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Tissue-resident macrophages (TRMs) are critical for tissue homeostasis/repair. We previously showed that dermal TRMs produce CCL24 (eotaxin2) which mediates their interaction with IL-4 producing eosinophils, required to maintain their number and M2-like properties in the TH1 environment of the Leishmania major infected skin. Here, we unveil another layer of TRM self-maintenance involving their production of TSLP, an alarmin typically characterized as epithelial cell-derived. Both TSLP signaling and IL-5+ innate lymphoid cell 2 (ILC2s) were shown to maintain the number of dermal TRMs and promote infection. Single cell RNA sequencing identified the dermal TRMs as the sole source of TSLP and CCL24. Development of Ccl24-cre mice permitted specific labeling of dermal TRMs, as well as interstitial TRMs from other organs. Genetic ablation of TSLP from dermal TRMs reduced the number of dermal TRMs, and disease was ameliorated. Thus, by orchestrating localized type 2 circuitries with ILC2s and eosinophils, dermal TRMs are self-maintained as a replicative niche for L. major.

Antibody blockade of programmed death-1 (PD-1) or its ligand, PD-L1, has led to unprecedented therapeutic responses in certain tumor-bearing individuals, but PD-L1 expression's prognostic value in stratifying cancer patients for such treatment remains unclear. Reports conflict on the significance of correlations between PD-L1 on tumor cells and positive clinical outcomes to PD-1/PD-L1 blockade. We investigated this issue using genomically related, clonal subsets from the same methylcholanthrene-induced sarcoma: a highly immunogenic subset that is spontaneously eliminated in vivo by adaptive immunity and a less immunogenic subset that forms tumors in immunocompetent mice, but is sensitive to PD-1/PD-L1 blockade therapy. Using CRISPR/Cas9-induced loss-of-function approaches and overexpression gain-of-function techniques, we confirmed that PD-L1 on tumor cells is key to promoting tumor escape. In addition, the capacity of PD-L1 to suppress antitumor responses was inversely proportional to tumor cell antigenicity. PD-L1 expression on host cells, particularly tumor-associated macrophages (TAM), was also important for tumor immune escape. We demonstrated that induction of PD-L1 on tumor cells was IFNγ-dependent and transient, but PD-L1 induction on TAMs was of greater magnitude, only partially IFNγ dependent, and was stable over time. Thus, PD-L1 expression on either tumor cells or host immune cells could lead to tumor escape from immune control, indicating that total PD-L1 expression in the immediate tumor microenvironment may represent a more accurate biomarker for predicting response to PD-1/PD-L1 blockade therapy, compared with monitoring PD-L1 expression on tumor cells alone. Cancer Immunol Res; 5(2); 106–17. ©2017 AACR.

Supplementary Figure S1. Genomic sequence of the PD-L1 locus and expression of immunogenic neoantigens in T3deltaPDL1 lines. Supplementary Figure S2. Expression of PD-L1 and neoantigens in the escape T3deltaPDL1 cells. Supplementary Figure S3. PD-L1 but not PD-L2 is upregulated on MCA sarcomas in vitro and in vivo following exposure to IFNgamma. Supplementary Figure S4. T9-PDL1 cells form progressively growing tumors in WT mice. Supplementary Figure S5. T9-PDL1ovr but not T9-PDL1phy cells inhibit antigen-specific T cell killing in vitro. Supplementary Figure S6. Extrinsic IFNgamma stimulation controls upregulation and maintenance of tumor PD-L1 expression. Supplementary Figure S7. Sixteen immune subsets in MCA sarcomas by flow cytometry. Supplementary Figure S8. Comprehensive analysis of cell types expressing PD-L1 in T3 tumors.

Supplementary Table S1. Staining panels for comprehensive analysis of cell types expressing PD-L1.

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Boundary-updating, a process of updating decision boundaries, has been known to induce a history effect on binary choices. However, the history effect that boundary-updating has on decision uncertainty has been previously overlooked. Our study revealed that boundary-updating can also impact decision uncertainty, as evidenced by changes in response time, pupil-size, and dACC response, suggesting that boundary-updating is a source of history effect not only on choice but also decision uncertainty.

