Risk Factors of Tuberculosis Destroyed Lung in Patients with Pulmonary Tuberculosis and Structural Lung Diseases: A Retrospective Observational Study.

Background: Tuberculosis destroyed lung constitutes a significant worldwide public health challenge, little is known about its associated risk factors and prognosis. Our study aimed to identify the risk factors of tuberculosis destroyed lung among pulmonary tuberculosis and structural lung diseases. Methods: Between January 2019 and December 2021, a case-control study was conducted at the Third People's Hospital of Shenzhen in China. We collected the clinical data among patients with pulmonary tuberculosis and structural lung diseases. Cases were defined as patients with tuberculosis destroyed lung. Controls were not diagnosed with the tuberculosis destroyed lung. A binary logistic regression was performed. Results: In our study, a total of 341 patients met the inclusion criteria, including 182 cases and 159 controls. We found that age ranges of 46-60 years (aOR: 4.879; 95% CI: 2.338-10.180), >60 years (aOR: 3.384; 95% CI: 1.481-7.735); history of TB treatment (aOR: 2.729; 95% CI: 1.606-4.638); malnutrition (aOR: 5.126; 95% CI: 1.359-19.335); respiratory failure (aOR: 5.080; 95% CI: 1.491-17.306); and bronchiarctia (aOR: 3.499; 95% CI: 1.330-9.209) were the independent risk factors for tuberculosis destroyed lung. Conversely, having a normal (aOR: 0.207; 95% CI: 0.116-0.371) or overweight BMI (aOR: 0.259; 95% CI: 0.090-0.747) emerged as a protective factor against tuberculosis destroyed lung. Conclusion: This study indicated that tuberculosis destroyed lung is a common condition among patients with pulmonary tuberculosis and structural lung diseases. The independent risk factors for tuberculosis destroyed lung were identified as being within the age groups of 46-60 and over 60 years, having a previous history of TB treatment, malnutrition, respiratory failure, and bronchiarctia. It is essential to closely monitor patients possessing these risk factors to prevent the progression towards tuberculosis destroyed lung.

Improving predictions: Enhancing in-hospital mortality forecast for ICU patients with sepsis-induced coagulopathy using a stacking ensemble model.

The incidence of sepsis-induced coagulopathy (SIC) is high, leading to increased mortality rates and prolonged hospitalization and intensive care unit (ICU) stays. Early identification of SIC patients at risk of in-hospital mortality can improve patient prognosis. The objective of this study is to develop and validate machine learning (ML) models to dynamically predict in-hospital mortality risk in SIC patients. A ML model is established based on the Medical Information Mart for Intensive Care IV (MIMIC-IV) database to predict in-hospital mortality in SIC patients. Utilizing univariate feature selection for feature screening. The optimal model was determined by calculating the area under the curve (AUC) with a 95% confidence interval (CI). The optimal model was interpreted using Shapley Additive Explanation (SHAP) values. Among the 3112 SIC patients included in MIMIC-IV, a total of 757 (25%) patients experienced mortality during their ICU stay. Univariate feature selection helps us to pick out the 20 most critical variables from the original feature. Among the 10 developed machine learning models, the stacking ensemble model exhibited the highest AUC (0.795, 95% CI: 0.763-0.827). Anion gap and age emerged as the most significant features for predicting the mortality risk in SIC. In this study, an ML model was constructed that exhibited excellent performance in predicting in-hospital mortality risk in SIC patients. Specifically, the stacking ensemble model demonstrated superior predictive ability.

Systematic Analysis of the Relationship Between Elevated Zinc and Epilepsy.

