bluuebunny/crossref_metadata_2025 huggingface dataset:
Trends in Bleeding Events Among Patients With Acute Coronary Syndrome in China, 2015 to 2019: Insights From the CCC-ACS Project
Authors: Wang Xiao , Zhao Guanqi , Zhou Mengge , Ma Changsheng , Ge Junbo , Huo Yong , Smith Sidney C. , Fonarow Gregg C. , Hao Yongchen , Liu Jun , Morgan Louise , Gong Wei , Yan Yan , Liu Jing , Zhao Dong , Han Yaling , Nie Shaoping
Published: December 2021

Objective: Major bleeding is a common complication following treatment for an acute coronary syndrome (ACS) and is associated with increased mortality. We aimed to explore the temporal trend of bleeding events in relation to changes of therapeutic strategies among patients hospitalized for ACS in China.

Methods: The CCC-ACS project (Improving Care for Cardiovascular Disease in China–Acute Coronary Syndrome) is a collaborative initiative of the American Heart Association and the Chinese Society of Cardiology. We analyzed 113,567 ACS patients from 241 hospitals in China from 2015 to 2019. Major bleeding was defined as intracranial bleeding, retroperitoneal bleeding, a decline in hemoglobin levels ≥3 g/dL, transfusion with overt bleeding, bleeding requiring surgical intervention, and fatal bleeding. Kruskal–Wallis test was used to examine the trend of major bleeding over time.

Results: The rate of in-hospital major bleeding decreased from 6.3% in 2015 to 4.7% in 2019 (unadjusted OR = 0.74, 95% CI: 0.68–0.80, and P < 0.001). The relative changes were consistent across almost all subgroups including patients with NSTE-ACS and STEMI, although the trend was more pronounced in NSTE-ACS patients. The decrease in bleeding was accompanied by a decrease in use of GP IIb/IIIa inhibitors and parenteral anticoagulation therapy during hospitalization. The annual reduced risk of bleeding (OR = 0.91, 95% CI: 0.89–0.93) was attenuated after stepwise adjusting for baseline characteristics and antithrombotic treatments (OR = 0.95, 95% CI: 0.93–0.97), but did not change after adjusting for invasive treatment (OR = 0.95, 95% CI: 0.93–0.97).

Conclusions: There was a temporal reduction in in-hospital bleeding among Chinese ACS patients during the last 5 years, which was associated with more evidence-based use of antithrombotic therapies.

Clinical Trial Registration:https://www.clinicaltrials.gov, identifier: NCT02306616.
Central and Peripheral Cannulation for Cardiopulmonary Bypass in Fetal Sheep: A Comparative Study
Authors: Teng Yun , Tian Miao , Huang Bingxin , Wu Wentao , Jiang Qiuping , Luo Xiaokang , Pan Wei , Zhuang Jian , Zhou Chengbin , Chen Jimei
Published: December 2021

Objective:In-utero correction is an option for treatment of critical congenital heart diseases (CHDs). Fetal cardiac surgery for CHDs is dependent on the reliable use of fetal cardiopulmonary bypass (CPB), but this technology remains experimental. In this study, we established fetal CPB models with central and peripheral cannulation to explore the differences between the two cannulation strategies.

Methods: Ten fetal sheep with 90–110 gestational days were randomized into central cannulation (n = 5) and peripheral cannulation (n = 5) groups. All fetal CPB models were successfully established. At each time point (0, 30, and 60 min after initiation of CPB), echocardiography was performed. Blood samples were also collected for blood gas analysis and tests of myocardial enzymes and liver and kidney function.

Results: In the central cannulation group, right ventricular Tei index significantly increased (p = 0.016) over time. Compared with the peripheral cannulation group, the left ventricular Tei index of the central cannulation group was significantly higher (1.96 ± 0.31 vs. 0.45 ± 0.19, respectively; p = 0.028) and the stroke volume was lower (0.46 ± 0.55 vs. 2.13 ± 0.05, respectively; p = 0.008) at 60 min after CPB. Levels of liver and kidney injury markers and of acid-base balance, including alanine aminotransferase (ALT), aspartate aminotransferase/ALT ratio, blood urea nitrogen (BUN), BUN/creatinine ratio, base excess and bicarbonates, were significantly higher for peripheral than for central cannulation. Other important physiologic parameters, including heart rate, blood pressure, myocardial enzymes, umbilical artery beat index and resistance index, left ventricular Tei index, and left and right ventricular stroke volume, were comparable between the two groups.

Conclusions: Both central and peripheral cannulations can be used to establish fetal CPB models. Central cannulation causes more adverse impacts for cardiac function, whereas peripheral cannulation is more susceptible to complications related to inadequate organ perfusion.
Development of a Lexicon for Pain
Authors: Chaturvedi Jaya , Mascio Aurelie , Velupillai Sumithra U. , Roberts Angus
Published: December 2021

