Anthropogenic fingerprints in daily precipitation revealed by deep learning.

According to twenty-first century climate-model projections, greenhouse warming will intensify rainfall variability and extremes across the globe1-4. However, verifying this prediction using observations has remained a substantial challenge owing to large natural rainfall fluctuations at regional scales3,4. Here we show that deep learning successfully detects the emerging climate-change signals in daily precipitation fields during the observed record. We trained a convolutional neural network (CNN)5 with daily precipitation fields and annual global mean surface air temperature data obtained from an ensemble of present-day and future climate-model simulations6. After applying the algorithm to the observational record, we found that the daily precipitation data represented an excellent predictor for the observed planetary warming, as they showed a clear deviation from natural variability since the mid-2010s. Furthermore, we analysed the deep-learning model with an explainable framework and observed that the precipitation variability of the weather timescale (period less than 10 days) over the tropical eastern Pacific and mid-latitude storm-track regions was most sensitive to anthropogenic warming. Our results highlight that, although the long-term shifts in annual mean precipitation remain indiscernible from the natural background variability, the impact of global warming on daily hydrological fluctuations has already emerged.

Complicated urinary tract infection in patients with benign prostatic hyperplasia.

Complicated urinary tract infection (UTI) is a symptomatic urinary infection accompanied by functional or structural abnormalities of the genitourinary tract. Benign prostatic hyperplasia (BPH) is a major cause of lower urinary tract obstruction in male patients, and bladder outlet obstruction (BOO) secondary to BPH can lead to UTIs in men. However, no evidence has clearly shown that UTI in the aging male population is associated with either post-void residual urine or BOO. Screening for the presence of bacteriuria is recommended prior to any procedure manipulating the urinary tract, and imaging studies of the upper urinary tract are recommended to identify underlying abnormalities. Recurrent or persistent UTI in men with BPH is an indication for surgical treatment. Asymptomatic bacteriuria should be screened for and treated before transurethral resection of the prostate (TURP). In addition, antibiotic prophylaxis reduced the risk of UTI in patients undergoing TURP. The choice of specific antimicrobial for prophylaxis should be based on local pathogen prevalence and individual antibiotic susceptibility. Patients with severe systemic infections require hospitalization, and empirical therapy should include an intravenous antimicrobial regimen. Further prospective studies are needed to refine the treatment process for complicated UTI in patients diagnosed with BPH.

Recent surgical treatments for urinary stone disease in a Korean population: National population-based study.

OBJECTIVES: To provide surgical treatment trends for urinary stone disease in Korea. METHODS: We analyzed medical service claim data of surgical treatments to urinary stone disease submitted by medical service providers from the Health Insurance Review and Assessment Service from 2009 to 2016. RESULTS: There was a significantly increasing trend among outpatients and inpatients for urinary stone disease from 2009 to 2016 (R2  = 0.643, P = 0.017; R2  = 0.575, P = 0.029). The number of shock wave lithotripsy for treating urinary stone disease increased by 16% from 89 553 in 2009 to 104 013 in 2016 (R2  = 0.684). The number of ureteroscopic lithotripsy increased by 97% from 6106 in 2009 to 12 057 in 2016 (R2  = 0.99). The number of flexible ureteroscopic lithotripsy increased by 16-fold from 219 in 2009 to 3712 in 2016 (R2  = 0.756). The number of percutaneous nephrolithotomy increased by 99.7% from 919 in 2009 to 1835 in 2016 (R2  = 0.987). The use of non-contrast and contrast-enhanced computed tomography in the diagnostic codes for urinary stone disease increased by 394.8% and 263.3% from 2009 to 2016, respectively (R2  = 0.83; R2  = 0.967). Conversely, the use of intravenous pyelography decreased 26.2% over the same period (R2  = 0.945). CONCLUSIONS: Outpatient and inpatient procedures for urinary stone disease have increased over the past 8 years in Korea. Shock wave lithotripsy is the most widely used treatment modality for urinary stone disease, and endoscopic surgical procedures are rapidly being implemented. There has been a steep increase in the use of computed tomography, whereas conventional intravenous pyelography is declining.

Human contribution to more-intense precipitation extremes.

