Synthesis, Structure, and Reactivity of Molybdenum- and Tungsten-Indane Complexes with Tris(pyrazolyl)borate Ligand.

The reaction of molybdenum complexes with a tris(pyrazolyl)borate ligand (Et4N[TpMo(CO)3] and Et4N[Tp*Mo(CO)3] (Tp = hydridotris(pyrazolyl)borate, Tp* = hydridotris(3,5-dimethylpyrazolyl)borate)) and InBr3 at a 1:1 molar ratio afforded molybdenum-indane complexes (Et4N[TpMo(CO)3(InBr3)] 1 and Et4N[Tp*Mo(CO)3(InBr3)] 2). In addition, tungsten-indane complexes, Et4N[TpW(CO)3(InBr3)] 3 and Et4N[Tp*W(CO)3(InBr3)] 4, were obtained by the reaction of corresponding tungsten complexes. Complex 4 reacted with H2O to form the hydrido complex Tp*W(CO)3H, in which the W-In bond was cleaved. On the other hand, 4 reacted with three equiv. of AgNO3 to form Et4N[Tp*W(CO)3{In(ONO2)}] 5, in which three substituents on the In were exchanged while retaining the W-In dative bond. Complexes 1-5 were fully characterized using NMR measurements and elemental analyses, and the structures of 1-5 and Et4N[Tp*W(CO)3] were determined via X-ray crystallography. These are the first examples of mononuclear molybdenum- and tungsten-indane complexes with Mo-In and W-In dative bonds.

Human papillomavirus vaccine impact on invasive cervical cancer in Japan: Preliminary results from cancer statistics and the MINT study.

The first prophylactic vaccine against human papillomavirus (HPV) 16 and HPV18 was licensed in Japan in 2009. HPV vaccine effectiveness against high-grade cervical lesions has been demonstrated among young Japanese women, but evidence of its effects on invasive cervical cancer (ICC) is lacking. Using data from two different cancer registries, we compared recent trends of new ICC cases by age group using Poisson regression analysis. We also analyzed time trends in HPV16/18 prevalence among 1414 Japanese women aged <40 years newly diagnosed with ICC in the past decade. Based on the population-based cancer registry, the incidence of ICC among young women aged 20-29 years showed a significant decline from 3.6 to 2.8 per 100 000 women-years during 2016-2019, but no similar decline was observed for older age groups (p < 0.01). Similarly, using data from the gynecological cancer registry of the Japan Society of Obstetrics and Gynecology, the annual number of ICCs among women aged 20-29 years also decreased from 256 cases to 135 cases during 2011-2020 (p < 0.0001). Furthermore, a declining trend in HPV16/18 prevalence in ICC was observed only among women aged 20-29 years during 2017-2022 (90.5%-64.7%, p = 0.05; Cochran-Armitage trend test). This is the first report to suggest population-level effects of HPV vaccination on ICC in Japan. Although the declining trend in HPV16/18 prevalence among young women with ICC supports a causal linkage between vaccination and results from cancer registries, further studies are warranted to confirm that our findings are attributable to vaccination.

A case series title: femoral nerve injury with an episode of motor neuropathy caused by gynecological surgery: a case series.

