Spent coffee grounds as feedstock for the production of biosurfactants and the improved recovery of melanoidins.

Spent coffee grounds (SCG) are wastes generated in high amounts worldwide. Their composition makes them a promising feedstock for biotechnological processes. Here we show that the production of the biosurfactant surfactin by submerged culture of a Bacillus subtilis strain growing on SCG is possible, reaching concentrations up to 8.8 mg/L when using SCG at 8.3 g/L in the medium. In addition, we report a synergy between the production of surfactin and the recovery of melanoidins, an added-value compound already present in SCG. More specifically, the concentration of melanoidins in the culture medium increased between 2.1 and 2.5 times thanks to the presence of the B. subtilis in the culture. Furthermore, we have observed a strong interaction between surfactin and melanoidin aggregates through dynamic light scattering measurements, and that both of them can be co-purified with an acid precipitation. We have also characterized the interfacial and antioxidant properties of the cell-free supernatant and surfactin extract, as well as the distribution of the congeners of the biosurfactant. Altogether, this work describes a promising approach to obtain biosurfactants and antioxidant molecules in a single operation, which can be used to design several new formulations of interest for bioremediation, amendment of soils, food and cosmetics.

Role of Innate and Adaptive Cytokines in the Survival of COVID-19 Patients.

SARS-CoV-2 is a new coronavirus characterized by a high infection and transmission capacity. A significant number of patients develop inadequate immune responses that produce massive releases of cytokines that compromise their survival. Soluble factors are clinically and pathologically relevant in COVID-19 survival but remain only partially characterized. The objective of this work was to simultaneously study 62 circulating soluble factors, including innate and adaptive cytokines and their soluble receptors, chemokines and growth and wound-healing/repair factors, in severe COVID-19 patients who survived compared to those with fatal outcomes. Serum samples were obtained from 286 COVID-19 patients and 40 healthy controls. The 62 circulating soluble factors were quantified using a Luminex Milliplex assay. Results. The patients who survived had decreased levels of the following 30 soluble factors of the 62 studied compared to those with fatal outcomes, therefore, these decreases were observed for cytokines and receptors predominantly produced by the innate immune system-IL-1α, IL-1α, IL-18, IL-15, IL-12p40, IL-6, IL-27, IL-1Ra, IL-1RI, IL-1RII, TNFα, TGFα, IL-10, sRAGE, sTNF-RI and sTNF-RII-for the chemokines IL-8, IP-10, MCP-1, MCP-3, MIG and fractalkine; for the growth factors M-CSF and the soluble receptor sIL2Ra; for the cytokines involved in the adaptive immune system IFNγ, IL-17 and sIL-4R; and for the wound-repair factor FGF2. On the other hand, the patients who survived had elevated levels of the soluble factors TNFß, sCD40L, MDC, RANTES, G-CSF, GM-CSF, EGF, PDGFAA and PDGFABBB compared to those who died. Conclusions. Increases in the circulating levels of the sCD40L cytokine; MDC and RANTES chemokines; the G-CSF and GM-CSF growth factors, EGF, PDGFAA and PDGFABBB; and tissue-repair factors are strongly associated with survival. By contrast, large increases in IL-15, IL-6, IL-18, IL-27 and IL-10; the sIL-1RI, sIL1RII and sTNF-RII receptors; the MCP3, IL-8, MIG and IP-10 chemokines; the M-CSF and sIL-2Ra growth factors; and the wound-healing factor FGF2 favor fatal outcomes of the disease.

Climate change decreases the cooling effect from postfire albedo in boreal North America.

Fire is a primary disturbance in boreal forests and generates both positive and negative climate forcings. The influence of fire on surface albedo is a predominantly negative forcing in boreal forests, and one of the strongest overall, due to increased snow exposure in the winter and spring months. Albedo forcings are spatially and temporally heterogeneous and depend on a variety of factors related to soils, topography, climate, land cover/vegetation type, successional dynamics, time since fire, season, and fire severity. However, how these variables interact to influence albedo is not well understood, and quantifying these relationships and predicting postfire albedo becomes increasingly important as the climate changes and management frameworks evolve to consider climate impacts. Here we developed a MODIS-derived 'blue sky' albedo product and a novel machine learning modeling framework to predict fire-driven changes in albedo under historical and future climate scenarios across boreal North America. Converted to radiative forcing (RF), we estimated that fires generate an annual mean cooling of -1.77 ± 1.35 W/m2 from albedo under historical climate conditions (1971-2000) integrated over 70 years postfire. Increasing postfire albedo along a south-north climatic gradient was offset by a nearly opposite gradient in solar insolation, such that large-scale spatial patterns in RF were minimal. Our models suggest that climate change will lead to decreases in mean annual postfire albedo, and hence a decreasing strength of the negative RF, a trend dominated by decreased snow cover in spring months. Considering the range of future climate scenarios and model uncertainties, we estimate that for fires burning in the current era (2016) the cooling effect from long-term postfire albedo will be reduced by 15%-28% due to climate change.

