Fatal SARS-CoV-2 Infection among Children, Japan, January-September 20221.

To determine the characteristics of pediatric patients 0-19 years of age who died after onset of SARS-CoV-2 infection in Japan during January 1-September 30, 2022, we reviewed multiple sources. We identified 62 cases, collected detailed information from medical records and death certificates, and conducted interviews, resulting in 53 patients with detailed information for our study. Among 46 patients with internal causes of death (i.e., not external causes such as trauma), 15% were <1 year of age, 59% had no underlying disease, and 88% eligible for vaccination were unvaccinated. Nonrespiratory symptoms were more common than respiratory symptoms. Out-of-hospital cardiac arrest affected 46% of patients, and time from symptom onset to death was <7 days for 77%. Main suspected causes of death were central nervous system abnormalities (35%) and cardiac abnormalities (20%). We recommend careful follow-up of pediatric patients after SARS-CoV-2 infection during the first week after symptom onset, regardless of underlying diseases.

Formation of chalcogen-bonding interactions and their role in the trans-trans conformation of thiourea.

The chalcogen-bonding interactions formed at both sides of the thiocarbonyl group in thiourea were investigated. In particular, the role of these chalcogen-bonding interactions in the trans-trans conformation of thiourea was evaluated via single-crystal X-ray diffraction analysis and DFT calculations. The obtained results indicate that the Se⋯S⋯Se dual chalcogen-bonding interactions play a stronger role in controlling the planar structure than the S⋯S⋯S interactions.

Palladium-catalyzed C-C bond cleavage of N-cyclopropyl acylhydrazones.

Despite their utility as directing groups, the C-C bond cleavage of cyclopropanes utilizing hydrazones has not been explored. Herein, Pd-catalyzed C-C bond cleavage reaction of N-cyclopropyl acylhydrazones, followed by cycloisomerization to yield pyrazoles, has been developed. The protocol enables the synthesis of various α-pyrazole carbonyl compounds, which have a potential of biological activity. Control experiments and DFT calculations suggest that ß-carbon elimination of a stable 6-membered chelate palladium complex occurs, generating a conjugated azine as a reaction intermediate for the following cycloisomerization.

Favorable changes in the eGFR slope after dapagliflozin treatment and its association with the initial dip.

BACKGROUND: Renoprotective effects of sodium glucose transporter 2 (SGLT2) inhibitors, including dapagliflozin, were observed in randomized controlled trials (RCTs). The suspected underlying mechanism is a correction of hyperfiltration, observed as an "initial dip". Whether SGLT2 inhibitors can attenuate the rate of decline in the estimated glomerular filtration rate (eGFR) in clinical settings, even when considering the pre-treatment decline rate, is unknown. Although several RCTs identified an association between the initial dip and long-term renal prognoses, a conclusion has not been reached. METHODS: We collected the eGFR data of patients for whom dapagliflozin was initiated in our hospital and then calculated their eGFR slopes before and after the start of the treatment. We investigated the changes in the eGFR slopes (ΔeGFR slope) and the association between the ΔeGFR slope and the initial dip. Risks for rapid eGFR decliners (eGFR slope < - 3 mL/min/1.73 m2/year) were also examined. RESULTS: The eGFR slope was significantly milder after dapagliflozin treatment (p < 0.01). A deeper initial dip was associated with a milder rate of eGFR decline (adjusted beta: - 0.29, p < 0.001). Dapagliflozin treatment reduced the proportion of rapid eGFR decliners from 52.9 to 14.7%, and a smaller initial dip was identified as a significant risk for post-treatment rapid eGFR decline (adjusted odds ratio: 1.73, p < 0.05). CONCLUSIONS: Compared to before the administration of dapagliflozin, the rate of eGFR decline was significantly milder after its administration. The initial dip was significantly associated with long-term renoprotective effects and may be a useful predictor of treatment response.

HBD1 protein with a tandem repeat of two HMG-box domains is a DNA clip to organize chloroplast nucleoids in Chlamydomonas reinhardtii.