Background: To prepare for future work stoppages in the medical industry, this study aimed to identify the effects of healthcare worker strikes on the mortality rate of patients visiting the emergency department (ED) at six training hospitals in Daegu, Korea. Methods: We used a retrospective, cross-sectional, multicenter design to analyze the medical records of patients who visited six training hospitals in Daegu (August 21–September 8, 2020). For comparison, control period 1 was set as the same period in the previous year (August 21–September 8, 2019) and control period 2 was set as July 1–19, 2020. Patient characteristics including age, sex, and time of ED visit were investigated along with mode of arrival, length of ED stay, and in-hospital mortality. The experimental and control groups were compared using t-tests, and Mann-Whitney U-test, chi-square test, and Fisher exact tests, as appropriate. Univariate logistic regression was performed to identify significant factors, followed by multivariate logistic regression analysis. Results: During the study period, 31,357 patients visited the ED, of which 7,749 belonged to the experimental group. Control periods 1 and 2 included 13,100 and 10,243 patients, respectively. No significant in-hospital mortality differences were found between study periods; however, the results showed statistically significant differences in the length of ED stay. Conclusion: The ED resident strike did not influence the mortality rate of patients who visited the EDs of six training hospitals in Daegu. Furthermore, the number of patients admitted and the length of ED stay decreased during the strike period.

Anti-cancer chemotherapy is an effective therapeutic approach. Milk extracellular vesicles (EVs) loaded with chemotherapeutics have a potential anticancer effect by acting as a drug delivery system. Thus, our study aimed to explore the effect of engineered milk extracellular vesicles.To treat epidermal growth factor receptor (EGFR) expressing solid tumors, we established oxaliplatin-loaded milk EV conjugated with GE11 peptide (Drug-loadedAnti-cancer drug-loaded engineered milk EVs might be a novel therapeutic approach for treating patients with EGFR expressing solid tumors.

Mag-spinner, a system in which magnets are combined with a spinner system, is a new type of magnetic separation system for the preprocessing of biological and medical samples. Interference by undesired components restricts the detection accuracy and efficiency. Thus, the development of appropriate separation techniques is required for better detection of the desired targets, to enrich the target analytes and remove the undesired components. The strong response of iron oxide nanoclusters can successfully capture the targets quickly and with high efficiency. As a result, cancer cells can be effectively separated from blood using the developed mag-spinner system. Indeed, this system satisfies the requirements for desirable separation systems, namely (i) fast sorting rates, (ii) high separation efficiency, (iii) the ability to process native biological fluids, (iv) simple operating procedures, (v) low cost, (vi) operational convenience, and (vii) portability. Therefore, this system is widely applicable to sample preparation without limitations on place, cost, and equipment.

Background: High-resolution magnetic resonance imaging (HRMRI) can provide information on the histopathological characteristics of intracranial atherosclerotic lesions causing arterial stenosis; however, its clinical application in intracranial atherosclerosis lacks standardization for predicting stenosis. Therefore, this study investigated the characteristics of HRMRI that can predict progression based on comparisons of follow-up HRMRI. Methods: We retrospectively enrolled patients who underwent HRMRI within 7 days of symptom onset to evaluate the characteristics associated with intracranial stenotic lesions. Among them, patients diagnosed with severe stenosis due to atherosclerosis and who underwent follow-up HRMRI 12–24 months after initial HRMRI were included in the final study. We analyzed distinct features, such as stenosis aggravation, the presence of initial plaque enhancement, increment of plaque enhancement, the existence of both eccentric and concentric plaques, and the presence of initial intraplaque hematoma on initial and follow-up HRMRI. Results: Among 442 patients who underwent HRMRI for severe stenosis due to atherosclerosis, 35 underwent follow-up HRMRI 12–24 months later. Patients with stenosis aggravation showed a higher incidence of plaque enhancement (87.5% vs. 3.7%, p < 0.001) and the presence of both concentric and eccentric plaques (75.0% vs. 11.1%; p = 0.001). The area under the curve for the increment of plaque enhancement was 0.92 (95% confidence interval [CI] 0.78–1.00, p ≤ 0.001), while that for the presence of both concentric and eccentric plaques was 0.82 (95% CI 0.63–1.00, p < 0.007). Conclusions: The presence of both concentric and eccentric plaques and an increase in plaque enhancement were the strongest predictors of aggravation of intracranial artery stenosis.

