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Abstract We report 14 cases of immune effector cell (IEC)-associated enterocolitis following chimeric antigen receptor T-cell (CAR-T) therapy in multiple myeloma, with a 1.2% incidence overall (0.2% for idecabtagene vicleucel and 2.2% for ciltacabtagene autoleucel). Patients developed acute-onset symptoms (typically non-bloody Grade 3+ diarrhea) with negative infectious workup beginning a median of 92.5 days (range: 22–210 days) after CAR-T therapy and a median of 85 days after cytokine release syndrome resolution. Gut biopsies uniformly demonstrated inflammation, including intra-epithelial lymphocytosis and villous blunting. In one case where CAR-specific immunofluorescence stains were available, CAR T-cell presence was confirmed within the lamina propria. Systemic corticosteroids were initiated in 10 patients (71%) a median of 25.5 days following symptom onset, with symptom improvement in 40%. Subsequent infliximab or vedolizumab led to improvement in 50% and 33% of corticosteroid-refractory patients, respectively. Five patients (36%) have died from bowel perforation or treatment-emergent sepsis. In conclusion, IEC-associated enterocolitis is a distinct but rare complication of CAR-T therapy typically beginning 1–3 months after infusion. Thorough diagnostic workup is essential, including evaluation for potential T-cell malignancies. The early use of infliximab or vedolizumab may potentially hasten symptom resolution and lower reliance on high-dose corticosteroids during the post-CAR-T period.

Abstract Employing machine learning methods for mapping surface ocean pCO2 has reduced the uncertainty in estimating sea-air CO2 flux. However, a general discrepancy exists between the Southern Ocean carbon sinks derived from pCO2 products and those from biogeochemistry models. Here, by performing a boosting ensemble learning feed-forward neural networks method, we have identified an underestimation of the surface Southern Ocean pCO2 due to notably uneven density of pCO2 measurements between summer and winter, which resulted in about 16% overestimating of Southern Ocean carbon sink over the past three decades. In particular, the Southern Ocean carbon sink since 2010 was notably overestimated by approximately 29%. This overestimation can be mitigated by a winter correction in algorithms, with the average Southern Ocean carbon sink during 1992-2021 corrected to −0.87 PgC yr−1 from the original −1.01 PgC yr−1. Furthermore, the most notable underestimation of surface ocean pCO2 mainly occurred in regions south of 60°S and was hiding under ice cover. As the surface ocean pCO2 under sea ice coverage in the winter is much higher than the atmosphere, if sea ice melts completely, there could be a further reduction of about 0.14 PgC yr−1 in the Southern Ocean carbon sink.

Abstract Fluorescence analysis is a fast and sensitive method, and has great potential application in trace detection of environmental toxins. However, many important environmental toxins are non-fluorescent substances, and it is still a challenge to construct a fluorescence detection method for non-fluorescent substances. Here, by means of charge transfer effect and smart molecular imprinting technology, we report a sensitive indirect fluorescent sensing mechanism (IFSM) and microcystin (MC-RR) is selected as a model target. A molecular imprinted thin film is immobilized on the surface of zinc ferrite nanoparticles (ZnFe2O4 NPs) by using arginine, a dummy fragment of MC-RR. By implementation of IFSM on the paper-based microfluidic chip, a versatile platform for the quantitative assay of MC-RR is developed at trace level (the limit of detection of 0.43 μg/L and time of 20 min) in real water samples without any pretreatment. Importantly, the proposed IFSM can be easily modified and extended for the wide variety of species which lack direct interaction with the fluorescent substrate. This work offers the potential possibility to meet the requirements for the on-site analysis and may explore potential applications of molecularly imprinted fluorescent sensors.