Previous studies have indicated a potential relationship between zinc and epilepsy. The aim of this study is to investigate the causal relationship between zinc, zinc-dependent carbonic anhydrase, and gray matter volume in brain regions enriched with zinc and epilepsy, as well as explore the possible mechanisms by which zinc contributes to epilepsy. First, this study assessed the risk causality between zinc, carbonic anhydrase, and gray matter volume alterations in zinc-enriched brain regions and various subtypes of epilepsy based on Two-sample Mendelian randomization analysis. And then, this study conducted GO/KEGG analysis based on colocalization analysis, MAGMA analysis, lasso regression, random forest model, and XGBoost model. The results of Mendelian randomization analyses showed a causal relationship between zinc, carbonic anhydrase-4, and generalized epilepsy (p = 0.044 , p = 0.010). Additionally, carbonic anhydrase-1 and gray matter volume of the caudate nucleus were found to be associated with epilepsy and focal epilepsy (p = 0.014, p = 0.003 and p = 0.022, p = 0.009). A colocalization relationship was found between epilepsy and focal epilepsy (PP.H4.abf = 97.7e - 2). Meanwhile, the MAGMA analysis indicated that SNPs associated with epilepsy and focal epilepsy were functionally localized to zinc-finger-protein-related genes (p < 1.0e - 5). The genes associated with focal epilepsy were found to have a molecular function of zinc ion binding (FDR = 2.3e - 6). After the onset of epilepsy, the function of the gene whose expression changed in the rats with focal epilepsy was enriched in the biological process of vascular response (FDR = 4.0e - 5). These results revealed mechanism of the increased risk of epilepsy caused by elevated zinc may be related to the increase of zinc ion-dependent carbonic anhydrase or the increase of the volume of zinc-rich caudate gray matter.

Hollow cubic CuSe@CdS with tunable size for plasmon-induced Vis-NIR driven photocatalytic properties.

The rational design of the dimension and geometry of a plasmonic semiconductor cocatalyst is vitally important for efficient utilization of near-infrared (NIR) light and superior photocatalytic hydrogen generation. Herein, hollow cubic CuSe@CdS composites with different sizes and strong localized surface plasmon resonance (LSPR) were prepared by selenizing size-tunable Cu2O templates and loading CdS nanoparticles. The size of hollow cubic CuSe can affect the surface area and the conduction band potential through the size effect, regulating the carrier behavior of the CuSe@CdS heterojunction. The CuSe@CdS composites show enhanced and wide absorption in the full spectrum due to the LSPR effect of CuSe. Meanwhile, the composites show excellent photocatalytic hydrogen capacity in the full spectrum in a 0.35 M Na2S/0.25 M Na2SO3 sacrificial reagent solution. The best hydrogen production rate of CSCE2 is 1.518 mmol g-1 h-1 (5.54 times higher than that of CdS) under Vis light (780 > λ > 420 nm) irradiation and 0.28 mmol g-1 h-1 under NIR light (λ > 780 nm) illumination. Interestingly, the photocatalytic activity for H2 under Vis-NIR light (λ > 420 nm) is about 3 times (up to 4.45 mmol g-1 h-1) higher than that without NIR light assistance, due to the photothermal effect. Various analyses and DFT calculations demonstrate that the p-n heterojunction formed in the composites consists of p-type CuSe and n-type CdS, which achieves efficient carrier transfer and separation under the synergistic effect of the size effect and the photothermal effect. In addition, the expansion of the photocatalytic performance to the NIR range is mainly due to the "hot-electron" injection mechanism induced by the LSPR effect of CuSe. The reasonable design coupled with the plasmonic materials offers a new path to achieving the highly efficient conversion of solar energy to hydrogen energy.

The impact of intermittent hypoxemia on type 1 retinopathy of prematurity in preterm infants.

