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We report the result of a search for neutrinos in coincidence with solarflares from the GOES flare database. The search was performed on a 10.8kton-year exposure of KamLAND collected from 2002 to 2019. This large exposureallows us to explore previously unconstrained parameter space for solar flareneutrinos. We found no statistical excess of neutrinos and established 90%confidence level upper limits of $8.4 \times 10^7$ cm$^{-2}$ ($3.0 \times10^{9}$ cm$^{-2}$) on electron anti-neutrino (electron neutrino) fluence at 20MeV normalized to the X12 flare, assuming that the neutrino fluence isproportional to the X-ray intensity.

We present the results of a search for MeV-scale electron antineutrino events in KamLAND coincident with the 60 gravitational wave events/candidates reported by the LIGO/Virgo collaboration during their second and third observing runs. We find no significant coincident signals within a 500 s timing window from each gravitational wave and present 90% C.L. upper limits on the electron antineutrino fluence between 108 and 1013 cm-2 for neutrino energies in the energy range of 1.8-111 MeV.

There are many theories where a dark matter particle is part of a multipletwith an electrically charged state. If WIMP dark matter ($\chi^{0}$) isaccompanied by a charged excited state ($\chi^{-}$) separated by a small massdifference, it can form a stable bound state with a nucleus. In supersymmetricmodels, the $\chi^{0}$ and the $\chi^{-}$ could be the neutralino and a chargedslepton, such as the neutralino-stau degenerate model. The formation bindingprocess is expected to result in an energy deposition of {\it O}(1--10 MeV),making it suitable for detection in large liquid scintillator detectors. Wedescribe new constraints on the bound state formation with a xenon nucleususing the KamLAND-Zen 400 Phase-II dataset. In order to enlarge the searchableparameter space, all xenon isotopes in the detector were used. For a benchmarkparameter set of $m_{\chi^{0}} = 100$ GeV and $\Delta m = 10$ MeV, this studysets the most stringent upper limits on the recombination cross section$\langle\sigma v\rangle$ and the decay-width of $\chi^{-}$ of $2.0 \times10^{-31}$ ${\rm cm^3/s}$ and $1.1 \times 10^{-18}$ GeV, respectively (90\%confidence level).

The tomato industry is a relevant socio-economic activity in the European Union, while it generates a large variety of residues. Tomatoes unfit for consumption, tomato peels, seeds, industrial pomace, and plants are examples of residues of this industry. Commonly, some of the residues can be left in the field, composted, used for animal feeding, or valorized through anaerobic digestion. However, more economic value can be attributed to these residues if a biorefinery approach is applied. Indeed, many value-added compounds can be obtained by the integration of different processes while closing the carbon and nutrient loops. The extraction of bioactive compounds followed by anaerobic digestion and composting seems to be a viable proposal for a biorefinery approach. Thus, this study aims to review the biorefinery strategies for valorizing tomato residues, highlighting the main processes proposed. The recovery of lycopene, β-carotene, and phenolic compounds has been widely studied at the lab scale, while energy recovery has already been applied at the industrial scale. Although techno-economic analysis is scarce for tomato residue valorization processes, positive net present values (NPV) and low payback times (PBT) have been reported in the literature. Thus, more work comparing multiple extraction technologies and biorefinery strategies coupled with economic and environmental assessment should be performed to select the most promising management route for tomato residues.