Compaction of bulky DNA is a universal issue for all DNA-based life forms. Chloroplast nucleoids (chloroplast DNA-protein complexes) are critical for chloroplast DNA maintenance and transcription, thereby supporting photosynthesis, but their detailed structure remains enigmatic. Our proteomic analysis of chloroplast nucleoids of the green alga Chlamydomonas reinhardtii identified a protein (HBD1) with a tandem repeat of two DNA-binding high mobility group box (HMG-box) domains, which is structurally similar to major mitochondrial nucleoid proteins transcription factor A, mitochondrial (TFAM), and ARS binding factor 2 protein (Abf2p). Disruption of the HBD1 gene by CRISPR-Cas9-mediated genome editing resulted in the scattering of chloroplast nucleoids. This phenotype was complemented when intact HBD1 was reintroduced, whereas a truncated HBD1 with a single HMG-box domain failed to complement the phenotype. Furthermore, ectopic expression of HBD1 in the mitochondria of yeast Δabf2 mutant successfully complemented the defects, suggesting functional similarity between HBD1 and Abf2p. Furthermore, in vitro assays of HBD1, including the electrophoretic mobility shift assay and DNA origami/atomic force microscopy, showed that HBD1 is capable of introducing U-turns and cross-strand bridges, indicating that proteins with two HMG-box domains would function as DNA clips to compact DNA in both chloroplast and mitochondrial nucleoids.

Dual Chalcogen-Bonding Interactions for the Conformational Control of Urea.

Dual chalcogen-bonding interactions is proposed as a novel means for the conformational control of urea derivatives. The formation of a chalcogen-bonding interaction at both sides of the urea carbonyl group was unambiguously confirmed by X-ray diffraction as well as computational studies including non-covalent interaction (NCI) plot index analysis, quantum theory of atoms in molecules (QTAIM) analysis, and natural bond orbital (NBO) analysis via DFT calculations. By virtue of this dual interaction, urea derivatives that bear chalcogen atoms (X=S and Se) adopt a planar structure via the carbonyl oxygen (O) with an X⋅⋅⋅O⋅⋅⋅X arrangement on the same side of the molecule. The rigidity of the conformational lock was evaluated using the molecular arrangement in the crystal and the rotational barrier of benzochalcogenophene ring, which indicated a stronger conformational lock in benzoselenophene than in benzothiophene urea derivatives. Furthermore, the acidity of the urea derivatives increases according to the Lewis-acidic properties of the chalcogen-bonding interactions, whereby benzoselenophene urea is more acidic than benzothiophene urea. Tweezer-shaped urea derivatives were prepared, and their stereostructure proved the viability of the conformational control for defining the location of the substituents on the urea framework.

Cigarette smoke induces mitochondrial DNA damage and activates cGAS-STING pathway: application to a biomarker for atherosclerosis.

Cigarette smoking is a major risk factor for atherosclerosis. We previously reported that DNA damage was accumulated in atherosclerotic plaque, and was increased in human mononuclear cells by smoking. As vascular endothelial cells are known to modulate inflammation, we investigated the mechanism by which smoking activates innate immunity in endothelial cells focusing on DNA damage. Furthermore, we sought to characterize the plasma level of cell-free DNA (cfDNA), a result of mitochondrial and/or genomic DNA damage, as a biomarker for atherosclerosis. Cigarette smoke extract (CSE) increased DNA damage in the nucleus and mitochondria in human endothelial cells. Mitochondrial damage induced minority mitochondrial outer membrane permeabilization, which was insufficient for cell death but instead led to nuclear DNA damage. DNA fragments, derived from the nucleus and mitochondria, were accumulated in the cytosol, and caused a persistent increase in IL-6 mRNA expression via the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway. cfDNA, quantified with quantitative PCR in culture medium was increased by CSE. Consistent with in vitro results, plasma mitochondrial cfDNA (mt-cfDNA) and nuclear cfDNA (n-cfDNA) were increased in young healthy smokers compared with age-matched nonsmokers. Additionally, both mt-cfDNA and n-cfDNA were significantly increased in patients with atherosclerosis compared with the normal controls. Our multivariate analysis revealed that only mt-cfDNA predicted the risk of atherosclerosis. In conclusion, accumulated cytosolic DNA caused by cigarette smoke and the resultant activation of the cGAS-STING pathway may be a mechanism of atherosclerosis development. The plasma level of mt-cfDNA, possibly as a result of DNA damage, may be a useful biomarker for atherosclerosis.

