Utility of synthetic MRI in predicting pathological complete response of various breast cancer subtypes prior to neoadjuvant chemotherapy.

AIM: To evaluate the usefulness of synthetic magnetic resonance imaging (MRI) performed before the initiation of neoadjuvant chemotherapy (NAC) in predicting whether breast cancers can achieve a pathological complete response (pCR) after the completion of NAC. MATERIALS AND METHODS: This retrospective study investigated 37 consecutive patients with 39 breast cancers (pCR: 14, and non-pCR: 25) who underwent dynamic contrast-enhanced (DCE)-MRI and synthetic MRI before the initiation of NAC. Using synthetic MRI images, quantitative values (T1 and T2 relaxation times, proton density [PD] and their standard deviations [SD]) were obtained in breast lesions, before (Pre-T1, Pre-T2, Pre-PD, SD of Pre-T1, SD of Pre-T2, SD of Pre-PD) and after (Gd-T1, Gd-T2, Gd-PD, SD of Gd-T1, SD of Gd-T2, SD of Gd-PD) contrast agent injection. The aforementioned quantitative values and several morphological features that were identified on DCE-MRI were compared between pCR and non-pCR. RESULTS: Multivariate analyses revealed that the SD of Pre-T2 (p=0.038) was significant and was an independent predictor of pCR, with an area under the receiver operating characteristics curve of 0.829. The sensitivity, specificity, and accuracy of the SD of Pre-T2 with an optimal cut-off value of 11.5 were 71.4%, 80%, and 76.3%, respectively. CONCLUSIONS: The SD of Pre-T2 obtained from synthetic MRI was used successfully to predict those breast cancers that would achieve a pCR after the completion of NAC; however, these results are preliminary and need to be verified by further studies.

Increased expression of Filaggrin and Claudin-1 in the ocular surface of patients with atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is an itchy, chronic and inflammatory skin condition, with dysfunctional immune response and skin barrier defects. Reduction of filaggrin (FLG) and tight junctions (TJ) proteins, such as claudin-1 (CLDN-1), expression in cutaneous epithelial barrier is remarkable in AD pathogenesis. Ocular involvement occurs in approximately 40% of AD patients leading to changes in the structure of the conjunctiva. OBJECTIVES: We aimed to evaluate the expression of FLG and CLDN-1 in the ocular surface of adults with AD, analysing bulbar conjunctival cells collected by a novel non-invasive cellular imprint. METHODS: Bulbar conjunctival epithelial cells were collected by cellular imprint technique, and FLG and CLDN-1 expression were assessed by immunofluorescence (IF) and real-time polymerase chain reaction (RT-PCR). RESULTS: We detected increased expression of FLG and CLDN-1, as well as their transcript levels in AD patients compared with healthy controls (HC). There was a positive correlation between tear film break-up time (TBUT) and FLG expression. Fluorescein staining was inversely associated with FLG expression. CONCLUSIONS: Our results may reflect a reactive response of the ocular surface to AD-related ocular inflammation and associated dry eye disease. Further investigations focusing on the role of FLG and TJ expression in the ocular surface of AD patients may increment the understanding of the pathophysiology of extracutaneous AD and developing future targeted therapies.

E_{8} Spectra of Quasi-One-Dimensional Antiferromagnet BaCo_{2}V_{2}O_{8} under Transverse Field.

We report ^{51}V NMR and inelastic neutron scattering (INS) measurements on a quasi-1D antiferromagnet BaCo_{2}V_{2}O_{8} under transverse field along the [010] direction. The scaling behavior of the spin-lattice relaxation rate above the Néel temperatures unveils a 1D quantum critical point (QCP) at H_{c}^{1D}≈4.7 T, which is masked by the 3D magnetic order. With the aid of accurate analytical analysis and numerical calculations, we show that the zone center INS spectrum at H_{c}^{1D} is precisely described by the pattern of the 1D quantum Ising model in a magnetic field, a class of universality described in terms of the exceptional E_{8} Lie algebra. These excitations are nondiffusive over a certain field range when the system is away from the 1D QCP. Our results provide an unambiguous experimental realization of the massive E_{8} phase in the compound, and open a new experimental route for exploring the dynamics of quantum integrable systems as well as physics beyond integrability.