Phosphorus (P) is a critical element for life, and wastewater treatment systems can be strategic points for its recovery, thereby avoiding eutrophication pollution in nature. The aim of this research was to investigate P recovery via struvite, namely in terms of the influence of operating parameters, coexisting interfering ions, and seeding. This paper focuses on synthetic solutions, although an assessment was performed on wastewater. The results of the assessment indicated that, in the synthetic solution, the minimum concentration for struvite precipitation is about 30 mg P/L, and that the Mg/P molar ratio of 1 promotes P removal efficiency with less contribution from other minerals. In order to assess the results in terms of real-world scenarios, the influence of coexisting ions (calcium and sodium) was investigated. Calcium was shown to have the greatest impact on the process, as 80% was removed for an initial concentration of 200 mg Ca/L. Indeed, these experiments generated an amorphous precipitate that did not contain struvite. The utilization of biomass ash (size < 63 µm) as seeding in crystallization increased the P removal efficiency compared to the sample without seed and helped to control the pH. The precipitation experiments with wastewater demonstrated good P removal efficiencies (over 90%) but indicated a reduction in the purity of the final product (struvite was a minor crystalline phase identified in XRD—15%wt).

Coagulopathy is a severe and frequent complication in critically ill patients, for which the pathogenesis and presentation may be variable depending on the underlying disease. Based on the dominant clinical phenotype, the current review differentiates between hemorrhagic coagulopathies, characterized by a hypocoagulable and hyperfibrinolysis state, and thrombotic coagulopathies with a systemic prothrombotic and antifibrinolytic phenotype. We discuss the differences in pathogenesis and treatment of the common coagulopathies., Author(s): Julie Helms [sup.1] [sup.2], Toshiaki Iba [sup.3], Jean Marie Connors [sup.4], Satoshi Gando [sup.5] [sup.6], Marcel Levi [sup.7] [sup.8], Ferhat Meziani [sup.1] [sup.2], Jerrold H. Levy [sup.9] Author Affiliations: [...]

Cabozantinib, which is used to treat renal cell and hepatocellular carcinomas, is often associated with dose-dependent adverse events. Monitoring the levels of cabozantinib in the blood may maximize the therapeutic effect and prevent serious adverse events. In this study, we developed a high-performance liquid chromatography–ultraviolet (HPLC–UV) method of measuring plasma cabozantinib concentration. Human plasma samples (50 µL) were processed by simple deproteinization with acetonitrile, followed by chromatographic separation on a reversed-phase column with an isocratic mobile phase of 0.5% KH₂PO4 (pH 4.5) and acetonitrile (43:57, v/v) at a flow rate of 1.0 mL/min, with a 250 nm ultraviolet detector. The calibration curve was linear over the concentration range (0.05–5 µg/mL) with a coefficient of determination of 0.99999. The accuracy of the assay ranged from −4.35% to 0.98%, and recovery was >96.04%. The measurement time was 9 min. These findings confirm the effectiveness of this HPLC–UV method for cabozantinib quantification in human plasma, which is sufficiently simple for use for monitoring patients in clinical settings.

Abstract This study aimed to identify the modifiable cardiovascular risk factors associated with longitudinal changes, which are nine functional and structural biological vascular aging indicators (BVAIs), to propose an effective method to prevent biological vascular aging. We conducted a longitudinal study of 697 adults (a maximum of 3636 BVAI measurements) who were, at baseline, aged between 26 and 85 years and whose BVAIs were measured at least twice between 2007 and 2018. The nine BVAIs were measured using vascular testing and an ultrasound device. Covariates were assessed using validated questionnaires and devices. During the mean follow-up period of 6.7 years, the average number of BVAI measurements ranged from 4.3 to 5.3. The longitudinal analysis showed a moderate positive correlation between the common carotid intima-media thickness (IMT) and chronological age in both men (r = 0.53) and women (r = 0.54). In the multivariate analysis, BVAIs were associated with factors such as age, sex, residential area, smoking status, blood clinical chemistry test levels, number of comorbidities, physical fitness, body mass, physical activity, and dietary intake. The IMT is the most useful BVAI. Our findings suggest that modifiable cardiovascular risk factors are associated with longitudinal changes in BVAI as represented by IMT.