Differences between residual and primary choledocholithiasis in cholecystectomy patients.

INTRODUCTION: choledocholithiasis can be primary from stones originally formed in the choledocho or secondary from stones that have migrated from the gallbladder to the choledocho. The objective of this study was to determine the clinical differences between both types of choledocholithiasis in cholecystectomy patients. MATERIAL AND METHODS: a comparative and retrospective study was performed of cholecystectomy patients who presented choledocholithiasis. Residual or secondary choledocholithiasis (group 1) was defined as those which appear in the first two years after cholecystectomy and primary choledocholithiasis (group 2) was defined as those which appear two years after cholecystectomy. Choledocholithiasis was confirmed by endoscopic retrograde cholangiopancreatography (ERCP) or surgery. RESULTS: patients with primary choledocholithiasis (n = 14) were older (61.5 ± 20.3 vs 74.4 ± 10.5 years; p = 0.049) and had a greater body mass index (BMI) (27.7 ± 4.3 vs 31.6 ± 4.6 kg/m2; p = 0.043) and a larger extrahepatic bile duct diameter (10.7 ± 2.7 vs 14.7 ± 3.5 mm; p = 0.004) compared to patients with residual or secondary choledocholithiasis (n = 11). All patients were treated by ERCP. There were no differences between groups 1 and 2 regarding recurrences (36.2 % vs 14.3 %; p = 0.350), disease-free survival (64.6 ± 30.9 vs 52.2 ± 37.7 months; p = 0.386) and overall survival (73.6 ± 32.4 vs 54 ± 41.9 months; p = 0.084). CONCLUSIONS: patients with primary choledocholithiasis were older and had a greater BMI and a larger diameter of the bile duct compared to patients with residual or secondary choledocholithiasis. ERCP is a good therapeutic option for the resolution of both types of choledocholithiasis.

Colonic stent vs surgical resection of the primary tumor. Effect on survival from stage-IV obstructive colorectal cancer.

BACKGROUND AND OBJECTIVES: the impact of surgical primary tumor resection on survival of obstructive metastatic colorectal cancer remains controversial. The primary goal of this study was to analyze survival in patients with obstructive metastatic colorectal cancer after treatment with either resection surgery or a colonic stent. MATERIAL AND METHODS: a prospective study was performed of all patients with stage-IV colorectal cancer and obstructive manifestations, diagnosed from 2005 to 2012 and managed with either resection surgery or a colonic stent. Cases with a perforation, abscess, right colon or distal rectal malignancy, multiple colorectal cancer or derivative surgery were excluded. RESULTS: a total of 95 patients were included, 49 were managed with resection surgery and 46 with a colonic stent. The colonic stent group had a higher Charlson index (9.5 ± 2.1 vs 8.6 ± 1.5, p = 0.01), a shorter time to oral intake (0.9 ± 1.1 vs 16.4 ± 53.5 days, p = 0.05), a shorter hospital stay (4 ± 4.8 vs 16.7 ± 15.5 days, p = 0.0001), less need for stomata (11.1 % vs 32.7 %, p = 0.01), fewer early complications (4.3 % vs 46.9 %, p = 0.0001) and more late complications (33.3 % vs 6.4 %, p = 0.001). Undergoing chemotherapy (p = 0.008) was the only independent factor related to increased survival. In the subgroup of patients managed with chemotherapy, surgical primary tumor resection was an independent factor associated with increased survival. CONCLUSION: both treatments are effective for resolving obstructive manifestations in patients diagnosed with stage-IV obstructive colorectal cancer. Resection surgery has no positive impact on survival and thus cannot be recommended as a therapy of choice.

Routine lower gastrointestinal endoscopy for radiographically confirmed acute diverticulitis. In whom and when is it indicated?

