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Variable-temperature single-crystal X-ray diffraction analyses of 1,3-diethyl-spiro[imidazolidine-2,2'-[2H]indene]-1',3'-dione (1) were performed at low temperatures. The temperature dependence of the cell parameters exhibited a discontinuous change between 158 and 153 K, indicating the existence of a phase transition and hence the occurrence of two polymorphs, I and II, which was also confirmed by DSC analysis: reversible exothermic and endothermic peaks with ΔH= 2.1 kJ mol-1 were observed in the cooling and heating processes, respectively. The molecular packing in I and II at 200 and 90 K, respectively, remained essentially unchanged, retaining the space group Pnma. I and II are conformationally isomorphic crystals, including two crystallographically independent molecules, A and B, with different conformations in a 1:2 ratio. Upon the phase transition from I to II with decreasing temperature, the dynamic disorder of the imidazolidine ring of A in I, which interconverts between quasi-half-chair conformations, is frozen to settle in an envelope conformation, whereas Bis retained in a half-chair conformation in both I and II. The close intermolecular contacts in I and II were compared on the basis of Hirshfeld surface analysis. DFT calculations at the B3LYP/6-311G(d,p) level show that the half-chair structure is more stable than the envelope conformer by 2.6 kJ mol-1 in the gas phase. The quasi-half-chair conformation was not obtained as an energy-minimum geometry on the potential energy surface. Temperature-dependent IR spectroscopy along with theoretical calculation using the QST method gave assignments of the carbonyl stretching bands for each conformation. Compound 1 provides a unique example of the isostructural polymorphs in which the structural differences are small, being only at the order-disorder level in the ring conformation; nevertheless, the existence of the enantiotropic phase transition clearly indicates that they are polymorphs. [ABSTRACT FROM AUTHOR]

Indantrione 1,2-dioxime (1) afforded crystals solvated by different species of alcohols and in different stoichiometries. Among those, three pairs of polymorphic forms, which are of the same solvent and stoichiometry, were obtained. The crystal structures of those polymorphs, formulated as α- and β-1·MeOH, α- and β-1·1/2MeOH, and α- and β-1·EtOH, were elucidated along with that of 1·i-PrOH. The common building block in the crystal structures is a centrosymmetric planar dimer linked by bifurcated hydrogen bonding. The dimer is further assembled through alcohol molecules to form tapelike linear chains. The difference in crystal structure between all pairs of the polymorphs is principally attributed to a distinct hydrogen bonding motif between the dimer and solvated alcohol molecules. Carbonyl−carbonyl interaction is also recognized to play a role in molecular alignment in most cases; the carbonyl groups of neighboring molecules are in close contact and have an all-planar antiparallel arrangement. [ABSTRACT FROM AUTHOR]

Objective: In Japan, perioperative prophylaxis of pulmonary embolism (PE) in gynecologic cancer patients with preoperative asymptomatic venous thromboembolism (VTE) has not been well established yet. The GOTIC-VTE trial was a prospective, multi-center, single-arm clinical trial to investigate the prevention of postoperative symptomatic PE onset by seamless anticoagulant therapy from the preoperative period to 4 weeks after surgery instead of using intermittent pneumatic compression. Methods: Anticoagulant therapy was started immediately after asymptomatic VTE diagnosis and stopped preoperatively according to the rules of each institution. Unfractionated heparin administration was resumed within 12 hours postoperatively, and this was followed by the switch to low-molecular-weight heparin and subsequently, edoxaban; this cycle was continued for 28 days. Primary outcome was the occurrence of symptomatic PE in 28 days postoperatively. Secondary outcomes were the incidence of VTE-related events in 28 days and 6 months postoperatively and protocol-related adverse events. Results: Between February 2018 and September 2020, 99 patients were enrolled; of these, 82 patients were assessed as the full analysis set, including 58 for ovarian cancer, fallopian tube, or peritoneal cancer; 21 for endometrial cancer; and 3 for cervical cancer. No symptomatic PE was observed within 28 days postoperatively; two patients had bleeding events (major bleeding and clinically relevant nonmajor bleeding) and three had grade 3 adverse events (increased alanine transaminase, aspartate aminotransferase, or gamma-glutamyl transferase). Conclusion: The multifaceted perioperative management for gynecologic malignancies with asymptomatic VTE effectively prevented postoperative symptomatic PE. [ABSTRACT FROM AUTHOR]