Oxidative Deprotection of Benzyl Protecting Groups for Alcohols by an Electronically Tuned Nitroxyl-Radical Catalyst.

The oxidative deprotection of benzyl (Bn) groups using nitroxyl-radical catalyst 1 and co-oxidant phenyl iodonium bis(trifluoroacetate) (PIFA) is reported. This catalyst is highly active for the oxidation of benzylic ethers because of the electronic tuning on account of the electron-withdrawing ester groups next to the catalytically active center. This catalytic system promotes deprotections at ambient temperature and has a broad substrate scope, including substrates possessing hydrogenation-sensitive functional groups, while the deprotection hardly proceeds when using well-known nitroxyl-radical catalysts such as 2,2,6,6-tetramethylpiperidine N-oxyl (TEMPO). The 1/PIFA system also promotes the deprotection of several benzylic protecting groups, including 2-naphthylmethyl (NAP) and 4-methylbenzyl (MBn) groups. Catalyst 1 was also effective for the direct synthesis of ketones and aldehydes from Bn ethers via deprotected alcohols using an excess of the co-oxidant PIFA.

The implication of calf circumference and grip strength in osteoporosis and bone mineral density among hemodialysis patients.

BACKGROUND: Chronic kidney disease-mineral and bone disorder (CKD-MBD), nutritional status, and uremia management have been emphasized for bone management in hemodialysis patients. Nevertheless, valuable data on the importance of muscle mass in bone management are limited, including whether conventional management alone can prevent osteoporosis. Thus, the importance of muscle mass and strength, independent of the conventional management in osteoporosis prevention among hemodialysis patients, was evaluated. METHODS: Patients with a history of hemodialysis 6 months or longer were selected. We assessed the risk for osteoporosis associated with calf circumference or grip strength using multivariable adjustment for indices of CKD-MBD, nutrition, and dialysis adequacy. Moreover, the associations between bone mineral density (BMD), calf circumference, grip strength, and bone metabolic markers were also evaluated. RESULTS: A total of 136 patients were included. The odds ratios (95% confidence interval) for osteoporosis at the femoral neck were 1.25 (1.04-1.54, P < 0.05) and 1.08 (1.00-1.18, P < 0.05) per 1 cm shorter calf circumference or 1 kg weaker grip strength, respectively. Shorter calf circumference was significantly associated with a lower BMD at the femoral neck and lumbar spine (P < 0.001). Weaker grip strength was also associated with lower BMD at the femoral neck (P < 0.01). Calf circumference or grip strength was negatively correlated with bone metabolic marker values. CONCLUSION: Shorter calf circumference or weaker grip strength was associated with osteoporosis risk and lower BMD among hemodialysis patients, independent of the conventional therapies.

Novel Capped-Needle Device: A Novel Safety Feature to Eliminate Air Bubbles in Hemodialysis.

INTRODUCTION: Air bubbles in the dialysis circuit are rarely visible after automatic priming; however, they are often visible after the needles are manually connected to the circuit. To prevent this issue, we thought to prime needles with a circuit at automatic priming by the hemodialysis machine. In order to achieve this idea, we designed and manufactured a novel capped needle to connect the needles to the extracorporeal circuit before the automatic priming of the hemodialysis machine. This study investigated the effectiveness of this novel capped needle and compared it with the conventional method for preventing air bubble contamination. METHODS: We tested novel capped needles ten times to evaluate whether the dialysis machine works appropriately and removes air bubbles even with the attached capped needle. Next, we performed 25 trials using the conventional method, in which skilled nurses manually connect the needle. In both methods, we thoroughly counted the air bubbles with our naked eyes. We predicted that the capped needle would leave few bubbles in the circuit. In order to evaluate fewer bubbles, we conducted an additional experiment using a microparticle counter to measure the size and number of the bubbles. RESULTS: We thoroughly searched for air bubbles during each of the ten tests but could not find any bubbles visible to the naked eye. In the conventional method, bubbles were visible in 29 out of 50 cases. The bubble count was significantly lower in the capped-needle method than in the conventional method (p < 0.0001, Pearson's χ2 test). In the additional experiments using the microparticle counter, the average remaining air volume in the extracorporeal circuit was 0.0999 ± 0.2438 nL when the priming was performed using the novel capped needles. CONCLUSION: The novel capped needle eliminated all visible bubbles efficiently and effectively; therefore, it could be a valuable device for hemodialysis treatment. The reduction of air from the dialysis circuit may improve patient prognosis.