BackgroundNear-infrared fluorescence indocyanine green (NIRF-ICG) lymphangiography, a primary modality for detecting lymphedema, which is a disease due to lymphatic obstruction, enables real-time observations of lymphatic flow and reveals not only the spatial distribution of drainage (static analysis), but also information on the lymphatic contraction (dynamic analysis).MethodsWe have produced lymphatic obstruction models in upper limbs through the dissection of proximal lymph nodes (LNs) and radiation (dissection limbs). After the model formation during 1 week, the static and dynamic analysis using NIRF-ICG lymphangiography were performed for six weeks. The drainage pattern and leakage of lymph fluid were observed and time-domain signals of lymphatic contraction were measured in the distal lymph vessels. The obtained signals were converted to the frequency-domain spectrums using the signal processing.ResultsThe results of both static and dynamic analyses proved to be effective in accurately identify the extent of lymphatic disruption in the dissection limbs. The static analysis showed abnormal drainage patterns and an increased leakage of lymph fluid to the periphery of the vessels compared to the control limbs. Meanwhile, the waveforms were changed and the frequency of the contractile signals was increased by 58% in the dynamic analysis. Specifically, our findings revealed that regular lymphatic contractions, observed at a frequency range of 0.08 ∼ 0.13 Hz in the control limbs, were absent in the dissection limbs. The contractile regularity was not fully restored until the end of the follow-up, indicating a persistent lymphatic disruption in the dissected limbs.ConclusionThe dynamic analysis was consistent with the static analysis, and it could detect the abnormalities of lymphatic circulation by observing the characteristics of signals without the need for a control group. As NIRF-ICG lymphangiography is currently used in clinical practice, our findings may be useful for the early detection of the lymphatic circulation problem.

An object occupies an enclosed region in the visual field, which defines its spatial extent. Humans display exquisite finesse in spatial extent perception. Recent series of human neuroimaging and monkey single-cell studies suggest the spatial representation encoded in the early visual cortex (EVC) as the neural substrate of spatial extent estimation. Guided by this “EVC hypothesis” on spatial extent estimation, we predicted that human estimation of spatial extents would reflect the topographic biases known to exist in EVC’s spatial representation, the co-axial and radial biases. To test this prediction, we concurrently assessed those two spatial biases in both EVC’s and perceptual spatial representations by probing the anisotropy of EVC’s population receptive fields, on the one hand, and that of humans’ spatial extent estimation, on the other hand. To our surprise, we found a marked topographic mismatch between EVC’s and perceptual representations of oriented visual patterns, the radial bias in the former and the co-axial bias in the latter. Amid this topographic mismatch, the extent to which the anisotropy of spatial extents is modulated by stimulus orientation is correlated across individuals between EVC and perception. Our findings seem to require a revision of the current understanding of EVC’s functional architecture and contribution to visual perception: EVC’s spatial representation (i) is governed by the radial bias but only weakly modulated by the co-axial bias, and (ii) do contribute to spatial extent perception, but in a limited way where additional neural mechanisms are called in to counteract the radial bias in EVC.Significant statementPrevious anatomical and functional studies suggest both radial and co-axial biases as topographic factors governing the spatial representation of the early visual cortex (EVC). On the other hand, EVC’s fine-grained spatial representation has been considered the most plausible neural substrate for exquisite human perception of spatial extents. Based on these suggestions, we reasoned that these two topographic biases are likely to be shared between EVC’s and perceptual representations of spatial extents. However, our neuroimaging and psychophysics experiments implicate a need for revising those two suggestions. Firstly, the co-axial bias seems to exert only a modulatory influence on EVC’s functional architecture. Secondly, human spatial extent perception requires further contribution from neural mechanisms that correct EVC’s spatial representation for its radial bias.

Mutations in the Presenilin genes (PSEN1 and PSEN2) are the major cause of familial Alzheimer’s disease (AD), highlighting the importance of Presenilin (PS) in AD pathogenesis. Previous studies of PS function in the hippocampus demonstrated that loss of PS results in the impairment of short- and long-term synaptic plasticity and neurotransmitter release at hippocampal Schaffer collateral (SC) and mossy fiber (MF) synapses. Cortical input to the hippocampus through the lateral perforant pathway (LPP) and the medial perforant pathway (MPP) is critical for normal cognitive functions and is particularly vulnerable during aging and early stages of AD. Whether PS regulates synaptic function in the perforant pathways, however, remained unknown. In the current study, we investigate PS function in the LPP and MPP by performing whole-cell and field-potential electrophysiological recordings using acute hippocampal slices from postnatal forebrain-restricted excitatory neuron-specific PS conditional double knockout (cDKO) mice. We found that paired-pulse ratio (PPR) is reduced in the LPP and MPP of PS cDKO mice. Moreover, synaptic frequency facilitation or depression in the LPP or MPP, respectively, is impaired in PS cDKO mice. Notably, depletion of intracellular Ca2+ stores by inhibition of sarcoendoplasmic reticulum Ca2+ ATPase (SERCA) minics and occludes the effects of PS inactivation, as evidenced by decreases of the evoked excitatory postsynaptic currents (EPSCs) amplitude in the LPP and MPP of control neurons but no effect on the EPSC amplitude in PS cDKO neurons, suggesting that impaired intracellular calcium homeostasis in the absence of PS may contribute to the observed deficits in synaptic transmission. While spontaneous synaptic events, such as both the frequency and the amplitude of spontaneous or miniature EPSCs, are similar between PS cDKO and control neurons, long-term potentiation (LTP) is impaired in the LPP and MPP of PS cDKO mice, accompanied with reduction of evoked NMDA receptor-mediated responses. These findings show the importance of PS in the regulation of synaptic plasticity and intracellular calcium homeostasis in the hippocampal perforant pathways.