INTRODUCTION: international guidelines recommend a routine colonoscopy to rule out advanced neoplasm after an acute diverticulitis event. However, in recent years, this recommendation has been called into question following the advent of computerized tomography (CT), particularly with regard to uncomplicated diverticulitis. Furthermore, colonoscopy is associated with a risk and additional costs. OBJECTIVE: to understand the diagnostic yield, quality and safety of colonoscopy in the setting of acute diverticulitis. METHODS: this was a retrospective study of all patients diagnosed with acute diverticulitis via CT between 2005 and 2013, who subsequently underwent a colonoscopy. RESULTS: two hundred and sixteen patients diagnosed with acute diverticulitis via CT were enrolled. These included 58 cases with complicated diverticulitis (27%) and 158 with uncomplicated diverticulitis (73%). An advanced neoplasm was found in 12 patients (5.6%); 11.7% were complicated and 3.2% were uncomplicated (p = 0.02). No major complications were identified. The quality was low but improved over time; the complete procedure rate was 88%, an effective preparation was achieved in 75% and excision of polyps < 2 cm was performed in 78% of cases. The optimum colonoscopy quality cu-off was 9.5 weeks. CONCLUSION: routine colonoscopy is advisable after a complicated diverticulitis event but its recommendation is unclear with regard to uncomplicated episodes. Colonoscopy is safe even when performed early. The overall quality is low but may be optimized via a subsequent endoscopy, two months after a diverticulitis diagnosis.

Monitoring land surface albedo and vegetation dynamics using high spatial and temporal resolution synthetic time series from Landsat and the MODIS BRDF/NBAR/albedo product.

Seasonal vegetation phenology can significantly alter surface albedo which in turn affects the global energy balance and the albedo warming/cooling feedbacks that impact climate change. To monitor and quantify the surface dynamics of heterogeneous landscapes, high temporal and spatial resolution synthetic time series of albedo and the enhanced vegetation index (EVI) were generated from the 500 m Moderate Resolution Imaging Spectroradiometer (MODIS) operational Collection V006 daily BRDF/NBAR/albedo products and 30 m Landsat 5 albedo and near-nadir reflectance data through the use of the Spatial and Temporal Adaptive Reflectance Fusion Model (STARFM). The traditional Landsat Albedo (Shuai et al., 2011) makes use of the MODIS BRDF/Albedo products (MCD43) by assigning appropriate BRDFs from coincident MODIS products to each Landsat image to generate a 30 m Landsat albedo product for that acquisition date. The available cloud free Landsat 5 albedos (due to clouds, generated every 16 days at best) were used in conjunction with the daily MODIS albedos to determine the appropriate 30 m albedos for the intervening daily time steps in this study. These enhanced daily 30 m spatial resolution synthetic time series were then used to track albedo and vegetation phenology dynamics over three Ameriflux tower sites (Harvard Forest in 2007, Santa Rita in 2011 and Walker Branch in 2005). These Ameriflux sites were chosen as they are all quite nearby new towers coming on line for the National Ecological Observatory Network (NEON), and thus represent locations which will be served by spatially paired albedo measures in the near future. The availability of data from the NEON towers will greatly expand the sources of tower albedometer data available for evaluation of satellite products. At these three Ameriflux tower sites the synthetic time series of broadband shortwave albedos were evaluated using the tower albedo measurements with a Root Mean Square Error (RMSE) less than 0.013 and a bias within the range of ±0.006. These synthetic time series provide much greater spatial detail than the 500 m gridded MODIS data, especially over more heterogeneous surfaces, which improves the efforts to characterize and monitor the spatial variation across species and communities. The mean of the difference between maximum and minimum synthetic time series of albedo within the MODIS pixels over a subset of satellite data of Harvard Forest (16 km by 14 km) was as high as 0.2 during the snow-covered period and reduced to around 0.1 during the snow-free period. Similarly, we have used STARFM to also couple MODIS Nadir BRDF Adjusted Reflectances (NBAR) values with Landsat 5 reflectances to generate daily synthetic times series of NBAR and thus Enhanced Vegetation Index (NBAR-EVI) at a 30 m resolution. While normally STARFM is used with directional reflectances, the use of the view angle corrected daily MODIS NBAR values will provide more consistent time series. These synthetic times series of EVI are shown to capture seasonal vegetation dynamics with finer spatial and temporal details, especially over heterogeneous land surfaces.

