Increase in CFC-11 emissions from eastern China based on atmospheric observations.

The recovery of the stratospheric ozone layer relies on the continued decline in the atmospheric concentrations of ozone-depleting gases such as chlorofluorocarbons1. The atmospheric concentration of trichlorofluoromethane (CFC-11), the second-most abundant chlorofluorocarbon, has declined substantially since the mid-1990s2. A recently reported slowdown in the decline of the atmospheric concentration of CFC-11 after 2012, however, suggests that global emissions have increased3,4. A concurrent increase in CFC-11 emissions from eastern Asia contributes to the global emission increase, but the location and magnitude of this regional source are unknown3. Here, using high-frequency atmospheric observations from Gosan, South Korea, and Hateruma, Japan, together with global monitoring data and atmospheric chemical transport model simulations, we investigate regional CFC-11 emissions from eastern Asia. We show that emissions from eastern mainland China are 7.0 ± 3.0 (±1 standard deviation) gigagrams per year higher in 2014-2017 than in 2008-2012, and that the increase in emissions arises primarily around the northeastern provinces of Shandong and Hebei. This increase accounts for a substantial fraction (at least 40 to 60 per cent) of the global rise in CFC-11 emissions. We find no evidence for a significant increase in CFC-11 emissions from any other eastern Asian countries or other regions of the world where there are available data for the detection of regional emissions. The attribution of any remaining fraction of the global CFC-11 emission rise to other regions is limited by the sparsity of long-term measurements of sufficient frequency near potentially emissive regions. Several considerations suggest that the increase in CFC-11 emissions from eastern mainland China is likely to be the result of new production and use, which is inconsistent with the Montreal Protocol agreement to phase out global chlorofluorocarbon production by 2010.

Respiratory microbiome profiles are associated with distinct inflammatory phenotype and lung function in children with asthma.

BACKGROUND: Respiratory microbiome studies have fostered our understanding of various phenotypes and endotypes of heterogeneous asthma. However, the relationship between the respiratory microbiome and clinical phenotypes in children with asthma remains unclear. We aimed to identify microbiome-driven clusters reflecting the clinical features of asthma and their dominant microbiotas in children with asthma. METHODS: Induced sputum was collected from children with asthma, and microbiome profiles were generated via sequencing of the V3-V4 region of the 16S rRNA gene. Cluster analysis was performed using the partitioning around medoid clustering method. The dominant microbiota in each cluster was determined using the Linear Discriminant Effect Size analysis. Each cluster was analyzed for association among the dominant microbiota, clinical phenotype, and inflammatory cytokine. RESULTS: Eighty-three children diagnosed with asthma were evaluated. Among four clusters reflecting the clinical characteristics of asthma, cluster 1, dominated by Haemophilus and Neisseria, demonstrated lower post-bronchodilator (BD) forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) than that in the other clusters and more mixed granulocytic asthma. Neisseria negatively correlated with pre-BD and post-BD FEV1/FVC. Haemophilus and Neisseria positively correlated with programmed death-ligand (PD-L)1. CONCLUSION: To our knowledge, this study is the first to analyze the relationship between an unbiased microbiome-driven cluster and clinical phenotype in children with asthma. The cluster dominated by Haemophilus and Neisseria showed fixed airflow obstruction and mixed granulocytic asthma, which correlated with PD-L1 levels. Thus, microbiome-driven unbiased clustering can help identify new asthma phenotypes related to endotypes in childhood asthma.

Single-incision robotic colorectal surgery with the da Vinci SP® surgical system: initial results of 50 cases.