Clinical availability and characteristics of multigene panel testing for recurrent/advanced gynecologic cancer.

BACKGROUND: Japan's health insurance covers multigene panel testing. This study aimed to determine the potential availability and utility of gene panel testing clinically in gynecologic oncology. METHODS: We analyzed the characteristics of patients with gynecologic cancer who underwent gene panel testing using FoundationOne® CDx or OncoGuide™ NCC Oncopanel between November 2019 and October 2022. RESULTS: Out of 102 patients analyzed, 32, 18, 43, 8, and 1 had cervical, endometrial, ovarian cancers, sarcoma, and vaginal cancer, respectively. Druggable gene alteration was found in 70 patients (68.6%; 21 with cervical cancer, 15 with endometrial cancer, 28 with ovarian cancer, 5 with sarcoma, and 1 with other). The most common druggable gene alteration was PIK3CA mutation (n = 21), followed by PTEN mutation (n = 12) and high tumor mutation burden (TMB-H) (n = 11). TMB-H was detected in 5 patients with cervical cancer, 5 with endometrial cancer, and 1 with endometrial stromal sarcoma. Eleven patients (10.8%) received molecularly targeted therapy according to their gene aberrations. Gene panel testing was mostly performed when the second-line treatment was ineffective. Of all 102 patients, 60 did not have recommended treatment, and 15 died or had worsened conditions before obtaining the test results. CONCLUSION: Through multigene panel testing, although many patients had druggable gene alterations, 10.8% of them received the recommended treatment. TMB-H was mainly observed in cervical/endometrial cancer, suggesting its potential as a therapeutic biomarker of immune checkpoint inhibitors. Furthermore, patients' prognosis and performance status should be considered before performing the test.

Chapter 2:indications and dosing of anticancer drug therapy in patients with impaired kidney function, from clinical practice guidelines for the management of kidney injury during anticancer drug therapy 2022.

This comprehensive review discusses the dosing strategies of cancer treatment drugs for patients with impaired kidney function, specifically those with chronic kidney disease (CKD), undergoing hemodialysis, and kidney transplant recipients. CKD patients often necessitate dose adjustments of chemotherapeutic agents, e.g., platinum preparations, pyrimidine fluoride antimetabolites, antifolate agents, molecularly targeted agents, and bone-modifying agents, to prevent drug accumulation and toxicity due to diminished renal clearance of the administered drugs and their metabolites. In hemodialysis patients, factors such as drug removal from hemodialysis and altered pharmacokinetics demand careful optimization of anticancer drug therapy, including dose adjustment and timing of administration. While free cisplatin is removed by hemodialysis, most of the tissue- and protein-bound cisplatin remains in the body and rebound cisplatin elevations are observed after hemodialysis. It is not recommended hemodialysis for drug removal, regardless of timing. Kidney transplant patients encounter unique challenges in cancer treatment, as maintaining the balance between reduction of immunosuppression, switching to mTOR inhibitors, and considering potential drug interactions with chemotherapeutic agents and immunosuppressants are crucial for preventing graft rejection and achieving optimal oncologic outcomes. The review underscores the importance of personalized, patient-centric approaches to anticancer drug therapy in patients with impaired kidney function.

Cytopathological features associated with POLE mutation in endometrial cancer.