BACKGROUND: Intermittent hypoxemia (IH) may influence retinopathy of prematurity (ROP) development in preterm infants, however, previous studies had mixed results. This study tests the hypothesis that increased IH is associated with Type 1 ROP; a stage beyond which treatment is indicated. METHODS: IH was quantified by continuously monitoring oxygen saturation (SpO2) using high-resolution pulse oximeters during the first 10 weeks of life. Statistical analyses assessed the relationship and predictive ability of weekly and cumulative IH for Type 1 ROP development. RESULTS: Most analyses showed no association between IH and Type 1 ROP adjusting for gestational age (GA) and birth weight (BW). However, cumulative IH of longer duration during weeks 5-10, 6-10, and 7-10 were significantly associated with Type 1 ROP adjusting for GA and BW, e.g., the adjusted odds ratio of Type 1 ROP was 2.01 (p = 0.03) for every 3.8 seconds increase in IH duration from week 6-10. IH did not provide statistically significant added predictive ability above GA and BW. CONCLUSIONS: For most analyses there was no significant association between IH and Type 1 ROP adjusting for GA and BW. However, infants with longer IH duration during the second month of life had higher risk for Type 1 ROP. IMPACT: The relationship and predictive ability of intermittent hypoxemia (IH) on retinopathy of prematurity (ROP) is controversial. This study shows no significant association between IH events and Type 1 ROP after adjusting for gestational age (GA) and birth weight (BW), except for cumulative IH of longer duration in the second month of life. In this cohort, IH does not provide a statistically significant improvement in ROP prediction over GA and BW. This study is the first to assess the cumulative impact of IH measures on Type 1 ROP. Interventions for reducing IH duration during critical postnatal periods may improve ROP outcomes.

Exploring the Role of Quantitative CT in Diagnosing Pancreatic Fat Deposition in Type 2 Diabetes Mellitus.

Objective: This study aimed to assess the correlation and consistency between quantitative CT (QCT) and MRI asymmetric echo least squares estimation iterative water-lipid separation sequence (IDEAL-IQ) in determining pancreatic fat content in patients with type 2 diabetes. Methods: A total of 67 patients with type 2 diabetes mellitus who met the inclusion criteria were included in the study. QCT and MRIIDEAL-IQ technologies were utilized to evaluate the patients quantitatively. The pancreatic head, body, and tail regions were examined to measure the fat content and obtain the CT pancreatic fat fraction (CT-PFF) and MRI pancreatic fat fraction (MR-PFF). Pearson correlation analysis examined the relationship between diabetes-related factors and CT-PFF/MR-PFF. Additionally, Bland-Altman analysis assessed the consistency between CT-PFF and MR-PFF. Results: Among the 67 patients, 33 were males and 34 were females. The average age was (66.55±6.23) years, with an average abdominal circumference of (83.34 ± 10.10) cm. The mean values for glycated hemoglobin, fasting blood glucose, BMI, and liver fat content were (6.97±1.07) mmol • L-1, (6.83±1.82) mmol • L-1, (24.02 ± 2.96) kg/m², and (5.28±2.76)%, respectively. Pearson correlation analysis indicated a significant correlation between abdominal circumference, liver fat content, and MR-PFF (r=0.261, 0.267, P < .05). However, no significant correlation was observed between age, glycated hemoglobin, fasting blood glucose, BMI, and MR-PFF (all, P > .05). The minimum and maximum values for CT-PFF among the 67 patients were 7.3% and 60.3%, respectively, with an average value of (19.90±10.61)%. For MR-PFF, the minimum and maximum values were 2% and 48%, respectively, with an average value of (12.21±10.71)%. Pearson correlation analysis demonstrated a significant correlation between CT-PFF and MR-PFF (r = .842, P < .05). Bland-Altman analysis revealed an average bias value of 7.7% and a standard deviation of 5.6% for CT-PFF and MR-PFF. The mean 95% confidence interval ranged from 4.15% to 19.75% (P < .05), with 64 cases falling within this interval and 3 cases falling outside. Conclusion: A correlation exists between pancreatic fat content, abdominal circumference, and liver fat content. Both QCT and MRI can accurately quantify pancreatic fat content, and their correlation and consistency are relatively ideal. QCT technology is particularly suitable for patients with contraindications for magnetic resonance examination.