Pain has been an area of growing interest in the past decade and is known to be associated with mental health issues. Due to the ambiguous nature of how pain is described in text, it presents a unique natural language processing (NLP) challenge. Understanding how pain is described in text and utilizing this knowledge to improve NLP tasks would be of substantial clinical importance. Not much work has previously been done in this space. For this reason, and in order to develop an English lexicon for use in NLP applications, an exploration of pain concepts within free text was conducted. The exploratory text sources included two hospital databases, a social media platform (Twitter), and an online community (Reddit). This exploration helped select appropriate sources and inform the construction of a pain lexicon. The terms within the final lexicon were derived from three sources—literature, ontologies, and word embedding models. This lexicon was validated by two clinicians as well as compared to an existing 26-term pain sub-ontology and MeSH (Medical Subject Headings) terms. The final validated lexicon consists of 382 terms and will be used in downstream NLP tasks by helping select appropriate pain-related documents from electronic health record (EHR) databases, as well as pre-annotating these words to help in development of an NLP application for classification of mentions of pain within the documents. The lexicon and the code used to generate the embedding models have been made publicly available.
Geochemistry of Water and Gas Emissions From Cuicocha and Quilotoa Volcanic Lakes, Ecuador
Authors: Melián G. V. , Toulkeridis T. , Pérez N. M. , Hernández P. A. , Somoza L. , Padrón E. , Amonte C. , Alonso M. , Asensio-Ramos M. , Cordero M.
Published: December 2021

There are hundreds of volcanic lakes around the world that represent an important hazard due to the potential occurrence of phreatomagmatic or limnic eruptions. Variations in geochemical and geophysical parameters could help to identify potential risks for these events. Cuicocha and Quilota volcanic lakes, located at the North Andean Volcanic Zone of Ecuador, are geologically young, with gas emissions manifested mainly as CO2via bubbling gases. Both lakes present a limited monitoring record. Therefore, volcanic monitoring is a priority task due to the potential hazard they represent by the possibility of water stratification and CO2accumulation. During 2012-2018 period, geochemical investigation based mainly on diffuse CO2surveys and analyzing the chemical and isotopic composition of bubbling gases has been carried out at Cuicocha and Quilotoa lakes. Additionally, vertical profiles of water columns were conducted in both lakes to investigate the possibility of water stratification and CO2accumulation in the lakes. A bathymetric study was also carried out in Quilotoa in 2017, giving further information about the degasification processes and the morphology of the lake bottom. The computed diffuse CO2output for Cuicocha volcanic lake (3.95 km2) showed a range from 53 to 652 t d−1for the period 2006–2018, with a maximum value in 2012, coinciding with a maximum of the3He/4He ratio measured at the bubbling gases and an increase in the seismic activity with an episode of long-period seismicity recorded in 2011–2012. For Quilotoa volcanic lake (3.50 km2) diffuse CO2output was estimated between 141 and 536 t d−1for the period 2014–2018. The chemical and isotopic data show that Cuicocha has a chemical composition typical of worldwide superficial shallow waters and aquifers, while Quilotoa shows a chemical composition typical of crater lakes in active volcanic systems. The distribution of the dissolved gas composition along the vertical profiles shows the existence of different water masses in both lakes, with an increase in the concentration of dissolved gases with depth. The carbon isotopic signature indicates an endogenous origin of the CO2, with a greater contribution in the stratification zone in both lakes. This study shows methods applicable to other volcanic lakes of the world to monitor their activity and potential risks.
The Association Between Cardiovascular Autonomic Function and Changes in Kidney and Myocardial Function in Type 2 Diabetes and Healthy Controls
Authors: Laursen Jens Christian , Rasmussen Ida Kirstine B. , Zobel Emilie H. , Hasbak Philip , von Scholten Bernt Johan , Holmvang Lene , Ripa Rasmus S. , Hansen Christian S. , Frimodt-Moeller Marie , Kjaer Andreas , Rossing Peter , Hansen Tine W.
Published: December 2021

Background

The mechanisms linking cardiovascular autonomic neuropathy, diabetic kidney disease and cardiovascular mortality in type 2 diabetes are widely unknown. We investigated the relationship between baseline cardiovascular autonomic function and changes in kidney and myocardial function over six years in patients with type 2 diabetes and healthy controls.

Methods

Post-hoc analysis of a cohort study in 24 patients with type 2 diabetes and 18 healthy controls. Baseline determinants were cardiovascular autonomic reflex tests (heart rate response to: standing (30:15); deep breathing (E:I); and the Valsalva test) and time- and frequency-domain heart rate variability indices. Outcomes were changes in estimated glomerular filtration rate (eGFR), albuminuria, myocardial flow reserve (MFR) measured by cardiac 82Rb Positron emission tomography computed tomography (PET/CT), and coronary artery calcium score (CACS).

Results

Mean age at inclusion was 61 ± 10 years and 36% were female. Mean follow up time was 6 ± 0 years. A lower response in heart rate to the Valsalva test (corresponding to weaker autonomic function) was associated with a larger decline in eGFR (p=0.04), but not significantly after adjustment for sex, baseline age, smoking status, systolic blood pressure, heart rate, HbA1c, body mass index and baseline eGFR (p=0.12). A higher baseline response in heart rate to standing (30:15) was associated with a larger decline in myocardial flow reserve in the unadjusted analysis (p=0.02) and after adjustment (p=0.02). A higher response in heart rate to the Valsalva maneuver was associated with a larger increase in CACS (p = 0.02), but the association became insignificant after adjustment (p = 0.16).

Conclusion

A lower response in heart rate to the Valsalva test was associated with a larger decline in kidney function, indicating that autonomic dysfunction may predict future loss of kidney function. However, we did not find any association between lower values in cardiovascular autonomic function at baseline and a worsening in albuminuria, myocardial function, or atherosclerotic burden.
Survival of Patients Following First Diagnosis of Diabetic Foot Complications: A Nationwide 15-Year Longitudinal Analysis
Authors: Lin Chia-Hung , Armstrong David G. , Liu Pi-Hua , Lin Cheng-Wei , Huang Chung-Huei , Huang Yu-Yao
Published: December 2021

Background and Aims

The long-term survival in people with type 2 diabetes following first diagnosis of diabetic foot complications (FDDFC) is unclear. The object is to evaluate the mortality rate in subjects with type 2 diabetes following FDDFC and the impacts of the major cardiovascular comorbidities.