OBJECTIVE: For patients with endometrial cancer, the POLE (polymerase epsilon) mutation (POLEmut)-subtype, one of four molecular-analysis-based categories in the Cancer Genome Atlas (TCGA), has the best prognosis. The following histological characteristics are typically observed in endometroid carcinoma cases with the POLEmut-subtype: (1) the presence of tumour giant cells, (2) numerous tumour-infiltrating lymphocytes (TILs) and/or peri-tumoral lymphocytes, and (3) a high grade. However, in the context of cytology, the morphological characteristics of this subtype remain unknown. METHODS: DNA extracted from formalin-fixed paraffin-embedded (FFPE) tissues was subjected to next-generation sequencing analysis and categorised according to the TCGA classifications. Genomic mutation, tumour mutation burden (TMB), and microsatellite instability were also assessed. Cytological specimens of resected uteri obtained using the Papanicolaou method were histologically separated into three types. RESULTS: Seven out of 112 patients (6%) with endometrial cancer were diagnosed with the POLEmut-subtype between January 2019 and August 2021. Tumour giant cells were observed in three cases (43%) on histology and cytology. TIL and/or peritumoral lymphocytes with inflammatory cells were detected in five cases (71%) on histology and three cases (43%) on cytology. Cases in which these three characteristics were observed on both cytology and histology may have belonged to the POLEmut-subtype. There were no cases in which these characteristics were absent on histology but present on cytology. TMB tended to be higher in cases when the three characteristics were observed in both cytological and histological findings. CONCLUSIONS: Preoperative endometrial cytology highlighted the characteristics of the POLEmut-subtype in the histological analysis of resected uterine specimens and has the potential to play an important role in treatment decisions.

Molecular biological analysis revealed a case of synchronous endometrial and ovarian cancer with different histological grade as metastatic ovarian cancer from endometrial cancer: Case report and review of literature.

The diagnosis of synchronous endometrial and ovarian cancer or metastatic cancer of the same histological type is difficult. In this study, molecular biology analysis was performed to determine ovarian metastasis from endometrial cancer. A 38-year-old woman had pathological evidence of endometrial cancer (endometrioid carcinoma, grade 1) and ovarian cancer (endometrioid carcinoma, grade 3); a disseminated nodule in the serosa uteri was also diagnosed as endometrioid carcinoma (grade 3). Customized panel sequencing revealed a common mutation pattern in ovarian cancer and disseminated nodules. Furthermore, endometrial cancer showed the same mutation patterns for FGFR3 and PTEN as ovarian cancer and disseminated nodules. All tumors were microsatellite instability high. Clinicopathological and molecular biology analyses suggested that the patient had ovarian metastasis from endometrial cancer. The patient underwent adjuvant chemotherapy with paclitaxel and carboplatin, with no recurrence. Molecular biology techniques may enable appropriate treatment based on clinically accurate diagnosis.

Effect of quantitative partial valgus stress during baseball pitching on ball velocity and subjective pitch-effort.

BACKGROUND: Excessive elbow valgus stress can often cause pitching elbow injuries, and rehabilitation is usually required before an athlete can resume playing. However, there is a lack of information on the partial load rehabilitation of pitching elbow injuries caused by valgus extension overload based on elbow valgus stress. The purpose of this study was to clarify how quantitative partial elbow valgus stress while pitching affects ball velocity and subjective pitch-effort. METHODS: Forty-six male baseball pitchers participated in this study. Each player wore a wearable device on the elbow that collected their pitch parameters. Ball velocity was measured using a radar gun. Each elbow valgus stress was measured while each player was instructed to throw 5 fastballs at full effort. Then, based on the average stress of the 5 throws (100% partial valgus stress), the 75% and 50% stresses were calculated (75% and 50% partial valgus stress, respectively). Each pitcher continued to pitch until the number of pitches thrown at the targeted elbow stress reached 5. Each player was asked about their subjective pitch-effort after completing each type of partial valgus stress pitch. Outcomes were statistically evaluated using either a 1-way repeated measures analysis of variance or 2-way analysis of variance. RESULTS: The ball velocity was 72% (95% confidence interval [CI], 69%-75%) and 58% (95% CI, 55%-61%) during the 75% and 50% partial valgus stress, respectively (P < .001). Subjective pitch-effort was 41% (95% CI, 38%-44%) and 19% (95% CI, 16%-22%) while pitching at 75% and 50% partial valgus stress, respectively (P < .001). CONCLUSIONS: It may be desirable to instruct pitchers to throw at less than 20% subjective pitch-effort of the max if they want to pitch at 50% partial valgus stress. Elbow valgus stress might correlate with ball velocity at 75% partial valgus stress pitch. These results could enable clinicians and coaches to perform safer return-to-throwing programs and prevent excessive load on the elbow.

Renin-angiotensin-aldosterone system inhibitors as a risk factor for chronic subdural hematoma recurrence: A matter of debate.