Extremes of weather and climate can have devastating effects on human society and the environment. Understanding past changes in the characteristics of such events, including recent increases in the intensity of heavy precipitation events over a large part of the Northern Hemisphere land area, is critical for reliable projections of future changes. Given that atmospheric water-holding capacity is expected to increase roughly exponentially with temperature--and that atmospheric water content is increasing in accord with this theoretical expectation--it has been suggested that human-influenced global warming may be partly responsible for increases in heavy precipitation. Because of the limited availability of daily observations, however, most previous studies have examined only the potential detectability of changes in extreme precipitation through model-model comparisons. Here we show that human-induced increases in greenhouse gases have contributed to the observed intensification of heavy precipitation events found over approximately two-thirds of data-covered parts of Northern Hemisphere land areas. These results are based on a comparison of observed and multi-model simulated changes in extreme precipitation over the latter half of the twentieth century analysed with an optimal fingerprinting technique. Changes in extreme precipitation projected by models, and thus the impacts of future changes in extreme precipitation, may be underestimated because models seem to underestimate the observed increase in heavy precipitation with warming.

A prospective Korean multicenter study for infectious complications in patients undergoing prostate surgery: risk factors and efficacy of antibiotic prophylaxis.

This multicenter study was undertaken to determine the efficacy of antibiotic prophylaxis and identify the risk factors for infectious complications after prostate surgery in Korean patients. A total of 424 patients who underwent surgery of the prostate were reviewed. All patients underwent urinalysis and urine culture preoperatively and postoperatively. Efficacy of antibiotic prophylaxis and risk factors for infectious complications were investigated. Infectious complications were observed in 34.9% of all patients. Factors independently associated with infectious complications were diabetes mellitus (adjusted OR, 1.99; 95% CI, 1.09-3.65, P=0.025) and operation time (adjusted OR, 1.08; 95% CI, 1.03-1.13, P=0.004). Clinicians should be aware of the high risk of infectious complications in patients with diabetes and those who undergo a prolonged operation time. Neither the type nor duration of prophylactic antibiotics resulted in differences in infectious complications.

Leveraging physics-based and explainable machine learning approaches to quantify the relative contributions of rain and air pollutants to wet deposition.

A quantitative understanding of the roles of rainfall and pollutant concentrations in wet deposition is important because they critically influence terrestrial and aquatic ecosystems. However, their relative contributions to wet deposition, which vary across regions, have not yet been identified. We propose two methods that quantitatively separate the contributions of rain and pollutant concentrations to wet deposition: one is based on simplified equations describing the wet scavenging of pollutants and the other is based on random forest models employing SHapley Additive exPlanations. Three-dimensional long-term air quality simulations from 2003 to 2019 are used as inputs for both the physics-based and machine learning models. Remarkably, the results drawn from the explainable machine learning model are consistent with those from the physics-based approach: overall, rain is a more important limiting factor than pollutant concentrations and the relative contribution of rain is larger than that of pollutants by up to a factor of 3-4 in polluted regions. In polluted regions, pollutant concentrations can remain relatively high even in the presence of precipitation owing to continuous and intense emissions; therefore, wet deposition is limited by rainfall. The contribution of rainfall is larger by 1.5-2.5 than that of pollutant concentrations in regions even with low emissions and this considerably large role of rain suggests that regional or transboundary pollutant transport plays a key role in modulating wet deposition. However, in very remote regions, once the rainfall amount exceeds a certain value, rainfall no longer contributes to increasing wet deposition because atmospheric pollutants are readily removed by rain. So, the contributions of the two factors are comparable in pristine regions. Our results can serve as a basis for explaining interannual variations in wet deposition and for future projections of wet deposition under emission control plans and climate change scenarios across regions.

Synthesized Pheophorbide a-mediated photodynamic therapy induced apoptosis and autophagy in human oral squamous carcinoma cells.