Methods

Nationwide data were analyzed for subjects with T2D and DFC between 2003 and 2017 according to ICD-9 coding. DFC was defined with the codes of ulcers, infections, or severe peripheral artery disease that required intervention (PAD) to mimic the real world diagnosis. Criteria of FDDFC were preceded by a period without any DFC for at least 5 years. Major cardiovascular comorbidities: established PAD and cardiovascular diseases (CVD: including coronary heart disease (CHD), stroke, or heart failure) before the index date as well as lower-extremity amputations (LEA) at the index episode were analyzed.

Results

Among 300,115 subjects with DFC, a total of 103,396 patients had FDDFC. The mean 5-year survival rate of these subjects was 81.05%. Using subjects without associated major cardiovascular comorbidity as baseline, the adjusted hazard ratios (aHR) were1.43 (95% confidence interval 1.38–1.49) in group PAD-/CVD+, followed by 1.70 (1.59–1.80) in PAD+/CVD- and 1.98 (1.89–2.08) in PAD+/CVD+. The aHR was further increased in patients with PAD who additionally had heart failure (3.77, 3.50–4.05), stroke (2.06, 1.95–2.18), or CHD (1.89, 1.79–2.00). Subjects with PAD rather than other CVD were associated with LEA at FDDFC. Patients with major LEA (above the ankle) at FDDFC episode had lower 5-year survival rate (65.01%) followed by those with minor LEA (72.24%) and without LEA (81.61%).

Conclusions

Cardiovascular comorbidity as well as LEA status at the event of FDDFCs were both associated with patient survival outcomes. Earlier identification of this large population could lead to higher survival rates.
Programmed Degradation of Pericarp Cells in Wheat Grains Depends on Autophagy
Authors: Li Yong-Bo , Yan Mei , Cui De-Zhou , Huang Chen , Sui Xin-Xia , Guo Feng Zhi , Fan Qing-Qi , Chu Xiu-Sheng
Published: December 2021

Wheat is one of the most important food crops in the world, with development of the grains directly determining yield and quality. Understanding grain development and the underlying regulatory mechanisms is therefore essential in improving the yield and quality of wheat. In this study, the developmental characteristics of the pericarp was examined in developing wheat grains of the new variety Jimai 70. As a result, pericarp thickness was found to be thinnest in grains at the top of the spike, followed by those in the middle and thickest at the bottom. Moreover, this difference corresponded to the number of cell layers in the pericarp, which decreased as a result of programmed cell death (PCD). A number of autophagy-related genes (ATGs) are involved in the process of PCD in the pericarp, and in this study, an increase in ATG8-PE expression was observed followed by the appearance of autophagy structures. Meanwhile, following interference of the key autophagy gene ATG8, PCD was inhibited and the thickness of the pericarp increased, resulting in small premature grains. These findings suggest that autophagy and PCD coexist in the pericarp during early development of wheat grains, with both processes increasing from the bottom to the top of the spike. Moreover, PCD was also found to rely on ATG8-mediated autophagy. The results of this study therefore provide a theoretical basis for in-depth studies of the regulatory mechanisms of wheat grain development.
A New Method for Recognizing Protein Complexes Based on Protein Interaction Networks and GO Terms
Authors: Wang Xiaoting , Zhang Nan , Zhao Yulan , Wang Juan
Published: December 2021

Motivation: A protein complex is the combination of proteins which interact with each other. Protein–protein interaction (PPI) networks are composed of multiple protein complexes. It is very difficult to recognize protein complexes from PPI data due to the noise of PPI.

Results: We proposed a new method, called Topology and Semantic Similarity Network (TSSN), based on topological structure characteristics and biological characteristics to construct the PPI. Experiments show that the TSSN can filter the noise of PPI data. We proposed a new algorithm, called Neighbor Nodes of Proteins (NNP), for recognizing protein complexes by considering their topology information. Experiments show that the algorithm can identify more protein complexes and more accurately. The recognition of protein complexes is vital in research on evolution analysis.

Availability and implementation: https://github.com/bioinformatical-code/NNP.
Intrapleural Injection of Anti-PD1 Antibody: A Novel Management of Malignant Pleural Effusion
Authors: Li Xinying , Wu Guannan , Chen Cen , Zhao Yuan , Zhu Suhua , Song Xincui , Yin Jie , Lv Tangfeng , Song Yong
Published: December 2021

Background

Malignant tumors accompanied with malignant pleural effusion (MPE) often indicate poor prognosis. The therapeutic effect and mechanism of intrapleural injection of anti-programmed cell death protein 1 (PD1) on MPE need to be explored.

Methods

A preclinical MPE mouse model and a small clinical study were used to evaluate the effect of intrapleural injection of anti-PD1 antibody. The role of immune cells was observedviaflow cytometry, RNA-sequencing, quantitative PCR, western blot, immunohistochemistry, and other experimental methods.