Practices and perspectives of primary care physicians in Japan and the United States about diagnosing dementia: a qualitative study.

BACKGROUND: While dementia is a common problem in Japan and the US, primary care physicians' practices and perspectives about diagnosing dementia in these different healthcare systems are unknown. METHODS: Qualitative research was conducted in an ethnographic tradition using semi-structured interviews and thematic analysis in primary care settings across Japan and in the Midwest State of Michigan, US. Participants were a total of 48 primary care physicians, 24 each from Japan and the US participated. Both groups contained a mixture of geographic areas (rural/urban), gender, age, and years of experience as primary care physicians. RESULTS: Participants in Japan and the US voiced similar practices for making the diagnosis of dementia and held similar views about the desired benefits of diagnosing dementia. Differences were found in attitudes about the appropriate timing of formally diagnosing dementia. Japanese physicians tended to make a formal diagnosis when problems that would benefit from long-term care services emerged for family members. US physicians were more proactive in diagnosing dementia in the early stages by screening for dementia in health check-ups and promoting advance directives when the patients were still capable of decision-making. Views about appropriate timing of diagnostic testing for dementia in the two systems reflect what medical or nursing care services physicians can use to support dementia patients and caregivers. CONCLUSIONS: Benefits of making the diagnosis included the need to activate the long-term care services in Japan and for early intervention and authoring advance directives in the US. Testing to establish an early diagnosis of dementia by primary care physicians only partly relates to testing and treatment options available. Benefits of making the diagnosis included the need to activate the long-term care services in Japan and for early intervention and authoring advance directives in the US.

Intratumoural immune cell landscape in germinoma reveals multipotent lineages and exhibits prognostic significance.

AIMS: Alterations in microenvironments are a hallmark of cancer, and these alterations in germinomas are of particular significance. Germinoma, the most common subtype of central nervous system germ cell tumours, often exhibits massive immune cell infiltration intermingled with tumour cells. The role of these immune cells in germinoma, however, remains unknown. METHODS: We investigated the cellular constituents of immune microenvironments and their clinical impacts on prognosis in 100 germinoma cases. RESULTS: Patients with germinomas lower in tumour cell content (i.e. higher immune cell infiltration) had a significantly longer progression-free survival time than those with higher tumour cell contents (P = 0.03). Transcriptome analyses and RNA in-situ hybridization indicated that infiltrating immune cells comprised a wide variety of cell types, including lymphocytes and myelocyte-lineage cells. High expression of CD4 was significantly associated with good prognosis, whereas elevated nitric oxide synthase 2 was associated with poor prognosis. PD1 (PDCD1) was expressed by immune cells present in most germinomas (93.8%), and PD-L1 (CD274) expression was found in tumour cells in the majority of germinomas examined (73.5%). CONCLUSIONS: The collective data strongly suggest that infiltrating immune cells play an important role in predicting treatment response. Further investigation should lead to additional categorization of germinoma to safely reduce treatment intensity depending on tumour/immune cell balance and to develop possible future immunotherapies.

Utility of synthetic MRI in predicting the Ki-67 status of oestrogen receptor-positive breast cancer: a feasibility study.

AIM: To evaluate the utility of synthetic magnetic resonance imaging (MRI) of the breast in predicting the Ki-67 status in patients with oestrogen receptor (ER)-positive breast cancer. MATERIALS AND METHODS: Forty-nine patients with 50 histopathologically proven breast cancers who underwent additional synthetic MRI were enrolled in the present study. Using synthetic MRI images, T1 and T2 relaxation times and their standard deviations (SD) in the breast lesions before (T1-Pre, T2-Pre, PD-Pre, SD of T1-Pre, SD of T2-Pre, SD of PD-Pre) and after (T1-Gd, T2-Gd, PD-Gd, SD of T1-Gd, SD of T2-Gd, SD of PD-Gd) contrast agent injection were obtained. These quantitative values were compared between the low Ki-67 expression (<14%) lesions (low-proliferation group: n=23) and high Ki-67 expression (≥14%) lesions (high-proliferation group: n=27). RESULTS: The univariate analysis showed that the SD of T1-Gd (p<0.001) and T2-Gd (p=0.042) were significantly higher in the high-proliferation group than in the low-proliferation group. Multivariate analysis further showed that the SD of T1-Gd was a significant and independent predictor of Ki-67 expression, with an area under the receiver operating characteristic (AUROC) curve of 0.885. The sensitivity, specificity, and accuracy of the SD of T1-Gd with an optimal cut-off value of 98.5 were 77.8%, 87%, and 82%, respectively. CONCLUSION: The SD of T1-Gd obtained from synthetic MRI was useful to predict Ki-67 status.