BACKGROUND: Pheophorbide a (Pa) is a chlorine-based photosensitizer derived from an ethnopharmacological herb, and our group recently synthesized Pa by the removal of a magnesium ion and a phytyl group from chlorophyll-a. In this study, the effect of photodynamic therapy (PDT) with synthesized Pa was examined in a human oral squamous cell carcinoma (OSCC) cells. METHODS: Cells were treated with PDT with Pa, and reactive oxygen species (ROS) and mitochondrial membrane potential [ΔΨ (m)] were examined. Apoptosis was measured using annexin V staining and immunoblot. Autophagy was characterized by the increase in LC3B-II and the formation of autophagosome and acidic vesicular organelles (AVOs). RESULTS: Pa-PDT inhibited the proliferation of OSCC cells in a dose-dependent manner. Pa-PDT increased the number of apoptotic cells by inactivating ERK pathway. Pa-PDT also induced autophagy in OSCC cells evidenced by the increased levels of LC3 type II expression and the accumulation of AVOs. The inhibition of autophagy enhanced Pa-PDT-mediated cytotoxicity through an increase in necrosis. CONCLUSIONS: These results suggest that synthesized Pa-PDT exerts anti-tumor effects by inducing apoptosis and autophagy and provide novel evidence that Pa-PDT induces autophagy, and autophagy inhibition enhances Pa-PDT-mediated necrosis in OSCC cells.

Observationally-constrained projections of an ice-free Arctic even under a low emission scenario.

The sixth assessment report of the IPCC assessed that the Arctic is projected to be on average practically ice-free in September near mid-century under intermediate and high greenhouse gas emissions scenarios, though not under low emissions scenarios, based on simulations from the latest generation Coupled Model Intercomparison Project Phase 6 (CMIP6) models. Here we show, using an attribution analysis approach, that a dominant influence of greenhouse gas increases on Arctic sea ice area is detectable in three observational datasets in all months of the year, but is on average underestimated by CMIP6 models. By scaling models' sea ice response to greenhouse gases to best match the observed trend in an approach validated in an imperfect model test, we project an ice-free Arctic in September under all scenarios considered. These results emphasize the profound impacts of greenhouse gas emissions on the Arctic, and demonstrate the importance of planning for and adapting to a seasonally ice-free Arctic in the near future.

Increase in convective extreme El Niño events in a CO2 removal scenario.

Convective extreme El Niño (CEE) events, characterized by strong convective events in the eastern Pacific, are known to have a direct link to anomalous climate conditions worldwide, and it has been reported that CEE will occur more frequently under greenhouse warming. Here, using a set of CO2 ramp-up and ramp-down ensemble experiments, we show that frequency and maximum intensity of CEE events increase further in the ramp-down period from the ramp-up period. These changes in CEE are associated with the southward shift of the intertropical convergence zone and intensified nonlinear rainfall response to sea surface temperature change in the ramp-down period. The increasing frequency of CEE has substantial impacts on regional abnormal events and contributed considerably to regional mean climate changes to the CO2 forcings.

Hemispherically asymmetric Hadley cell response to CO2 removal.

A poleward shift of the Hadley cell (HC) edge in a warming climate, which contributes to the expansion of drought-prone subtropical regions, has been widely documented. The question addressed here is whether this shift is reversible with CO2 removal. By conducting large-ensemble experiments where CO2 concentrations are systematically increased and then decreased to the present-day level, we show that the poleward-shifted HC edge in a warming climate does not return to its present-day state when CO2 concentrations are reduced. While the Southern Hemisphere HC edge remains poleward of its present-day state, the Northern Hemisphere HC edge ends up farther equatorward of its present-day state. Such hemispherically asymmetric HC edge changes are closely associated with the changes in vertical wind shear in the subtropical atmosphere, which result from the long adjustment time of the ocean response to CO2 removal. Our findings suggest that CO2 removal may not guarantee the recovery of the subtropical dryness associated with the HC changes.

Toll-like receptor 7 agonist, imiquimod, inhibits oral squamous carcinoma cells through apoptosis and necrosis.