Based on the "dual core" framework for assessing the health status of the offshore ecological environment, the marine environmental health status of Jiaozhou Bay in the past 40 years was comprehensively evaluated, and the evolution process of the ecological environment of Jiaozhou Bay along with the economic and social development of Qingdao was combed. Taking every 10 years as an interval, the "double core" assessment results of the marine ecological environment health of Jiaozhou Bay in the past 40 years are as follows: "good +0.22" from 1981 to 1990, "excellent +0.53" from 1991 to 2000, "good +0.87" from 2001 to 2010 and "excellent +0.90" from 2011 to 2020. With the economic and social development of Qingdao, human beings have made greater efforts to develop and utilize the marine resources and environment of Jiaozhou Bay, and various ecological problems have also occurred in Jiaozhou Bay: the water quality deteriorated in the 1980s, the health status of biological communities declined in the 1990s, and the problem of eutrophication was serious in the 2000s. Since 2010, Qingdao has strengthened ecological protection and environmental governance, and the marine ecological environment of Jiaozhou Bay has been significantly improved. With the acceleration of the transformation of old and new kinetic energy and the continuous optimization and upgrading of industrial structure, the disturbance of economic development activities to the marine ecological environment of Jiaozhou Bay has been continuously reduced. Qingdao has finally realized a benign and healthy green development model between marine economy and ecological environment for Jiaozhou Bay.

ABSTRACT Hypervirulent Klebsiella pneumoniae with capsular polysaccharides (CPSs) causes severe nosocomial- and community-acquired infections. Phage-derived depolymerases can degrade CPSs from K. pneumoniae to attenuate bacterial virulence, but their antimicrobial mechanisms and clinical potential are not well understood. In the present study, Klebsiella phage GH-K3-derived depolymerase Depo32 (encoded by gene gp32) was identified to exhibit high efficiency in specifically degrading the CPSs of K2 serotype K. pneumoniae. The cryo-electron microscopy structure of trimeric Depo32 at a resolution up to 2.32 Å revealed potential catalytic centers in the cleft of each of the two adjacent subunits. K. pneumoniae subjected to Depo32 became more sensitive to phagocytosis by RAW264.7 cells and activated the cells by the mitogen-activated protein kinase signaling pathway. In addition, intranasal inoculation with Depo32 (a single dose of 200 µg, 20 µg daily for 3 days, or in combination with gentamicin) rescued all C57BL/6J mice infected with a lethal dose of K. pneumoniae K7 without interference from its neutralizing antibody. In summary, this work elaborates on the mechanism by which Depo32 targets the degradation of K2 serotype CPSs and its potential as an antivirulence agent. IMPORTANCE Depolymerases specific to more than 20 serotypes of Klebsiella spp. have been identified, but most studies only evaluated the single-dose treatment of depolymerases with relatively simple clinical evaluation indices and did not reveal the anti-infection mechanism of these depolymerases in depth. On the basis of determining the biological characteristics, the structure of Depo32 was analyzed by cryo-electron microscopy, and the potential active center was further identified. In addition, the effects of Depo32 on macrophage phagocytosis, signaling pathway activation, and serum killing were revealed, and the efficacy of the depolymerase (single treatment, multiple treatments, or in combination with gentamicin) against acute pneumonia caused by Klebsiella pneumoniae was evaluated. Moreover, the roles of the active sites of Depo32 were also elucidated in the in vitro and in vivo studies. Therefore, through structural biology, cell biology, and in vivo experiments, this study demonstrated the mechanism by which Depo32 targets K2 serotype K. pneumoniae infection.

IntroductionSeagrass meadows are among the most valuable ecosystems, providing numerous ecosystem services and functions. Despite its importance, there is a lack of knowledge about soil’s biogeochemical process variability, which can control microbiological communities. Thus, this study aimed to evaluate whether seagrass meadows in different geo-environments exhibit varying Fe and sulfate reduction intensities, shaping distinct archaea and bacteria communities.MethodsSoil samples were collected in seagrass meadows under contrasting climatic, geological, vegetational and hydrological settings along the Brazilian coast (e.g., Semiarid Coast - SC, Southeastern Granitic Coast – GC, and Southern Quaternary Coast - QC). The soils were characterized by particle size, pH, redox potential (Eh), total organic C and total N content, acid-volatile sulfides (AVS), and simultaneously extracted Fe. Furthermore, a solid-phase Fe fractionation was performed to characterize the decomposition pathways in these soils, and the shifts in the microbial community along this spatial variation were analyzed using denaturing gradient gel electrophoresis.ResultsThe studied soils presented a sandy texture (values ranging from 74 ± 11.8 to 80.5 ± 6.4%) caused by energetic hydrodynamic conditions. The pH values were circumneutral, while redox conditions presented significant distinction among the studied sites, ranging from anoxic to oxic (values ranging from -63 to +334 mV). The degree of pyritization (DOP) ranged from< 10% to values higher than 80%, highly influenced by rhizospheric oxidation, and higher AVS content was recorded for sites with lower DOP (i.e., GC and QC).DiscussionsThus, biogeochemical processes in the seagrass soils present a wide variation in response to the geo-environmental settings. Plants influence the soil’s geochemical and microbiological communities, retaining fine particles, promoting rhizosphere oxidation, and inducing anoxic conditions controlling the Fe and S forms. Moreover, the same plant species can result in distinct soil conditions and microbial communities due to geoenvironmental settings.