Aquatic toxicity and biodegradability of a surfactant produced by Bacillus subtilis ICA56.

In this work, the environmental compatibility of a biosurfactant produced by a Bacillus subtilis strain isolated from the soil of a Brazilian mangrove was investigated. The biosurfactant, identified as surfactin, is able to reduce surface tension (ST) to 31.5 ± 0.1 mN m-1 and exhibits a lowcritical micelle concentration (CMC) value (0.015 ± 0.003 g L-1). The highest crude biosurfactant concentration (224.3 ± 1.9 mg L-1) was reached at 72 h of fermentation. Acute toxicity tests, carried out with Daphnia magna, Vibrio fischeri and Selenastrum capricornutum indicated that the toxicity of the biosurfactant is lower than that of its chemically derived counterparts. The results of the biodegradability tests demonstrated that the crude surfactin extract was degraded by both Pseudomonas putida and a mixed population from a sewage-treatment plant, in both cases the biodegradation efficiency being dependent on the initial concentration of the biosurfactant. Finally, as the biodegradation percentages obtained fall within the acceptance limits established by the Organization for Economic Co-operation and Development (Guidelines for Testing of Chemicals, OECD 301E), crude surfactin can be classified as a "readily" biodegradable compound.

Early spring post-fire snow albedo dynamics in high latitude boreal forests using Landsat-8 OLI data.

Taking advantage of the improved radiometric resolution of Landsat-8 OLI which, unlike previous Landsat sensors, does not saturate over snow, the progress of fire recovery progress at the landscape scale (< 100m) is examined. High quality Landsat-8 albedo retrievals can now capture the true reflective and layered character of snow cover over a full range of land surface conditions and vegetation densities. This new capability particularly improves the assessment of post-fire vegetation dynamics across low- to high- burn severity gradients in Arctic and boreal regions in the early spring, when the albedos during recovery show the greatest variation. We use 30 m resolution Landsat-8 surface reflectances with concurrent coarser resolution (500m) MODIS high quality full inversion surface Bidirectional Reflectance Distribution Functions (BRDF) products to produce higher resolution values of surface albedo. The high resolution full expression shortwave blue sky albedo product performs well with an overall RMSE of 0.0267 between tower and satellite measures under both snow-free and snow-covered conditions. While the importance of post-fire albedo recovery can be discerned from the MODIS albedo product at regional and global scales, our study addresses the particular importance of early spring post-fire albedo recovery at the landscape scale by considering the significant spatial heterogeneity of burn severity, and the impact of snow on the early spring albedo of various vegetation recovery types. We found that variations in early spring albedo within a single MODIS gridded pixel can be larger than 0.6. Since the frequency and severity of wildfires in Arctic and boreal systems is expected to increase in the coming decades, the dynamics of albedo in response to these rapid surface changes will increasingly impact the energy balance and contribute to other climate processes and physical feedback mechanisms. Surface radiation products derived from Landsat-8 data will thus play an important role in characterizing the carbon cycle and ecosystem processes of high latitude systems.

Transitioning from MODIS to VIIRS Global Water Reservoir Product.

Reservoirs play a crucial role in regulating water availability and enhancing water security. Here, we develop NASA's Visible Infrared Imaging Radiometer Suite (VIIRS) based Global Water Reservoir (GWR) product, consisting of measurements of reservoir area, elevation, storage, evaporation rate, and evaporation loss for 164 large global reservoirs. The dataset is available at 8-day and monthly temporal resolutions. Since the Moderate Resolution Imaging Spectroradiometer (MODIS) is close to the end of its life, we further evaluated the consistency between MODIS and VIIRS-based GWR to ensure continuity to the 20+ year MODIS GWR product. Independent assessment of VIIRS reservoir storage (8-day) retrievals against in-situ measurements shows an average of R2 = 0.84, RMSE = 0.47 km3, and NRMSE = 16.45%. The evaporation rate has an average of R2 = 0.56, RMSE = 1.32 mm/day, and NRMSE = 28.14%. Furthermore, results show good consistency (R2 ≥ 0.90) between the VIIRS and MODIS-based product components, confirming that long-term data continuity can be achieved. This dataset can provide valuable insights for long-term trend analysis, hydrological modeling, and understanding hydroclimatic extremes in the context of reservoirs.

Efficacy of pulmonary rehabilitation in patients with moderate chronic obstructive pulmonary disease: a randomized controlled trial.