Results

Intrathoracic injection of anti-PD1 monoclonal antibody (mAb) has significantly prolonged the survival time of mice (P = 0.0098) and reduced the amount of effusion (P = 0.003) and the number of cancer nodules (P = 0.0043). Local CD8+ T cells participated in intrapleural administration of anti-PD1 mAb. The proportion of CD69+, IFN-γ+, and granzyme B+ CD8+ T cells in the pleural cavity was increased, and the expression of TNF-α and IL-1β in MPE also developed significantly after injection. Local injection promoted activation of the CCL20/CCR6 pathway in the tumor microenvironment and further elevated the expression of several molecules related to lymphocyte activation. Clinically, the control rate of intrathoracic injection of sintilimab (a human anti-PD1 mAb) for 10 weeks in NSCLC patients with MPE was 66.7%. Local injection improved the activity and function of patients’ local cytotoxic T cells (CTLs).

Conclusions

Intrapleural injection of anti-PD1 mAb could control malignant pleural effusion and the growth of cancer, which may be achieved by enhancing local CTL activity and cytotoxicity.
A Potent and Protective Human Neutralizing Antibody Against SARS-CoV-2 Variants
Authors: Shan Sisi , Mok Chee Keng , Zhang Shuyuan , Lan Jun , Li Jizhou , Yang Ziqing , Wang Ruoke , Cheng Lin , Fang Mengqi , Aw Zhen Qin , Yu Jinfang , Zhang Qi , Shi Xuanling , Zhang Tong , Zhang Zheng , Wang Jianbin , Wang Xinquan , Chu Justin Jang Hann , Zhang Linqi
Published: December 2021

As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants continue to emerge and spread around the world, antibodies and vaccines to confer broad and potent neutralizing activity are urgently needed. Through the isolation and characterization of monoclonal antibodies (mAbs) from individuals infected with SARS-CoV-2, we identified one antibody, P36-5D2, capable of neutralizing the major SARS-CoV-2 variants of concern. Crystal and electron cryo-microscopy (cryo-EM) structure analyses revealed that P36-5D2 targeted to a conserved epitope on the receptor-binding domain of the spike protein, withstanding the three key mutations—K417N, E484K, and N501Y—found in the variants that are responsible for escape from many potent neutralizing mAbs, including some already approved for emergency use authorization (EUA). A single intraperitoneal (IP) injection of P36-5D2 as a prophylactic treatment completely protected animals from challenge of infectious SARS-CoV-2 Alpha and Beta. Treated animals manifested normal body weight and were devoid of infection-associated death up to 14 days. A substantial decrease of the infectious virus in the lungs and brain, as well as reduced lung pathology, was found in these animals compared to the controls. Thus, P36-5D2 represents a new and desirable human antibody against the current and emerging SARS-CoV-2 variants.
Ecosystem Metabolism Modulates the Dynamics of Hypoxia and Acidification Across Temperate Coastal Habitat Types
Authors: Wallace Ryan B. , Peterson Bradley J. , Gobler Christopher J.
Published: December 2021

Changes in photosynthetic and respiration rates in coastal marine habitats cause considerable variability in ecosystem metabolism on timescales ranging from diel to tidal to seasonal. Here, temporal and spatial dynamics of dissolved oxygen (DO), carbonate chemistry, and net ecosystem metabolism (NEM) were quantified from spring through fall in multiple, distinct, temperate estuarine habitats: seagrass meadows, salt marshes, an open water estuary, and a shallow water habitat dominated by benthic macroalgae. DO and pHT (total scale) measurements were made via high frequency sensor arrays coupled with discrete measurements of dissolved inorganic carbon (DIC) and high-resolution spatial mapping was used to document intra-habitat spatial variability. All habitats displayed clear diurnal patterns of pHT and DO that were stronger than tidal signals, with minimums and maximums observed during early morning and afternoon, respectively. Diel ranges in pHT and DO varied by site. In seagrass meadows and the open estuarine site, pHT ranged 7.8–8.4 and 7.5–8.2, respectively, while DO exceeded hypoxic thresholds and aragonite was typically saturated (ΩAr > 1). Conversely, pHT in a shallow macroalgal and salt marsh dominated habitats exhibited strong diel oscillations in pHT (6.9–8.4) with diel acidic (pHT < 7) and hypoxic (DO < 3 mg L–1) conditions often observed during summer along with extended periods of aragonite undersaturation (ΩAr < 1). The partial pressure of carbon dioxide (pCO2) exceeded 3000 and 2000 μatm in the salt marsh and macroalgal bed, respectively, while pCO2 never exceeded 1000 μatm in the seagrass and open estuarine site. Mesoscale (50–100 m) spatial variability was observed across sites with the lowest pHT and DO found within regions of more restricted flow. NEM across habitats ranged from net autotrophic (macroalgae and seagrass) to metabolically balanced (open water) and net heterotrophic (salt marsh). Each habitat exhibited distinct buffering capacities, varying seasonally, and modulated by adjacent biological activity and variations in total alkalinity (TA) and DIC. As future predicted declines in pH and DO are likely to shrink the spatial extent of estuarine refuges from acidification and hypoxia, efforts are required to expand seagrass meadows and the aquaculture of macroalgae to maximize their ecosystem benefits and maintain these estuarine refuges.
Using Virtual AChE Homology Screening to Identify Small Molecules With the Ability to Inhibit Marine Biofouling
Authors: Arabshahi Homayon John , Trobec Tomaž , Foulon Valentin , Hellio Claire , Frangež Robert , Sepčić Kristina , Cahill Patrick , Svenson Johan
Published: December 2021