Abstract Objective This study aimed to investigate the effect of conventional drugs combined with acupuncture therapy on the conversion of sinus rhythm in patients with atrial fibrillation. Methods We searched databases, such as PubMed, Embase, WOS, Cochrane, CNKI (China National Knowledge Infrastructure), Wan fang Data, VIP, and CBM to collect data in randomized controlled trials of acupuncture included patients with atrial fibrillation. Publication time was limited from the beginning to May 15, 2021. The primary outcome is the number of participants who converted successfully. Results A total of 11 papers were included in this study. The combined effect indicated that acupuncture significantly effectively benefitted the patients with atrial fibrillation (RR = 1.208, 95% CI 1.123, 1.298, P

Abstract Bacterial metabolism largely drives the sequestration of refractory organic matter in the ocean. However, a lack of understanding exists regarding the abundance and reactivity of bacterial particulate organic matter (POM). Here we report the bacterial contributions to suspended POM collected in the oligotrophic Western Pacific Warm Pool (WPWP). Around 27% of particulate organic carbon (POC) and ∼39% of particulate nitrogen (PN) in the surface ocean were derived from bacteria. Most of the bacterial POM (∼87%) was labile or semi‐labile, and ∼85% of bacterial POM was removed between depths of ∼100–300 m. Bacterial POM constituted only ∼8% and ∼13% of refractory POC and PN, respectively. The rapid cycling of bacterial POM in upper waters was likely related to oligotrophic conditions and facilitated by higher temperatures in the WPWP. Taken together, these observations indicate that bacterial POM plays a crucial role in supplying energy for bacterial respiration.

Abundant bitumen can be discovered in the wells of Upper Sinian Dengying Formation in the Sichuan Basin and their peripheral outcrops sections. As the cracking product of a paleo-oil reservoir, the occurrence morphologies and distribution characteristics of bitumen in carbonate reservoirs can indicate the preservation, migration and other key information of (paleo-) oil and gas reservoirs. In order to provide reference and basis for the deep and ultra-deep oil and gas exploration in the Sichuan Basin and the basins in western China, this paper systematically studies the occurrence morphological characteristics of bitumen in deep and ultra-deep carbonate reservoirs in well Gaoshi 1 of the Sichuan Basin by carrying out thin section observation, scanning electron microscope-energy spectrum analysis and fluid inclusion organic geochemical analysis on the cores of the fourth member of Dengying Formation (Deng 4 Member). In addition, the coupling relationship between the occurrence morphology of bitumen and the key event of hydrocarbon accumulation is revealed. And the following research results are obtained. First, solid bitumen in the Deng 4 Member deep and ultra-deep reservoir has two types of occurrence morphology. The first type of bitumen adheres to pore walls in the shape of a rim or exists in pores in the form of sticky branch (e.g., Wells Chuanshen 1 and Gaoshi 1). There are more obvious shrinkage fractures and residual pores generated by in-situ thermal cracking in this type of bitumen. And combined with fluid inclusion and burial thermal history, it can effectively indicate that a paleo-gas reservoir has been preserved so far since the paleo-oil reservoir was thermally cracked into carbonaceous bitumen. The second type of bitumen is distributed in intra- and inter-neogenic mineral crystals in pores disorderly in the shape of grain and band (e.g., Wells Mashen 1 and Wutan 1) and it has obvious breaking edges. It reveals that after a paleo-oil reservoir was thermally cracked into carbonaceous bitumen, the paleo-gas reservoir suffered blowdown and gas escape and neogenic fluid minerals moved into reservoirs to fill in pores. In conclusion, the occurrence morphologies and distribution characteristics of bitumen in deep and ultra-deep carbonate reservoirs can effectively indicate the hydrocarbon accumulation and evolution process of paleo-oil and gas reservoirs.