PURPOSE: The da Vinci SP® (dVSP) surgical system (Intuitive Surgical, Sunnyvale, CA, USA), a robotic platform designed for single-incision surgery, overcame the need for multiple ports in traditional robotic surgery and issues including triangulation and retraction in single-incision laparoscopic surgery. However, previous studies only included case reports or series with small sample sizes. The aim of this study was to assess the safety and performance of the dVSP surgical system and its instruments and accessories for colorectal procedures. METHODS: The medical records of patients who had surgery with the dVSP from March 2019 to September 2021 at Ewha Womans University Seoul Hospital were investigated. The pathologic and follow-up data of patients who had malignant tumors were analyzed separately to evaluate oncological safety. RESULTS: Fifty patients (26 male and 24 female) with a median age of 59 years (interquartile range 52.5-63.0 years) were enrolled. The procedures included low anterior resection with total mesorectal excision (n = 16), sigmoid colectomy with complete mesocolic excision and central vessel ligation (CME + CVL) (n = 14), right colectomy with CME + CVL (n = 9), left colectomy with CME + CVL (n = 4), right colectomy (n = 6), and sigmoid colectomy (n = 1). Operative time significantly decreased after 25 cases (early phase vs. late phase; operative time 295.0 min vs. 250.0 min, p = 0.015; docking time 16.0 min vs. 12.0 min, p = 0.001; console time 212.0 min vs. 190.0 min, p = 0.019). Planned procedures were successfully completed in all patients. Postoperative outcomes were acceptable with only six cases of mild adverse events through a 3-month follow-up. No local recurrence and only one case of systemic recurrence occurred within 1 year postoperatively. CONCLUSIONS: This study demonstrated the surgical and oncological safety and feasibility of dVSP, which may be a novel surgical platform for colorectal surgery.

Eosinophil-derived TGFß1 controls the new bone formation in chronic rhinosinusitis with nasal polyps

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by chronic eosinophilic inflammation and new bone formation (NBF). These processes may be associated with each other in the pathogenesis and influence the severity and prognosis of the disease. However, it is still unclear how eosinophilic inflammation is involved in the NBF. METHODOLOGY: Sinus bone cells were isolated from ethmoid bone tissues of patients with CRSwNP and controls. Transforming growth factor beta 1 (TGFß1) and alkaline phosphatase (ALP) expression in sinus bone cells was determined using quantitative RT-PCR, immunoblotting, and immunohistochemistry. The co-localization of TGFß1 with eosinophils was assessed by immunofluorescence staining. Sinus bone cells were co-cultured with eosinophils (Eol-1 cell line), which were differentiated with butyrate, to measure the osteoblast differentiation activity of sinus bone cells. RESULTS: TGFß1 expression was increased in sinus bone tissues and correlated with CT scores in CRSwNP. TGFß1 was also increased in the submucosa of CRSwNP and co-localized predominantly with eosinophils compared with neutrophils Differentiated Eol-1 cells-derived TGFß1 increased ALP expression in sinus bone cells. Treatment with a TGFß inhibitor attenuated TGFß1-induced ALP expression and staining in sinus bone cells of CRSwNP, leading to loss of bone formation. CONCLUSIONS: Eosinophil-derived TGFß1 was enriched in the submucosa of CRSwNP, which induced ALP expression in sinus bone cells and NBF. Therefore, eosinophil-derived TGFß1 may mediate aberrant bone remodeling in CRSwNP.

Range and Frequency of Congenital Malformations Among Children With Cleft Lip and/or Palate.

To assess the range and frequency of additional congenital malformations identified among children born alive with CL/P.Analysis of patient-level data from a national registry of cleft births linked to national administrative data of hospital admissions.National Health Service, England.Children born between 2000 and 2012 receiving cleft care in English NHS hospitals.The proportion of children with ICD-10 codes for additional congenital malformations, according to cleft type.The study included 9403 children. Of these 2114 (22.5%) had CL±A, 4509 (48.0%) had CP, 1896 (20.2%) had UCLP, and 884 (9.4%) had BCLP. A total of 3653 (38.8%) children had additional congenital malformations documented in their hospital admission records. The prevalence of additional congenital malformations was greatest among children with CP (53.0%), followed by those with BCLP (33.5%), UCLP (26.3%), and then CL±A (22.2%) (P < .001). Among those with UCLP, children with right-sided clefts were more likely to have additional malformations than those with left-sided clefts (31.6% vs 23.0%, P < .001). Malformations of the skeletal system and circulatory system were most common, affecting 10.5% and 10.2% of the included children, respectively. A total of 16.8% of children had additional congenital malformations affecting 2 or more structural systems.Congenital malformations are common among children born alive with a cleft, affecting over half of some cleft subgroups. Given the frequency of certain structural malformations, clinicians should consider standardized screening for these children. Establishing good links with pediatric and genetic services is recommended.

Effect of supplementation of cryoprotectant solution with hydroxypropyl cellulose for vitrification of bovine oocytes.