Abstract Background The development of disseminated intravascular coagulation (DIC) in patients with sepsis has been repeatedly confirmed as a factor associated with poor prognosis. Anticoagulant therapy has been expected to improve sepsis patient outcomes, whereas no randomized controlled trials have demonstrated the survival benefit of anticoagulant therapies in non-specific overall sepsis. Patient selection based on the component of “high disease severity” in addition to “sepsis with DIC” has recently proved important in identifying appropriate targets for anticoagulant therapy. The aims of this study were to characterize “severe” sepsis DIC patients and to identify the patient population benefiting from anticoagulant therapy. Methods This retrospective sub-analysis of a prospective multicenter study included 1,178 adult patients with severe sepsis from 59 intensive care units in Japan from January 2016 to March 2017. We examined the association of patient outcomes, including organ dysfunction and in-hospital mortality, with the DIC score and prothrombin time-international normalized ratio (PT-INR), one of the components of the DIC score, using multivariable regression models including the cross-product term between these indicators. Multivariate Cox proportional hazard regression analysis with non-linear restricted cubic spline including a three-way interaction term (anticoagulant therapy × the DIC score × PT-INR) was also performed. Anticoagulant therapy was defined as the administration of antithrombin, recombinant human thrombomodulin, or their combination. Results In total, we analyzed 1013 patients. The regression model showed that organ dysfunction and in-hospital mortality deteriorated with higher PT-INR values in the range of

Preceding a core-collapse supernova (CCSN), various processes produce an increasing amount of neutrinos of all flavors characterized by mounting energies from the interior of massive stars. Among them, the electron antineutrinos are potentially detectable by terrestrial neutrino experiments such as KamLAND and Super-Kamiokande (SK) via inverse beta decay interactions. Once these pre-supernova (pre-SN) neutrinos are observed, an early warning of the upcoming CCSN can be provided. In light of this, KamLAND and SK, both located in the Kamioka mine in Japan, have been monitoring pre-SN neutrinos since 2015 and 2021, respectively. Recently, we performed a joint study between KamLAND and SK on pre-SN neutrino detection. A pre-SN alert system combining the KamLAND detector and the SK detector was developed and put into operation, which can provide a supernova alert to the astrophysics community. Fully leveraging the complementary properties of these two detectors, the combined alert is expected to resolve a pre-SN neutrino signal from a 15 M _⊙ star within 510 pc of the Earth at a significance level corresponding to a false alarm rate of no more than 1 per century. For a Betelgeuse-like model with optimistic parameters, it can provide early warnings up to 12 hr in advance.

Radiation accidents pose a significant risk, often stemming from inadequate calibration of radiation output, procedural lapses, and faults in radiation monitoring systems. Addressing these risks is pivotal, particularly in radiotherapy, where the precise functioning of linear accelerator (Linac) devices is crucial. This study delves into the quality control procedures applied to the Linac radiotherapy device within the Department of Radiotherapy at Pasar Minggu District Hospital. Drawing upon the renowned reference standards set by the AAPM Task Group 142 and BAPETEN Regulation No. K2N.2/MT-08, this research, conducted in November 2022, rigorously evaluated the mechanical, dosimetry, and safety aspects of the Linac device. The examination encompassed critical elements, including gantry angles, optical distance indicators, laser precision, collimator angles, light field size, and photon and electron beam outputs. Safety features such as door interlocks, audiovisual indicators, and radiation alert systems were scrutinized. The analysis reveals a reassuring finding: the Linac device at Pasar Minggu District Hospital adheres commendably to tolerance limits specified by reference standards across all measured parameters, indicating robust performance in mechanics, dosimetry, and safety. This meticulous quality control regimen has proven highly effective in ensuring the device's operational integrity and safety, affirming its reliability for precise radiotherapy treatments.

