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According to the Polarity Hypothesis, the presence or absence of a processing cost for Scalar Inferences (SIs) depends on their polarity. This hypothesis predicts, among other things, that the processing of lower-bounding SIs should not be affected by cognitive load the same way upper-bounding SIs are. To date, evidence in support of this prediction comes from the comparison between upper-bounding and lower-bounding SIs elicited by disparate scalar words. In this paper, we report on two dual-task experiments testing this prediction in a more controlled way by comparing upper-bounding and lower-bounding SIs arising from the same scalar words or scale-mates operating over the same dimension. Results show that, for these more minimal comparisons, lower-bounding SIs involve comparable cognitive demands as their upper-bounding counterparts. These findings challenge the idea that load effects are consistently modulated by SI polarity and suggest instead that these effects are relatively consistent across different types of SIs.

Experimental studies show that the tendency to derive Scalar Implicatures (SIs) varies considerably between individuals: some individuals accept sentences that are literally true but carry a false SI, while others systematically reject them. The question of what factors drive these differences is crucial to understanding the mechanisms involved in SIs and currently at the center of numerous discussions. To date, there is no agreement on how to quantify individual differences in SI rates. In this article, we show how a hierarchical Bayesian modelling approach can be used to quantify subjects' preferences observed in the results of a truth value judgement task that investigated intra-individual and inter-individual variability in the rates of upper-bounding and lower-bounding SIs associated with the -scale. The results provide further evidence that the robustness of an SI is modulated within individuals by certain linguistic features, such as the presence of negation.

No studies have reported breast cancer cases developed in the chronic expanding hematoma (CEH). Case presentation: A 47-year-old woman was referred to our hospital for the treatment of a large breast mass. Ultrasound showed that the tumor had an intra-cystic tumor pattern. Magnetic resonance imaging (MRI) of the mass component showed a hypo intense pattern on T1-weighted images, a mosaic pattern on T2 weighted images, and a faint enhancement on time-signal intensity images. Core needle biopsy pathologically showed connective tissue, hematoma, and hemosiderin laden macrophages neither with any mammary gland components nor with malignant cells. These image findings and the presence of hemosiderin laden macrophages led us to the diagnosis of CEH despite the lack of prior breast surgery. The large tumor size of the presumed CEH and its tendency for rapid growth made us attempt to treat the breast lesion with lumpectomy. Frozen section, however, revealed malignant cells in the hard part of the capsule, leading to the conversion of breast surgery from lumpectomy to nipple-preserving mastectomy. Postoperative pathological study showed that the tumor was composed of atypical cells growing in cribriform, tubular, and papillary fashions. In addition to the malignant cells, cyst wall of the CEH had abundant fibrosis and hemosiderin deposits. This is the first CEH case after no prior breast surgery, which had breast cancer within it. When a breast CEH is suspected, careful follow-up is imperative to avoid underestimating a possible concomitant breast cancer.

Introduction: Osteochondromas are benign tumors that arise primarily in the metaphyseal region of long bones. The malignant transformation rate is estimated to be less than 1% and 1–3% in solitary and multiple osteochondromas, respectively. Transformation to osteosarcoma is very rare. Little information is available on treatment or outcome. A rare case of osteosarcoma arising from hereditary multiple osteochondromas of the right iliac bone is reported. Case Presentation: A 66-year-old woman presented with recurrent right abdominal pain. Computed tomography (CT) showed a mass protruding into the pelvic cavity, 9 cm × 7 cm × 7 cm, with bone destruction and internal calcification in the right iliac bone. A CT-guided biopsy was performed, and the diagnosis was osteosarcoma. After one course of chemotherapy with doxorubicin and ifosfamide, extensive resection of the tumor was performed. The pathology showed proliferation of highly pleomorphic dysplastic cells with bone formation inside the tumor just below the osteochondroma tissue, which led to the diagnosis of osteosarcoma arising from the osteochondroma. Three years after surgery, there was no evidence of recurrence or metastasis, and the patient was able to walk unassisted. Conclusion: A case of osteosarcoma arising from an iliac lesion of hereditary multiple osteochondromas was described. Although no recurrence or metastasis has been observed 3 years after surgery, further follow-up is necessary due to the short time after surgery.