BACKGROUND: Toll-like receptor (TLR) agonists have anticancer effect by inducing apoptosis or activating immune cells. In this study, we investigated whether imiquimod, TLR7 agonist, inhibits the proliferation of oral cancer cells. METHODS: Toll-like receptor 7 expression and IL-6/8 production by imiquimod were examined using RT-PCR and Enzyme-linked immunosorbent assay, respectively. Cell viability was examined by MTT assay. To examine apoptotic cell death, Annexin V/PI staining for flow cytometry and Western blot analysis were performed. Necrotic cell death was determined by leakage of lactate dehydrogenase (LDH), HMGB1, and PI staining in imiquimod-treated oral squamous cell carcinoma (OSCC) cells. RESULTS: Toll-like receptor 7 mRNA was expressed in OSCC cells. Imiquimod induced IL-6 and IL-8 production in OSCC cells, suggesting the functional expression of TLR7. Imiquimod inhibited cells proliferation in a dose-dependent manner. The ratio of annexin V-positive cells and cleaved caspase-3/7 was increased by imiquimod treatment in OSCC cells, suggesting that imiquimod-induced cell death in OSCC cells may be owing to apoptosis. In addition, LDH secretion and PI staining were detected in OSCC cells treated with imiquimod, showing that imiquimod also induced necrotic cell death in the OSCC cells. CONCLUSIONS: Imiquimod inhibited effectively the growth of OSCC cells by inducing apoptosis and necrosis.

Synchronous central giant cell granuloma and ossifying fibroma of the mandible.

Central giant cell granuloma (CGCG) is a benign lesion of the jaws. In most cases, the lesion presents as a painless, slow-growing swelling of the jaws. Ossifying fibroma (OF) of the jaw is a benign neoplasm that consists of variable amounts of mineralized material embedded in a fibrous stroma. The simultaneous occurrence of CGCG with odontogenic fibroma or OF has been described as combined lesions. However, synchronous presentation of CGCG and OF in the mandible is a rare occurrence. This report describes a case of 2 completely independent CGCG and OF located on both posterior regions of the mandible.

Evaluation of early bone response to fluoride-modified and anodically oxidized titanium implants through continuous removal torque analysis.

PURPOSE: To compare between a bioactive and a bioinert implant with different geometries by continuous measurement of the removal torque and calculation of the angular momentum of each surfaced implant. MATERIALS AND METHODS: Six New Zealand white rabbits were used in the study. Each rabbit received 2 implants. A bioactive fluoride-modified implant with a conical connection and microthread design was inserted into one tibia, and a bioinert anodically oxidized implant with an external connection design was inserted into the other. After 2 weeks of implant insertion, the removal torque values were continuously measured according to time. Using the time-torque curve resulting from the measurements, the maximum values were determined, and the angular momenta were calculated. RESULTS: The anodically oxidized implant had significantly higher peak removal torque and angular momentum values than the fluoride-modified implant (P < 0.05). CONCLUSIONS: The impact of the fluoride-modified bioactive implant on early bone response remains unclear. Considering the angular momentum of dental implants may assist in the elucidation of the effect of implant geometry on bone response.

Greenhouse warming and anthropogenic aerosols synergistically reduce springtime rainfall in low-latitude East Asia.

Low-latitude East Asia, particularly southern China, has experienced a markedly decreasing springtime rainfall in recent years whereas rainfall trends are weak in mid-latitude East Asia. Details of human influences on this contrasting feature remain uncertain. This study provides a quantification of the relative roles of greenhouse warming and aerosols in the observed spring rainfall trends over East Asia using a state-of-the-art numerical model. Greenhouse warming drives more rapid temperature increases over high-latitude East Asia potentially associated with reduced spring snow than the western North Pacific, which induces an anomalous anticyclone over the East China Sea. This circulation change results in a northwestward extension of the western North Pacific subtropical high, reducing rainfall at low latitudes while moderately increasing rainfall at mid-latitudes. In contrast, anthropogenic aerosols reduce rainfall in both low- and mid-latitude East Asia. Hence, the two anthropogenic factors synergistically reduce rainfall at low latitudes, with a stronger contribution of greenhouse warming (~34%) than aerosols (~17%). In mid-latitude East Asia, their contributions are offset, resulting in weak rainfall trends. Further, the anthropogenic influences are found to be relatively larger under drier conditions, suggesting that a more severe drought can occur in low-latitude East Asia under future drought-conducive conditions.

Asymmetrical response of summer rainfall in East Asia to CO2 forcing.