Background: Although iatrogenic nerve injury is sometimes diagnosed after gynecological surgery, its incidence is underestimated because most cases are self-limiting and underreported. Herein, we report on six cases of femoral nerve injury after gynecological surgery with both sensory and motor neuropathy. Methods: We retrospectively analyzed 785 patients with gynecological cancer requiring surgery, including lymph node dissection, between 2012 and 2016 at our center. The functional damage due to femoral nerve injury was postoperatively assessed and classified according to the Medical Research Council (MRC) scale by an orthopedist and a physiatrist. The eligibility criteria were grade 3 or less hip joint bending and muscular weakness due to nerve injury. Patients were excluded if they had been diagnosed with an isolated sensory disorder. Results: We found six cases (0.76%) of femoral motor neuropathy resulting from gynecological surgery. All six patients underwent laparotomy using energy devices under general anesthesia with epidural anesthesia in the lithotomy position. Four of them recovered fully within 8 months from surgery with either physical therapy or no treatment, while the other two died within a year post-treatment; thus, recovery evaluation could not be accurately performed. Conclusion: Postoperative femoral nerve injury can be diagnosed based on gait disturbances and difficulties climbing stairs. It is difficult to identify risk factors for femoral nerve injury as they may involve a combination of features, such as intraoperative compression with self-retaining retractors, the lithotomy position, and the use of energy devices. The surgeon should be familiar with the nature of energy devices, make every effort to understand the necessary anatomy, and make every effort to avoid femoral nerve injury. Iatrogenic femoral nerve injury caused by gynecological surgery should be further investigated regarding the patients' quality of life postoperatively.

Research on inorganic activators of dibromo Co-terpyridine complex precatalyst for hydrosilylation.

The search for a stable, inexpensive, and easy-to-handle activator toward the catalyst precursor [Co(tpy)Br2] in the hydrosilylation of olefins with hydrosilane revealed that K2CO3 is an effective activator. This inorganic salt is available on substrates with some functional groups and can be readily removed by simple filtration or centrifugation after the reaction. After examining and comparing the activator abilities of various salts, it was proposed that low MX lattice energy, high X-nucleophilicity, and a strong Si-X bond are necessary for an inorganic salt (MX) to be an excellent activator.

Synthesis and Characterization of Phosphinecarboxamide and Phosphinecarbothioamide, and Their Complexation with Palladium(II) Complex.

Reactions of isocyanates/isothiocyanates with primary and secondary phosphines without solvent at room temperature afforded phosphinecarboxamide/phosphinecarbothioamide, respectively, in excellent yields. Furthermore, palladium complex Pd(COD)Cl2 was allowed to react with Ph2PC(O)NHPh (1a) to afford [Pd{Ph2PC(O)NHPh-κP}2Cl2] (3). On the other hand, the reaction of Pd(COD)Cl2 with 1 eq. of Ph2PC(S)NHPh (2a) afforded [PdCl2{Ph2PC(S)NHPh-κP,S}] (4). In the case of a 1:2 molar ratio, [PdCl{Ph2PC(S)NHPh-κP,S}{Ph2PC(S)NHPh-κP}]Cl (5) was formed. The newly obtained compounds were fully characterized using multielement NMR measurements and elemental analyses. In addition, the molecular structures of Ph2PC(O)NH(CH2)2Cl (1j), Ph2PC(S)NHPh(4-Cl) (2c), and 3-5 were determined using single-crystal X-ray diffraction.

Effect of prior olaparib maintenance therapy for platinum sensitive recurrent ovarian cancer on response to subsequent platinum-based chemotherapy.

AIM: Several years have passed since olaparib maintenance therapy was approved in patients with platinum sensitive recurrent ovarian cancer (PSROC). We speculated that the response to platinum-based chemotherapy (PBC) would be impaired at the time of recurrence after olaparib maintenance therapy. We conducted a noninterventional retrospective study to clarify this clinical question in a single institution. METHODS: We included all patients with PSROC who received olaparib after second or later line of PBC between April 18, 2018, and August 31, 2021. We evaluated the effect of olaparib maintenance therapy on PBC after progression. RESULTS: We identified 42 patients who received olaparib maintenance therapy after second or later line of PBC. Twenty-four patients relapsed after olaparib maintenance therapy, and 17 patients received PBC again. Four of 17 patients (complete response 2, partial response 2) responded to the PBC. The median progression-free survival was longer in patients with platinum-free interval ≥12 months than platinum-free interval of 6-12 months (9.7 vs 2.6 months, hazard ratio, 0.20: 95% confidence interval, 0.04-0.90; p = 0.04). CONCLUSIONS: In the patients with PSROC who experienced disease progression after olaparib maintenance therapy, especially in those with platinum-free interval of 6-12 months, the response to subsequent PBC was extremely poor. The efficiency of re-administration of PBC for PSROC patients with a short-term recurrence after olaparib treatment may need to be reconsidered.