Background Supraphysiological oxygen administration causes unfavourable clinical outcomes in various diseases. This study aimed to determine whether hyperoxia would be associated with increased mortality in patients with severe infection.Methods A post-hoc analysis of a nationwide multicentre prospective observational study on sepsis (SPICE Study) was conducted, including adult patients admitted to the intensive care unit with available arterial partial pressure of oxygen (PaO2) at the treatment initiation for severe infection. Hyperoxia was defined as a PaO2 level of ≥300 mm Hg and in-hospital mortality was compared between patients with and without hyperoxia.Results Of the 563 patients eligible for the study, 49 had hyperoxia at treatment initiation for severe infection. The in-hospital all-cause mortality rates of patients with and without hyperoxia were 14 (29.2%) and 90 (17.6%), respectively. Inverse probability weighting analyses with propensity scores revealed the association between hyperoxia and increased in-hospital mortality rate (28.8% vs 18.8%; adjusted OR 1.75 (1.03 to 2.97); p=0.038), adjusting for patient demographics, comorbidities, site of infection, severity of infection, haemodynamic and respiratory status, laboratory data and location of patient at infection development. Acute lung injury developed more frequently in patients with hyperoxia on the following days after infection treatment, whereas sepsis-related mortality was comparable regardless of hyperoxia exposure.Conclusion Hyperoxia with PaO2 ≥300 mm Hg at treatment initiation of severe infection was associated with an increased in-hospital mortality rate in patients requiring intensive care. The amount of oxygen to administer to patients with severe infection should be carefully determined.Trial registration number University Hospital Medical Information Network Clinical Trial Registry (UMIN000027452).

We present a precision analysis of the ^{136}Xe two-neutrino ββ electron spectrum above 0.8 MeV, based on high-statistics data obtained with the KamLAND-Zen experiment. An improved formalism for the two-neutrino ββ rate allows us to measure the ratio of the leading and subleading 2νββ nuclear matrix elements (NMEs), ξ_{31}^{2ν}=-0.26_{-0.25}^{+0.31}. Theoretical predictions from the nuclear shell model and the majority of the quasiparticle random-phase approximation (QRPA) calculations are consistent with the experimental limit. However, part of the ξ_{31}^{2ν} range allowed by the QRPA is excluded by the present measurement at the 90% confidence level. Our analysis reveals that predicted ξ_{31}^{2ν} values are sensitive to the quenching of NMEs and the competing contributions from low- and high-energy states in the intermediate nucleus. Because these aspects are also at play in neutrinoless ββ decay, ξ_{31}^{2ν} provides new insights toward reliable neutrinoless ββ NMEs.

We present a precision analysis of the ^{136}Xe two-neutrino ββ electron spectrum above 0.8 MeV, based on high-statistics data obtained with the KamLAND-Zen experiment. An improved formalism for the two-neutrino ββ rate allows us to measure the ratio of the leading and subleading 2νββ nuclear matrix elements (NMEs), ξ_{31}^{2ν}=-0.26_{-0.25}^{+0.31}. Theoretical predictions from the nuclear shell model and the majority of the quasiparticle random-phase approximation (QRPA) calculations are consistent with the experimental limit. However, part of the ξ_{31}^{2ν} range allowed by the QRPA is excluded by the present measurement at the 90% confidence level. Our analysis reveals that predicted ξ_{31}^{2ν} values are sensitive to the quenching of NMEs and the competing contributions from low- and high-energy states in the intermediate nucleus. Because these aspects are also at play in neutrinoless ββ decay, ξ_{31}^{2ν} provides new insights toward reliable neutrinoless ββ NMEs.

Abstract The phase angle (PhA), measured via bioelectrical impedance analysis, is considered an indicator of cellular health, where higher values reflect higher cellularity, cell membrane integrity, and better cell function. This study aimed to examine the relationship between PhA and exercise habits or objectively measured physical activity. We included 115 people aged 32–69 years. The body composition and PhA were measured using a bioelectrical impedance device. Physical activity and sedentary behavior (SB) were assessed using a triaxial accelerometer. Exercise habits were also obtained through structured interviews, and participants were categorized into the no exercise habit (No-Ex), resistance training exercise habit (RT), or aerobic training exercise habit (AT) groups. Objectively measured moderate-to-vigorous physical activity or step count significantly correlated with PhA, independent of age, sex, height, percent body fat, body cell mass, and leg muscle power. In contrast, SB was not significant determinants of PhA. People who exercised regularly (RT or AT) had significantly higher PhA values than did those in the No-Ex group. Furthermore, the PhA was not significantly different between the RT and AT groups. Regularly engaging in exercise with moderate-to-vigorous intensity may improve or maintain muscle cellular health and muscle quality.

