bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impacts of Freshwater Input and Surface Wind Velocity on the Strength and Extent of a Large High Latitude River Plume
Authors: Clark J. Blake , Mannino Antonio
Published: February 2022

Arctic Ocean physical and biogeochemical properties are strongly influenced by freshwater input from land and through the Bering Strait, where the mean currents transport water northward from the Bering Sea. The Yukon River is one of the largest rivers in North America and the Arctic, contributing large quantities of freshwater and terrigenous material to the coastal ocean in the northern Bering Sea. However, a detailed analysis of the coastal hydrodynamics at the outflow of the river has not been conducted in this remote but regionally important river. A three-dimensional hydrodynamic model was built to represent the lower Yukon River and coastal ocean for the ice-free months in 7 years. On average, a large anticyclonic eddy persisted at the main outflow of the Yukon that recirculates water back toward the coast where the currents converge to form a mean northward transport along the delta. Interannual spatial variance in salinity was relatively small, while there was substantial variance in u and v current velocity. u velocity spatial variance was correlated to the volume of freshwater discharge across years, while v velocity spatial variance was correlated to the N–S wind velocity. During strong wind events, plume structure was substantially altered: southerly winds deepened the plume and enhanced northward transport, while northerly winds shoaled and strengthened the pycnocline, and reversed the flow toward the south. The variability in plume dispersion on short time scales due to wind forcing has implications for where terrigenous material is processed in and settles out of the water column.
Acquired Phototrophy and Its Implications for Bloom Dynamics of the Teleaulax-Mesodinium-Dinophysis-Complex
Authors: Anschütz Anna-A. , Flynn Kevin J. , Mitra Aditee
Published: February 2022

The dinoflagellate Dinophysis is responsible for causing diarrhetic shellfish poisoning impacting shellfish aquaculture globally. Dinophysis species are invariably plastidic specialist non-constitutive mixoplankton (pSNCM), combining phagotrophy with acquired phototrophy. Dinophysis acquires phototrophy from another pSNCM, the ciliate Mesodinium, which in turn acquires phototrophy from cryptophytes within the Teleaulax-Plagioselmis-Geminigera clade. Despite this trophic linkage, the temporal dynamics of cryptophyte-Mesodinium-Dinophysis remain poorly understood. In this study, we present the first Teleaulax-Mesodinium-Dinophysis (TMD)-complex system dynamics model. Using this, we explored the dynamics of TMD interactions under different ecological settings. Temperature, nutrient load, mixed layer depth, and irradiance all greatly influenced the timing and magnitude of the TMD-complex interactions and, as a result, Dinophysis bloom duration and peak. Availability of Mesodinium and temporal matching of its growth to that of Dinophysis are also key biotic factors; the timing of Mesodinium availability impacts the potential of Dinophysis growth for up to 3 months. Integrating our TMD-complex model with a suitable hydrodynamic model could greatly improve our understanding of bloom formation and aid in forecasting harmful algal bloom (HAB) events. Future monitoring of Dinophysis would also be enhanced by the monitoring of the precursor prey species, Teleaulax and Mesodinium, which are rarely accorded the same effort as the HAB forming dinoflagellate.
Macrofauna and Nematode Abundance in the Abyssal and Hadal Zones of Interconnected Deep-Sea Ecosystems in the Kuril Basin (Sea of Okhotsk) and the Kuril-Kamchatka Trench (Pacific Ocean)
Authors: Kamenev Gennady M. , Mordukhovich Vladimir V. , Alalykina Inna L. , Chernyshev Alexei V. , Maiorova Anastassya S.
Published: February 2022