Understanding the regional hydrological response to varying CO2 concentration is critical for cost-benefit analysis of mitigation and adaptation polices in the near future. To characterize summer monsoon rainfall change in East Asia in a changing CO2 pathway, we used the Community Earth System Model (CESM) with 28 ensemble members in which the CO2 concentration increases at a rate of 1% per year until its quadrupling peak, i.e., 1468 ppm (ramp-up period), followed by a decrease of 1% per year until the present-day climate conditions, i.e., 367 ppm (ramp-down period). Although the CO2 concentration change is symmetric in time, the amount of summer rainfall anomaly in East Asia is increased 42% during a ramp-down period than that during a ramp-up period when the two periods of the same CO2 concentration are compared. This asymmetrical rainfall response is mainly due to an enhanced El Niño-like warming pattern as well as its associated increase in the sea surface temperature in the western North Pacific during a ramp-down period. These sea surface temperature patterns enhance the atmospheric teleconnections and the local meridional circulations around East Asia, resulting in more rainfall over East Asia during a ramp-down period. This result implies that the removal of CO2 does not guarantee the return of regional rainfall to the previous climate state with the same CO2 concentration.

Prognosis of pancreatic head cancer with different patterns of lymph node metastasis.

BACKGROUND: The nodal stage of pancreatic ductal adenocarcinoma (PDAC) is revised in the AJCC 8th edition. Studies on the prognosis of PDAC according to lymph node metastasis (LNM) are still ongoing. We attempted to find the patterns of nodal involvement and to reveal its clinical significance to overall survival (OS). METHODS: We analyzed 585 patients who received pancreatic head cancer surgery diagnosed as PDAC from January 2007 to December 2016. Patients were classified into three groups: Group 1 (G1, patients without LNM), Group 2 (G2, those with LNM only in the peripancreatic area), and Group 3 (G3 those with LNM in the other area and/or peripancreatic LNM). Risk factors were analyzed by Cox-regression test and overall survival was compared by Kaplan-Meier analysis. RESULTS: LNM in peripancreatic area was the most common (88.7%). In the multivariate analysis, T stage, nuclear differentiation, adjuvant treatment, and the G2 and G3 were independent risk factors for OS (G2 over G1, HR 1.384, 95% CI 1.046-1.802; P = .036 and G3 over G1, HR 2.383, 95% CI 1.378-4.103; P = .001). G3 showed worse OS than G2 (P = .006). In the N1 status, LNM to the pericholedochal (PC) and superior mesenteric artery (SMA) areas resulted in worse OS than the G2 (P = .011 and P = .019). CONCLUSIONS: We found that LNM beyond the peripancreatic area significantly affects OS in pancreatic head cancer patients. Depending on the station of the LNM, different risk-stratification and treatment strategies will need to be considered.

Relation Between Tumor Size and Lymph Node Metastasis According to Subtypes of Breast Cancer.

PURPOSE: Tumor size and lymph node metastasis are important factors that contribute to the progression of breast cancer. We aimed to analyze the relationship between tumor size and lymph node metastasis molecular subtype and examine the effects of nodal metastasis on overall survival (OS). METHODS: We retrospectively reviewed the data of 16,552 patients who underwent breast surgery in Samsung Medical Center between 2000 and 2015. Information on tumor size (largest diameter of the invasive component), number of positive lymph nodes, and molecular subtype were obtained. We constructed a linear regression model to evaluate the relationship between tumor size and lymph node metastasis. To determine the effect of nodal metastasis on OS, we performed a Cox proportional regression analysis with Np/T (number of metastatic lymph nodes [n]/tumor size [cm]). RESULTS: This study included 12,007 patients with a median follow-up of 62 months. The linear regression coefficients were 1.043 for luminal A, 1.024 for luminal B, 0.656 for HER2, and 0.435 for triple-negative breast cancer (TNBC) subtypes. No significant difference was observed in the coefficients between the luminal A and B subtypes (p =0.797), while all other coefficients showed significant difference. After adjusting for other risk factors, the hazard ratio (HR) of Np/T for each subtype was significant for OS: luminal A (HR, 1.134; 95% confidence interval [CI], 1.097-1.171; p < 0.001), luminal B (HR, 1.049; 95% CI, 1.013-1.086; p =0.007), HER2 (HR, 1.069; 95% CI, 1.014-1.126; p =0.013), and TNBC (HR, 1.038; 95% CI, 1.01-1.067; p =0.008). CONCLUSION: The incidence of lymph node metastasis differed according to molecular subtype. Luminal types have higher incidence of nodal metastasis than HER2 and TNBC. The HR of Np/T was highest in luminal A subtypes and lowest in TNBC subtypes.