(1) Background: The number of patients with cancer undergoing cancer genome profiling is increasing; however, it remains unclear how accurately they understand the details of the tests and treatments. This study aimed to clarify the awareness of cancer genome profiling tests among patients with cancer who visited cancer genome medical clinics. (2) Methods: A questionnaire survey was conducted on awareness, anxiety, sources of information, and psychological states concerning cancer genome profiling tests. (3) Results: In total, 265 patients with cancer (117 men, 142 women, 6 no response, average age of 58.29 ± 11.9 years) were included in the study, of which 218 (82.3%) were aware of the term “cancer genomic medicine” and 90 (34.0%) were aware of its details. Thus, only a few respondents understood that cancer genome profiling tests facilitate the discovery of secondary findings and of genes associated with hereditary tumors. Regarding their psychological state when visiting the cancer genome clinic, the respondents were anxious about standard treatment and prognosis limits. (4) Conclusions: From the viewpoint of advance care planning, we suggest that medical professionals build a support system that links palliative care and cancer treatment and coordinates genetic counseling at an early stage.

Takaaki Matsui,1 Emi Ushigome,1 Masahide Hamaguchi,1 Kazuki Sudo,2 Nobuko Kitagawa,1 Yuriko Kondo,1 Yuka Hasegawa,1 Dan Imai,1 Tomohiro Hattori,1 Masahiro Yamazaki,1 Teiji Sawa,2 Michiaki Fukui1 1Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, 602-8566, Japan; 2Department of Anesthesiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, 602-8566, JapanCorrespondence: Emi Ushigome, Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465, Kajii cho, Kamigyo-ku, Kyoto-city, Kyoto, 621-8585, Japan, Tel/Fax +81-75-251-5505, Email emis@koto.kpu-m.ac.jpPurpose: Despite the low overall death rate of coronavirus disease 2019 (COVID-19), no study has examined the association between COVID-19 severity and the total daily insulin dose required for glycemic control. The aim of this study was to determine the maximum total daily insulin dose required according to COVID-19 severity, and the number of days required to reach the maximum insulin dose in patients with COVID-19 who used insulin during hospitalization.Patients and Methods: This retrospective cohort study included participants aged 20– 90 years with a confirmed diagnosis of COVID-19 who used insulin during hospitalization at Kyoto Prefectural University of Medicine Hospital between March 4, 2020, and May 31, 2021. Factors associated with maximum insulin dose during hospitalization were evaluated using linear regression analyses.Results: The maximum insulin doses were 31.8, 76.8, and 230.7 U/day, and the numbers of days between COVID-19 diagnosis and the need for maximum insulin were 15.6, 17.1, and 13.7 days in patients without ventilator management, with ventilator management, and with ventilator and extracorporeal membrane oxygenation management, respectively. Multivariate linear regression analyses revealed that hemoglobin A1c level (β = 15.87, P = 0.001), use of a ventilator (β = 50.53, P < 0.001), and use of extracorporeal membrane oxygenation (β = 150.36, P < 0.001) were independent determinants of maximum insulin dose.Conclusion: Patients with severe COVID-19 required a significantly higher maximum insulin dose than did those with moderate COVID-19. The maximum insulin dose was reached approximately 2 weeks after onset. Furthermore, the hemoglobin A1c level on admission and the use of a ventilator or extracorporeal membrane oxygenation during hospitalization were associated with the need for maximum insulin dose.Plain language summary: Why was the study done?More than 769 million infections and 6.9 million fatalities have resulted from the coronavirus disease 2019 (COVID-19), which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).In relation to the degree of sickness, what is the maximum daily insulin dosage and the number of days required to achieve the maximum insulin dose?What did the researchers do and find?The maximum total daily insulin dose required according to COVID-19 severity and the number of days required to reach the maximum insulin dose in patients with COVID-19 who used insulin during hospitalization were determined in this study.The maximum daily insulin requirement in this study was reached approximately 2 weeks after the onset of COVID-19, regardless of severity.What do these results mean?The results of this study may be useful as an indicator of insulin dosage and incremental acceleration in future COVID-19 clinical practice.Predicting the maximum amount of insulin and the time required to reach this maximum during hospitalization will lead to more appropriate glycemic management.Keywords: COVID-related diabetes, SARS-CoV-2, insulin resistance, glycemic control, retrospective cohort study