Enhancing predictions with a stacking ensemble model for ICU mortality risk in patients with sepsis-associated encephalopathy.

OBJECTIVE: We identified predictive factors and developed a novel machine learning (ML) model for predicting mortality risk in patients with sepsis-associated encephalopathy (SAE). METHODS: In this retrospective cohort study, data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) and eICU Collaborative Research Database were used for model development and external validation. The primary outcome was the in-hospital mortality rate among patients with SAE; the observed in-hospital mortality rate was 14.74% (MIMIC IV: 1112, eICU: 594). Using the least absolute shrinkage and selection operator (LASSO), we built nine ML models and a stacking ensemble model and determined the optimal model based on the area under the receiver operating characteristic curve (AUC). We used the Shapley additive explanations (SHAP) algorithm to determine the optimal model. RESULTS: The study included 9943 patients. LASSO identified 15 variables. The stacking ensemble model achieved the highest AUC on the test set (0.807) and 0.671 on external validation. SHAP analysis highlighted Glasgow Coma Scale (GCS) and age as key variables. The model (https://sic1.shinyapps.io/SSAAEE/) can predict in-hospital mortality risk for patients with SAE. CONCLUSIONS: We developed a stacked ensemble model with enhanced generalization capabilities using novel data to predict mortality risk in patients with SAE.

Wearable fiber-free optical sensor for continuous monitoring of neonatal cerebral blood flow and oxygenation.

BACKGROUND: Unstable cerebral hemodynamics places preterm infants at high risk of brain injury. We adapted an innovative, fiber-free, wearable diffuse speckle contrast flow-oximetry (DSCFO) device for continuous monitoring of both cerebral blood flow (CBF) and oxygenation in neonatal piglets and preterm infants. METHODS: DSCFO uses two small laser diodes as focused-point and a tiny CMOS camera as a high-density two-dimensional detector to detect spontaneous spatial fluctuation of diffuse laser speckles for CBF measurement, and light intensity attenuations for cerebral oxygenation measurement. The DSCFO was first validated against the established diffuse correlation spectroscopy (DCS) in neonatal piglets and then utilized for continuous CBF and oxygenation monitoring in preterm infants during intermittent hypoxemia (IH) events. RESULTS: Significant correlations between the DSCFO and DCS measurements of CBF variations in neonatal piglets were observed. IH events induced fluctuations in CBF, cerebral oxygenation, and peripheral cardiorespiratory vitals in preterm infants. However, no consistent correlation patterns were observed among peripheral and cerebral monitoring parameters. CONCLUSIONS: This pilot study demonstrated the feasibility of DSCFO technology to serve as a low-cost wearable sensor for continuous monitoring of multiple cerebral hemodynamic parameters. The results suggested the importance of multi-parameter measurements for understanding deep insights of peripheral and cerebral regulations. IMPACT: The innovative DSCFO technology may serve as a low-cost wearable sensor for continuous bedside monitoring of multiple cerebral hemodynamic parameters in neonatal intensive care units. Concurrent DSCFO and DCS measurements of CBF variations in neonatal piglet models generated consistent results. No consistent correlation patterns were observed among peripheral and cerebral monitoring parameters in preterm neonates, suggesting the importance of multi-parameter measurements for understanding deep insights of peripheral and cerebral regulations during IH events. Integrating and correlating multiple cerebral functional parameters with clinical outcomes may identify biomarkers for prediction and management of IH associated brain injury.

Etoposide combined with cytarabine and pegfilgrastim for poorly mobilizing patients with multiple myeloma and lymphoma: A prospective multicentre study.