BACKGROUND: Successful cryopreservation of bovine oocytes is very important for research and commercial applications. However, the survival and development rate of vitrified-thawed (VT) oocytes are lower than those of non-vitrified-thawed (non-VT) oocytes. OBJECTIVE: To investigate the effect of adding hydroxypropyl cellulose (HPC) to the vitrification solution for bovine oocytes. MATERIALS AND METHODS: For vitrification, bovine metaphase II oocytes were pretreated with a solution containing 10% ethylene glycol supplemented with 0, 10, 50, or 100 ug/mL HPC for 5 min, exposed to a solution containing 30% ethylene glycol supplemented with 0, 10, 50, or 100 ug/mL HPC for 30 s, and then directly plunged into liquid nitrogen. RESULTS: The survival rate of oocytes was significantly higher in the 50 HPC group than in the 0, 10, and 100 HPC groups. The reactive oxygen species level was lower in the non-VT and 50 HPC groups than in the other groups. The mRNA levels of proapoptotic genes (Bax) were lower in the non-VT, 0, and 50 HPC groups than in the other groups. The mRNA levels of antiapoptotic genes (BCl2) were higher in the non-VT than in the other groups. The development rates of embryos (day 8) obtained via parthenogenetic activation (PA) were determined in the non-VT, 0 HPC, and 50 HPC groups. The cleavage rate was significantly higher in the non-VT group. CONCLUSION: Supplementation of vitrification solution with HPC improves the survival of VT bovine oocytes and the development capacity of embryos derived from these oocytes via PA. doi.org/10.54680/fr23110110212.

The effect of the national scaling program on tooth loss: a claim-based matched large cohort study in Korea.

OBJECTIVE: Tooth loss affects quality of life. Scaling is a measure to prevent periodontal disease and tooth loss. This study aimed to determine the effect of scaling on tooth loss. BASIC RESEARCH DESIGN: Secondary analysis of the Korean National Health Insurance Services database, comprising 514,866 Koreans as an initial cohort, followed for 14 years up to 2015. The study population comprised people who had received an oral check-up in 2002-2003. Using propensity score matching, we matched the intervention group (receipt of scaling) and controls (no scaling) 1:1. The outcome, tooth loss was defined as including all teeth except for third molars until 2015. The final sample included 94,738 people. Analysis used a Cox proportional hazard regression model. RESULTS: Scaling showed conflicting results in univariate and multivariable analyses. In univariate analysis, people who received scaling were more likely to lose teeth (HR, 1.04; 95% CI, 1.02-1.05). After adjusting for confounders in the multivariable analysis, those who didn't receive scaling were more likely to lose teeth (HR, 0.97; 95% CI, 0.95, 0.99). The effects of scaling were identified in people without diabetes (HR, 0.97; 95% CI, 0.95, 0.99) but not in people with diabetes (HR, 0.97; 95% CI, 0.89-1.06). CONCLUSIONS: Scaling was associated with less tooth loss. Regular scaling might be encouraged for vulnerable groups, such as males, older adults, lower income, handicapped, chronic diseases, and smokers.

Prediction of long-term survival after gastrectomy using random survival forests.

BACKGROUND: No well validated and contemporaneous tools for personalized prognostication of gastric adenocarcinoma exist. This study aimed to derive and validate a prognostic model for overall survival after surgery for gastric adenocarcinoma using a large national dataset. METHODS: National audit data from England and Wales were used to identify patients who underwent a potentially curative gastrectomy for adenocarcinoma of the stomach. A total of 2931 patients were included and 29 clinical and pathological variables were considered for their impact on survival. A non-linear random survival forest methodology was then trained and validated internally using bootstrapping with calibration and discrimination (time-dependent area under the receiver operator curve (tAUC)) assessed. RESULTS: The median survival of the cohort was 69 months, with a 5-year survival of 53.2 per cent. Ten variables were found to influence survival significantly and were included in the final model, with the most important being lymph node positivity, pT stage and achieving an R0 resection. Patient characteristics including ASA grade and age were also influential. On validation the model achieved excellent performance with a 5-year tAUC of 0.80 (95 per cent c.i. 0.78 to 0.82) and good agreement between observed and predicted survival probabilities. A wide spread of predictions for 3-year (14.8-98.3 (i.q.r. 43.2-84.4) per cent) and 5-year (9.4-96.1 (i.q.r. 31.7-73.8) per cent) survival were seen. CONCLUSIONS: A prognostic model for survival after a potentially curative resection for gastric adenocarcinoma was derived and exhibited excellent discrimination and calibration of predictions.