Location recognition at the molecular scale provides valuable information about the nature of functional molecular materials. This study presents a novel location sensing approach based on an endohedral metallofullerene, Ce@C82, using its anisotropic magnetic properties, which lead to temperature-dependent paramagnetic shifts in 1H NMR spectra. Five site-isomers of Ce@C82CH2-3,5-C6H3Me2 were synthesized to demonstrate the spatial sensing ability of Ce@C82. Single-crystal structures, absorption spectra, and density functional theory calculations were used to select the plausible addition positions in the radical coupling reaction, which preferentially happens on the carbon atoms with high electron density of the singly occupied molecular orbital (SOMO) and positive charge. Temperature-dependent NMR measurements demonstrated unique paramagnetic shifts of the 1H peaks, which were derived from the anisotropic magnetism of the f-electron in the Ce atom of the isomers. It was found that the magnetic anisotropy axes can be easily predicted by theoretical calculations using the Gaussian 09 package. Further analysis revealed that the temperature-dependent trend in the shifts is clearly predictable from the distance and relative position of the proton from the Ce atom. Hence, the Ce-encapsulated metallofullerene Ce@C82 can provide spatial location information about nearby atoms through the temperature-dependent paramagnetic shifts of its NMR signals. It can act as a molecular probe for location sensing by utilizing the anisotropic magnetism of the encapsulated Ce atom. The potentially low toxicity and stability of the endohedral fullerene would make Ce@C82 suitable for applications in biology and material science. [ABSTRACT FROM AUTHOR]

Fullerenyl radicals can be generated by addition of a free radical to a fullerene surface, by nucleophilic addition followed by one-electron oxidation, or by thermal dissociation of singly bonded fullerene dimers. However, fullerenyl radicals are usually very reactive and generally cannot be isolated. On the contrary, we have found that the reactions of the dimetallic endofullerenes, La2@Ih-C80 and La2@D5h-C80, with 3-chloro-5,6-diphenyltriazine resulted in mono-addition of the triazinyl radical to the fullerene cages to yield isolable fullerenyl radicals. The unusual stability of these fullerenyl radicals arises from the confinement of the unpaired electron to an internal, metal--metal bonding orbital. Accordingly, the fullerene cage protects the radical center from other reactive species. Furthermore, we demonstrate that the fullerenyl radical adduct of La2@Ih-C80 reacts with toluene to afford additional benzylation. Interestingly, the benzylated derivative is diamagnetic in solution, while it forms a paramagnetic dimer when crystallized. [ABSTRACT FROM AUTHOR]

The endohedral fullerene once erroneously identified as Sc3@C82 was recently shown to be Sc3C2@Ih-C80, the first example of an open-shell cluster metallofullerene. We herein report that benzyl bromide (1) reacts with Sc3C2@Ih-C80 via a regioselective radical addition that affords only one isomer of the adduct Sc3C2@Ih-C80 (CH2C6H5) (2) in high yield. An X-ray crystallographic study of 2 demonstrated that the benzyl moiety is singly bonded to the fullerene cage, which eliminates the paramagnetism of the endohedral in agreement with the ESR results. Interestingly, X-ray results further reveal that the 3-fold disordered Sc3C2 cluster adopts two different configurations inside the cage. These configurations represent the so-called “planar” form and the computationally predicted, but not crystallographically characterized, “trifoliate” form. It is noteworthy that this is the first crystallographic observation of the “trifoliate” form for the Sc3C2 cluster. In contrast, crystallographic investigation of a Sc3C2@Ih-C80/Ni(OEP) cocrystal, in which the endohedral persists in an open-shell structure with paramagnetism, indicates that only the former form occurs in pristine Sc3C2@Ih-C80. These results demonstrate that the cluster configuration in EMFs is highly sensitive to the electronic structure, which is tunable by exohedral modification. In addition, the electrochemical behavior of Sc3C2@Ih-C80 has been markedly changed by the radical addition, but the absorption spectra of the pristine and the derivative are both featureless. These results suggest that the unpaired electron of Sc3C2@Ih-C80 is buried in the Sc3C2 cluster and does not affect the electronic configuration of the cage. [ABSTRACT FROM AUTHOR]