OBJECTIVES: Chronic subdural hematoma (cSDH) is a common central nervous system condition. Recent reports indicate that cSDH affects long-term prognosis; however, its definitive risk factors remain unknown. An antihypertensive drug, renin-angiotensin-aldosterone system inhibitors (RAASi), can affect vascular permeability and cell proliferation processes, which may suppress the recurrence of cSDH. However, several studies have reported negative results to this effect. Therefore, we aimed to evaluate antihypertensive drugs, including RAASi, as risk factors for recurrent cSDH. MATERIALS AND METHODS: A total of 203 consecutive cases of surgically treated cSDH were retrospectively reviewed. Clinical and radiological parameters were compared between the groups with and without cSDH recurrence to identify risk factors. RESULTS: Of the included cases, 68 (33.5%) used RAASi and 37 (18.2%) developed recurrence within 60 days of surgery. In the multiple logistic regression analysis adjusted by composite risk score, the odds ratios (95% confidence interval) of RAASi, calcium channel blockers, diuretics, ß and α blockers, for the recurrent risk of cSDH after surgery were 2.49 (1.16, 5.42), 1.79 (0.84, 3.82), 1.83 (0.62, 4.87), 0.90 (0.28, 2.44), and 0.96 (0.21, 3.20), respectively. The Cox proportional hazard model also demonstrated that RAASi-use was an independent risk factor for cSDH recurrence. CONCLUSIONS: Present series suggests RAASi-use as a risk factor for cSDH recurrence, although the role of RAASi-use in cSDH remains debatable. Further studies for deeper understanding of the microenvironment of hematoma and the surroundings are preferable. (235 words).

Omega-3 Fatty Acids Reduce Remnant-like Lipoprotein Cholesterol and Improve the Ankle-Brachial Index of Hemodialysis Patients with Dyslipidemia: A Pilot Study.

Background and Objectives: Omega-3 fatty acids have potent lipid-lowering and antiplatelet effects; however, randomized controlled trials have yet to examine the effect of high-dose omega-3 fatty acid administration on peripheral artery disease (PAD) in hemodialysis patients with dyslipidemia. Therefore, this study aimed to evaluate the effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on the ankle-brachial index (ABI) and remnant-like lipoprotein cholesterol (RLP-C) levels, which are indicators of PAD severity. Materials and Methods: Thirty-eight participants (mean age: 73.6 ± 12.7 years) were randomly assigned using stratified block randomization to either conventional therapy alone or conventional therapy supplemented with high-dose EPA/DHA (EPA: 1860 mg; DHA: 1500 mg) for a three-month intervention period. Patients in the conventional therapy alone group who opted to continue were provided with a low-dose EPA/DHA regimen (EPA: 930 mg; DHA: 750 mg) for an additional three months. The baseline and 3-month values for RLP-C, an atherogenic lipid parameter, and the ABI were recorded. Results: The results of the 3-month assessments revealed that the mean RLP-C changes were -3.25 ± 3.15 mg/dL and 0.44 ± 2.53 mg/dL in the EPA/DHA and control groups, respectively (p < 0.001), whereas the changes in the mean ABI values were 0.07 ± 0.11 and -0.02 ± 0.09 in the EPA/DHA and control groups, respectively (p = 0.007). In the EPA/DHA group, a significant negative correlation was found between the changes in RLP-C levels and the ABI (r = -0.475, p = 0.04). Additionally, the change in the RLP-C levels independently influenced the change in the ABI in the EPA/DHA group, even after adjusting for age, sex, and statin use (p = 0.042). Conclusions: Add-on EPA/DHA treatment improved the effectiveness of conventional therapy (such as statin treatment) for improving the ABI in hemodialysis patients with dyslipidemia by lowering RLP-C levels. Therefore, clinicians involved in dialysis should focus on RLP-C when considering residual cardiovascular disease risk in hemodialysis patients and should consider screening patients with elevated levels.

One-Pot Preparation of (NH)-Phenanthridinones and Amide-Functionalized [7]Helicene-like Molecules from Biaryl Dicarboxylic Acids.