In this study the authors used a large nationwide dataset from England and Wales and tried to make a predictive model that estimated how long patients would survive after surgery for gastric cancer. They found that using a machine learning methodology provided excellent results and accuracy in predictions, significantly in excess of any other published model and traditional staging methods. The model will be useful to provide individualized prediction of survival to patients and in the future could be used to stratify treatments.

Antifungal activity of streptavidin C1 and C2 against pathogens causing Fusarium wilt.

Fusarium wilt is caused by the soil-inhabiting fungus Fusarium oxysporum ff. spp. and is one of the most devastating plant diseases, resulting in losses and decreasing the quality and safety of agricultural crops. We recently reported the structures and biochemical properties of two biotin-binding proteins, streptavidin C1 and C2 (isolated from Streptomyces cinnamonensis strain KPP02129). In the present study, the potential of the biotin-binding proteins as antifungal agent for Fusarium wilt pathogens was investigated using recombinant streptavidin C1 and C2. The minimum inhibitory concentration of streptavidin C2 was found to be 16 µg ml-1 for inhibiting the mycelial growth of F. oxysporum f.sp. cucumerinum and F. oxysporum f.sp. lycopersici, while that of streptavidin C1 was found to be 64 µg ml-1 . Compared with the nontreated control soil, the population density of F. oxysporum f.sp. lycopersici in the soil was reduced to 49·5% and 39·6% on treatment with streptavidin C1 (500 µg ml-1 ) and C2 (500 µg ml-1 ), respectively. A greenhouse experiment revealed that Fusarium wilt of tomato plants was completely inhibited on soil drenching using a 50-ml culture filtrate of the streptavidin-producing strain KPP02129.

Association between air pollution and chronic rhinosinusitis: a nested case-control study using meteorological data and national health screening cohort data.

BACKGROUND: Inconsistent results about the effect of air pollution on chronic rhinosinusitis (CRS) have been reported. This study aimed to evaluate the impact of meteorological conditions/air pollution on the prevalence of CRS in adult Koreans. METHODOLOGY: The data from the Korean National Health Insurance Service-Health Screening Cohort from 2002 through 2015 were used. A CRS group (defined as ICD-10 codes J32, n=6159) was matched with a control group (n=24,636) in 1:4 ratios by age, sex, income, and region of residence. The meteorological conditions and air pollution data included the daily mean, highest, and lowest temperature (°C), daily temperature range (°C), relative humidity (%), ambient atmospheric pressure (hPa), sunshine duration (hr), and the rainfall (mm), SO2 (ppm), NO2 (ppm), O3 (ppm), CO (ppm), and PM10 (λg/m3) levels before the CRS diagnosis. Crude and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for CRS were analyzed using logistic regression analyses. RESULTS: When the NO2 level increased by 0.1 ppm, the odds for CRS increased 5.40 times, and when the CO level increased by 1 ppm and PM10 increased by 10 λg/m3, the odds for CRS decreased 0.75 times and 0.93 times, respectively. Other meteorological conditions, such as the mean/highest/lowest temperature, temperature range, rainfall and other air pollution, such as SO2 and O3, were not statistically significant. NO2 for 90 days before the index date increased the risk of CRS in all subgroups, except for the nasal polyp and older age subgroups. CONCLUSION: CRS is related to high concentrations of NO2.

Increased risk of chronic otitis media in chronic rhinosinusitis patients: a longitudinal follow-up study using a national health screening cohort.

BACKGROUND: Chronic rhinosinusitis (CRS) and chronic otitis media (COM) share pathophysiological mechanisms such as bacterial infection, biofilm, and persistence of the obstruction state of ventilation routes. However, only a few studies have investigated the relationship between these two diseases nationwide and in the general population. The purpose of this study was to determine whether the incidence of COM in patients with CRS differed from that of a matched control from the national health screening cohort. METHODS: Data from the Korean Health Insurance Review and Assessment Service-National Patient Samples were collected from 2002 to 2015. Participants who were treated ≥ ≥ ≥2 times and underwent head and neck computed tomography evaluation were selected. A 1:4 matched CRS group (n=8,057) and a control group (n=32,228) were selected. The control group included participants who were never treated with the ICD-10 code J32 from 2002 to 2015. The CRS group included CRS patients with/without nasal polyps. RESULTS: The incidence of COM was significantly higher in the CRS group than in the control group. In a subgroup analysis, the incidence of COM in all age groups and in men and women was significantly higher in the CRS group than in the control group. More, CRS increased the risk of COM. CONCLUSIONS: A significant association was observed between CRS and COM. This indicates that CRS patients have a high risk of developing COM.