Base Metal-terpyridine Complex Immobilized on Stationary Phase Aimed as Reusable Hydrosilylation Catalyst.

The catalytic activity of a base metal-terpyridine complex immobilized on silica gel (M(tpy)X2 @SiO2 /H2 O: M=Mn, Fe, Co, Ni, Cu; X=Cl, Br) for hydrosilylation was investigated. Co(tpy)Br2 @SiO2 /H2 O in the presence of NaBHEt3 exhibited the highest catalytic activity for hydrosilylation of 1-octene with diphenylsilane (Ph2 SiH2 ) to form the anti-Markovnikov-type hydrosilylation compound as the main product. The reusability of Co(tpy)Br2 @SiO2 /H2 O activated by NaBHEt3 was examined. It was found that the catalytic activity decreased with repeated use because of the peeling off of the Co complex anchor portion from the silica gel surface upon the attack of NaBHEt3 . The introduction of Co(OAc)2 instead of CoBr2 to silica gel formed Co(tpy)(OAc)2 - and Co(tpy)(OH)2 -immobilized silica gel, which exhibited catalytic activity for the hydrosilylation in the absence of an activator such as NaBHEt3 . The glassware in which Co(tpy)(OH)2 was immobilized on the inner wall was prepared. It was found that the hydrosilylation catalytically occurred on the surface of a pretreated glassware and that the catalytic activity did not decrease even after 10 repeated uses.

Interpersonal Sensitivity Mediates the Effects of Childhood Maltreatment on the Evaluation of Life Events and Anxiety States in Adult Community Volunteers.

BACKGROUND: Childhood maltreatment has long-lasting psychological effects, which often manifest in adulthood. Previous studies have suggested that the effects of childhood maltreatment are not only direct but also indirect, being mediated by other factors. In this study, we hypothesized that the effects of childhood maltreatment on state anxiety in adulthood are mediated by interpersonal sensitivity and the evaluation of life events, and investigated this possibility by covariance structure analysis. SUBJECTS AND METHODS: Self-administered questionnaires (Child Abuse and Trauma Scale, State-Trait Anxiety Inventory Form Y, Life Experiences Survey, and Interpersonal Sensitivity Measure) were distributed to adult community volunteers in Japan, and 404 eligible responses were collected. A structural equation model was constructed to analyze the direct and indirect effects of childhood maltreatment on state anxiety, with interpersonal sensitivity and the evaluation of life events as potential mediators. RESULTS: Our model showed that childhood maltreatment increases state anxiety in adulthood both directly and indirectly via interpersonal sensitivity. In addition, interpersonal sensitivity mediated the effects of childhood maltreatment on the negative evaluation of life events, and the negative evaluation of life events mediated the effects of interpersonal sensitivity on anxiety symptoms. LIMITATIONS: There may be possible recall bias owing to the self-administration of the questionnaire. In addition, this study had a cross-sectional design, and hence the results should be validated by a prospective study. CONCLUSION: The effects of childhood maltreatment on the state anxiety of adult volunteers are not only direct but are also mediated by interpersonal sensitivity. Our results suggest that assessing interpersonal sensitivity may help to determine optimal treatments for patients with anxiety who experienced maltreatment in childhood.

Survival impact of adjuvant concurrent chemoradiotherapy after radical hysterectomy in FIGO stage IIIC1 cervical adenocarcinoma.