A chemotherapy-based mobilization regimen in patients who mobilize poorly, based on etoposide, cytarabine and pegfilgrastim (EAP), has recently been introduced. The aim of this prospective study was to investigate the efficacy and safety of the EAP regimen in patients with poorly mobilizing multiple myeloma (MM) or lymphoma. This single-arm clinical trial was performed at eight public hospitals in China and was registered as a clinical trial (NCT05510089). The inclusion criteria were; (1) diagnosis of MM or lymphoma, (2) defined as a 'poor mobilizer' and (3) aged 18-75 years. The EAP regimen consisted of etoposide 75 mg/m2 /day on days 1-2, cytarabine 300 mg/m2 every 12 h on days 1-2 and pegfilgrastim 6 mg on day 6. The primary endpoint of the study was the ratio of patients achieving adequate mobilization (≥2.0 × 106 CD34+ cells/kg). From 1 September 2022 to 15 August 2023, a total of 58 patients were enrolled, 53 (91.4%) achieved adequate mobilization, while 41 (70.7%) achieved optimal mobilization with a median number of cumulative collected CD34+ cells was 9.2 (range 2.1-92.7) × 106 /kg and the median number of apheresis per patient of 1.2. The median time from administration of the EAP regimen to the first apheresis was 12 days. Approximately 8.6% of patients required plerixa for rescue, which was successful. Twelve (20.7%) of the 58 patients suffered grade 2-3 infections, while 25 (43.1%) required platelet transfusions. The duration of neutrophil and platelet engraftment was 11 days. In conclusion, these results suggest that the EAP mobilization regimen might be a promising option for poorly mobilizing patients with MM or lymphoma.

A Wearable Fluorescence Imaging Device for Intraoperative Identification of Human Brain Tumors.

Malignant glioma (MG) is the most common type of primary malignant brain tumors. Surgical resection of MG remains the cornerstone of therapy and the extent of resection correlates with patient survival. A limiting factor for resection, however, is the difficulty in differentiating the tumor from normal tissue during surgery. Fluorescence imaging is an emerging technique for real-time intraoperative visualization of MGs and their boundaries. However, most clinical grade neurosurgical operative microscopes with fluorescence imaging ability are hampered by low adoption rates due to high cost, limited portability, limited operation flexibility, and lack of skilled professionals with technical knowledge. To overcome the limitations, we innovatively integrated miniaturized light sources, flippable filters, and a recording camera to the surgical eye loupes to generate a wearable fluorescence eye loupe (FLoupe) device for intraoperative imaging of fluorescent MGs. Two FLoupe prototypes were constructed for imaging of Fluorescein and 5-aminolevulinic acid (5-ALA), respectively. The wearable FLoupe devices were tested on tumor-simulating phantoms and patients with MGs. Comparable results were observed against the standard neurosurgical operative microscope (PENTERO® 900) with fluorescence kits. The affordable and wearable FLoupe devices enable visualization of both color and fluorescence images with the same quality as the large and expensive stationary operative microscopes. The wearable FLoupe device allows for a greater range of movement, less obstruction, and faster/easier operation. Thus, it reduces surgery time and is more easily adapted to the surgical environment than unwieldy neurosurgical operative microscopes. Clinical and Translational Impact Statement-The affordable and wearable fluorescence imaging device developed in this study enables neurosurgeons to observe brain tumors with the same clarity and greater flexibility compared to bulky and costly operative microscopes.

Distinct human stem cell subpopulations drive adipogenesis and fibrosis in musculoskeletal injury.

Fibroadipogenic progenitors (FAPs) maintain healthy skeletal muscle in homeostasis but drive muscle degeneration in chronic injuries by promoting adipogenesis and fibrosis. To uncover how these stem cells switch from a pro-regenerative to pro-degenerative role we perform single-cell mRNA sequencing of human FAPs from healthy and injured human muscles across a spectrum of injury, focusing on rotator cuff tears. We identify multiple subpopulations with progenitor, adipogenic, or fibrogenic gene signatures. We utilize full spectrum flow cytometry to identify distinct FAP subpopulations based on highly multiplexed protein expression. Injury severity increases adipogenic commitment of FAP subpopulations and is driven by the downregulation of DLK1. Treatment of FAPs both in vitro and in vivo with DLK1 reduces adipogenesis and fatty infiltration, suggesting that during injury, reduced DLK1 within a subpopulation of FAPs may drive degeneration. This work highlights how stem cells perform varied functions depending on tissue context, by dynamically regulating subpopulation fate commitment, which can be targeted improve patient outcomes after injury.