STIM1 knock-down decreases the affinity of obinutuzumab for CD20 by altering CD20 localization to Triton-soluble membrane.

Obinutuzumab is thought to exert its effects through its high antibody-dependent cellular cytotoxicity (ADCC) via glyco-engineering of the Fc region. In addition, obinutuzumab causes direct binding-induced cell death (DCD) only by specifically binding to its target CD20, a Ca2+ channel. However, the specific features of CD20 related to obinutuzumab binding-induction of cell death are not clearly understood. In this study, we evaluated the relationship between the Ca2+ channel features of CD20 as a store-operated Ca2+ channel (SOC) and obinutuzumab binding-induced cell death. Ca2+ channel function and biochemical analysis revealed that CD20 is an Orai1- and stromal interaction molecule (STIM1)-dependent Ca2+ pore. However, binding of obinutuzumab on CD20 did not have any effect on Ca2+ influx activity of CD20; the direct cell death rate mediated by obinutuzumab binding was almost equivalent with or without the extracellular Ca2+ condition. Given the apparent interaction between STIM1 and CD20, we observed Triton-X solubilized obinutuzumab-bound CD20 accompanied by STIM1. Subsequently, obinutuzumab binding and cell death were decreased by STIM1 knock-down in Ramos B cells. Thus, STIM1 directly contributes to cell death by increasing the affinity of cells for obinutuzumab by transferring CD20 to the Triton-soluble membrane region.

Liquid crystal filter based tunable transmitter for 25Gps wavelength division multiplexing-passive optical network fronthaul.

A novel tunable transmitter structure based on liquid crystal filter, to the best of our knowledge, is presented. The structure is designed for application to 5G fronthaul and supports 25 Gbps dense wavelength division multiplexing (WDM) transmission and tunable range of 35 nm. The design takes into account easy change of operation band over coarse WDM grid. Prototype samples are developed to test feasibility of the design.

Modification of the RANKL-RANK-binding site for the immunotherapeutic treatment of osteoporosis.

Here, we proposed the use of mutated RANKL as an immunogen for active immunization and to induce anti-cytokine antibodies for osteoporosis treatment. INTRODUCTION: Osteoclasts are responsible for bone resorption in bone-related disorders. Anti-cytokine therapeutic antibodies such as denosumab are effective for the treatment of osteoporosis. However, problems with antibody manufacturing and the immunogenicity caused by multiple antibody doses have led to the use of auto-cytokines as immunogens to induce anti-cytokine antibodies. METHODS: RANKL was point-mutated based on the crystal structure of the complex of RANKL and its receptor RANK. RESULTS: As a proof of concept, immunization with RANKL produced high levels of specific antibodies and blocked osteoclast development in vitro and inhibited osteoporosis in RANKL-treated or ovariectomized mouse models. CONCLUSIONS: The results demonstrate the successful use of mutated RANKL as an immunogen for the induction of anti-RANKL immune response. This strategy is useful in general anti-cytokine immunotherapy to avoid toxic side effects of osteoporosis treatment.

Incidence of oral anticoagulant interruption among stroke patients with atrial fibrillation and subsequent stroke.