IntroductionThe overall prevalence of Klebsiella spp., a group of important zoonotic pathogens, in the global dairy herds and the risk of cross-species transmission between humans and dairy cows remain to be clarified. This systematic review aimed to determine the prevalence of Klebsiella spp. in milk samples from dairy cows with mastitis worldwide and to assess the factors influencing the prevalence of these strains.MethodsQualified studies published from 2007 to 2021 were retrieved from ScienceDirect, Web of Science, PubMed, WanFang Database, China National Knowledge Infrastructure (CNKI), and VIP Chinese Journal Database. Calculations of prevalence and their 95% confidence intervals (CIs) were performed for all the studies using the Freeman-Tukey double arcsine transformation (PFT).ResultsA total of 79,852 milk samples from 55 manuscripts were examined in this meta-analysis, and 2,478 samples were found to be positive for Klebsiella spp. The pooled prevalence estimates worldwide were 7.95% (95% CI: 6.07%–10.06%), with significant heterogeneity (I2 = 98.8%, p = 0). The sampling period of 2013–2020 had a higher (p < 0.05) Klebsiella-positive proportion of milk samples (12.16%, 95% CI: 8.08%–16.90%) than that of 2007–2012 (3.85%, 95% CI: 2.67%–5.21%), indicating that bovine mastitis caused by Klebsiella may become increasingly prevalent. The risk factors for the high prevalence of Klebsiella in milk samples mainly included: economic development level (developing countries; 11.76%, 95% CI: 8.25%–15.77%), mastitis type (CM; 11.99%, 95% CI: 8.62%–15.79%), and population density (>500 per sq km; 10.28%, 95% CI: 2.73%–21.58%). Additionally, a bivariate meta-regression analysis revealed that the multidrug-resistance (MDR) rate of the epidemic strains was also closely related to economic development level (R2 = 78.87%) and population density (R2 = 87.51%).DiscussionDue to the potential risk of cross-species transmission between humans and cows, the prevalence of mastitis milk-derived Klebsiella and its high MDR rate need to be monitored, especially in developing countries with high population densities.

Seawater stratification is an important ecological indicator and typical feature in the marine environment, which is of great significance to the material cycle and distribution of organisms. In March 2016, a survey was conducted in the M2 seamount of the Western Pacific Ocean, seawater stratification of temperature, salinity, dissolved oxygen (DO), nutrients, bacteria, and the impact of the M2 seamount were discussed. It is found that the seawater stratification of each parameter is obvious in this area. At the depth of 0–75 m, there is a mixed layer, and these parameters remain relatively stable; at 75–500 m, there are obvious thermocline, gradient layer of bacteria, and nutricline; at the depth deeper than 500 m, these parameters remain relatively stable. In addition, at 75–150 m, there is a high-salt zone dominated by the North Pacific Tropic Water, while at 270–1370 m, there is an oxygen minimum zone with low DO. There is a close relationship in seawater stratification of different parameters. At 75–500 m, the density gradient dominated by the thermocline limits the water exchange, then directly controls the gradient layer of DO, nutrients, and bacteria. Additionally, the double actions of the high-salt zone and thermocline affect the stratification of other parameters. At 0–75 m, due to the abundant DO, sufficient carbon source, and low nutrients, the bacteria could grow largely, while at 75–500 m, bacteria could consume a large amount of DO to decompose organic matter, leading to a decrease in DO and an increase of nutrients. Although the M2 seamount is a shallow seamount, there is no upwelling around it, which weakly influences the seawater stratification of different parameters. This study will provide a new perspective on seawater stratification and its ecological effects.

Chronic myeloid leukemia (CML) and chronic myelomonocytic leukemia (CMML) are two common myeloid neoplasms with overlapping morphologic features. We report a patient initially diagnosed with CML and treated with Tyrosine kinase inhibitor (TKI) but who then developed persistent monocytosis and worsening thrombocytopenia one year later. Repeat bone marrow biopsies only showed CML at the molecular level. However, markedly hypercellular bone marrow, megakaryocytic dysplasia, and SRSF2, TET2, and RUNX1 mutations by NextGen sequencing pointed to a diagnosis of CMML. For CML patients with persistent monocytosis and cytopenia, a mutational profile by NGS is helpful to exclude or identify the coexisting CMML.