The search for effective yet environmentally friendly strategies to prevent marine biofouling is hampered by the large taxonomic diversity amongst fouling organisms and a lack of well-defined conserved molecular targets. The acetylcholinesterase enzyme catalyses the breakdown of the neurotransmitter acetylcholine, and several natural antifouling allelochemicals have been reported to display acetylcholinesterase inhibitory activity. Our study is focussed on establishing if acetylcholinesterase can be used as a well-defined molecular target to accelerate discovery and development of novel antifoulants via sequential high-throughput in silico screening, in vitro enzymatic studies of identified compound libraries, and in vivo assessment of the most promising lead compounds. Using this approach, we identified potent cholinesterase inhibitors with inhibitory concentrations down to 3 μM from a 10,000 compound library. The most potent inhibitors were screened against five microfouling marine bacteria and marine microalgae and the macrofouling tunicate Ciona savignyi. No activity was seen against the microfoulers but a potent novel inhibitor of tunicate settlement and metamorphosis was discovered. Although only one of the identified active cholinesterase inhibitors displayed antifouling activity suggesting the link between cholinesterase inhibition and antifouling is limited to certain compound classes, the study highlights how in silico screening employed regularly for drug discovery can also facilitate discovery of antifouling leads.
Microbial Growth and Organic Matter Cycling in the Pacific Ocean Along a Latitudinal Transect Between Subarctic and Subantarctic Waters
Authors: Giebel Helge-Ansgar , Arnosti Carol , Badewien Thomas H. , Bakenhus Insa , Balmonte John Paul , Billerbeck Sara , Dlugosch Leon , Henkel Rohan , Kuerzel Birgit , Meyerjürgens Jens , Milke Felix , Voss Daniela , Wienhausen Gerrit , Wietz Matthias , Winkler Holger , Wolterink Mathias , Simon Meinhard
Published: December 2021

The Pacific Ocean constitutes about half of the global oceans and thus microbial processes in this ocean have a large impact on global elemental cycles. Despite several intensely studied regions large areas are still greatly understudied regarding microbial activities, organic matter cycling and biogeography. Refined information about these features is most important to better understand the significance of this ocean for global biogeochemical and elemental cycles. Therefore we investigated a suite of microbial and geochemical variables along a transect from the subantarctic to the subarctic Pacific in the upper 200 m of the water column. The aim was to quantify rates of organic matter processing, identify potential controlling factors and prokaryotic key players. The assessed variables included abundance of heterotrophic prokaryotes and cyanobacteria, heterotrophic prokaryotic production (HPP), turnover rate constants of amino acids, glucose, and acetate, leucine aminopeptidase and β-glucosidase activities, and the composition of the bacterial community by fluorescence in situ hybridization (FISH). The additional quantification of nitrate, dissolved amino acids and carbohydrates, chlorophyll a, particulate organic carbon and nitrogen (POC, PON) provided a rich environmental context. The oligotrophic gyres exhibited the lowest prokaryotic abundances, rates of HPP and substrate turnover. Low nucleic acid prokaryotes dominated in these gyres, whereas in temperate and subpolar regions further north and south, high nucleic acid prokaryotes dominated. Turnover rate constants of glucose and acetate, as well as leucine aminopeptidase activity, increased from (sub)tropical toward the subpolar regions. In contrast, HPP and bulk growth rates were highest near the equatorial upwelling and lowest in the central gyres and subpolar regions. The SAR11 clade, the Roseobacter group and Flavobacteria constituted the majority of the prokaryotic communities. Vertical profiles of the biogeochemical and microbial variables markedly differed among the different regions and showed close covariations of the microbial variables and chlorophyll a, POC and PON. The results show that hydrographic, microbial, and biogeochemical properties exhibited distinct patterns reflecting the biogeographic provinces along the transect. The microbial variables assessed contribute to a better and refined understanding of the scales of microbial organic matter processing in large areas of the epipelagic Pacific beyond its well-studied regions.
Participatory Risk Assessment of Humpback Whale (Megaptera novaeangliae) and Leatherback Turtle (Dermochelys coriacea) Bycatch in Northern Peru
Authors: Costanza Anna B. , Guidino Chiara , Mangel Jeffrey C. , Alfaro-Shigueto Joanna , Verutes Gregory , Caillat Marjolaine , Samanta Aritree , Hines Ellen
Published: December 2021

Uncertainties about the magnitude of bycatch in poorly assessed fisheries impede effective conservation management. In northern Peru, small-scale fisheries (SSF) bycatch negatively impacts marine megafauna populations and the livelihoods of fishers which is further elevated by the under-reporting of incidents. Within the last decade, accounts of entangled humpback whales (HBW) (Megaptera novaeangliae) off the northern coast of Peru have increased, while Eastern Pacific leatherback turtles (LBT) (Dermochelys coriacea) have seen over a 90% decline in nesting populations related in large part to bycatch mortality. By leveraging the experience and knowledge of local fishers, our research objectives were to use a low-cost public participation mapping approach to provide a spatio-temporal assessment of bycatch risk for HBW and LBT off two Peruvian fishing ports. We used an open-source, geographic information systems (GIS) model, the Bycatch Risk Assessment (ByRA), as our platform. Broadly, ByRA identifies high bycatch risk areas by estimating the intersection of fishing areas (i.e., stressors) with species habitat and evaluating the exposure and consequence of possible interaction between the two. ByRA outputs provided risk maps and gear risk percentages categorized as high, medium, and low for the study area and seven subzones for HBW in the austral winter and LBT in the austral summer. Overall, the highest bycatch risk for both species was identified within gillnet fisheries near the coast. Bycatch risk for most gear types decreased with distance from the coast. When we separated the ByRA model by port, our map outputs indicate that bycatch management should be port specific, following seasonal and spatial variations for HBW, and specific fishing gear impacts for HBW and LBT. Combined with direct bycatch mitigation techniques, ByRA can be a supportive and informative tool for addressing specific bycatch threats and marine megafauna conservation goals. ByRA supports a participatory framework offering rapid visual information via risk maps and replicable methods for areas with limited resources and data on fisheries and species habitat.
From Settlers to Subspecies: Genetic Differentiation in Commerson’s Dolphins Between South America and the Kerguelen Islands
Authors: Kraft Sebastián , Pérez-Alvarez MJosé , Olavarría Carlos , Moraga Rodrigo , Baker C. Scott , Steel Debbie , Tixier Paul , Guinet Christophe , Viricel Amelia , Brickle Paul , Costa Marina , Crespo Enrique , Durante Cristian , Loizaga Rocio , Poulin Elie
Published: December 2021