BACKGROUND AND PURPOSE: We analyzed the incidence and causes of oral anticoagulant (OAC) cessation and subsequent stroke after OAC withdrawal in a cohort of Korean stroke patients with atrial fibrillation. METHODS: The Korean Atrial Fibrillation Evaluation Registry in Ischemic Stroke patients (K-ATTENTION) is a multicenter cohort study, merging stroke registries from 11 tertiary centers in Korea. The number of OAC interruption episodes and the reasons were reviewed from hospital records. Stroke after OAC withdrawal was defined when a patient experienced ischaemic stroke within 31 days after OAC withdrawal. Clinical variables were compared between patients who experienced stroke recurrence during OAC interruption and those who did not experience recurrence. RESULTS: Among 3213 stroke patients with atrial fibrillation, a total of 329 episodes of OAC interruption were detected in 229 patients after index stroke (mean age 72.9 ± 8.3 years, 113 female patients). The most frequent reason for OAC withdrawal was poor compliance [103 episodes (31.3%)] followed by extracranial bleeding [96 episodes (29.2%)]. Stroke after OAC withdrawal was noted in 13 patients. Mean age, vascular risk factor profile and mean CHA2 DS2 -VASc score were not significantly different between patients with and without recurrent stroke. CONCLUSIONS: A considerable number of stroke patients with atrial fibrillation experienced temporary interruption of OAC after index stroke, which was associated with stroke recurrence of 4.0 cases per 100 interruption episodes.

Association between time to treatment and functional outcomes according to the Diffusion-Weighted Imaging Alberta Stroke Program Early Computed Tomography Score in endovascular stroke therapy.

BACKGROUND AND PURPOSE: The rate at which the chance of a good outcome of endovascular stroke therapy (EVT) decays with time when eligible patients are selected by baseline diffusion-weighted magnetic resonance imaging (DWI-MRI) and whether ischaemic core size affects this rate remain to be investigated. METHODS: This study analyses a prospective multicentre registry of stroke patients treated with EVT based on pretreatment DWI-MRI that was categorized into three groups: small [Diffusion-Weighted Imaging Alberta Stroke Program Early Computed Tomography Score (DWI-ASPECTS)] (8-10), moderate (5-7) and large (<5) cores. The main outcome was a good outcome at 90 days (modified Rankin Scale 0-2). The interaction between onset-to-groin puncture time (OTP) and DWI-ASPECTS categories regarding functional outcomes was investigated. RESULTS: Ultimately, 985 patients (age 69 ± 11 years; male 55%) were analysed. Potential interaction effects between the DWI-ASPECTS categories and OTP on a good outcome at 90 days were observed (Pinteraction  = 0.06). Every 60-min delay in OTP was associated with a 16% reduced likelihood of a good outcome at 90 days amongst patients with large cores, although no associations were observed amongst patients with small to moderate cores. Interestingly, the adjusted rates of a good outcome at 90 days steeply declined between 65 and 213 min of OTP and then remained smooth throughout 24 h of OTP (Pnonlinearity  = 0.15). CONCLUSIONS: Our study showed that the probability of a good outcome after EVT nonlinearly decreased, with a steeper decline at earlier OTP than at later OTP. Discrepant effects of OTP on functional outcomes by baseline DWI-ASPECTS categories were observed. Thus, different strategies for EVT based on time and ischaemic core size are warranted.

Short communication: Dietary bovine milk-derived exosomes improve bone health in an osteoporosis-induced mouse model.

Osteoporosis is a systemic skeletal disease characterized by low bone mass and micro-architectural deterioration of bone tissue, with a consequent increase in bone fragility and fracture susceptibility. In an aged society with increased life expectancy, the incidence rate of osteoporosis is also rapidly increasing. Inadequate nutrition may negatively influence bone metabolism. Recently, many studies have investigated the functionality of milk-derived exosomes, which play important roles in cell-to-cell communication. However, there are few reports of how milk-derived exosomes influence osteoblast proliferation and differentiation. Here, we determined whether bovine colostrum-derived exosomes promote anti-osteoporosis in vitro and in vivo. Tartrate-resistant acid phosphatase-stained cells were significantly inhibited in Raw264.7 cells treated with exosomes, indicating reduced osteoclast differentiation. We induced osteoporosis in mice using glucocorticoid pellets after orally administering exosomes for 2 mo. Interestingly, the bone mineral density of exosome-fed mouse groups was significantly improved compared with the glucocorticoid-induced osteoporosis group without exosome treatment. In addition, Lactobacillus were decreased in the gut microbiota community of osteoporosis-induced mice, but the gut microbiota community composition was effectively restored by exosome intake. Taken together, we propose that exosomes isolated from bovine colostrum could be a potential candidate for osteoporosis prevention, bone remodeling improvement, and inhibition of bone resorption. To our knowledge, this is the first time that a protective effect of milk exosomes against osteoporosis has been demonstrated in vivo. Our results strongly suggest that bovine colostrum exosomes might be used as a prophylaxis to prevent the onset of osteoporosis. Indeed, our results offer promising alternative strategies in the nutritional management of age-related bone complications.