BACKGROUND: Pulmonary Rehabilitation for moderate Chronic Obstructive Pulmonary Disease in primary care could improve patients' quality of life. METHODS: This study aimed to assess the efficacy of a 3-month Pulmonary Rehabilitation (PR) program with a further 9 months of maintenance (RHBM group) compared with both PR for 3 months without further maintenance (RHB group) and usual care in improving the quality of life of patients with moderate COPD.We conducted a parallel-group, randomized clinical trial in Majorca primary health care in which 97 patients with moderate COPD were assigned to the 3 groups. Health outcomes were quality of life, exercise capacity, pulmonary function and exacerbations. RESULTS: We found statistically and clinically significant differences in the three groups at 3 months in the emotion dimension (0.53; 95%CI0.06-1.01) in the usual care group, (0.72; 95%CI0.26-1.18) the RHB group (0.87; 95%CI 0.44-1.30) and the RHBM group as well as in fatigue (0.47; 95%CI 0.17-0.78) in the RHBM group. After 1 year, these differences favored the long-term rehabilitation group in the domains of fatigue (0.56; 95%CI 0.22-0.91), mastery (0.79; 95%CI 0.03-1.55) and emotion (0.75; 95%CI 0.17-1.33). Between-group analysis only showed statistically and clinically significant differences between the RHB group and control group in the dyspnea dimension (0.79 95%CI 0.05-1.52). No differences were found for exacerbations, pulmonary function or exercise capacity. CONCLUSIONS: We found that patients with moderate COPD and low level of impairment did not show meaningful changes in QoL, exercise tolerance, pulmonary function or exacerbation after a one-year, community based rehabilitation program. However, long-term improvements in the emotional, fatigue and mastery dimensions (within intervention groups) were identified. TRIAL REGISTRATION: ISRCTN94514482.

Remote consultations in primary care across low-, middle- and high-income countries: Implications for policy and care delivery.

The COVID-19 pandemic mandated a substantial switch in primary health care delivery from an in-person to a mainly remote telephone or video service. As the COVID-19 pandemic approaches its third year, limited progress appears to have been made in terms of policy development around consultation methods for the post-acute phase of the pandemic. In September 2020, the International Primary Care Respiratory Group convened a global panel of primary care clinicians - including family physicians, paediatricians, pharmacists, academics and patients - to consider the policy and health management implications of the move to remote consultations in the primary care setting. The group gave special consideration to how and how far remote consultations should be integrated into routine primary health care delivery. Remote consultations can be a useful alternative to in-person consultations in primary care not only in situations where there is a need for viral infection control but also for the routine delivery of chronic disease management. However, they may not be more time efficient for the clinician, and they can add to the workload and work-related stress for primary care practitioners if they remain the dominant consultation mode. Remote consultations are also less appropriate than in-person consultations for new disease diagnosis, dealing with multiple issues and providing complex care. Ensuring health care professionals have the appropriate skill set to effectively deliver remote consultations, administrative and/or IT support and appropriate reimbursement will be key to achieving optimal integration of remote consultations into routine clinical practice. Addressing digital access and digital literacy issues at a societal level will also be essential to ensure individuals have fair and equitable access to the internet and sufficient security for exchange of personal and health-related data.

Risk factors for complications in acute calculous cholecystitis. Deconstruction of the Tokyo Guidelines.

OBJECTIVE: To challenge the risk factors described in Tokyo Guidelines in Acute Calculous Cholecystitis. METHODS: Retrospective single center cohort study with 963 patients with Acute Cholecystitis during a period of 5 years. Some 725 patients with a "pure" Acute Calculous Cholecystitis were selected. The analysis included 166 variables encompassing all risk factors described in Tokyo Guidelines. The Propensity Score Matching method selected two subgroups of patients with equal comorbidities, to compare the severe complications rate according to the initial treatment (Surgical vs Non-Surgical). We analyzed the Failure-to-rescue as a quality indicator in the treatment of Acute Calculous Cholecystitis. RESULTS: the median age was 69 years (IQR 53-80). 85.1% of the patients were ASA II or III. The grade of the Acute Calculous Cholecystitis was mild in a 21%, moderate in 39% and severe in 40% of the patients. Cholecystectomy was performed in 95% of the patients. The overall complications rate was 43% and the mortality was 3.6%. The Logistic Regression model isolated 3 risk factor for severe complication: ASA > II, cancer without metastases and moderate to severe renal disease. The Failure-to-Rescue (8%) was higher in patients with non-surgical treatment (32% vs. 7%; P = 0.002). After Propensity Score Matching, the number of severe complications was similar between Surgical and Non-Surgical treatment groups (48.5% vs 62.5%; P = 0.21). CONCLUSIONS: the recommended treatment for Acute Calculous Cholecystitis is the Laparoscopic Cholecystectomy. Only three risk factors from the Tokyo Guidelines list appeared as independent predictors of severe complications. The failure-to-rescue is higher in non-surgically treated patients.