Binary classification, an act of sorting items into two classes by setting a boundary, is biased by recent history. One common form of such biases is repulsive bias, a tendency to sort an item into the class opposite to its preceding items. Sensory-adaptation and boundary-updating are considered as two contending sources of the repulsive bias, yet no neural support has been provided for either source. Here we explored human brains, using fMRI, to find such supports by relating the brain signals of sensory-adaptation and boundary-updating to human classification behavior. We found that the stimulus-encoding signal in the early visual cortex adapted to previous stimuli, yet its adaptation-related changes were dissociated from current choices. Contrastingly, the boundary-representing signals in the inferior-parietal and superior-temporal cortices shifted to previous stimuli and covaried with current choices. Our exploration points to boundary-updating, rather than sensory-adaptation, as the origin of the repulsive bias in binary classification.

Corrective feedback is vital to learning about the environment, exerting its influence on subsequent episodes of perceptual decision-making (PDM) on a trial-to-trial basis. However, its intricate interplay with other history factors in PDM challenges a principled account of the history effects of feedback. One popular account, grounded in animal behavior and extended to human behavior, grafted the principle proven successful in reward-based decision-making— reinforcement-learning—onto the PDM processes. It assumes that decision-makers, although engaged in PDM, treat feedback asrewardsfrom which they learnchoice values. Here we report that human decision-makers do not conform to this assumption. Instead, humans acted like treating feedback asevidencefor a specific world state and combining it with sensory evidence to learn thestatistical structurecrucial to perform a PDM task. A Bayesian implementation of our account reproduces human history effects, both retrospectively and prospectively, with an unprecedented level of correspondence and finesse.

Background Flap congestion related with venous thrombosis is a major cause for microsurgical lower extremity reconstruction failure. Conducting dual venous anastomosis has been suggested to reduce risks for the adverse outcomes; however, its efficacy remains controversial. This study evaluated a potential association of dual venous anastomosis with the development of flap congestion in diverse clinical situations. Methods This multicenter study included patients who underwent microsurgical lower extremity reconstruction at two institutions. They were divided into two groups based on the number of venous anastomoses—single and dual groups. Their perfusion-related complications (PRCs), including total/partial flap loss, arterial or venous insufficiency, and emergent reoperation, were compared. Independent association of the number of venous anastomoses with the outcomes was evaluated. Further analyses were conducted using propensity score matching. Results In total, 225 cases were analyzed, of which 92 were included in the single group and the other 133 in the dual group. The two groups had generally similar baseline characteristics. The dual group presented significantly lower rates of PRC, including total/partial flap loss, flap congestion, and emergent reoperation. Multivariable analyses showed that conducting dual venous anastomoses was associated with reduced risks for the development of overall PRC and flap congestion. These associations were more prominent when restricting analyses for cases with chronic wound and trauma (vs. oncologic defects). Similar associations were observed in the propensity score matching analysis. Conclusion Conducting dual venous anastomosis seems associated with reduced risks for flap congestion in microsurgical lower extremity reconstruction, especially for cases with unfavorable conditions.

Plain film X-ray scanners are indispensable for medical diagnostics and clinical procedures. This type of device typically produces two radiographic images of the human spine, including the anteroposterior and lateral views. However, these two photographs presented perspectives that were distinct. The proposed procedure consists of three fundamental steps. For automated cropping, the grayscale lumbar input image was initially projected vertically using its vertical pattern. Then, Delaunay triangulation was performed with the SURF features serving as the triangle nodes. The posture area of the vertebrae was calculated by utilizing the edge density of each node. The proposed method provided an automated estimation of the position of the human lumbar vertebrae, thereby decreasing the radiologist’s workload, computing time, and complexity in a variety of bone-clinical applications. Numerous applications can be supported by the results of the proposed method, including the segmentation of lumbar vertebrae pose, bone mineral density examination, and vertebral pose deformation. The proposed method can estimate the vertebral position with an accuracy of 80.32 percent, a recall rate of 85.37 percent, a precision rate of 82.36%, and a false-negative rate of 15.42 percent.