Abstract Background Protection of privacy data published in the health care field is an important research field. The Health Insurance Portability and Accountability Act (HIPAA) in the USA is the current legislation for privacy protection. However, the Institute of Medicine Committee on Health Research and the Privacy of Health Information recently concluded that HIPAA cannot adequately safeguard the privacy, while at the same time researchers cannot use the medical data for effective researches. Therefore, more effective privacy protection methods are urgently needed to ensure the security of released medical data. Methods Privacy protection methods based on clustering are the methods and algorithms to ensure that the published data remains useful and protected. In this paper, we first analyzed the importance of the key attributes of medical data in the social network. According to the attribute function and the main objective of privacy protection, the attribute information was divided into three categories. We then proposed an algorithm based on greedy clustering to group the data points according to the attributes and the connective information of the nodes in the published social network. Finally, we analyzed the loss of information during the procedure of clustering, and evaluated the proposed approach with respect to classification accuracy and information loss rates on a medical dataset. Results The associated social network of a medical dataset was analyzed for privacy preservation. We evaluated the values of generalization loss and structure loss for different values of k and a, i.e. $$k$$ k = {3, 6, 9, 12, 15, 18, 21, 24, 27, 30}, a = {0, 0.2, 0.4, 0.6, 0.8, 1}. The experimental results in our proposed approach showed that the generalization loss approached optimal when a = 1 and k = 21, and structure loss approached optimal when a = 0.4 and k = 3. Conclusion We showed the importance of the attributes and the structure of the released health data in privacy preservation. Our method achieved better results of privacy preservation in social network by optimizing generalization loss and structure loss. The proposed method to evaluate loss obtained a balance between the data availability and the risk of privacy leakage.

The Pacific Ocean is one of the important carbon sink regions, and there is a significant west-east difference in sea-air CO2 flux. However, the influence of the long-standing greater CO2 uptakes in the western Pacific than in the east and the dynamic change of this west-east difference remain unclear. In this paper, using the gridded surface ocean pCO2 product constructed by the stepwise FFNN algorithm, we reported an increasing west-east CO2 flux difference from 0.41 PgC yr-1 in 1992 to 0.73 PgC yr-1 in 2020. This increase was mainly attributed to the strengthening western Pacific carbon sink and relatively stable eastern Pacific carbon source. During El Nino events, the west-east CO2 flux difference decreased significantly in a few years, and it then rose back rapidly when El Nino events ended. In addition, the increasing west-east difference in CO2 uptakes during the last three decades did not lead to a higher acidification speed in the western surface temperate Pacific than the east. The greater CO2 absorbed in the west was mainly transported to the deeper waters and caused a more significant carbon inventory change at 200-600 m than the eastern Pacific.

The migration and enrichment of redox-sensitive trace elements (RSEs) from seawater to sediments are controlled not only by their geochemical properties but also by marine redox conditions. Therefore, RSEs, such as Mo, U, and V, are extensively used to indicate redox states in marine environments. To retrieve the historical redox state in the hypoxic zone near the Changjiang River Estuary and its adjacent waters, the distribution and enrichment degree of Mo, U, and V in a sediment core collected from the recurrently hypoxic region were investigated. The correlation analysis shows that the authigenic enrichment of Mo and U in sediment core 3,050–2 is primarily controlled by redox conditions, rather than sediment grain size, adsorption on organic matters, Fe–Mn (hydr)oxides, and terrigenous detritus input. Mo-U covariation is selected to analyze the evolution of redox conditions in the seasonally hypoxic zone. The MoEF/UEF values in this sediment core are almost between 0.1 and 0.3×Mo/Umodern seawater value and show a general decreasing trend with depth, indicating an overall progressive transition from oxic to suboxic conditions in this area since 2005. The close MoEF/UEF values and similar chronological Mo-U variations by comparing our results with previous studies in adjacent areas offer common evidence for the gradually intensified bottom water–oxygen stress, suggesting the possible application of MoEF/UEF in retrieving redox development in this coastal hypoxic zone.