Sustained effects of intralymphatic pollen-specific immunotherapy on Japanese cedar pollinosis.

BACKGROUND: Intralymphatic immunotherapy (ILIT) for allergic patients requires only a few intralymphatic injections of the allergen. However, the effectiveness and safety for Japanese cedar pollinosis are unclear. The objectives of this study were to clarify whether and how long ILIT is effective for pollinosis, and its safety. METHODS: In an open pilot investigation followed by a double-blind, placebo-controlled study, patients with Japanese cedar pollinosis received 3 intralymphatic inguinal injections of the pollen extracts before the first pollen season. The symptom medication score (SMS), nasal provocation testing and scoring visual analogue scale (VAS) were assessed after the first-third seasons. RESULTS: (1) Although mild adverse events were induced at the injected site, severe adverse events were not noted. (2) During the latter part of the first season, ILIT-treated patients (n=12) tended to show improved SMS compared to placebo-treated (n=6) without statistical significance. When assessed by nasal provocation testing and VAS scoring after the first season, the effectiveness of ILIT was significant. (3) The effects of ILIT continued until the second or third season. (4) Neither allergen-specific antibodies nor Treg/Breg cells changed in the peripheral blood. CONCLUSIONS: ILIT was safe and effective for Japanese cedar pollinosis. The clinical effects remained for 1-2 years.

Magnetic-Competition-Induced Colossal Magnetoresistance in n-Type HgCr_{2}Se_{4} under High Pressure.

The n-type HgCr_{2}Se_{4} exhibits a sharp semiconductor-to-metal transition (SMT) in resistivity accompanying the ferromagnetic order at T_{C}=106 K. Here, we investigate the effects of pressure and magnetic field on the concomitant SMT and ferromagnetic order by measuring resistivity, dc and ac magnetic susceptibility, as well as single-crystal neutron diffraction under various pressures up to 8 GPa and magnetic fields up to 8 T. Our results demonstrate that the ferromagnetic metallic ground state of n-type HgCr_{2}Se_{4} is destabilized and gradually replaced by an antiferromagnetic, most likely a spiral magnetic, and insulating ground state upon the application of high pressure. On the other hand, the application of external magnetic fields can restore the ferromagnetic metallic state again at high pressures, resulting in a colossal magnetoresistance (CMR) as high as ∼ 3×10^{11}% under 5 T and 2 K at 4 GPa. The present study demonstrates that n-type HgCr_{2}Se_{4} is located at a peculiar critical point where the balance of competition between ferromagnetic and antiferromagnetic interactions can be easily tipped by external stimuli, providing a new platform for achieving CMR in a single-valent system.

Coexistence of Ferromagnetic and Stripe-Type Antiferromagnetic Spin Fluctuations in YFe_{2}Ge_{2}.

We report neutron scattering measurements of single-crystalline YFe_{2}Ge_{2} in the normal state, which has the same crystal structure as the 122 family of iron pnictide superconductors. YFe_{2}Ge_{2} does not exhibit long-range magnetic order but exhibits strong spin fluctuations. Like the iron pnictides, YFe_{2}Ge_{2} displays anisotropic stripe-type antiferromagnetic spin fluctuations at (π, 0, π). More interesting, however, is the observation of strong spin fluctuations at the in-plane ferromagnetic wave vector (0, 0, π). These ferromagnetic spin fluctuations are isotropic in the (H, K) plane, whose intensity exceeds that of stripe spin fluctuations. Both the ferromagnetic and stripe spin fluctuations remain gapless down to the lowest measured energies. Our results naturally explain the absence of magnetic order in YFe_{2}Ge_{2} and also imply that the ferromagnetic correlations may be a key ingredient for iron-based materials.