Objective: The present study assessed the safety and benefits of laparoscopic-assisted adenomyomectomy compared to laparoscopic or laparotomic adenomyomectomy. Materials and methods: This study was a retrospective comparative study. A total of 277 patients underwent adenomyomectomy between January 2016 and January 2019 at the Department of Obstetrics and Gynaecology, Ulsan University Hospital, including 25 with laparoscopic-assisted adenomyomectomy, 82 with laparoscopic adenomyomectomy, and 170 with laparotomic adenomyomectomy. Laparoscopic-assisted adenomyomectomy consisted of a laparoscopic uterine artery procedure to reduce blood loss and a minimal incisional for laparotomic adenomyomectomy. An additional laparoscopic surgery was performed for possible pelvic pathology. Results: Data on patient demographics, surgical indications, operative times, estimated blood loss (EBL), short-term complications, and postoperative hospital stays were compared. The laparoscopic-assisted surgery (LAS) and laparotomic groups were comparable in average EBL (208.0 ± 128.8 vs. 193.6 ± 193.0 ml, p = 0.11), weight of removed mass (85.5 ± 71.7 vs. 108.2 ± 91.9 g, p = 0.39), and postoperative hospital days (HDs) (4.5 ± 1.0 vs. 4.7 ± 0.8 days, p = 0.27). These values were lower in the laparoscopic group (EBL 119.5 ± 79.6 ml, mass weight 39.3 ± 25.9 g, HD 3.6 ± 0.8 days). Additional procedures, including myomectomy and combined severe endometriosis surgery, were more frequently performed in the LAS group than the laparotomic group. The mean operating time was longer in the LAS group (179.8 ± 36.6 min) than the other groups (laparoscopy 99.9 ± 40.6 min, p

Non-contact biometric identification technology is once again receiving social attention these days when untact technology is required due to the Covid-19. Face recognition technology is being used in a variety of platforms such as airport immigration systems, hospital patient management systems, financial self-authentication systems, criminal suspect detection systems, and personal authentication systems for mobile devices, and is showing its effectiveness. In this paper, multiple face recognition technology is applied to the automatic attendance system. Unlike when only one person is recognized, multiple face recognition results in lower accuracy and slower processing speed. In this paper, a frontal face detection algorithm is proposed. Using the frontal face detection algorithm, only the frontal face was used for recognition, and when 36 people were recognized, 97.2% accuracy was achieved. In addition, we proposed an erasing multiple face recognition method and increased the average number of frames processed per second as the recognition completion rate increased. Copyright © The Korean Institute of Electrical Engineers.

Developing methods to improve the regenerative capacity of somatic stem cells (SSCs) is a major challenge in regenerative medicine. Here, we propose the forced expression of LIN28A as a method to modulate cellular metabolism, which in turn enhances self-renewal, differentiation capacities, and engraftment after transplantation of various human SSCs. Mechanistically, in undifferentiated/proliferating SSCs, LIN28A induced metabolic reprogramming from oxidative phosphorylation (OxPhos) to glycolysis by activating PDK1-mediated glycolysis-TCA/OxPhos uncoupling. Mitochondria were also reprogrammed into healthy/fused mitochondria with improved functional capacity. The reprogramming allows SSCs to undergo cell proliferation more extensively with low levels of oxidative and mitochondrial stress. When the PDK1-mediated uncoupling was untethered upon differentiation, LIN28A-SSCs differentiated more efficiently with an increase of OxPhos by utilizing the reprogrammed mitochondria. This study provides mechanistic and practical approaches of utilizing LIN28A and metabolic reprogramming in order to improve SSCs utility in regenerative medicine.

Whether Transient global amnesia (TGA) is related to ischemic pathogenesis remains unclear. The recurrence of TGA is rare. We report a rare case of recurrent attacks of TGA with intracranial vertebral artery dissection in young men without other triggers and any associated factor. A 39-year-old man was hospitalized for amnesia. Diffusion-weighted imaging (DWI) revealed a tiny focus of high-intensity signals in the left. High-resolution MRI showed the dissecting aneurysm of the V4 portion of the right vertebral artery. Two years later, the patient experienced sudden memory loss again. On DWI, a new punctate restricted diffusion lesion was observed in the left hippocampus. Considering the recurrence in young men with no other triggers, this case raises the hypothesis that a pure TGA in a young patient could potentially be a vertebrobasilar TIA. Therefore, when a patient presents with TGA, without any associated factors, it is important to investigate and exclude sinister causes of global amnesia and we recommend that a vascular examination be conducted.