BACKGROUND: We evaluated the survival effect of adjuvant concurrent chemoradiotherapy after radical hysterectomy in patients with clinical pelvic node-positive cervical adenocarcinoma. METHODS: Patients with pelvic node-positive cervical adenocarcinoma diagnosed between 2000 and 2016 at our institution were identified. Survival was compared between patients who underwent radical hysterectomy alone and those who received concurrent chemoradiotherapy as an adjuvant treatment. Survival analysis using log-rank test and Cox proportional hazards model was performed. RESULTS: We identified 80 patients who underwent radical hysterectomy for clinical pelvic node-positive cervical adenocarcinoma; of these, four with pathological pelvic node-negative adenocarcinoma were excluded. Of the 76 patients, 27 underwent radical hysterectomy alone and 49 received radical hysterectomy followed by concurrent chemoradiotherapy. With a median follow-up of 53 months, the 5-year overall survival rate was 51.0% in patients who underwent radical hysterectomy alone versus 53.0% in patients who received additional concurrent chemoradiotherapy (log-rank p = 0.455). CONCLUSION: The addition of concurrent chemoradiotherapy after radical hysterectomy did not significantly improve survival among patients with pelvic node-positive cervical adenocarcinoma. More appropriate treatment strategies are needed to improve the survival outcomes of these patients.

Quality of life assessment of cell-free and concentrated ascites reinfusion therapy during initial treatment for advanced ovarian cancer: A prospective cohort study.

AIM: Cell-free and concentrated ascites reinfusion therapy (CART) is applied to relieve symptoms in patients with malignant ascites. We performed a prospective cohort study to evaluate the efficacy and safety of CART performed on patients with advanced ovarian and peritoneal cancers with massive ascites during the initial treatment. METHODS: From April 2018 to July 2020, CART was performed during the initial treatment of 31 patients with advanced ovarian and peritoneal cancers with cancerous ascites. Patient characteristics and clinical information before and after CART were collected. We performed quality of life assessment using the Japanese version of the M.D. Anderson Symptom Inventory (MDASI-J) 24 h before and after CART. RESULTS: CART was performed 38 times in 24 patients before or during neoadjuvant chemotherapy and 11 times in 11 patients prior to surgery. Four patients underwent CART before primary surgery and before and/or during chemotherapy. Grade 1-2 fever was observed in 18 of 31 cases (58%), and all were controllable by nonsteroidal anti-inflammatory drugs. CART did not adversely affect the main treatment, chemotherapy, or surgery. CART significantly improved the MDASI-J symptom and interference scores within 24 h after the procedure. The symptom and interference scores decreased from 2.4 to 1.8 and from 4.8 to 3.0, respectively. CONCLUSIONS: CART can be safely performed and is useful for symptom relief and improvement of general condition prior to initial surgery and during initial chemotherapy in ovarian and peritoneal cancers. Performing CART at the time of initial treatment may facilitate initiation of the main treatment.

Allergen Stability and Immunological Reactivity during Co-dissolution and Incubation of House Dust Mite and Japanese Cedar Pollen SLIT-Tablets.

Japanese allergic subjects are commonly sensitized to both house dust mite (HDM) and Japanese cedar pollen (JCP) and combined treatment with sublingual immunotherapy (SLIT) tablets is desirable. However, mixing extracts of two non-homologous allergens may compromise allergen stability and affect the clinical outcome. Therefore, we investigated the stability of major allergens and total allergenic reactivity of HDM and JCP SLIT-tablets following dissolution in human saliva or artificial gastric juice. Two fast-dissolving freeze-dried SLIT-tablets were completely dissolved and incubated at 37 °C. Major allergen concentrations and total allergenic reactivity were measured. After mixing and co-incubation of HDM and JCP SLIT tablets in human saliva for 10 min at 37°C, there were no statistically significant changes in major allergen concentrations. In addition, no loss of allergenic reactivity of the mixed two SLIT-tablet solutions was seen. In contrast, complete loss of allergenic reactivity and detectable major allergen concentrations occurred when the two SLIT-tablets were dissolved and incubated in artificial gastric juice. These results demonstrate that HDM or JCP major allergens and the total allergenic reactivity of both SLIT-tablets measured here remain intact after dissolution and co-incubation in human saliva, supporting the possibility of a dual HDM and JCP SLIT-tablet administration regimen if clinically indicated. The complete loss of allergenic reactivity after incubation in artificial gastric juice can furthermore be taken to indicate that the immunological activity of the allergen extracts contained in the two SLIT-tablets is likely to be lost or severely compromised upon swallowing.