Hepatobiliary phase hypointense nodule without arterial phase hyperenhancement as a risk factor for late recurrence (>1 year) of hepatocellular carcinoma after surgery.

AIM: To evaluate the value of magnetic resonance imaging (MRI) features, including liver stiffness measured by magnetic resonance elastography (MRE) and the presence of hepatobiliary phase (HBP) hypointense nodule without arterial phase hyperenhancement (APHE), for predicting late recurrence (>1 year) after surgery for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This retrospective study included 124 consecutive patients who had undergone surgery for HCC and preoperative MRI. After excluding patients with early recurrence within 1 year after surgery, 89 patients were analysed. Preoperative MRI images were reviewed by a radiologist to record imaging findings, including (1) liver stiffness by MRE, (2) size of the HCCs, (3) number of HCCs, and (4) presence of HBP hypointense nodule without APHE. Pathological findings included tumour grade, vascular/biliary/capsule invasion, and fibrosis stage of the liver. Considering imaging/pathological findings and patients' characteristics as dependent variables, Cox proportional hazards model analysis was performed to identify independent factors associated with late recurrence after surgery. RESULTS: The median follow-up period was 37.3 months. During follow-up, 29 patients (32.5%) developed late recurrence after surgery. In multivariate analysis, underlying liver disease (viral hepatitis) and presence of HBP hypointense nodules without APHE (p=0.010 and 0.033, respectively) were independently associated with disease-free survival (DFS). Kaplan-Meier analysis revealed that patients with HBP hypointense nodules without APHE had a significantly lower DFS rate than those without the nodule (39.2% versus 74.1% at 3 years after surgery, p=0.008). CONCLUSION: The presence of HBP hypointense nodules without APHE was an indicator of late recurrence after surgery for HCC.

Itinerant Antiferromagnetism in RuO_{2}.

Bulk rutile RuO_{2} has long been considered a Pauli paramagnet. Here we report that RuO_{2} exhibits a hitherto undetected lattice distortion below approximately 900 K. The distortion is accompanied by antiferromagnetic order up to at least 300 K with a small room temperature magnetic moment of approximately 0.05µ_{B} as evidenced by polarized neutron diffraction. Density functional theory plus U (DFT+U) calculations indicate that antiferromagnetism is favored even for small values of the Hubbard U of the order of 1 eV. The antiferromagnetism may be traced to a Fermi surface instability, lifting the band degeneracy imposed by the rutile crystal field. The combination of high Néel temperature and small itinerant moments make RuO_{2} unique among ruthenate compounds and among oxide materials in general.

Orbital Glass State of the Nearly Metallic Spinel Cobalt Vanadate.

Strain, magnetization, dielectric relaxation, and unpolarized and polarized neutron diffraction measurements were performed to study the magnetic and structural properties of spinel Co_{1-x}V_{2+x}O_{4}. The strain measurement indicates that, upon cooling, ΔL/L in the order of ∼10^{-4} starts increasing below T_{C}, becomes maximum at T_{max}, and then decreases and changes its sign at T^{*}. Neutron measurements indicate that a collinear ferrimagnetic order develops below T_{C} and upon further cooling noncollinear ferrimagnetic ordering occurs below T_{max}. At low temperatures, the dielectric constant exhibits a frequency dependence, indicating slow dynamics. These results indicate the existence of an orbital glassy state at low temperatures in this nearly metallic frustrated magnet.

Static and Dynamical Properties of the Spin-1/2 Equilateral Triangular-Lattice Antiferromagnet Ba_{3}CoSb_{2}O_{9}.

We present single-crystal neutron scattering measurements of the spin-1/2 equilateral triangular-lattice antiferromagnet Ba_{3}CoSb_{2}O_{9}. Besides confirming that the Co^{2+} magnetic moments lie in the ab plane for zero magnetic field and then determining all the exchange parameters of the minimal quasi-2D spin Hamiltonian, we provide conclusive experimental evidence of magnon decay through observation of intrinsic line broadening. Through detailed comparisons with the linear and nonlinear spin-wave theories, we also point out that the large-S approximation, which is conventionally employed to predict magnon decay in noncollinear magnets, is inadequate to explain our experimental observation. Thus, our results call for a new theoretical framework for describing excitation spectra in low-dimensional frustrated magnets under strong quantum effects.