Commerson’s dolphins (Cephalorhynchus commersonii) are separated into the subspecies C. c. commersonii, found along southern South America (SA) and the Falkland Islands/Islas Malvinas (FI/IM), and C. c. kerguelenensis, restricted to the subantarctic Kerguelen Islands (KI). Following the dispersal model proposed for the genus, the latter is thought to have originated from SA after a long-distance dispersal event. To evaluate this biogeographic scenario, a distribution-wide, balanced sampling of mitochondrial DNA (mtDNA) control region sequences was designed. New tissue samples from southern Chile, Argentina, FI/IM, and KI were added to published sequences from SA and KI, for a total of 256 samples. Genetic diversity indices, genetic and phylogeographic structure, and migration rates were calculated. One haplotype was shared between subspecies, with which all haplotypes of C. c. kerguelenensis formed a distinct group in the haplotype network. A new haplotype for C. c. kerguelenensis is reported. Differentiation in haplotype frequencies was found among localities within the distribution of C. c. commersonii, yet the phylogeographic signal was only statistically significant between subspecies. Coalescent-based historical gene flow estimations indicated migration between the northern and southern portions of the species’ range in SA as well as between SA and the FI/IM, but not between these and the KI. The net nucleotide divergence between dolphins from SA and the FI/IM was lower than the recommended threshold value suggested for delimiting subspecies, unlike that found between C. c. commersonii and C. c. kerguelenensis. The results are consistent with the model of post-glacial colonization of KI by South American C. commersonii, followed by an ongoing divergence process and subspecies status. Thus, C. c. kerguelenensis may represent the most recent diversification step of Cephalorhynchus, where isolation from their source population is driving a process of incipient speciation.
Study on Metakaolin Impact on Concrete Performance of Resisting Complex Ions Corrosion
Authors: Xupeng Chen , Zhuowen Sun , Jianyong Pang
Published: December 2021

The main purpose of this study is to determine the metakaolin (MK) impacts on the concrete durability when the concrete is subjected to joint corrosion of SO42−,Mg2+ and, Cl−. Four groups of concrete test samples, which contained different MK contents, were designed and tested in order to see their physical property changes and macro-morphology differences during the cyclic corrosion process. And a series of approaches, including XRD, FTIR, SEM, and EDS, were applied to study the concrete phase composition changes and the micro-morphology features of all groups. According to the test results, when reaching 20 cycles, the concrete sample with 10% MK showed the best concrete physical properties; when reaching 120 cycles, the concrete with 5% MK content showed the best durability, produced similar amount of corrosion products to ordinary concrete, and presented relatively compacted micro-structure and small internal porosity. Mg2+ actually has a great impact on metakaolin. The corrosion product quantity increased significantly when MK admixture reached 15%. Due to the great number of produced M-S-H, the corrosive ions damaged the concrete for a second time, leading to serious aggregate peeling-off, powder surface of test samples, and porous micro-structure.
Impact of Comorbidities on Beneficial Effect of Lactated Ringers vs. Saline in Sepsis Patients
Authors: Tseng Chien-Hua , Chen Tzu-Tao , Chan Ming-Cheng , Chen Kuan-Yuan , Wu Sheng-Ming , Shih Ming-Chieh , Tu Yu-Kang
Published: December 2021

Background: Lactated Ringers reduced mortality more than saline in sepsis patients but increased mortality more than saline in traumatic brain injury patients.

Method: This prospective cohort study was conducted in a medical intensive care unit (ICU) in central Taiwan. We applied standard sepsis evaluation protocol and identified heart, lung, liver, kidney, and endocrine comorbidities. We also evaluated resuscitation response with central venous pressure, central venous oxygen saturation, and serum lactate level simultaneously. Propensity-score matching and Cox regression were used to estimate mortality. The competing risk model compared the lengths of hospital stays with the subdistribution hazard ratio (SHR).

Results: Overall, 938 patients were included in the analysis. The lactated Ringers group had a lower mortality rate (adjusted hazard ratio, 0.59; 95% CI 0.43-0.81) and shorter lengths of hospital stay (SHR, 1.39; 95% C.I. 1.15-1.67) than the saline group; the differences were greater in patients with chronic pulmonary disease and small and non-significant in those with chronic kidney disease, moderate to severe liver disease and cerebral vascular disease. The resuscitation efficacy was the same between fluid types, but serum lactate levels were significantly higher in the lactated Ringers group than in the saline group (0.12 mg/dl/h; 95% C.I.: 0.03, 0.21), especially in chronic liver disease patients. Compared to the saline group, the lactated Ringers group achieved target glucose level earlier in both diabetes and non-diabetes patients.

