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A major limitation of immunotherapy is the development of resistance resulting from cancer-mediated inhibition of host lymphocytes. Cancer cells release CCL2 to recruit classical monocytes expressing its receptor CCR2 for the promotion of metastasis and resistance to immunosurveillance. In the circulation, some CCR2-expressing classical monocytes lose CCR2 and differentiate into intravascular nonclassical monocytes that have anticancer properties but are unable to access extravascular tumor sites. We found that in mice and humans, an ontogenetically distinct subset of naturally underrepresented CCR2-expressing nonclassical monocytes was expanded during inflammatory states such as organ transplant and COVID-19 infection. These cells could be induced during health by treatment of classical monocytes with small-molecule activators of NOD2. The presence of CCR2 enabled these inducible nonclassical monocytes to infiltrate both intra- and extravascular metastatic sites of melanoma, lung, breast, and colon cancer in murine models, and they reversed the increased susceptibility of [Nod2.sup.-/-] mutant mice to cancer metastasis. Within the tumor colonies, [CCR2.sup.+] nonclassical monocytes secreted CCL6 to recruit NK cells that mediated tumor regression, independent of T and B lymphocytes. Hence, pharmacological induction of [CCR2.sup.+] nonclassical monocytes might be useful for immunotherapy-resistant cancers., Introduction Tumors augment monopoiesis and orchestrate the epigenetic reprogramming of [CCR2.sup.+] classical monocytes (CMs) into tumor-associated macrophages that drive immune suppression to promote tumor progression, metastasis, and resistance to immunotherapy [...]

Akio Sakamoto, Shuzo Okudaira, Yuta Onishi, Takashi Noguchi, Shuichi Matsuda The Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, JapanCorrespondence: Akio Sakamoto, The Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Shogoin, Kawahara-cho 54, Sakyo-ku, Kyoto, 606-8507, Japan, Tel +8175-751-3366, Fax +81-75-751-8409, Email akiosaka@kuhp.kyoto-u.ac.jpAbstract: Stress fractures of the first rib are uncommon and thought to be associated with overhead-throwing athletes. Soft tennis is similar to regular tennis but uses a much softer rubber ball. In the current report, a 14-year-old girl suffered from shoulder girdle pain, especially at the end of her tennis ground stroke. Plain radiographs showed overgrowth of bone with a fracture line on the first rib, and a diagnosis of stress fracture was made. She was advised to amend her stroke form to reduce force to the shoulder and was able to continue sports activity without pain 10 months after the appearance of her symptoms and before confirmation of bone healing. The current case is not associated with overhead-throwing, but possibly with repetitive exercises of her tennis ground strokes. Conservative medical follow-up with proper sport-specific professional advice allows continuation of the sport.Plain Language Summary: Stress fractures of the first rib are rare, mainly linked to overhead-throwing athletes. Soft tennis resembles regular tennis but uses a softer rubber ball. In this case, a 14-year-old girl with shoulder girdle pain, especially during tennis strokes, was diagnosed with a first rib stress fracture via plain radiographs. She improved by adjusting her stroke and resumed sports pain-free within 10 months, even before full bone healing. This case was not linked to overhead-throwing but potentially resulted from repetitive ground strokes. Proper medical guidance supports sport continuation.Keywords: first rib, stress fracture, tennis, tennis stroke

Soichiro Matsuda,1 Yuki Igawa,1,2 Hidekazu Uchisawa,1,2 Shinya Iki,3 Michihiro Osumi1,4 1Graduate School of Health Sciences, Kio University, Nara, Japan; 2Department of Rehabilitation, Nishiyamato Rehabilitation Hospital, Nara, Japan; 3Department of Rehabilitation, Kawaguchi Neurosurgery Rehabilitation Clinic, Osaka, Japan; 4Neurorehabilitation Research Center, Kio University, Nara, JapanCorrespondence: Soichiro Matsuda, Graduate School of Health Sciences, Kio University, 4-2-2 Umaminaka, Kitakatsuragigun, Nara, 635-0832, Japan, Tel +745-54-1601, Fax +745-54-1600, Email f1996957@kio.ac.jpPurpose: In the thermal grill illusion, participants experience a feeling similar to burning pain. The illusion is induced by simultaneously touching warm and cool stimuli in alternating positions. In post-stroke pain, central sensitization is caused by a variety of factors, including damage to the spinothalamic tract and shoulder pain. Because the thermal grill illusion depends on central mechanisms, it has recently been suggested that it may be a useful indicator of central sensitization. Therefore, we hypothesized that post-stroke patients who are more likely to experience central sensitization may also be more likely to experience a thermal grill sensation of pain and discomfort than the likelihood among those who are less likely to experience central sensitization. However, the effects of the thermal grill illusion in post-stroke patients have not yet been reported. In this pilot study, we conducted the thermal grill illusion procedure in post-stroke patients and analyzed the relationship between clinical somatosensory functions and thermal grill sensations. We also conducted brain imaging analysis to identify brain lesion areas that were associated with thermal grill sensations.Patients and Methods: Twenty patients (65.7 ± 11.9 years old) with post-stroke patients participated in this study. The thermal grill illusion procedure was performed as follows: patients simultaneously touched eight water-filled copper bars, with the water temperature adjusted to provide alternate warm (40°C) and cold (20°C) stimuli.Results: Thermal grill sensation of pain and discomfort tended to be associated with the wind-up phenomenon in bedside quantitative sensory testing and thermal grill sensation of discomfort was also related to damage to the thalamic lateral nucleus.Conclusion: These findings suggest that the thermal grill illusion might measure central sensitization, and that secondary brain hyperactivity might lead to increased thermal grill sensations.Keywords: thermal grill illusion, post stroke pain, central sensitization, thalamus, insula