Efficacy and costs of a workplace wellness programme.

BACKGROUND: Research investigating the efficacy of workplace wellness programmes to promote exercise, and by extension, reduce obesity and increase productivity has proliferated in recent years. Although preliminary work is encouraging, more work is needed. AIMS: To evaluate the effects and overall cost of a workplace exercise programme on multiple physical outcomes, including body mass index, aerobic fitness and muscular fitness. METHODS: Data from the Bruin Health Improvement Programme .5 (BHIP) between August 2013 and July 2018 were analysed. BHIP is a 12-week workplace wellness programme that assesses multiple areas of physical and mental health. For this study, changes in weight, waist-to-hip ratio, aerobic fitness and muscular endurance were analysed using paired samples t-tests and chi-squared tests. Using results from a prior analysis of Medical Expenditure Panel Survey, the estimated medical expenditure savings associated with weight loss were also analysed. RESULTS: A total of 518 participants (84% female) took part in the BHIP programme (mean age = 41 years, SD = 1.17). There were significant decreases in all anthropometric indices and significant increases in all fitness outcomes (P < 0.01) from baseline to follow-up. Estimated programme cost per participant, per session was $473 US Dollars (USD), and weight loss is estimated to reduce annual medical care costs by ~$2200 USD. CONCLUSIONS: Results showed significant improvements in all physical outcomes of interest. Additionally, there appears to be an inverse relationship between improvements in employee health and employer healthcare costs. Strengths, limitations and future directions are discussed.

Cooper Pair Density of Bi2Sr2CaCu2O8+ x in Atomic scale at 4.2 K.

In pursuit of the elusive mechanism of high- T C superconductors (HTSC), spectroscopic imaging scanning tunneling microscopy (SI-STM) is an indispensable tool for surveying local properties of HTSC. Since a conventional STM utilizes metal tips, which allow the examination of only quasiparticles and not superconducting (SC) pairs, Josephson tunneling using STM has been demonstrated by many authors in the past. An atomically resolved scanning Josephson tunneling microscopy (SJTM), however, was realized only recently on Bi2Sr2CaCu2O8+ x (Bi-2212) below 50 mK and on the Pb(110) surface at 20 mK. Here we report the atomically resolved SJTM on Bi2Sr2CaCu2O8+ x at 4.2 K using Bi-2212 tips created in situ. The I- V characteristics show clear zero bias conductance peaks following Ambegaokar-Baratoff (AB) theory. A gap map was produced for the first time using an atomically resolved Josephson critical current map I C( r) and AB theory. Surprisingly, we found that this new gap map is anticorrelated to the gap map produced by a conventional method relying on the coherence peaks. Quasiparticle resonance due to a single isolated zinc atom impurity was also observed by SJTM, indicating that atomically resolved SJTM was achieved at 4.2 K. Our result provides a starting point for realizing SJTM at even higher temperatures, rendering possible investigation of the existence of SC pairs in HTSC above the T C.

Scoring of tumor-infiltrating lymphocytes: From visual estimation to machine learning.

The extent of tumor-infiltrating lymphocytes (TILs), along with immunomodulatory ligands, tumor-mutational burden and other biomarkers, has been demonstrated to be a marker of response to immune-checkpoint therapy in several cancers. Pathologists have therefore started to devise standardized visual approaches to quantify TILs for therapy prediction. However, despite successful standardization efforts visual TIL estimation is slow, with limited precision and lacks the ability to evaluate more complex properties such as TIL distribution patterns. Therefore, computational image analysis approaches are needed to provide standardized and efficient TIL quantification. Here, we discuss different automated TIL scoring approaches ranging from classical image segmentation, where cell boundaries are identified and the resulting objects classified according to shape properties, to machine learning-based approaches that directly classify cells without segmentation but rely on large amounts of training data. In contrast to conventional machine learning (ML) approaches that are often criticized for their "black-box" characteristics, we also discuss explainable machine learning. Such approaches render ML results interpretable and explain the computational decision-making process through high-resolution heatmaps that highlight TILs and cancer cells and therefore allow for quantification and plausibility checks in biomedical research and diagnostics.