Convenient synthesis of phosphinecarboxamide and phosphinecarbothioamide by hydrophosphination of isocyanates and isothiocyanates.

Reactions of isocyanates with primary and secondary phosphines without solvent at room temperature afforded the corresponding phosphinecarboxamide (RN(H)COPR'2) in excellent yields. This reaction system is applicable for isothiocyanates. The compounds newly obtained were fully characterized using multielement NMR spectroscopy. In addition, the molecular structure of Cl(CH2)2N(H)COPPh2 was studied by single-crystal X-ray diffraction.

Palladium-Borane Cooperation: Evidence for an Anionic Pathway and Its Application to Catalytic Hydro-/Deutero-dechlorination.

Metal-Lewis acid cooperation provides new opportunities in catalysis. In this work, we report a new type of palladium-borane cooperation involving anionic Pd0 species. The air-stable DPB palladium complex 1 (DPB=diphosphine-borane) was prepared and reacted with KH to give the Pd0 borohydride 2, the first monomeric anionic Pd0 species to be structurally characterized. The boron moiety acts as an acceptor towards Pd in 1 via Pd→B interaction, but as a donor in 2 thanks to B-H-Pd bridging. This enables the activation of C-Cl bonds and the system is amenable to catalysis, as demonstrated by the hydro-/deutero-dehalogenation of a variety of (hetero)aryl chlorides (20 examples, average yield 85 %).

The Effective Allergenic Reactivity of House Dust Mite Sublingual Immunotherapy Tablets Is Determined by Tablet Formulation.

House dust mite (HDM) sublingual immunotherapy (SLIT) in the form of SLIT-tablets is now an established treatment option for HDM allergy and HDM-induced allergic asthma. In SLIT-tablet immunotherapy allergen extracts are formulated as dry tablets and administered under the tongue where it must be solubilized in saliva in order to be able to interact with the immune system of the sublingual mucosa. Solubilization of the extract must occur within a short time span of about one minute after administration, determined by the sublingual holding time recommended by the manufacturer. Currently, two types of HDM SLIT-tablets are available. Both tablet types contain natural HDM extracts from two common HDM species as the active ingredient, but differ with regard to formulation as one tablet type is based on a freeze-dried tablet formulation while the other is based on a compressed formulation. HDM extracts contain a number of major and minor allergens, which in combination provide the allergenic activity that drives the immunological response and in turn the clinical efficacy of the tablets. Here, a biologically relevant human immunoglobulin E (IgE)-based assay is used to compare the ability of the two HDM SLIT-tablet types to deliver HDM allergenic reactivity from the dry tablet into soluble form. The experiments demonstrate that the freeze-dried formulation delivers HDM allergenic activity into solution faster and more efficiently than the compressed formulation.

The Importance of Tablet Formulation on Allergen Release Kinetics and Efficiency: Comparison of Freeze-dried and Compressed Grass Pollen Sublingual Allergy Immunotherapy Tablet Formulations.