Conclusion: Lactate Ringer's solution provides greater benefits to patients with chronic pulmonary disease than to those with chronic kidney disease, or with moderate to severe liver disease. Comorbidities are important in choosing resuscitation fluid types.
Outcome of Initial Progression During Nivolumab Treatment for Hepatocellular Carcinoma: Should We Use iRECIST?
Authors: Lee Dong Ho , Hwang Sangyoun , Koh Young Hwan , Lee Kyung-Hun , Kim Ju Yeon , Kim Yoon Jun , Yoon Jung-Hwan , Lee Jeong-Hoon , Park Joong-Won
Published: December 2021

Immune response evaluation criteria in solid tumors (iRECIST) is recommended during immune checkpoint inhibitors (ICIs) treatment, due to the possibility of pseudoprogression. We evaluated the frequency of pseudoprogression in hepatocellular carcinoma (HCC) patients. This retrospective multicenter study involved 158 consecutive patients who underwent nivolumab treatment for HCC in Korea. At the initial evaluation, 94 patients presented with immune unconfirmed progressive disease, and 22 continued nivolumab. At the second evaluation, 21 of the 22 patients (95.5%) had confirmed progression and no pseudoprogression was observed. Considering low possibility of pseudoprogression, iRECIST may not be required for HCC.
The Effect of Dexmedetomidine as a Sedative Agent for Mechanically Ventilated Patients With Sepsis: A Systematic Review and Meta-Analysis
Authors: Wang Caimu , Chen Qijiang , Wang Ping , Jin Weisheng , Zhong Chao , Ge Zisheng , Xu Kangmin
Published: December 2021

Purpose: Dexmedetomidine has been shown to improve clinical outcomes in critically ill patients. However, its effect on septic patients remains controversial. Therefore, the purpose of this meta-analysis was to assess the effect of dexmedetomidine as a sedative agent for mechanically ventilated patients with sepsis.

Methods: We searched PubMed, Embase, Scopus, and Cochrane Library from inception through May 2021 for randomized controlled trials that enrolled mechanically ventilated, adult septic patients comparing dexmedetomidine with other sedatives or placebo.

Results: A total of nine studies involving 1,134 patients were included in our meta-analysis. The overall mortality (RR 0.97, 95%CI 0.82 to 1.13, P = 0.67, I2 = 25%), length of intensive care unit stay (MD −1.12, 95%CI −2.89 to 0.64, P = 0.21, I2 = 71%), incidence of delirium (RR 0.95, 95%CI 0.72 to 1.25, P = 0.70, I2 = 0%), and delirium free days (MD 1.76, 95%CI –0.94 to 4.47, P = 0.20, I2 = 80%) were not significantly different between dexmedetomidine and other sedative agents. Alternatively, the use of dexmedetomidine was associated with a significant reduction in the duration of mechanical ventilation (MD –0.53, 95%CI −0.85 to −0.21, P = 0.001, I2 = 0%) and inflammatory response (TNF-α: MD −5.27, 95%CI −7.99 to −2.54, P<0.001, I2 = 0%; IL-1β: MD −1.25, 95%CI −1.91 to –0.59, P<0.001, I2 = 0%).

Conclusions: For patients with sepsis, the use of dexmedetomidine as compared with other sedative agents does not affect all-cause mortality, length of intensive care unit stay, the incidence of delirium, and delirium-free days. But the dexmedetomidine was associated with the reduced duration of mechanical ventilation and inflammatory response.
Deep Learning for Automatic Image Segmentation in Stomatology and Its Clinical Application
Authors: Luo Dan , Zeng Wei , Chen Jinlong , Tang Wei
Published: December 2021

Deep learning has become an active research topic in the field of medical image analysis. In particular, for the automatic segmentation of stomatological images, great advances have been made in segmentation performance. In this paper, we systematically reviewed the recent literature on segmentation methods for stomatological images based on deep learning, and their clinical applications. We categorized them into different tasks and analyze their advantages and disadvantages. The main categories that we explored were the data sources, backbone network, and task formulation. We categorized data sources into panoramic radiography, dental X-rays, cone-beam computed tomography, multi-slice spiral computed tomography, and methods based on intraoral scan images. For the backbone network, we distinguished methods based on convolutional neural networks from those based on transformers. We divided task formulations into semantic segmentation tasks and instance segmentation tasks. Toward the end of the paper, we discussed the challenges and provide several directions for further research on the automatic segmentation of stomatological images.
Epidemic Preparedness—Leishmania tarentolae as an Easy-to-Handle Tool to Produce Antigens for Viral Diagnosis: Application to COVID-19
Authors: Varotto-Boccazzi Ilaria , Manenti Alessandro , Dapporto Francesca , Gourlay Louise J. , Bisaglia Beatrice , Gabrieli Paolo , Forneris Federico , Faravelli Silvia , Bollati Valentina , Rubolini Diego , Zuccotti Gianvincenzo , Montomoli Emanuele , Epis Sara , Bandi Claudio
Published: December 2021