The Kuril Basin and the Kuril-Kamchatka Trench are two interconnected deep-sea ecosystems both located in one of the most highly productive regions of the world’s oceans. The main distinguishing features of these deep-sea ecosystems are the low oxygen concentration in the near-bottom water in the Kuril Basin, and the high hydrostatic pressure in the trench. We investigated the abundance of meio- and macrobenthic nematodes and macrofauna on the Kuril Basin floor (depths of 3,300–3,366 m) and in the Kuril-Kamchatka Trench area (depths of 3,432–9,539 m), as well as the influence of some environmental factors on the quantitative distribution of bottom fauna. This was not studied so far. The study also focused on the species composition and quantitative distribution of Polychaeta and Bivalvia, which were dominant in abundance among macrofaunal samples. The main factors influencing the quantitative distribution of macrofauna and nematodes were depth, oxygen concentration, and structure of bottom sediments. The Kuril Basin bottom communities are characterized by a high abundance of nematodes and macrofauna, a high species richness of polychaetes, and a pronounced dominance of small-sized species of Polychaeta and Bivalvia, which are probably more tolerant to low oxygen concentrations. Compared to the Kuril Basin, the Kuril-Kamchatka Trench area (at depths of 3,432–5,741 m) had a more diverse and abundant macrofauna, and a very high abundance of meio- and macrobenthic nematodes. In the trench (at depths more than 6,000 m), the diversity of macrofauna and the abundance of macrobenthic nematodes decreased, while the abundance of macrofauna increased with increasing depth. On the trench floor, the macrofaunal abundance was highest due to the high density of populations of several bivalve and polychaete species, apparently adapted to the high hydrostatic pressure on the trench floor. Obviously, the high primary production of surface waters supports the diverse and abundant deep-sea bottom fauna in the studied areas of the northwestern Pacific. Furthermore, a large number of animals with chemosynthetic endosymbiotic bacteria were found in the bottom communities of the Kuril Basin and the Kuril-Kamchatka Trench. This suggests a significant contribution of chemosynthetic organic carbon to functioning of these deep-sea ecosystems.
Evaluation of the Pink Luminous Breast LED-Based Technology Device as a Screening Tool for the Early Detection of Breast Abnormalities
Authors: Ocasio-Villa Fernando , Morales-Torres Luisa , Velez-Medina Norma , Cubano Luis A. , Orengo Juan C. , Suarez Martinez Edu B.
Published: February 2022

Breast cancer is the leading cause of sex-specific female cancer deaths in the United States. Detection at earlier stages contributes to decreasing the mortality rate. The mammogram is the “Gold Standard” for breast cancer screening with an estimated sensitivity of 86.9% and a specificity of 88.9%. However, these values are negatively affected by the breast density considered a risk factor for developing breast cancer. Herein, we validate the novel LED-based medical device Pink Luminous Breast (PLB) by comparison with the mammogram using a double blinded approach. The PLB works by emitting a LED red light with a harmless spectrum of 640–800 nanometers. This allows the observation of abnormalities represented by dark or shadow areas. In this study, we evaluated the sensitivity and specificity of the PLB device as a screening tool for the early detection of breast abnormalities. Our results show that the PLB device has a high sensitivity (89.6%) and specificity (96.4%) for detecting breast abnormalities comparable to the adjusted mammogram values: 86.3 and 68.9%, respectively. The percentage of presence of breast density was 78.2% using PLB vs. 72.9% with the mammogram. Even with higher findings of breast density, the PLB is still capable of detecting 9.4% of calcifications compared to 6.2% in mammogram results and the reported findings for cysts, masses, or tumor-like abnormalities was higher using the PLB (6.5%) than the mammogram (5.6%). A 100% of the participants felt comfortable using the device without feeling pain or discomfort during the examination with 100% acceptability. The PLB positive validation shows its potential for routine breast screening at non-clinical settings. The PLB provides a rapid, non-invasive, portable, and easy-to-use tool for breast screening that can complement the home-based breast self-examination technique or the clinical breast examination. In addition, the PLB can be conveniently used for screening breasts with surgical implants. PLB provides an accessible and painless breast cancer screening tool. The PLB use is not intended to replace the mammogram for breast screening but rather to use it as an adjunct or complemental tool as part of more efficient earlier detection strategies contributing to decrease mortality rates.
Comparison of a New Optical Biometer That Combines Scheimpflug Imaging With Partial Coherence Interferometry With That of an Optical Biometer Based on Swept-Source Optical Coherence Tomography and Placido-Disk Topography
Authors: Chen Shihao , Zhang Qiaoyue , Savini Giacomo , Zhang Shuangzhe , Huang Xiaomin , Yu Jinjin , Wang Yirang , Ning Rui , Huang Jinhai , Tu Ruixue
Published: February 2022