The KamLAND-Zen 800 experiment is searching for the neutrinoless double-beta decay of 136Xe by using 136Xe-loaded liquid scintillator. The liquid scintillator is enclosed inside a balloon made of thin, transparent, low-radioactivity film that we call Inner Balloon (IB). The IB, apart from guaranteeing the liquid containment, also allows to minimize the background from cosmogenic muon-spallation products and 8B solar neutrinos. Indeed these events could contribute to the total counts in the region of interest around the Q-value of the double-beta decay of 136Xe. In this paper, we present an overview of the IB and describe the various steps of its commissioning minimizing the radioactive contaminations, from the material selection, to the fabrication of the balloon and its installation inside the KamLAND detector. Finally, we show the impact of the IB on the KamLAND background as measured by the KamLAND detector itself.

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.

With the advent of the Heliophysics/Geospace System Observatory (H/GSO), a complement of multi-spacecraft missions and ground-based observatories to study the space environment, data retrieval, analysis, and visualization of space physics data can be daunting. The Space Physics Environment Data Analysis System (SPEDAS), a grass-roots software development platform (www.spedas.org), is now officially supported by NASA Heliophysics as part of its data environment infrastructure. It serves more than a dozen space missions and ground observatories and can integrate the full complement of past and upcoming space physics missions with minimal resources, following clear, simple, and well-proven guidelines. Free, modular and configurable to the needs of individual missions, it works in both command-line (ideal for experienced users) and Graphical User Interface (GUI) mode (reducing the learning curve for first-time users). Both options have "crib-sheets," user-command sequences in ASCII format that can facilitate record-and-repeat actions, especially for complex operations and plotting. Crib-sheets enhance scientific interactions, as users can move rapidly and accurately from exchanges of technical information on data processing to efficient discussions regarding data interpretation and science. SPEDAS can readily query and ingest all International Solar Terrestrial Physics (ISTP)-compatible products from the Space Physics Data Facility (SPDF), enabling access to a vast collection of historic and current mission data. The planned incorporation of Heliophysics Application Programmer's Interface (HAPI) standards will facilitate data ingestion from distributed datasets that adhere to these standards. Although SPEDAS is currently Interactive Data Language (IDL)-based (and interfaces to Java-based tools such as Autoplot), efforts are under-way to expand it further to work with python (first as an interface tool and potentially even receiving an under-the-hood replacement). We review the SPEDAS development history, goals, and current implementation. We explain its "modes of use" with examples geared for users and outline its technical implementation and requirements with software developers in mind. We also describe SPEDAS personnel and software management, interfaces with other organizations, resources and support structure available to the community, and future development plans.Electronic supplementary materialThe online version of this article (10.1007/s11214-018-0576-4) contains supplementary material, which is available to authorized users.