To detect and prevent emerging epidemics, discovery platforms are urgently needed, for the rapid development of diagnostic assays. Molecular diagnostic tests for COVID-19 were developed shortly after the isolation of SARS-CoV-2. However, serological tests based on antiviral antibody detection, revealing previous exposure to the virus, required longer testing phases, due to the need to obtain correctly folded and glycosylated antigens. The delay between the identification of a new virus and the development of reliable serodiagnostic tools limits our readiness to tackle future epidemics. We suggest that the protozoanLeishmania tarentolaecan be used as an easy-to-handle microfactory for the rapid production of viral antigens to face emerging epidemics. We engineeredL. tarentolaeto express the SARS-CoV-2 receptor-binding domain (RBD) and we recorded the ability of the purified RBD antigen to detect SARS-CoV-2 infection in human sera, with a sensitivity and reproducibility comparable to that of a reference antigen produced in human cells. This is the first application of an antigen produced inL. tarentolaefor the serodiagnosis of a Coronaviridae infection. On the basis of our results, we proposeL. tarentolaeas an effective system for viral antigen production, even in countries that lack high-technology cell factories.
Cellular ATP Levels Determine the Stability of a Nucleotide Kinase
Authors: Brylski Oliver , Shrestha Puja , Gnutt Patricia , Gnutt David , Mueller Jonathan Wolf , Ebbinghaus Simon
Published: December 2021

The energy currency of the cell ATP, is used by kinases to drive key cellular processes. However, the connection of cellular ATP abundance and protein stability is still under investigation. Using Fast Relaxation Imaging paired with alanine scanning and ATP depletion experiments, we study the nucleotide kinase (APSK) domain of 3′-phosphoadenosine-5′-phosphosulfate (PAPS) synthase, a marginally stable protein. Here, we show that the in-cell stability of the APSK is determined by ligand binding and directly connected to cellular ATP levels. The observed protein stability change for different ligand-bound states or under ATP-depleted conditions ranges from ΔGf0 = -10.7 to +13.8 kJ/mol, which is remarkable since it exceeds changes measured previously, for example upon osmotic pressure, cellular stress or differentiation. The results have implications for protein stability during the catalytic cycle of APS kinase and suggest that the cellular ATP level functions as a global regulator of kinase activity.
Basilar Artery Dolichosis Increases the Risk of Long–Term Recurrence in Patients With Pontine Infarction: A Prospective Cohort Study
Authors: Cao Shugang , Zhu Xiaoxia , Wu Qian , Ni Xiaoxing , He Jun , Cui Ping , Ge Tingting , Wang Jian , Xu Wen'an , Xia Mingwu
Published: December 2021

Background and Purpose: Patients with basilar artery (BA) dolichosis are at high risk of acute pontine infarction (API), but the association between BA dolichosis and long–term stroke recurrence has received little attention. We aimed to identify the effect of BA dolichosis on the risk of long–term brainstem infarction recurrence in patients with API.

Methods: In this prospective cohort study, we enrolled 113 patients with API admitted to our department. BA dolichosis was diagnosed by a BA curve length >29.5 mm or bending length (BL) >10 mm on magnetic resonance angiography. The primary outcome was the occurrence of diffusion–weighted imaging (DWI)–confirmed brainstem infarction. The Cox proportional hazard model was used to detect possible predictors of brainstem infarction recurrence.

Results: Among 113 patients with API, 39 (34.5%) patients had BA dolichosis, and DWI–confirmed brainstem infarction recurred in 15 (13.3%) patients with a mean follow–up time of 31.2 months; the estimated 5–year incidence of brainstem infarction recurrence was 23.1% in patients with BA dolichosis, which was significantly higher than the incidence of 8.1% in patients without BA dolichosis. Cox proportional hazard analysis showed that age ≥65 years (hazard ratio (HR) = 3.341, 95% confidence interval (CI): 1.079–10.348, P = 0.036) and BA dolichosis (HR = 3.048, 95% CI: 1.069–8.693, P = 0.037) were significantly associated with a higher risk of brainstem infarction recurrence. In a subgroup analysis stratified by age, the patients aged ≥65 years with BA dolichosis had a higher risk of brainstem infarction recurrence (HR = 7.319, 95% CI: 1.525–35.123, P = 0.013).

Conclusions: This study indicates that BA dolichosis may increase the risk of long–term brainstem infarction recurrence in patients with API, especially in elderly patients, and therefore warrants more attention in clinical practice.
40 Hz Light Flicker Alters Human Brain Electroencephalography Microstates and Complexity Implicated in Brain Diseases
Authors: Zhang Yiqi , Zhang Zhenyu , Luo Lei , Tong Huaiyu , Chen Fei , Hou Sheng-Tao
Published: December 2021

Previous studies showed that entrainment of light flicker at low gamma frequencies provided neuroprotection in mouse models of Alzheimer’s disease (AD) and stroke. The current study was set to explore the feasibility of using 40 Hz light flicker for human brain stimulation for future development as a tool for brain disease treatment. The effect of 40 Hz low gamma frequency light on a cohort of healthy human brains was examined using 64 channel electroencephalography (EEG), followed by microstate analyses. A random frequency light flicker was used as a negative control treatment. Light flicker at 40 Hz significantly increased the corresponding band power in the O1, Oz, and O3 electrodes covering the occipital areas of both sides of the brain, indicating potent entrainment with 40 Hz light flicker in the visual cortex area. Importantly, the 40 Hz light flicker significantly altered microstate coverage, transition duration, and the Lempel-Ziv complexity (LZC) compared to the rest state. Microstate metrics are known to change in the brains of Alzheimer’s disease, schizophrenia, and stroke patients. The current study laid the foundation for the future development of 40 Hz light flicker as therapeutics for brain diseases.