Defining Endogenous Mitochondrial Transfer in Muscle After Rotator Cuff Injury.

BACKGROUND: Rotator cuff muscle degeneration leads to poor clinical outcomes for patients with rotator cuff tears. Fibroadipogenic progenitors (FAPs) are resident muscle stem cells with the ability to differentiate into fibroblasts as well as white and beige adipose tissue. Induction of the beige adipose phenotype in FAPs has been shown to improve muscle quality after rotator cuff tears, but the mechanisms of how FAPs exert their beneficial effects have not been fully elucidated. PURPOSE: To study the horizontal transfer of mitochondria from FAPs to myogenic cells and examine the effects of ß-agonism on this novel process. STUDY DESIGN: Controlled laboratory study. METHODS: In mice that had undergone a massive rotator cuff tear, single-cell RNA sequencing was performed on isolated FAPs for genes associated with mitochondrial biogenesis and transfer. Murine FAPs were isolated by fluorescence-activated cell sorting and treated with a ß-agonist versus control. FAPs were stained with mitochondrial dyes and cocultured with recipient C2C12 myoblasts, and the rate of transfer was measured after 24 hours by flow cytometry. PdgfraCreERT/MitoTag mice were generated to study the effects of a rotator cuff injury on mitochondrial transfer. PdgfraCreERT/tdTomato mice were likewise generated to perform lineage tracing of PDGFRA+ cells in this injury model. Both populations of transgenic mice underwent tendon transection and denervation surgery, and MitoTag-labeled mitochondria from Pdgfra+ FAPs were visualized by fluorescent microscopy, spinning disk confocal microscopy, and 2-photon microscopy; overall mitochondrial quantity was compared between mice treated with ß-agonists and dimethyl sulfoxide. RESULTS: Single-cell RNA sequencing in mice that underwent rotator cuff tear demonstrated an association between transcriptional markers of adipogenic differentiation and genes associated with mitochondrial biogenesis. In vitro cocultures of murine FAPs with C2C12 cells revealed that treatment of cells with a ß-agonist increased mitochondrial transfer compared to control conditions (17.8% ± 9.9% to 99.6% ± 0.13% P < .0001). Rotator cuff injury in PdgfraCreERT/MitoTag mice resulted in a robust increase in MitoTag signal in adjacent myofibers compared with uninjured mice. No accumulation of tdTomato signal from PDGFRA+ cells was seen in injured fibers at 6 weeks after injury, suggesting that FAPs do not fuse with injured muscle fibers but rather contribute their mitochondria. CONCLUSION: The authors have described a novel process of endogenous mitochondrial transfer that can occur within the injured rotator cuff between FAPs and myogenic cells. This process may be leveraged therapeutically with ß-agonist treatment and represents an exciting target for improving translational therapies available for rotator cuff muscle degeneration. CLINICAL RELEVANCE: Promoting endogenous mitochondrial transfer may represent a novel translational strategy to address muscle degeneration after rotator cuff tears.

Pooling sputum samples for the Xpert MTB/RIF assay: a practical screening strategy for highly infectious tuberculosis cases.