Abstract Objectives Carcinoembryonic-antigen-related cell-adhesion molecule 1 (CEACAM1) is an adhesion molecule that acts as a coinhibitory receptor in the immune system. We previously demonstrated that CEACAM1 is predominantly expressed on peripheral blood neutrophils in patients with RA. The aim of the present study was to investigate the effects of Janus kinase inhibitors (JAKi) on cytokine-activated human neutrophils and CEACAM1 expression. Methods Peripheral blood neutrophils were obtained from healthy subjects. Isolated neutrophils were stimulated with tumor necrosis factor-alpha (TNF-α) or granulocyte–macrophage colony-stimulating factor (GM-CSF) in the presence or absence of JAKi. The expression of CEACAM1 in peripheral blood neutrophils was analyzed by flow cytometry. Protein phosphorylation of signal transducer and activator of transcription (STAT)1, STAT3, and STAT5 was assessed by western blot using phospho-specific antibodies. Results We found that TNF-α-induced CEACAM1 expression was marginally suppressed after pretreatment with pan-JAK inhibitor, tofacitinib. Moreover, TNF-α induced STAT1 and STAT3 phosphorylation at the late stimulation phase (4 to 16 h). The expressions of CEACAM1 on neutrophils were markedly up-regulated by GM-CSF not by interleukin (IL)-6 stimulation. All JAKi inhibited GM-CSF-induced CEACAM1 expressions on neutrophils, however, the inhibitory effects of baricitinib were larger compared to those of tofacitinib or filgotinib. Moreover, CEACAM1 was marginally upregulated in interferon (IFN)-γ stimulated neutrophils. Similarly, JAKi inhibited IFN-γ-induced CEACAM1 expressions on neutrophils. Conclusions We demonstrated that JAKi prevent GM-CSF-induced CEACAM1 expression in neutrophils, and JAKi-induced inhibition depends on their selectivity against JAK isoforms. These findings suggest that JAKi can modulate the expression of CEACAM1 in cytokine-activated neutrophils, thereby limiting their activation.

Introduction: Despite that lateral lumbar interbody fusion (LLIF) is a minimally invasive surgery, some patients complain of severe site pain immediately after the surgery. This study aimed to explore the extent of perioperative pain after LLIF, compare the degree of perioperative pain after LLIF with that after other surgical procedures, and evaluate the factors associated with severe pain in the early postoperative period. Methods: In this study, 93 patients who underwent lumbar spine surgeries for lumbar degenerative diseases were analyzed. The patients were categorized into three groups based on the surgical procedure: Group L, LLIF with percutaneous pedicle screw (PPS); Group P, posterolateral fusion (PLF) or posterior lumbar interbody fusion (PLIF); and Group D, posterior decompression (fenestration). The extent of low back pain was evaluated using the visual analog scale (VAS) preoperatively and from postoperative days 1 to 14. Results: The VAS score for postoperative pain decreased in a time-dependent manner in all three groups (P

Abstract We propose to use the nuclear spin excitation in the ferromagnetic A1 phase of the superfluid 3He for the axion dark matter detection. This approach is striking in that it is sensitive to the axion-nucleon coupling, one of the most important features of the QCD axion introduced to solve the strong CP problem. We review a quantum mechanical description of the nuclear spin excitation and apply it to the estimation of the axion-induced spin excitation rate. We also describe a possible detection method of the spin excitation in detail and show that the combination of the squeezing of the final state with the Josephson parametric amplifier and the homodyne measurement can enhance the sensitivity. It turns out that this approach gives good sensitivity to the axion dark matter with the mass of O $$ \mathcal{O} $$ (1) μeV depending on the size of the external magnetic field. We estimate the parameters of experimental setups, e.g., the detector volume and the amplitude of squeezing, required to reach the QCD axion parameter space.

Abstract Background We examined whether denosumab-induced hypocalcaemia is evident in osteoporosis when given loop diuretics that promote urinary calcium excretion. Methods Japanese Spontaneous Adverse Drug Event Reports was analyzed to examine signals for denosumab-induced hypocalcaemia co-administered loop diuretics. We retrospectively included osteoporotic patients to detect predictors for denosumab-induced hypocalcaemia (corrected calcium level

Diabetes mellitus-related morbidity and mortality are primarily caused by long-term complications such as retinopathy, nephropathy, cardiomyopathy, and neuropathy. Diabetic neuropathy (DN) involves the progressive degeneration of axons and nerve fibers due to chronic exposure to hyperglycemia. This metabolic disturbance leads to excessive activation of the glycolytic pathway, inducing oxidative stress and mitochondrial dysfunction, ultimately resulting in nerve damage. There is no specific treatment for painful DN, and new approaches should aim not only to relieve pain but also to prevent oxidative stress and reduce inflammation. Given that existing therapies for painful DN are not effective for diabetic patients, mesenchymal stromal cells (MSCs)-based therapy shows promise for providing immunomodulatory and paracrine regulatory functions. MSCs from various sources can improve neuronal dysfunction associated with DN. Transplantation of MSCs has led to a reduction in hyperalgesia and allodynia, along with the recovery of nerve function in diabetic rats. While the pathogenesis of diabetic neuropathic pain is complex, clinical trials have demonstrated the importance of MSCs in modulating the immune response in diabetic patients. MSCs reduce the levels of inflammatory factors and increase anti-inflammatory cytokines, thereby interfering with the progression of DM. Further investigation is necessary to ensure the safety and efficacy of MSCs in preventing or treating neuropathic pain in diabetic patients.