Transparent exopolymer particle (TEP) is a transparent jellylike substance characterized with high carbon concentration, playing an important role in the marine carbon cycle. Based on a survey of the East China Sea coast in summer of 2020, the distribution, controlling factors of TEP and its impact on marine carbon transportation were discussed. The results showed that the TEP in the surface decreases from northwest to southeast gradually with an average concentration of 214.90 µg Xeq./L, which is basically consistent with the distribution of POC, Chl a and NO3-N. The TEP in the water of 10 m, 20 m, and 30 m also gradually decreases from northwest to southeast horizontally, while it is high in the surface and bottom layer, and low in the middle water layer vertically. The hydrological situation of the study area is complex and is the main factor affecting the distribution of various parameters including TEP. The TEP in the seawater has the characteristics of high TEP-C/POC, low settling ratio and high degradation ratio. The TEP-C/POC in the seawater is 32.03%, which is extremely higher than that of 14.46% in the surface sediments; the settling ratio of TEP is 17.67%, which is extremely lower than that of 50.31% for POC; the degradation ratio of TEP is 82.79%, which is extremely higher than that of 49.69% for POC. These results together indicated that TEP in the seawater has a longer residence time and is more easily degraded than other forms of POC.

The ecological knowledge of seamounts has accumulated plentifully in recent years. However, there are few studies on the distribution and degradation pattern of organic matter in seamounts morphology by using microorganisms and nutrients as indicators. In this research, we investigated the dynamic distribution of nutrients, particulates and microbial communities of the summits, flanks and base in the M5 Pair-summit Seamount, aiming to better understand the distribution and degradation pattern of organic matter around the seamount. The results indicate that TOC concentration presented a gradual decrease from summit to base, and obtained the lowest value at Base1 (0.65 mg L−1). Illumina Hiseq high-throughput sequencing analysis shows that Firmicutes (38.86%) and Bacteroidetes (6.86%) on the seamount Base1 obtained the highest relative abundance, which were related to the degradation of organic matter caused by denitrification. The distribution of organic matter and composition of microbial communities formed disparity due to the morphology of seamounts. In addition, shallow seamounts and deep seamounts exhibited a high degree of temporal and spatial specificity. Summit1 produced organic matter from phytoplankton, with the highest TOC content (1.23 mg L−1), dominated in microorganisms of Cyanobacteria (18.06%), and an upwelling of nutrients due to the “seamount effect”. However, Summit2 utilized nitrifying bacteria Taumarchaeota to degrade organic matter. This research suggests that the unique topographic features of seamounts is essential to sustain the surrounding microbial composition and hydrodynamics, which can further promote the study of seamount ecological environment.

Objective: To determine using a systematic assessment and meta-analysis if GFA injection is an appropriate substitute of propafenone for arrhythmic.Design: Conduct a systematic review and meta-analysis of randomized controlled trials.Data Source: PubMed, Web of Science, Cochrane Library, Embase, Wan-Fang Database, VIP, CNKI, and Sino Med from their inception to 7 March 2021.Eligibility Criteria for Selecting Studies: Inclusion of randomized controlled trials, which draws a comparison between GFA and propafenone. Evaluation of study integrity and conducted an extraction of independent data.Main Outcome Measure: Efficacy for supraventricular tachycardia, it is considered effective if it is reversed within 40 min (without considering recurrence); for premature ventricular beats, if they are reduced by more than 50% within 6 h.Results: Included in this current study are 1,294 research subjects pooled from 14 clinical studies. From the pooled assessment, GFA is demonstrated to be the equivalent of propafenone regarding the potency of effectiveness for tachycardia (RR = 1.11, 95% CI: 0.96, 1.28, P = 0.15). The subset analysis indicated that GFA has a better effect on premature ventricular beats (RR = 1.35, 95% CI: 1.07, 1.70, P = 0.01) and a similar effect on supraventricular tachycardia (RR = 1.07, 95% CI: 0.98, 1.12, P = 0.21). GFA effectiveness is lesser than propafenone in the case of mean converting time (WMD = −1.18, 95% CI: −2.30, −0.07, P = 0.04), systolic blood pressure (WMD = −3.53, 95% CI: −6.97, −0.09, P = 0.04), and QRS complex (WMD = −3.82, 95% CI: −6.96, −0.69, P = 0.02). Both GFA and propafenone have identical effects for diastolic blood pressure, heart rate, P-R interval, and QTc interval.Conclusion: A meta-analysis of RCTs was performed across 14 clinical trials, whereby 1,294 patients are used as research subjects. From the results, it is revealed that the effect exhibited by GFA injection is similar to the propafenone injection when treating premature ventricular beats or supraventricular tachycardia. Nevertheless, in certain academic disciplines, it was found that GFA is safer and beneficial compared to propafenone. Based on facts from relevant studies, GFA is deemed applicable during clinical practice.Systematic Review Registration:https://www.inplasy.com/inplasy-2021-3-0077/, identifier: INPLASY202130077.