Yasumasa Otori, Takanori Matsuoka, Miho Kumoi, Eri Tachibana, Chieko Tsujino, Satoshi Matsuda Department of Ophthalmology, National Hospital Organization, Osaka National Hospital, Osaka, JapanCorrespondence: Yasumasa Otori Email otori.yasumasa.fe@mail.hosp.go.jpPurpose: To compare the outcomes of ab interno suture trabeculotomy (AbI-TLO) and ab externo metal trabeculotomy (AbE-TLO) in adult patients with glaucoma aged over 40 years.Patients and Methods: A retrospective chart review was conducted, including adult patients with glaucoma who underwent AbI-TLO or AbE-TLO between January 2015 and June 2019. A single surgeon (YO) performed all the operations. Eighty-one patients (81 eyes) were included in this study. Surgical success was defined as a postoperative intraocular pressure (IOP) of ≤ 18 mmHg and an IOP reduction of ≥ 20% from the preoperative IOP, without requiring additional glaucoma surgery. Success rates were assessed using Kaplan–Meier survival curves and log-rank (Mantel–Cox) tests, while risk factors were analyzed using the Cox proportional hazards model.Results: Forty-nine patients who underwent AbI-TLO and 32 patients who underwent AbE-TLO were studied; the preoperative IOPs were 27.9 ± 7.3 (mean ± standard deviation) mmHg and 25.6 ± 8.1 mmHg in the AbI-TLO and AbE-TLO groups, respectively (p=0.217). The 12-month postoperative IOPs were 15.8 ± 4.0 mmHg and 16.3 ± 4.2 mmHg in the AbI-TLO and AbE-TLO groups, respectively (p=0.724). The surgical success rates at 12 months were 77.6% and 62.5% in the AbI-TLO and AbE-TLO groups, respectively (p=0.144). Postoperative hyphema with level formation and ocular hypertension over 30 mmHg were observed in 22.4% and 26.5% of patients in the AbI-TLO group and 18.8% and 12.5% of those in the AbE-TLO group, respectively. Stepwise multivariate Cox regression analysis showed that a longer axial length was a risk factor for surgical failure (hazard ratio: 2.030; p=0.042).Conclusion: AbI-TLO and AbE-TLO had similar surgical outcomes and postoperative complications. A longer axial length was associated with an insufficient IOP reduction.Keywords: axial length, gonio-assisted transluminal trabeculotomy, intraocular pressure, MIGS, outcomes, trabeculotomy

Pulsating Aurora (PsA) is one of the major classes of diffuse aurora associated with precipitation of a few to a few tens of keV electrons from the magnetosphere. Recent studies suggested that, during PsA, more energetic (i.e., sub‐relativistic/relativistic) electrons precipitate into the ionosphere at the same time. Those electrons are considered to be scattered at the higher latitude part of the magnetosphere by whistler‐mode chorus waves propagating away from the magnetic equator. However, there have been no actual cases of simultaneous observations of precipitating electrons causing PsA (PsA electrons) and chorus waves propagating toward higher latitudes; thus, we still do not quite well understand under what conditions PsA electrons become harder and precipitate to lower altitudes. To address this question, we have investigated an extended interval of PsA on 12 January 2021, during which simultaneous observations with the Arase satellite, ground‐based all‐sky imagers and the European Incoherent SCATter (EISCAT) radar were conducted. We found that, when the PsA shape became patchy, the PsA electron energy increased and Arase detected intense chorus waves at magnetic latitudes above 20°, indicating the propagation of chorus waves up to higher latitudes along the field line. A direct comparison between the irregularities of the magnetospheric electron density and the emission intensity of PsA patches at the footprint of the satellite suggests that the PsA morphology and the energy of PsA electrons are determined by the presence of "magnetospheric density ducts," which allow chorus waves to travel to higher latitudes and thereby precipitate more energetic electrons. Plain Language Summary: Pulsating Aurora (PsA) is a kind of diffuse aurora associated with periodic precipitation of energetic electrons from the near‐Earth space into the atmosphere. Recent research has shown that, during PsA events, energetic particles at the sub‐relativistic energy range precipitate into the atmosphere. We speculate that such particles are scattered by wave‐particle resonance with natural electromagnetic waves, called chorus waves, at higher magnetic latitude regions. However, there has been no experimental case of PsA during which propagation of the chorus waves to higher magnetic latitudes was confirmed; thus, we still do not fully understand when and why PsA electrons become more energetic. Here, we investigate a PsA event on 12 January 2021, simultaneously observed by the Arase satellite, ground‐based all‐sky imagers and the European Incoherent SCATter (EISCAT) radar. We found that, when the PsA shape was patchy, the energy of precipitating electrons increased and chorus waves were observed at high latitudes in the magnetosphere. Comparing the magnetospheric electron density with the PsA brightness seen from the ground, we suggest that both the PsA shape and the energy of precipitating electrons were influenced by the so‐called magnetospheric ducts, which guide chorus waves to high‐latitudes regions where they interact with more energetic electrons. Key Points: Examined simultaneous observations of Pulsating Aurora (PsA) with the Arase satellite, ground‐based all‐sky imagers, and the EISCAT radarFound a relationship among the patchy PsA, the enhanced energy of PsA electrons, and the chorus wave propagation to high‐latitudes (>20°)Arase observations suggest that the observed relationship can be explained by the ducted propagation of chorus waves [ABSTRACT FROM AUTHOR]

We present a search, using KamLAND, a kiloton-scale anti-neutrino detector, for low-energy anti-neutrino events that were coincident with the gravitational-wave (GW) events GW150914 and GW151226, and the candidate event LVT151012. We find no inverse beta-decay neutrino events within ±500 s of either GW signal. This non-detection is used to constrain the electron anti-neutrino fluence and the total integrated luminosity of the astrophysical sources.

This corrects the article DOI: 10.1103/PhysRevLett.117.082503.