The Xpert MTB/RIF test (Xpert) can help in the accurate screening of tuberculosis, however, its widespread use is limited by its high cost and lack of accessibility. Pooling of sputum samples for testing is a strategy to cut expenses and enhance population coverage but may result in a decrease in detection sensitivity due to the dilution of Mycobacterium tuberculosis (Mtb) by sample mixing. We investigated how the mixing ratio affected the detection performance of Xpert. We used frozen sputum samples that had been kept after individual Xpert assays of the sputa from Mtb-confirmed TB patients and non-TB patients. Our results showed that the overall sensitivity of the Xpert pooling assay remained higher than 80% when the mixing ratio was between 1/2 and 1/8. When the mixing ratio was raised to 1/16, the positive detection rate fell to 69.0%. For patients with either a high sputum Mtb smear score ≥ 2+, a time-to-positive culture ≤ 10 days, or an Xpert test indicating a high or medium abundance of bacteria, the pooling assay positivity rates were 93.3%, 96.8%, and 100% respectively, even at a 1/16 mixing ratio. For participants with cavities and cough, the pooling assay positivity rates were 86.2% and 90.0% at a 1/8 ratio, higher than for those without these signs. Our results show that the Xpert pooled assay has a high overall sensitivity, especially for highly infectious patients. This pooling strategy with lower reagent and labor costs could support TB screening in communities with limited resources, thereby facilitating reductions in the community transmission and incidence of TB worldwide.

The Proportion of Myeloid-derived Suppressor Cells in the Graft as a Potential Predictor of Acute Graft-versus-host Disease in Haploid Allogeneic Hematopoietic Stem Cell Transplantation.

Myeloid-derived suppressor cells (MDSC) are powerful immunomodulatory cells that play an important role in infectious and inflammatory disorders, but the correlation between graft MDSC amount and early transplant outcomes remains unknown in allogeneic hematopoietic stem cell transplantation. We collected data from 91 patients with acute leukemia undergoing haploidentical allogeneic hematopoietic stem cell transplantation. The grafts were analyzed in terms of CD34+ cells, CD3+ T cells and subpopulation, and MDSC (HLA-DR -/low CD33 + CD16 - ) by flow cytometry. The cutoff value of the MDSC proportion in the graft on the receiver operating curve was 8.89%, with a sensitivity of 0.833 and specificity of 0.852. Day +100 cumulative incidences of II-IV and III-IV acute graft-versus-host disease (aGVHD) in the low MDSC group were 73.5% and 38.8%, respectively, and that in the high MDSC group were 5.3% and 0%, with a significant difference in incidences of II-IV and III-IV aGVHD ( P <0.001). The overall survival, relapse-free survival, and GVHD-relapse-free survival (GRFS) at 1 year were 66.3% versus 80.5% ( P =0.043), 71.6% versus 71.7% ( P =0.248), and 22.1% versus 62.8% ( P <0.001), respectively. No significant difference in the cumulative incidence of relapse between the 2 groups was observed. Multivariate analysis revealed that higher MDSC proportions were associated with a lower risk of II-IV aGVHD. Graft MDSC proportion exceeding 8.89% was significantly associated with higher overall survival and GRFS. The prophylaxis of antithymocyte globulin+post-transplant cyclophosphamide and higher MDSC proportion in the graft were favorable factors for improving GRFS. In conclusion, graft MDSC proportion may be a significant predictor of aGVHD.

Depth-sensitive diffuse speckle contrast topography for high-density mapping of cerebral blood flow in rodents.