Magnetic Reversal of Electric Polarization with Fixed Chirality of Magnetic Structure in a Chiral-Lattice Helimagnet MnSb_{2}O_{6}.

The correlation between magnetic and dielectric properties has been investigated for the single crystal of the chiral triangular-lattice helimagnet MnSb_{2}O_{6}. We found that the spin-spiral plane in the ground state has a considerable tilting from the (110) plane and that the sign of the spin-spiral tilting angle is coupled to the clockwise or counterclockwise manner of spin rotation and accordingly to the sign of magnetically induced electric polarization. This leads to unique magnetoelectric responses such as the magnetic-field-induced selection of a single ferroelectric domain as well as the reversal of electric polarization just by a slight tilting of the magnetic field direction, where the chiral nature of the crystal structure plays a crucial role through the coupling of the chirality between the crystal and magnetic structures. Our results demonstrate that crystallographic chirality can be an abundant source of novel magnetoelectric functions with coupled internal degrees of freedom.

Transition from Sign-Reversed to Sign-Preserved Cooper-Pairing Symmetry in Sulfur-Doped Iron Selenide Superconductors.

An essential step toward elucidating the mechanism of superconductivity is to determine the sign or phase of the superconducting order parameter, as it is closely related to the pairing interaction. In conventional superconductors, the electron-phonon interaction induces attraction between electrons near the Fermi energy and results in a sign-preserved s-wave pairing. For high-temperature superconductors, including cuprates and iron-based superconductors, prevalent weak coupling theories suggest that the electron pairing is mediated by spin fluctuations which lead to repulsive interactions, and therefore that a sign-reversed pairing with an s_{±} or d-wave symmetry is favored. Here, by using magnetic neutron scattering, a phase sensitive probe of the superconducting gap, we report the observation of a transition from the sign-reversed to sign-preserved Cooper-pairing symmetry with insignificant changes in T_{c} in the S-doped iron selenide superconductors K_{x}Fe_{2-y}(Se_{1-z}S_{z})_{2}. We show that a rather sharp magnetic resonant mode well below the superconducting gap (2Δ) in the undoped sample (z=0) is replaced by a broad hump structure above 2Δ under 50% S doping. These results cannot be readily explained by simple spin fluctuation-exchange pairing theories and, therefore, multiple pairing channels are required to describe superconductivity in this system. Our findings may also yield a simple explanation for the sometimes contradictory data on the sign of the superconducting order parameter in iron-based materials.

Identification of Helicobacter pylori infection in symptomatic patients in Surabaya, Indonesia, using five diagnostic tests.

SUMMARY The prevalence of Helicobacter pylori infection in Indonesia is controversial. We examined the H. pylori infection rate in 78 patients in a hospital in Surabaya using five different tests, including culture, histology, immunohistochemistry, rapid urease test, and urine antibody test. Furthermore, we analysed virulence factors in H. pylori strains from Indonesia. The H. pylori infection rate was only 11.5% in all patients studied, and 2.3% of Javanese patients and 18.0% of Chinese patients were infected (P = 0.01). Although severe gastritis was not observed, activity and inflammation were significantly higher in patients positive for H. pylori than in patients negative for H. pylori. Among genotypes identified from five isolated strains, cagA was found in four; two were vacA s1m1. All cagA-positive strains were oipA 'on' and iceA1 positive. We confirmed both a low H. pylori infection rate and a low prevalence of precancerous lesions in dyspeptic patients in a Surabaya hospital, which may contribute to the low incidence of gastric cancer in Indonesia.

The association between risk factors and time of onset for thrombocytopenia in Japanese patients receiving linezolid therapy: a retrospective analysis.