We present an improved search for neutrinoless double-beta (0νββ) decay of ^{136}Xe in the KamLAND-Zen experiment. Owing to purification of the xenon-loaded liquid scintillator, we achieved a significant reduction of the ^{110m}Ag contaminant identified in previous searches. Combining the results from the first and second phase, we obtain a lower limit for the 0νββ decay half-life of T_{1/2}^{0ν}>1.07×10^{26}  yr at 90% C.L., an almost sixfold improvement over previous limits. Using commonly adopted nuclear matrix element calculations, the corresponding upper limits on the effective Majorana neutrino mass are in the range 61-165 meV. For the most optimistic nuclear matrix elements, this limit reaches the bottom of the quasidegenerate neutrino mass region.

In the late stages of nuclear burning for massive stars (M > 8 Mȯ), the production of neutrino-antineutrino pairs through various processes becomes the dominant stellar cooling mechanism. As the star evolves, the energy of these neutrinos increases and in the days preceding the supernova a significant fraction of emitted electron anti-neutrinos exceeds the energy threshold for inverse beta decay on free hydrogen. This is the golden channel for liquid scintillator detectors because the coincidence signature allows for significant reductions in background signals. We find that the kiloton-scale liquid scintillator detector KamLAND can detect these pre-supernova neutrinos from a star with a mass of 25 Mȯ at a distance less than 690 pc with 3σ significance before the supernova. This limit is dependent on the neutrino mass ordering and background levels. KamLAND takes data continuously and can provide a supernova alert to the community.

In the late stages of nuclear burning for massive stars (M > 8 Mȯ), the production of neutrino-antineutrino pairs through various processes becomes the dominant stellar cooling mechanism. As the star evolves, the energy of these neutrinos increases and in the days preceding the supernova a significant fraction of emitted electron anti-neutrinos exceeds the energy threshold for inverse beta decay on free hydrogen. This is the golden channel for liquid scintillator detectors because the coincidence signature allows for significant reductions in background signals. We find that the kiloton-scale liquid scintillator detector KamLAND can detect these pre-supernova neutrinos from a star with a mass of 25 Mȯ at a distance less than 690 pc with 3σ significance before the supernova. This limit is dependent on the neutrino mass ordering and background levels. KamLAND takes data continuously and can provide a supernova alert to the community.

A search for double-beta decays of 136Xe to excited states of 136Ba has been performed with the first phase data set of the KamLAND-Zen experiment. The 01+, 21+ and 22+ transitions of 0νββ decay were evaluated in an exposure of 89.5 kg⋅yr of 136Xe, while the same transitions of 2νββ decay were evaluated in an exposure of 61.8 kg⋅yr. No excess over background was found for all decay modes. The lower half-life limits of the 21+ state transitions of 0νββ and 2νββ decay were improved to T1/20ν(0+→21+)>2.6×1025 yr and T1/22ν(0+→21+)>4.6×1023 yr (90% C.L.), respectively. We report on the first experimental lower half-life limits for the transitions to the 01+ state of 136Xe for 0νββ and 2νββ decay. They are T1/20ν(0+→01+)>2.4×1025 yr and T1/22ν(0+→01+)>8.3×1023 yr (90% C.L.). The transitions to the 22+ states are also evaluated for the first time to be T1/20ν(0+→22+)>2.6×1025 yr and T1/22ν(0+→22+)>9.0×1023 yr (90% C.L.). These results are compared to recent theoretical predictions.

We report a measurement of the neutrino-electron elastic scattering rate of 862 keV Be7 solar neutrinos based on a 165.4 kt d exposure of KamLAND. The observed rate is 582±94(kt d)-1, which corresponds to an 862-keV Be7 solar neutrino flux of (3.26±0.52)×109cm-2s-1, assuming a pure electron-flavor flux. Comparing this flux with the standard solar model prediction and further assuming three-flavor mixing, a νe survival probability of 0.66±0.15 is determined from the KamLAND data. Utilizing a global three-flavor oscillation analysis, we obtain a total Be7 solar neutrino flux of (5.82±1.02)×109cm-2s-1, which is consistent with the standard solar model predictions.

We report a measurement of the neutrino-electron elastic scattering rate of 862 keV Be7 solar neutrinos based on a 165.4 kt d exposure of KamLAND. The observed rate is 582±94(kt d)-1, which corresponds to an 862-keV Be7 solar neutrino flux of (3.26±0.52)×109cm-2s-1, assuming a pure electron-flavor flux. Comparing this flux with the standard solar model prediction and further assuming three-flavor mixing, a νe survival probability of 0.66±0.15 is determined from the KamLAND data. Utilizing a global three-flavor oscillation analysis, we obtain a total Be7 solar neutrino flux of (5.82±1.02)×109cm-2s-1, which is consistent with the standard solar model predictions.