The geometries of fullerenes are governed by the isolated pentagon rule (IPR), which states that stable fullerenes have each of their 12 pentagons surrounded by five hexagons. At the dawn of fullerene science, it was widely believed that the IPR would also be applicable for endohedral fullerenes. In 2000, that idea was altered by the discovery of the first non-IPR fullerenes, Sc2@C66 and Sc3N@C68. The structural data for Sc2@C66 were interpreted to indicate the presence of a pair of doubly fused pentagons. However, that structure has remained a long-standing mystery, since it is thermodynamically unfavorable. Here, we demonstrate definitively that Sc2@C66 does not have the structure that was long believed to be but a brand new type. 2D NMR spectroscopic and single-crystal X-ray analyses disclose that Sc2@C66 has a C2v(4059)-C66 cage containing two sets of unsaturated linear triquinanes (ULTs), in which three pentagons abut one another and two scandium ions are located within the folds of each of the ULT units. [ABSTRACT FROM AUTHOR]

Objective: In Japan, no region has introduced primary HPV testing for cervical cancer screening. We assessed the diagnostic value and possible harm of HPV testing in Japan. Methods: This cross-sectional study with historical controls used cytology-based screening and co-testing data in Japan. As surrogate indicators of possible harm, colposcopy referral rate and cervical intraepithelial neoplasm (CIN) 1 detection rates were calculated. As surrogate indicators with diagnostic values, the detection rates of CIN2 or greater (CIN2+) and CIN3+ were calculated. Results: The data of 297 970 women (182 697 for cytology-based, 115 273 for cotesting) were examined. The detection rates of CIN1, CIN2+, and CIN3+ were significantly higher in the co-testing group than in the cytology-based group (P < 0.001, P < 0.0001, P < 0.01, respectively). Between ages 25-49, CIN2+ detection rates were significantly higher in the co-testing group than in the cytology-based group (P < 0.05 for each 5-year age group). Between ages 30-49, CIN3+ detection rates were significantly higher in the co-testing group than in the cytology-based group (P < 0.05 for each 5-year age group). Conclusion: Limiting the target age group may minimize the possible harm of screening. Cytology/HPV co-testing may be useful in Japanese populations if balance is maintained between benefit and harm. [ABSTRACT FROM AUTHOR]

The title compounds, 5-(2H-1,3-benzodioxol-5-yl)-N-cyclohexylpenta-2,4-dienamide, C18H21NO3 (I), and 5-(2H-1,3-benzodioxol-5-yl)-1-(pyrrolidin-1-yl)penta- 2,4-dien-1-one C16 H17NO3 (II), are derivatives of piperine, which is known as a pungent component of pepper. Their geometrical parameters are similar to those of the three polymorphs of piperine, which indicate conjugation of electrons over the length of the molecules. The extended structure of (I) features N--H…O amide hydrogen bonds, which generate C(4) [010] chains. The crystal of (II) features aromatic τ-τ stacking, as for two of three known piperine polymorphs. [ABSTRACT FROM AUTHOR]

We compared the chemical reactivity of D2d(23)-C84 and that of Sc2C2@D2d(23)-C84, both having the same carbon cage geometry, in the photolysis of 2-adamantane-2,3'-[3H]-diazirine, to clarify metal-atom doping effects on the chemical reactivity of the carbon cage. Experimental and computational studies have revealed that the chemical reactivity of the D2d(23)-C84 carbon cage is altered drastically by endohedral Sc2C2 doping. The reaction of empty D2d(23)-C84 with the diazirine under photoirradiation yields two adamantylidene (Ad) adducts. NMR spectroscopic studies revealed that the major Ad monoadduct (C84(Ad)-A) has a fulleroid structure and that the minor Ad monoadduct (C84(Ad)-B) has a methanofullerene structure. The latter was also characterized using X-ray crystallography. C84(Ad)-A is stable under photoirradiation, but it interconverted to C84(Ad)-B by heating at 80 °C. In contrast, the reaction of endohedral Sc2C2@D2d(23)-C84 with diazirine under photoirradiation affords four Ad monoadducts (Sc2C2@C84(Ad)-A, Sc2C2@C84(Ad)-B, Sc2C2@C84(Ad)-C, and Sc2C2@C84(Ad)-D). The structure of Sc2C2@C84(Ad)-C was characterized using X-ray crystallography. Thermal interconversion of Sc2C2@C84(Ad)-A and Sc2C2@C84(Ad)-B to Sc2C2@C84(Ad)-C was also observed. The reaction mechanisms of the Ad addition and thermal interconversion were elucidated from theoretical calculations. Calculation results suggest that C84(Ad)-B and Sc2C2@C84(Ad)-C are thermodynamically favorable products. Their different chemical reactivities derive from Sc2C2 doping, which raises the HOMO and LUMO levels of the D2d(23)-C84 carbon cage. [ABSTRACT FROM AUTHOR]