WHAT IS KNOWN AND OBJECTIVE: Linezolid (LZD) is an oxazolidinone antibiotic that is active against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci. The major adverse effect related to its use in humans is reversible myelosuppression, which mostly manifests as thrombocytopenia. This retrospective study was conducted to identify risk factors that might contribute towards the development of thrombocytopenia due to intravenous administration of LZD. METHOD: Patients who were administered LZD between January 2008 and March 2013 were included. Thrombocytopenia was defined as a decrease in platelet count of ≥10 × 10(4) cell/µL from baseline or of ≥30%. RESULTS: A total of 47 patients were included in this study. These patients were divided into two groups: 22 patients (46·8%) were assigned to a non-thrombocytopenia group and 25 patients (53·2%) to a thrombocytopenia group. Multivariate logistic regression analysis revealed significant intergroup differences in duration of LZD treatment [odds ratio (OR) = 1·278; 95% confidence interval (CI) = 1·068-1·529; P = 0·007] and white blood cell (WBC) count (>12000 cells/µL; OR = 10·399; 95% CI = 1·667-64·882; P = 0·012). WHAT IS NEW AND CONCLUSIONS: This finding suggests that duration of LZD treatment and WBC count (>12000 cells/µL) are risk factors associated with thrombocytopenia resulting from LZD administration.

Comparison of antibiotic susceptibility in viridans group streptococci in low and high antibiotic-prescribing General Practices.

WHAT IS KNOWN AND OBJECTIVE: Antibiotic resistance has become a global public health issue. Most antibiotics are prescribed in the community, although there is less stewardship of such agents in the community compared to secondary and tertiary care. Few studies have attempted to examine the prescribing practices in General Practice and its impact on antibiotic resistance and, therefore, a study was performed in order to compare antibiotic susceptibilities of commensal viridans group streptococci (VGS) obtained from patient cohorts in General Practices (GP), who were high and low prescribers of oral antibiotics. METHOD: Sixty-five patients (<1 month-81 years; 77% female: 23% male) were enrolled onto the study, and viridans group streptococci (n = 5/patient) were collected from each patient's nasal passages and oropharynx region and tested for antibiotic susceptibility against (i) tetracyclines (doxycycline); (ii) macrolides (erythromycin); (iii) ß-lactams (penicillin G); and (iv) fluoroquinolones (ofloxacin & levofloxacin). RESULTS AND DISCUSSION: There were no significant differences in MICs between high and low GP prescribers with doxycycline (P = 0·094), erythromycin (P = 0·122), ofloxacin (P = 0·193) and levofloxacin (P = 0·058). However, there was a significant difference between high and low GP practices with regard to penicillin G (P = 0·031). This finding is important as the ß-lactams are the most commonly prescribed oral antibiotic in the community. WHAT IS NEW AND CONCLUSION: This study demonstrates that high prescribing practices may lead to an altered (higher) level of resistance to these agents in the commensal VGS population, which may be important as reservoirs of antibiotic resistance determinants in subsequent horizontal gene transfer events, particularly with newly colonizing pathogens, including pneumococci. Primary care physicians should be aware that increased prescribing of antibiotics may led to increased level of penicillin resistance.

Features of an alternative hemodialysis method using a hemoconcentrator during cardiopulmonary bypass surgeries.

PURPOSE: This study clarified the features of a hemoconcentrator-based, alternative hemodialysis (ALTHD) method that improves the speed of serum potassium (K(+)) concentration adjustments, compared with dilutional ultrafiltration (DUF), during cardiopulmonary bypasses. METHODS: Standardized bovine blood was recirculated (300 ml/min) through an in vitro hemoconcentrator circuit; hematocrit, K(+) and glucose levels were measured at 5-20 min after DUF or ALTHD. We evaluated DUF at dialysis speeds of 50-250 ml/min and ALTHD at speeds of 50-1000 ml/min. RESULTS: ALTHD rapidly corrected K(+) and glucose concentrations at speeds up to 800 ml/min. ALTHD took 8.9 min to reach a K(+) level of 4.5 mmol/L, faster than DUF (12.8 min). The ALTHD efficiency curves plateaued at 600 ml/min. CONCLUSION: ALTHD allowed faster adjustment of electrolyte levels, with peak efficiency at 600 ml/min. ALTHD has possible clinical application if available for potential use during all cardiopulmonary bypass surgeries involving extracorporeal circulation.