A one-pot transformation of biaryl dicarboxylic acids to (NH)-phenanthridinone derivatives based on a Curtius rearrangement and subsequent basic hydrolysis was developed. This method is also applicable for the preparation of optically active amide-functionalized [7]helicene-like molecules. Furthermore, aza[5]helicene derivatives with a phosphate moiety were isolated as a product of the Curtius rearrangement step in the case of substrates that bear chalcogen atoms. The stereostructures of these products, revealed by X-ray diffraction analysis, suggested that chalcogen-bonding and pnictogen-bonding interactions might contribute to their stabilization. The configurational stability of the helicene-like molecules and their chiroptical properties were further investigated.

Clinical and pathological analysis of companion diagnostic testing of microsatellite instability-high for pembrolizumab in gynaecologic malignancy.

BACKGROUND: Microsatellite instability-high is a known biomarker for anti-PD-1/PD-L1 immune checkpoint therapy. It is also a known tumour feature of Lynch syndrome, detected most frequently in endometrial cancer. However, it remains unclear how microsatellite instability testing is carried out in the clinical field. METHODS: Ninety-nine patients with gynaecological malignant tumours who underwent microsatellite instability testing as a companion diagnosis for pembrolizumab and 16 patients who previously underwent microsatellite instability testing as a screening for Lynch syndrome were recruited. Clinical information, microsatellite instability status, outcomes, genetic assessments and information about cancer tissue were retrospectively analysed. RESULTS: Ninety-nine patients had 101 gynaecologic malignant tumours including 26 endometrial, 38 ovarian and 28 cervical cancers, 9 with other tumours including 2 synchronous endometrial and ovarian cancers. All tissue samples were successfully tested, even though some were ≥10-year-old samples. Three cases (3.0%, 3/99) showed microsatellite instability-high; all cases were endometrial cancers with one case of synchronous endometrial and ovarian cancer [11.5% (3/26) in endometrial cancer, 2.6% (1/38) in ovarian cancer], and there was no microsatellite instability-high in cervical and other cancers. One of the endometrial cancer patients received pembrolizumab treatment, but finally died of cancer. Two other cases underwent genetic testing; both were diagnosed as Lynch syndrome. Six cases (37.5%) showed microsatellite instability-high in screening for Lynch syndrome. CONCLUSIONS: Microsatellite instability-high was less commonly detected as a companion diagnosis for pembrolizumab in unselected gynaecologic patients. Genetic counselling should be always provided along with treatment selection.

Left ventricular longitudinal strain is a major determinant of CT-derived three-dimensional maximum principal strain: comparison with two-dimensional speckle tracking echocardiography.

Computed tomography (CT)-derived three-dimensional maximum principal strain (MP-strain) can provide incremental value to coronary CT angiography for cardiac dysfunction assessment with high diagnostic performance in patients with myocardial infarction. Global longitudinal strain (GLS) measured using two-dimensional speckle tracking echocardiography (2D-STE) is more sensitive than left ventricular ejection fraction (LVEF) for detecting early myocardial dysfunction. We aimed to compare CT-derived MP-strain with each of 2D-STE-derived strains (i.e., longitudinal, circumferential, and radial strains), and identify the major determinants of CT-derived MP-strain among 2D-STE-derived strains. We studied 51 patients who underwent cardiac CT and echocardiography. CT images were reconstructed at every 5% (0-95%) of the RR interval. A dedicated workstation was used to analyze CT-derived MP-strain on the 16-segment model. We calculated CT-derived global MP-strain with all the 16 segments on a per patient basis. Pearson's test was used to assess correlations between CT-derived MP-strain and STE-strain at global and segmental levels. The intra-class correlation coefficient for interobserver agreement for CT-derived global MP-strain was 0.98 (95% confidence interval 0.96-0.99). The low-CT-derived global MP-strain group (≤ 0.43) had more patients with LV dysfunction than the high-CT-derived global MP-strain group (> 0.43). CT-derived global MP-strain was associated with STE-GLS (r = 0.738, P < 0.001), global circumferential strain (r = 0.646, P < 0.001), and global radial strain (r = 0.432, P = 0.001). In multivariate analysis, STE-GLS had the strongest association to CT-derived global MP-strain among three directional STE-strains and LVEF by echocardiography (standardized coefficient = - 0.527, P < 0.001). STE-GLS is a major determinant of CT-derived global MP-strain. CT-derived MP-strain may enhance the value of coronary CT angiography by adding functional information to CT-derived LVEF.