Background: There are no definitive criteria for identifying which patients with The International Federation of Gynecology and Obstetrics (FIGO) stage IB cervical cancer will benefit from adjuvant therapy after radical hysterectomy. The aims of this study were to clarify the efficacy of adjuvant therapy and assess complications after radical hysterectomy in patients with FIGO stage IB1 cervical cancer with intermediate risk factors. Methods: Between January 2005 and December 2009, the medical records of 75 stage IB1 patients' intermediate risk factors (i.e., tumor size 2–4 cm, lymphovascular involvement, and/or deep stromal invasion >1/2) who underwent radical hysterectomy at six institutions were collected, and these patients were enrolled in this nonrandomized retrospective study. We simplified the criteria of intermediate risk factors as much as possible, as the criteria adopted in some clinical studies are complicated in practice. Results: The patients were grouped according to the receipt of adjuvant therapy as follows: 46 patients, no further treatment; 19 patients, external beam radiation treatment, including 9 patients who received brachytherapy; 5 patients, concurrent chemoradiotherapy (CCRT); and 5 patients, chemotherapy (CT). The clinical outcomes and complications in each group were analyzed. After an average follow-up of 82.6 months (range, 24–135 months), only one patient with all three risk factors who received radiotherapy (RT) experienced recurrence. Excluding this patient, the remaining patients who received RT, CCRT, or CT had two or three risk factors. Lymphedema was significantly more common among patients who received RT or CCRT, whereas the incidence of ileus and ureteral obstruction was not different among the treatment groups. However, an unsutured peritoneum increased the risk of ileus. Conclusions: The findings of this study suggest that RT and CCRT after radical hysterectomy are not beneficial in patients with intermediate risk factors. In particular, RT and CCRT appeared to increase the incidence of lymphedema. A prospective randomized study is needed to verify the findings of this study. [ABSTRACT FROM AUTHOR]

Primary gestational choriocarcinoma is commonly present in the uterus in cases of atypical genital bleeding. Symptoms similar to those of an ectopic pregnancy develop when an extra-uterine lesion is present in the abdominal cavity, and lesions have been detected in the ovaries and fallopian tubes in a number of cases. In the present study, we describe a patient with choriocarcinoma that metastasized to the uterine serosa and caused symptoms similar to those of an ectopic pregnancy. The patient was a 30-year-old female who presented to our hospital with atypical genital bleeding and a positive pregnancy test 3 months after missed abortion at 10 weeks of gestation. Transvaginal ultrasonography revealed the absence of a gestational sac in or outside the uterus, and intra-abdominal bleeding was noted. An ectopic pregnancy was suspected based on these findings, and emergency laparotomy was performed. A hemorrhagic mass was present on the uterine serosa, and was subsequently resected. Trophoblastic disease was suspected following histopathological examination, for which intra-uterine curettage was performed and choriocarcinoma was diagnosed. Lung metastasis was detected on computed tomography, and a high serum human chorionic gonadotropin (hCG) level persisted following surgery. The lesion disappeared following five cycles of methotrexate+ etoposide+actinomycin D therapy, which was performed as postoperative chemotherapy, and the patient's serum hCG level decreased to below the detection limit. In this case of choriocarcinoma, the primary lesion was present in the uterus and had metastasized to the uterine serosa, which is a very rare metastatic site. This uterine serosal metastatic lesion bled and caused symptoms similar to those of an ectopic pregnancy. Certain patients who undergo surgery for a suspected peritoneal pregnancy may have gestational choriocarcinoma, similar to this case. [ABSTRACT FROM AUTHOR]

Reactions of Sc3N@/h-C80 with aziridine derivatives were conducted to afford the corresponding mono-adducts. A pair of diastereomers of the mono-adduct [5,6]-pyrrolidino-Sc3N@/h-C80 was isolated and characterized by means of mass spectrometry, vis-NIR absorption spectroscopy, and electrochemical measurements. Structural analysis of the mono-adducts was conducted by NMR and single-crystal X-ray structure determinations. [ABSTRACT FROM AUTHOR]