Significance: Frequent assessment of cerebral blood flow (CBF) is crucial for the diagnosis and management of cerebral vascular diseases. In contrast to large and expensive imaging modalities, such as nuclear medicine and magnetic resonance imaging, optical imaging techniques are portable and inexpensive tools for continuous measurements of cerebral hemodynamics. The recent development of an innovative noncontact speckle contrast diffuse correlation tomography (scDCT) enables three-dimensional (3D) imaging of CBF distributions. However, scDCT requires complex and time-consuming 3D reconstruction, which limits its ability to achieve high spatial resolution without sacrificing temporal resolution and computational efficiency. Aim: We investigate a new diffuse speckle contrast topography (DSCT) method with parallel computation for analyzing scDCT data to achieve fast and high-density two-dimensional (2D) mapping of CBF distributions at different depths without the need for 3D reconstruction. Approach: A new moving window method was adapted to improve the sampling rate of DSCT. A fast computation method utilizing MATLAB functions in the Image Processing Toolbox™ and Parallel Computing Toolbox™ was developed to rapidly generate high-density CBF maps. The new DSCT method was tested for spatial resolution and depth sensitivity in head-simulating layered phantoms and in-vivo rodent models. Results: DSCT enables 2D mapping of the particle flow in the phantom at different depths through the top layer with varied thicknesses. Both DSCT and scDCT enable the detection of global and regional CBF changes in deep brains of adult rats. However, DSCT achieves fast and high-density 2D mapping of CBF distributions at different depths without the need for complex and time-consuming 3D reconstruction. Conclusions: The depth-sensitive DSCT method has the potential to be used as a noninvasive, noncontact, fast, high resolution, portable, and inexpensive brain imager for basic neuroscience research in small animal models and for translational studies in human neonates.

Algorithmic assessment of shoulder function using smartphone video capture and machine learning.

Tears within the stabilizing muscles of the shoulder, known as the rotator cuff (RC), are the most common cause of shoulder pain-often presenting in older patients and requiring expensive advanced imaging for diagnosis. Despite the high prevalence of RC tears within the elderly population, there is no previously published work examining shoulder kinematics using markerless motion capture in the context of shoulder injury. Here we show that a simple string pulling behavior task, where subjects pull a string using hand-over-hand motions, provides a reliable readout of shoulder mobility across animals and humans. We find that both mice and humans with RC tears exhibit decreased movement amplitude, prolonged movement time, and quantitative changes in waveform shape during string pulling task performance. In rodents, we further note the degradation of low dimensional, temporally coordinated movements after injury. Furthermore, a logistic regression model built on our biomarker ensemble succeeds in classifying human patients as having a RC tear with > 90% accuracy. Our results demonstrate how a combined framework bridging animal models, motion capture, convolutional neural networks, and algorithmic assessment of movement quality enables future research into the development of smartphone-based, at-home diagnostic tests for shoulder injury.

Polarized macrophages regulate fibro/adipogenic progenitor (FAP) adipogenesis through exosomes.

BACKGROUND: Macrophage polarization has been observed in the process of muscle injuries including rotator cuff (RC) muscle atrophy and fatty infiltration after large tendon tears. In our previous study, we showed that fibrogenesis and white adipogenesis of muscle residential fibro/adipogenic progenitors (FAPs) cause fibrosis and fatty infiltration and that brown/beige adipogenesis of FAPs promotes rotator cuff muscle regeneration. However, how polarized macrophages and their exosomes regulate FAP differentiation remains unknown. METHODS: We cultured FAPs with M0, M1, and M2 macrophages or 2 × 109 exosomes derived from M0, M1 and M2 with and without GW4869, an exosome inhibitor. In vivo, M0, M1, and M2 macrophages were transplanted or purified macrophage exosomes (M0, M1, M2) were injected into supraspinatus muscle (SS) after massive tendon tears in mice (n = 6). SS were harvested at six weeks after surgery to evaluate the level of muscle atrophy and fatty infiltration. RESULTS: Our results showed that M2 rather than M0 or M1 macrophages stimulates brown/beige fat differentiation of FAPs. However, the effect of GW4869, the exosome inhibitor, diminished this effect. M2 exosomes also promoted FAP Beige differentiation in vitro. The transplantation of M2 macrophages reduced supraspinatus muscle atrophy and fatty infiltration. In vivo injections of M2 exosomes significantly reduced muscle atrophy and fatty infiltration in supraspinatus muscle. CONCLUSION: Results from our study demonstrated that polarized macrophages directly regulated FAP differentiation through their exosomes and M2 macrophage-derived exosomes may serve as a novel treatment option for RC muscle atrophy and fatty infiltration.