Background: KATP channels have diverse roles, including regulation of insulin secretion and blood flow, and protection against biological stress responses and are excellent therapeutic targets. Different subclasses of KATP channels exist in various tissue types due to the unique assemblies of specific pore-forming (Kir6.x) and accessory (SURx) subunits. The majority of pharmacological openers and blockers act by binding to SURx and are poorly selective against the various KATP channel subclasses.Methods and Results: We used 3D models of the Kir6.2/SUR homotetramers based on existing cryo-EM structures of channels in both the open and closed states to identify a potential agonist binding pocket in a functionally critical area of the channel. Computational docking screens of this pocket with the Chembridge Core chemical library of 492,000 drug-like compounds yielded 15 top-ranked “hits”, which were tested for activity against KATP channels using patch clamping and thallium (Tl+) flux assays with a Kir6.2/SUR2A HEK-293 stable cell line. Several of the compounds increased Tl+ fluxes. One of them (CL-705G) opened Kir6.2/SUR2A channels with a similar potency as pinacidil (EC50 of 9 µM and 11 μM, respectively). Remarkably, compound CL-705G had no or minimal effects on other Kir channels, including Kir6.1/SUR2B, Kir2.1, or Kir3.1/Kir3.4 channels, or Na+ currents of TE671 medulloblastoma cells. CL-705G activated Kir6.2Δ36 in the presence of SUR2A, but not when expressed by itself. CL-705G activated Kir6.2/SUR2A channels even after PIP2 depletion. The compound has cardioprotective effects in a cellular model of pharmacological preconditioning. It also partially rescued activity of the gating-defective Kir6.2-R301C mutant that is associated with congenital hyperinsulinism.Conclusion: CL-705G is a new Kir6.2 opener with little cross-reactivity with other channels tested, including the structurally similar Kir6.1. This, to our knowledge, is the first Kir-specific channel opener.

Abstract Disseminated intravascular coagulation (DIC) is one of the major organ dysfunctions associated with sepsis. This retrospective secondary analysis comprised data from a prospective multicenter study to investigate the age-related differences in the survival benefit of anticoagulant therapy in sepsis according to the DIC diagnostic criteria. Adult patients with severe sepsis based on the Sepsis-2 criteria were enrolled and divided into the following groups: (1) anticoagulant group (patients who received anticoagulant therapy) and (2) non-anticoagulant group (patients who did not receive anticoagulant therapy). Patients in the former group were administered antithrombin, recombinant human thrombomodulin, or their combination. The increases in the risk of hospital mortality were suppressed in the high-DIC-score patients aged 60–70 years receiving anticoagulant therapy. No favorable association of anti-coagulant therapy with hospital mortality was observed in patients aged 50 years and 80 years. Furthermore, anticoagulant therapy in the lower-DIC-score range increased the risk of hospital mortality in patients aged 50–60 years. In conclusion, anticoagulant therapy was associated with decreased hospital mortality according to a higher DIC score in septic patients aged 60–70 years. Anticoagulant therapy, however, was not associated with a better outcome in relatively younger and older patients with sepsis.

The article discusses the case of a 39-year-old woman with a history of atrial septal defect and sick sinus syndrome, who received a dual-chamber pacemaker. Initially, the pacemaker functioned well with a ventricular pacing rate of 1.3%, but this increased to 7.4% within three months. The device's Managed Ventricular Pacing (MVP) mode, which prioritizes native AV conduction to minimize unnecessary ventricular pacing, was effective but revealed complications with junctional rhythms.