Isoprenoid glycerol dialkyl glycerol tetraethers (isoGDGTs) derived from archaea are lipid biomarkers that exhibit high sensitivity to changes in water temperature, leading to the widespread application of the isoGDGT-based tetraether index of 86 carbon atoms (TEX86) in surface seawater temperature (SST) reconstruction. However, there remain some uncertainties regarding the robustness of TEX86 under changing water conditions (e.g., variations in water depth, oxygen and pH). Here, we analyzed isoGDGTs in suspended particles at different depths of the East China Sea (ECS) during summer 2020, aiming to constrain the applicability of the TEX86 proxy in coastal waters. Our data showed that the isoGDGTs were mainly derived from planktonic Thaumarchaeota, as revealed by the low ratio of GDGT-0/crenarchaeol (

The Taylor column, a typical hydrological structure around a seamount, can help to explain the high biomass and biodiversity around the seamount. However, it is difficult to observe a Taylor column in the field because it is easy to be destroyed by the change of ocean environment. Fortunately, a Taylor column around the C4 seamount in the Tropical Western Pacific Ocean was identified during our cruise. The existence of a Taylor column was confirmed by multidisciplinary indicators: 1) the theoretical calculation values of Bl and Ro were 4.922 and 0.195, respectively, indicating the environmental conditions were sufficient for a Taylor column to form; 2) the uplifts of isotherms and isohalines indicated the existence of the upwelling around the C4 seamount summit; 3) the Acoustic Doppler current profilers (ADCP) data indicated the existence of an anticyclonic circulation at the water layers ranging from 200 to 300 m. Meanwhile, the Taylor column's ecological effects were obvious around the seamount. The isolines of the nutrients, chlorophyll a and heterotrophic bacteria had uplifts approximately consistent with isotherms and isohalines, indicating they were influenced by the upwelling in this region. Meanwhile, the planar graphs of these parameters in the water column above 200 m showing the values around the seamount were relatively high, indicating the effects of the Taylor column on the enhancement of productivity. These results further confirmed that a Taylor column indeed formed and caused ecological effects in the C4 seamount. Finally, the scope of the Taylor column was roughly estimated based on the Chl a concentrations, which centered around the station O with a radius of 6.1 km.

The hypoxia problem in the ocean is worsening, and the oxygen minimum zone (OMZ) continues to expand. The Tropical Western Pacific Ocean is one of the most sensitive areas in response to climate change and human activities, and the OMZ in this area has also expanded significantly. Based on a survey conducted in March 2018, the characteristics of OMZ in the Kocebu seamount area of the Tropical Western Pacific Ocean and its biogeochemical effects are discussed. The results showed that DO in the Kocebu seamount area first decreased and then increased, and the lowest value was 2.49 mg/L at a water depth of 750 m. Based on the oxycline and the threshold of 3.20 mg/L, OMZ in this area was located in the water column of 590–1,350 m. With the increase in water depth, the POC concentration decreased gradually and remained stable in the water column deeper than 1,000 m. The presence of OMZ reduced the decomposition rate of POC, causing more POC to sink into deeper waters. 38.77% of POC was decomposed in the water column of 150–300 m, whereas only 16.25% of POC was decomposed in the OMZ. In contrast to the vertical distribution of POC, δ13C-POC decreased rapidly in the water columns of 100–150 and 300–500 m, indicating the rapid decomposition of POC. This result suggests that POC and δ13C-POC should be combined in the evaluation of POC decomposition.