Volcanic-induced global monsoon drying modulated by diverse El Niño responses.

There remains large intersimulation spread in the hydrologic responses to tropical volcanic eruptions, and identifying the sources of diverse responses has important implications for assessing the side effects of solar geoengineering and improving decadal predictions. Here, we show that the intersimulation spread in the global monsoon drying response strongly relates to diverse El Niño responses to tropical eruptions. Most of the coupled climate models simulate El Niño-like equatorial eastern Pacific warming after volcanic eruptions but with different amplitudes, which drive a large spread of summer monsoon weakening and corresponding precipitation reduction. Two factors are further identified for the diverse El Niño responses. Different volcanic forcings induce systematic differences in the Maritime Continent drying and subsequent westerly winds over equatorial western Pacific, varying El Niño intensity. The internally generated warm water volume over the equatorial western Pacific in the pre-eruption month also contributes to the diverse El Niño development.

Second primary cancers in patients with oral cavity cancer included in the Korea Central Cancer Registry.

OBJECTIVES: The improved survival of patients with oral cavity cancer (OCC) has generated interest in factors affecting survivorship, particularly among second primary cancer (SPC) patients. This study aimed to assess the incidence, patterns, and risk factors for SPC after OCC treatment in the Korean population. MATERIALS AND METHODS: Data from 15,261 patients with OCC (ICD-O: C01-C06) identified between 1993 and 2014 were extracted from the Korean Central Cancer Registry. The standardized incidence ratio (SIR) for SPC after index OCC was calculated, and Poisson regression analysis was performed to evaluate the risk factors for SPC among survivors. RESULTS: The overall SIR for SPC among OCC survivors was 1.47 (95% confidence interval [CI] 1.39-1.56). SIR differed by sex (male: 1.51 vs. female: 1.37), age at diagnosis (<45 years: 2.47 vs. 45-64 years: 1.68 vs. ≥ 65 years: 1.10), index OCC subsite (floor of mouth: 1.95 vs. gum: 1.30), follow-up duration (6-23 months: 1.64 vs. 24-59 months: 1.51 vs. 60-119 months: 1.48 vs. ≥ 120 months: 1.24), histological OCC type (salivary gland malignancy: 1.77 vs. squamous cell carcinoma: 1.44 vs. others: 1.47), and radiation history (any: 1.94 vs. no radiation: 1.37). The risk factors for SPC development among OCC survivors included younger age at diagnosis and history of radiation therapy. CONCLUSION: OCC survivors have significantly increased risks of SPCs, exhibiting distinctive site distributions and chronological patterns. These patients would benefit from an SPC surveillance protocol.

Characteristics of inappropriate multiple medication use in older urological outpatients.

OBJECTIVES: To investigate polypharmacy and potentially inappropriate medications (PIMs) in elderly patients visiting the urology department for lower urinary tract symptoms (LUTS). METHODS: We retrospectively analyzed digital medical records of individuals over the age of 65 who visited the urology department for LUTS. This cross-sectional study was conducted in 10 hospitals located in South Korea, between September 2017 and December 2017. All prescribed medications were analyzed using electronic medical records. The updated 2015 Beers criteria were used to identify and assess the appropriateness of the prescribed drugs in elderly patients. RESULTS: We analyzed a total of 2143 patients aged over 65 years from 10 institutions. The mean age was 74.2 ± 6.26 years (65-97), 1634 (76.2%) were men. Patients took a mean of 6.48 ± 2.46 medications (range 0-18), and polypharmacy was found in 1762 patients (82.2%). The number of patients who received PIMs at least once was 1579 (73.7%). The average number of PIMs used per patient was 1.31 ± 1.25 (0-7). PIM use ratio was 18.9 ± 0.15% (0-67%). The number of chronic diseases, and concurrent medication and polypharmacy were predictive factors associated with PIM use. CONCLUSION: Our multi-institutional results show that a substantial proportion of elderly patients took PIMs when visiting the urology department. Factors associated with PIMs were the number of chronic diseases and polypharmacy. Medication use in elderly patients, especially in urology, should be monitored carefully.