Enhancing physicians' radiology diagnostics of COVID-19's effects on lung health by leveraging artificial intelligence.

Introduction: This study aimed to develop an individualized artificial intelligence model to help radiologists assess the severity of COVID-19's effects on patients' lung health. Methods: Data was collected from medical records of 1103 patients diagnosed with COVID-19 using RT- qPCR between March and June 2020, in Hospital Madrid-Group (HM-Group, Spain). By using Convolutional Neural Networks, we determine the effects of COVID-19 in terms of lung area, opacities, and pulmonary air density. We then combine these variables with age and sex in a regression model to assess the severity of these conditions with respect to fatality risk (death or ICU). Results: Our model can predict high effect with an AUC of 0.736. Finally, we compare the performance of the model with respect to six physicians' diagnosis, and test for improvements on physicians' performance when using the prediction algorithm. Discussion: We find that the algorithm outperforms physicians (39.5% less error), and thus, physicians can significantly benefit from the information provided by the algorithm by reducing error by almost 30%.

Tracking COVID-19 urban activity changes in the Middle East from nighttime lights.

In response to the COVID-19 pandemic, governments around the world have enacted widespread physical distancing measures to prevent and control virus transmission. Quantitative, spatially-disaggregated information about the population-scale shifts in activity that have resulted from these measures is extremely scarce, particularly for regions outside of Europe and the US. Public health institutions often must make decisions about control measures with limited region-specific data about how they will affect societal behavior, patterns of exposure, and infection outcomes. The Visible Infrared Imaging Radiometer Suite Day/Night Band (VIIRS DNB), a new-generation space-borne low-light imager, has the potential to track changes in human activity, but the capability has not yet been applied to a cross-country analysis of COVID-19 responses. Here, we examine multi-year (2015-2020) daily time-series data derived from NASA's Black Marble VIIRS nighttime lights product (VNP46A2) covering 584 urban areas, in 17 countries in the Middle East to understand how communities have adhered to COVID-19 measures in the first 4 months of the pandemic. Nighttime lights capture the onset of national curfews and lockdowns well, but also expose the inconsistent response to control measures both across and within countries. In conflict-afflicted countries, low adherence to lockdowns and curfews was observed, highlighting the compound health and security threats that fragile states face. Our findings show how satellite measurements can aid in assessing the public response to physical distancing policies and the socio-cultural factors that shape their success, especially in fragile and data-sparse regions.

A framework for research on recurrent acute disasters.

Disaster science examines the causes, behaviors, and consequences of hazardous events, from hurricanes to wildfires, flooding, and major industrial accidents. Individual disasters are recurring more frequently and with greater intensity. Recurrent acute disasters (RADs) are sequential disasters that affect a specific locale over time. While disaster science has matured in recent years, understanding of the distinctive characteristics of RADs varies by discipline and lacks predictive power. A theoretical framework is presented by borrowing in part from mathematical topology and disturbance ecology. The recurrent disasters affecting Puerto Rico 2017-2020 are examined as a case example to test the framework. A key variable is the complex characteristics of legacy conditions created by one disaster that influence the effects of subsequent disasters. Substantial improvements in disaster response, recovery, and preparedness can be gained by adopting a RAD-based approach.

Artificial light at night: an underappreciated effect on phenology of deciduous woody plants.