A variety of biomarkers of sediment core KET-1 were studied to reconstruct both paleoproductivity and phytoplankton community structure variations and to reflect the local climate change of Kuroshio mainstream of east Taiwan over the past millennium. The results showed that sterols in sediments derived from the mixed terrestrial and marine inputs, with the riverine input from eastern Taiwan as the main terrestrial sterol source. The upward increase of terrestrial organic matter over the past millennium suggested the increasing riverine input of eastern Taiwan. The variation of the marine primary productivity was mainly influenced by the nutrient supplements from the riverine input. The changes of brassicasterol to dinosterol ratio indicated a phytoplankton community shift from dinoflagellate-dominated to diatom-dominated since 1500 CE. The increasing terrestrial inputs and the change of phytoplankton community change over time were related to “dry-humid” climate change.

Sézary syndrome (SS) is a genetically and clinically distinct entity among cutaneous T-cell lymphomas (CTCL). SS is characterized by more aggressive disease compared to the most common indolent type of CTCL, mycosis fungoides. However, there are limited available genomic data regarding SS. To characterize and expand current mappings of the genomic landscape of CTCL, whole exome sequencing (WES) was performed on peripheral blood samples from seven patients with SS. We detected 21,784 variants, of which 21,140 were novel and 644 were previously described. Filtering revealed 551 nonsynonymous variants among 525 mutated genes−25 recurrent mutations and 1 recurrent variant. Several recurrently mutated genes crucial to pathogenesis pathways, including Janus kinase (JAK)/signal transducers and activators of transcription (STAT), peroxisome proliferator-activated receptors (PPAR), PI3K-serine/threonine protein kinases (AKT), and fibroblast growth factor receptors (FGFR), were identified. Furthermore, genetic mutations spanned both known and novel genes, supporting the idea of a long-tail distribution of mutations in lymphoma. Acknowledging these genetic variants and their affected pathways may inspire future targeted therapies. WES of a limited number of SS patients revealed both novel findings and corroborated complexities of the “long-tail” distribution of previously reported mutations.

With advancements in the understanding of human cancers (carcinomas, sarcomas, and hematopoietic malignancies), molecular profiling, especially by Next Generation Sequencing (NGS), is playing an increasingly important role in the diagnosis, prognostication, and therapeutic management of cancer patients. The final and critical step in NGS is the annotation of detected variants and reporting of their clinical significance. Automated bioinformatics tools are available to assist with annotation, but the final responsibility for interpretation and validation of the annotation rests with the pathologist who may be constrained by the pressures of clinical sign-out and limited training in NGS. In this manuscript, we detail our experience in outsourcing variant annotation to a high-quality vendor to improve quality, standardize reporting, and decrease turn-around time of NGS reporting in clinical practice. We describe the composition of the evaluation team, steps that should be taken to evaluate potential annotation vendors, and detailed parameters that should be addressed before contracting with a vendor to guarantee the clinical reliability of the reported annotations.

We presented a patient with CML who progressed to unclassical blast phase after Tyrosine Kinase Inhibitors (TKIs) therapy. The patient presented with 2 populations of blasts: one with no cytoplasmic granules and was CD117 weak+/tryptase-/CD34- (typical myeloblasts), and another with metochromatic granules in the cytoplasm and was CD117 strong+/tryptase+/CD25+/CD34 subset+ (myelomastocytic blasts). Almost all the cells were positive for BCR/ABL1 fusion and no KT V816F mutation was detected. The patient was misdiagnosed as having blast phase CML with coexisting mast cell leukemia at an outside institute. Three similar cases and previously described myelomastocytic leukemia are reviewed and discussed.

Here we described a patient with a history of mycosis fungoides who developed large cell transformation manifesting with generalized erythroderma, lymphocytosis, lymphadenopathy and impending acute liver failure (ALF). Three-phase computed tomography of the liver showed neither mass nor hepatomegaly. Liver biopsy confirmed infiltration with malignant CD4+ clonal T-cells. Combination chemotherapy with gemcitabine, dexamethasone, and cisplatin (GDP) resulted in the recovery of liver function and resolution of skin involvement. In Foundation Medicine Hematology Gene Panel, 31 genetic alterations with 11 clinically relevant mutations were identified including ARID2 mutation frequently observed in hepatocellular carcinoma but rarely observed in hematologic malignancies.