductive success under drought stress by harnessing CO2 fertilization for greater productivity.

Securing maize grain yield is crucial to meet food and energy needs for the future growing population, especially under frequent drought events and elevated CO2 (eCO2) due to climate change. To maximize the kernel setting rate under drought stress is a key strategy in battling against the negative impacts. Firstly, we summarize the major limitations to leaf source and kernel sink in maize under drought stress, and identified that loss in grain yield is mainly attributed to reduced kernel set. Reproductive drought tolerance can be realized by collective contribution with a greater assimilate import into ear, more available sugars for ovary and silk use, and higher capacity to remobilize assimilate reserve. As such, utilization of CO2 fertilization by improved photosynthesis and greater reserve remobilization is a key strategy for coping with drought stress under climate change condition. We propose that optimizing planting methods and mining natural genetic variation still need to be done continuously, meanwhile, by virtue of advanced genetic engineering and plant phenomics tools, the breeding program of higher photosynthetic efficiency maize varieties adapted to eCO2 can be accelerated. Consequently, stabilizing maize production under drought stress can be achieved by securing reproductive success by harnessing CO2 fertilization.

Late-stage Ligand Modification After Coordination Strengthens Stereoselectively Self-Assembled Hemiaminal Ether Complexes.

Fragile hemiaminal ether linkages present in the backbone of koneramines (LR OR'), tridentate ligands, bound to copper(II) in stereoselectively self-assembled syn-[Cu(LR OR')X2 ] complexes were transformed into sturdy methylene linkages to make corresponding rac-[Cu(LR H)Cl2 ] complexes by late-stage ligand modification after coordination with the retention of coordination sphere. The generality of stereoselective self-assembly of koneramine complexes is shown by utilising a number of metal ions, anions, amines, alcohols and thiols with complete characterisations.

Supramolecular interactions in some organic hydrated 2,4,6-triaminopyrimidinium carboxylate and sulfate salts.

Four salts, namely, 2,4,6-triaminopyrimidinium 6-chloronicotinate dihydrate, C4H8N5+·C6H3ClNO2-·2H2O, (I), 2,4,6-triaminopyrimidinediium pyridine-2,6-dicarboxylate dihydrate, C4H9N52+·C7H3NO42-·2H2O, (II), 2,4,6-triaminopyrimidinediium sulfate monohydrate, C4H9N52+·SO42-·H2O, (III), and 2,4,6-triaminopyrimidinium 3,5-dinitrobenzoate dihydrate, C4H8N5+·C7H3N2O6-·2H2O, (IV), were synthesized and characterized by X-ray diffraction techniques. Proton transfer from the corresponding acid to the pyrimidine base has occurred in all four crystal structures. Of the four salts, two [(I) and (IV)] exist as monoprotonated bases and two [(II) and (III)] exist as diprotonated bases. In all four crystal structures, the acid interacts with the pyrimidine base through N-H...O hydrogen bonds, generating an R22(8) ring motif. The sulfate group mimics the role of the carboxylate anions. The water molecules present in compounds (I)-(IV) form water-mediated large ring motifs. The formation of water-mediated interactions in these crystal structures can be used as a model in the study of the hydration of nucleobases. Water molecules play an important role in building supramolecular structures. In addition to these strong hydrogen-bonding interactions, some of the crystal structures are further enriched by aromatic π-π stacking interactions [(I) and (II)].

Minimally invasive colectomies can be performed with similar outcomes to open counterparts for colorectal cancer emergencies: a propensity score matching analysis utilizing ACS-NSQIP.

PURPOSE: The safety and feasibility of minimally invasive surgery (MIS) in the setting of colorectal cancer emergencies have been debated. We sought to compare postoperative outcomes of MIS with open techniques in the setting of colorectal cancer emergencies from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database. METHODS: We included patients undergoing colectomy for colorectal cancer emergency between 2012 and 2019 "2012-2019" from the ACS-NSQIP dataset. We compared short-term morbidity, mortality, short-term oncological outcomes, and secondary outcomes for MIS vs open colectomies using propensity score matching. We then evaluated the trends of MIS versus open colectomies using linear regression analysis. RESULTS: We examined a total of 5544 patients (open n = 4070; MIS n = 1474) and included 1352 patients for our postoperative outcome analyses after propensity score matching 1:1 (open n = 676; MIS n = 676). Within the matched cohort, mortality was significantly higher in the open group (open 6.95% vs MIS 3.99%, OR 1.8, p = 0.023). Anastomotic leak rates were comparable between the  two groups (open 4.46% vs MIS 4.02%, OR 1.12, p = 0.787). Pulmonary complications were significantly higher after open surgery (open 10.06% vs MIS 4.73%, OR 2.25, p < 0.001). Rates of ileus were significantly higher amongst open patients (open 29.08% vs MIS 19.94%, p < 0.001). Patients stayed on average 1 day longer in the hospital after open surgery (p < 0.001). Rates of MIS for early tumors (N0 and T1/T2, n = 289) did not significantly change over 7 years (p = 0.597, rate = - 0.065%/year); however, utilization of MIS for late tumors (N1 or T3/T4, n = 4359) increased by 2.06% per year (p < 0.001). CONCLUSIONS: This study demonstrates that MIS was associated with superior postoperative outcomes compared to open surgery without compromising oncological outcomes in patients undergoing emergency colectomy for colon cancer. Within the matched cohort, MIS was associated with lower rates of mortality, pulmonary complications, ileus, and shorter postoperative length of stay.

Synthesis, crystal structure and Hirshfeld surface analysis of tert-butyl 4-[4-(di-fluoro-meth-oxy)phen-yl]-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexa-hydro-quinoline-3-carboxyl-ate.

The 1,4-di-hydro-pyridine ring of the title compound, C24H29F2NO4, adopts a distorted boat conformation, while the cyclo-hexene ring is in an almost twist-boat conformation. In the crystal, N-H⋯O and C-H⋯O hydrogen bonds as well as C-H⋯π inter-actions connect mol-ecules, forming layers parallel to the (100) plane. These layers are linked by van der Waals forces and C-H⋯F inter-actions, which consolidate the crystal structure. Hirshfeld surface analysis shows the major contributions to the crystal packing are from H⋯H (54.1%), F⋯H/H⋯F (16.9%), O⋯H/H⋯O (15.4%) and C⋯H/H⋯C (12.6%) contacts.