Artificial light at night (ALAN), an increasing anthropogenic driver, is widespread and shows rapid expansion with potential adverse impact on the terrestrial ecosystem. However, whether and to what extent does ALAN affect plant phenology, a critical factor influencing the timing of terrestrial ecosystem processes, remains unexplored due to limited ALAN observation. Here, we used the Black Marble ALAN product and phenology observations from USA National Phenology Network to investigate the impact of ALAN on deciduous woody plants phenology in the conterminous United States. We found that (1) ALAN significantly advanced the date of breaking leaf buds by 8.9 ± 6.9 days (mean ± SD) and delayed the coloring of leaves by 6.0 ± 11.9 days on average; (2) the magnitude of phenological changes was significantly correlated with the intensity of ALAN (P < 0.001); and (3) there was an interaction between ALAN and temperature on the coloring of leaves, but not on breaking leaf buds. We further showed that under future climate warming scenarios, ALAN will accelerate the advance in breaking leaf buds but exert a more complex effect on the coloring of leaves. This study suggests intensified ALAN may have far-reaching but underappreciated consequences in disrupting key ecosystem functions and services, which requires an interdisciplinary approach to investigate. Developing lighting strategies that minimize the impact of ALAN on ecosystems, especially those embedded and surrounding major cities, is challenging but must be pursued.

Co-targeting of BAX and BCL-XL proteins broadly overcomes resistance to apoptosis in cancer.

Deregulation of the BCL-2 family interaction network ensures cancer resistance to apoptosis and is a major challenge to current treatments. Cancer cells commonly evade apoptosis through upregulation of the BCL-2 anti-apoptotic proteins; however, more resistant cancers also downregulate or inactivate pro-apoptotic proteins to suppress apoptosis. Here, we find that apoptosis resistance in a diverse panel of solid and hematological malignancies is mediated by both overexpression of BCL-XL and an unprimed apoptotic state, limiting direct and indirect activation mechanisms of pro-apoptotic BAX. Both survival mechanisms can be overcome by the combination of an orally bioavailable BAX activator, BTSA1.2 with Navitoclax. The combination demonstrates synergistic efficacy in apoptosis-resistant cancer cells, xenografts, and patient-derived tumors while sparing healthy tissues. Additionally, functional assays and genomic markers are identified to predict sensitive tumors to the combination treatment. These findings advance the understanding of apoptosis resistance mechanisms and demonstrate a novel therapeutic strategy for cancer treatment.

Atypical double colorectal metastasis: spleen and uterus.

Oligometastatic disease is a relatively new concept that refers to an intermediate stage between disseminated and localized cancer. Most frequent locations for colorectal metastasis are lung and liver. We present an a typical case of an 85-year-old woman who was diagnosed with a low-grade adenocarcinoma in left colon; she underwent a left laparoscopic hemicolectomy which resulted in a stage IIIb. After 24 months of follow-up, an increase of carcinoembryonic antigen (CEA) leads to the diagnosis of two metastatic lesions in two uncommon locations: spleen and myometrium. Stepwise surgical resection of both lesions was performed without complications. Spleen and uterus are organs that are rarely affected in colorectal cancer, the affection of both organs being even more infrequent. Despite the atypicality, surgical treatment is a valid strategy in this case of oligometastatic disease, which enables the disease-free survival of the patients.

Tumor-intrinsic PRC2 inactivation drives a context-dependent immune-desert microenvironment and is sensitized by immunogenic viruses.

Immune checkpoint blockade (ICB) has demonstrated clinical success in "inflamed" tumors with substantial T cell infiltrates, but tumors with an immune-desert tumor microenvironment (TME) fail to benefit. The tumor cell-intrinsic molecular mechanisms of the immune-desert phenotype remain poorly understood. Here, we demonstrated that inactivation of the polycomb-repressive complex 2 (PRC2) core components embryonic ectoderm development (EED) or suppressor of zeste 12 homolog (SUZ12), a prevalent genetic event in malignant peripheral nerve sheath tumors (MPNSTs) and sporadically in other cancers, drove a context-dependent immune-desert TME. PRC2 inactivation reprogramed the chromatin landscape that led to a cell-autonomous shift from primed baseline signaling-dependent cellular responses (e.g., IFN-γ signaling) to PRC2-regulated developmental and cellular differentiation transcriptional programs. Further, PRC2 inactivation led to diminished tumor immune infiltrates through reduced chemokine production and impaired antigen presentation and T cell priming, resulting in primary resistance to ICB. Intratumoral delivery of inactivated modified vaccinia virus Ankara (MVA) enhanced tumor immune infiltrates and sensitized PRC2-loss tumors to ICB. Our results identify molecular mechanisms of PRC2 inactivation-mediated, context-dependent epigenetic reprogramming that underline the immune-desert phenotype in cancer. Our studies also point to intratumoral delivery of immunogenic viruses as an initial therapeutic strategy to modulate the immune-desert TME and capitalize on the clinical benefit of ICB.