PURPOSE: Efficient delivery of allergens to the sublingual mucosa is a prerequisite for successful sublingual immunotherapy (SLIT) for allergy, and in order to become available to immune-competent cells embedded in the sublingual mucosa, allergens need to be delivered in a soluble form. Delivery of solubilized allergens poses a particular challenge for tablet-based allergy immunotherapy, in which allergens are administered under the tongue in the form of dry tablets and need to be dissolved rapidly in a small volume of saliva, with little or no agitation. The purposes of this article were to compare the properties of 2 different pharmaceutical SLIT-tablet formulations, freeze-dried and compressed, and to examine how the tablet formulation affects the efficiency with which allergen is delivered from the dry state of the tablet into soluble form. METHODS: Two SLIT-tablet formulations, both indicated for grass pollen allergic rhinitis and containing grass pollen extract as the active ingredient, were examined with regard to tablet disintegration times, allergen dissolution kinetics, dependency on solvent volume and agitation, and the achieved recovery of the grass allergen content in soluble form with each tablet. FINDINGS: The freeze-dried and the compressed SLIT-tablet formulations differed markedly with respect to efficiency of allergen release. The freeze-dried tablet disintegrated faster and released grass allergen into solution with a release rate higher than that of the compressed formulation and, in contrast to the compressed formulation, achieved full recovery of the allergen content in soluble form in a small volume of solvent. IMPLICATIONS: Rapid and complete release of soluble allergen in a small volume of solvent, as demonstrated by the freeze-dried formulation, are key elements of efficient sublingual allergen delivery by SLIT-tablets. Complete allergen release means that the full allergen dose of the tablet is recovered from the tablet and made available to the sublingual immune system in soluble form, and rapid release ensures that the immune system becomes exposed to the highest possible dose of soluble allergen for the maximal duration before swallowing. In contrast, a SLIT-tablet formulation that provides incomplete and slower allergen release will likely require a higher allergen content compared to the more efficient formulation, in order to achieve the same dose of soluble allergen, consequently leading to an excess load of allergen that becomes swallowed without having been made immunologically available.

Hydrosilylation of Ketones Catalyzed by Iron Iminobipyridine Complexes and Accelerated by Lewis Bases.

Fe-iminobipyridine complexes ((R BPIAr,R' )FeBr2 , R BPIAr,R' =iminobipyridine derivatives) were found to exhibit good catalytic activity for hydrosilylation of ketones. The highest TOF (turnover frequency) was obtained for the hydrosilylation of 2-octanone with phenylsilane (4190 min-1 ). The reactions of various 4-substituted acetophenone derivatives revealed that the introduction of an electron-withdrawing group at the 4-position retarded the reaction. The TOF of the hydrosilylation of 4-chloroacetophenone with diphenylsilane was quite low (30 min-1 ), however the addition of a catalytic amount of Lewis base, especially pyridine, dramatically accelerated this hydrosilylation (980 min-1 ). Comparison of this additive effect for several N-donor ligands revealed that the coordination ability of the N-donor ligand was responsible for the acceleration. The rate determining step in the hydrosilylation of ketones appeared to be the reductive elimination of alkoxy and silyl groups from the iron center, which was facilitated by the coordination of N-donor ligand to the iron. This coordination ability of the N-donor ligand, however, inhibited olefin hydrosilylation. Addition of KOt Bu instead of N-donor also showed the same acceleration and inhibition effects on ketone and olefin hydrosilylations, respectively.

Selective Double Addition Reaction of an E‒H Bond (E = Si, B) to a C≡N Triple Bond of Organonitriles.

The catalytic double hydrometalation such as hydrosilylation and hydroborylation of organonitriles has attracted considerable attention because the obtained products are widely used in organic synthesis and it is thought to be one of the effective methods for reduction of organonitriles. However, the examples of these reactions are quite limited to date. This paper summarizes the development of selective double hydrosilylation, double hydroborylation, and dihydroborylsilylation of organonitriles, including their reaction mechanisms and the role of the metal species in the catalytic cycle.

Iridium-Catalyzed Aerobic Coupling of Salicylaldehydes with Alkynes: A Remarkable Switch of Oxacyclic Product.

The iridium(III)/copper(II)-catalyzed dehydrogenative coupling of salicylaldehydes with internal alkynes proceeds efficiently under atmospheric oxygen through aldehyde C-H bond cleavage and decarbonylation. A variety of benzofuran derivatives can be synthesized by the environmentally benign procedure. DFT calculations suggest that this unique transformation involves the facile deinsertion of CO in the key metallacycle intermediate, which is in marked contrast to the corresponding rhodium(III) catalysis that leads to CO-retentive chromone derivatives.