A disintegrin and metalloproteinases (ADAMs) are members of the metzincin family of zinc-dependent metalloproteinases that play pivotal roles in the proteolytic degradation of the extracellular matrix for cell invasion. Few studies have investigated the ADAM subtypes that are expressed in first trimester trophoblast cells. The purpose of this study was to elucidate the differential expression profiles of ADAMs between first trimester villous trophoblast cells (VTs) and extravillous trophoblast cells (EVTs). We isolated EVTs from explanted human first trimester chorionic villi and investigated the mRNA expression levels of five members of the ADAM family (ADAMTS1, ADAMTS2, ADAM10, ADAM12, and ADAM17) using real-time PCR. Chorionic villous tips were defined as first trimester VTs. Of the differentially expressed ADAM genes between first trimester VTs and EVTs, ADAMTS1 was expressed at a significantly higher level in EVTs than in VTs. In contrast, both ADAM10 and ADAM12 were expressed at significantly higher levels in VTs than in EVTs. No differences were found in the mRNA levels of ADAMTS2 and ADAM17 between the two cell types. Moreover, we demonstrated that in VTs, the expression level of ADAM12 was significantly downregulated in the late first trimester (10-13 gestational weeks) compared to the middle first trimester (7-8 weeks). These results suggest that first trimester trophoblast cells express ADAM genes in cell type- and gestational age-dependent manners. Our data provide additional insight into the functions of ADAMs in the human placenta. [ABSTRACT FROM AUTHOR]

A leiomyoma rarely causes disseminated intravascular coagulopathy (DIC). In the present report, we describe a case of DIC caused by leiomyoma. A 36-year-old nulliparous woman presented with hypermenorrhea and a lower abdominal mass. On magnetic resonance imaging, we detected a 14 cm uterine tumor, which was suspected to be a sarcoma. Blood tests at the preoperative examination indicated platelet count of 9.6 × 104/µL, fibrin degradation product level of 107.1 µg/mL (normal value, 0-5.0 µg/mL), and fibrinogen level of 54 mg/dL (normal value, 129-271 mg/dL). Based on these findings, we diagnosed the patient with DIC. The patient was treated with nafamostat mesilate and fresh frozen plasma, but the DIC did not show any improvement. Subsequently, a hysterectomy was performed, after which the DIC improved. Clinicopathological findings indicated the presence of a leiomyoma with multiple vessels containing thromboemboli, and suggested that the DIC was caused by the leiomyoma. Therefore, it is essential to consider that that a benign leiomyoma may be a cause of DIC. [ABSTRACT FROM AUTHOR]

Regioselective cycloaddition of adamantylidene carbene to Pr@C2v(9)-C82 affords the first derivative of praseodymium-containing metallo-fullerenes. Single-crystal X-ray crystallographic data in combination with theoretical studies demonstrate that the addition is dictated by the single metal ion encapsulated inside the fullerene cage. [ABSTRACT FROM AUTHOR]

Objective We aim to measure the parameters of fetal cardiac dimension using M-mode echocardiography in twins Methods All including subjects were agreed about the study. Fetal echocardiography was performed in 50 fetuses of 25 twin pregnancies (DD = 14, MD = 11) at gestational age >27 weeks. The following cardiac parameters were measured: CTAR (Cardiothoracic Ratio), RVID (Right Ventricle Internal Diameter), and LVID (Left Ventricle Internal Diameter) during diastolic and systolic phase. After analyses using all cases, subgroup analyses (DD vs. MD, larger fetuses vs. smaller fetuses) were performed. The level of p < 0.05 was considered as significant Results These indices in DD twins were not different from those in MD twins at any gestational categories. LVIDs during systolic phase in larger MD twins (9.2 ± 2.5 mm) were larger than those in smaller MD fetuses (6.7 ± 2.3 mm) (P < 0.05). Those effect were also seen during diastolic phase in MD twins (12.8 ± 3.1 mm vs. 9.8 ± 2.9 mm) (P > 0.05). However, CTAR or RVID were not different between larger and smaller MD fetuses. In DD twins, the difference of CTAR, RVID, and LVID were not observed between larger and smaller fetuses Conclusion The LVID during systolic and diastolic in MD twin fetuses may be the sensitive indicator of fetal discordancy. [ABSTRACT FROM AUTHOR]