Purpose

To evaluate measurement precision and to compare the Pentacam AXL (Oculus Optikgeräte, Wetzlar, German), a new optical biometer based on Scheimpflug imaging and partial coherence interferometry (PCI) with that of the OA-2000 biometer (Tomey, Nagoya, Japan), which combines swept-source optical coherence tomography (SS-OCT) and Placido-disk topography.

Methods

Axial length (AL), central corneal thickness (CCT), anterior chamber depth (ACD), aqueous depth (AQD), mean keratometry (Km), astigmatism vectors J0, J45, and corneal diameter (CD) were measured in triplicate by two technical operators. Within-subject standard deviation (Sw), repeatability and reproducibility (2.77 Sw), coefficient of variation (CoV), and intraclass correlation coefficient (ICC) were used to assess the Pentacam AXL intra-observer repeatability and inter-observer reproducibility. Paired t-test and Bland-Altman plots were used to determine the agreement between the two biometers.

Results

The new optical biometer had high intra-observer repeatability [all parameters evaluated had low CoV (<0.71%) and high ICC (>0.88)]. Inter-observer reproducibility was also excellent, with high ICC (>0.95) and low CoV (<0.52%). The 95% LoA between the new biometer and OA-2000 were insignificant for most of the parameters evaluated, especially for AL. However, the measurement agreement was moderate for CCT.

Conclusions

Intra-observer repeatability and inter-observer reproducibility were excellent for all parameters evaluated using the new optical biometer based on Scheimpflug imaging and PCI. There was a high agreement between the two devices and hence could be clinically interchangeable for the measurement of most ocular parameters.
Health Professions Educational Debt: Personal, Professional, and Psychological Impacts 5 Years Post-graduation
Authors: Webster Patrick , North Sara E.
Published: February 2022

Introduction

Cost burden in health professions education is rising. To bridge the gap between growing tuition and stagnating wages, student loans are increasingly obtained to cover educational costs. The spiraling after-effects are a source of acute concern, raising alarms across institutions and occupations. There is little dissemination to date of feasible data collection strategies and outcomes beyond 1 year post-graduation. Research is needed in evaluating the impacts of healthcare educational debt on career and personal choices following transition to practice.

Materials and Methods

This study utilized a cross-sectional, mixed methods design. Doctor of Physical Therapy (DPT) Program graduates 5 years following degree completion completed a quantitative online survey, with topics including debt-to-income ratio, educational debt repayment strategies, impact on personal factors, non-education debt, and perceived value of their health professions education. Subsequent phone interviews were conducted by student researchers to gain insights into alumni perceptions of the impacts of educational debt on personal and professional decision-making. Data analysis involved descriptive and correlational quantitative statistics and open and axial coding of interview constructs.

Results

The mixed methods format was successful in obtaining desired depth of response data. Quantitative findings demonstrated primary factors impacted by educational debt as savings, housing, leisure, discretionary spending, and family planning. Qualitative findings revealed impacts on themes of “personal factors” (81%), “professional factors” (62.5%), and “psychological factors” (56%) 5 years after graduation. Most negatively impacted were housing decisions, hours worked, initial job selection, and ability to save for the future, contributing to decreased mental health wellbeing with anxiety, frustration, and guilt. The majority (75%) of respondents perceived a high degree of value during and following their DPT education, though many expressed discordance between expectations and realities of practice.

Discussion

Findings demonstrate that impacts of health professional educational debt in professional, personal, and psychological factors continue 5 years following degree completion, regardless of debt load. Successful implementation of this pilot methodology indicates potential for use of such extended data collection strategies. Further research is needed at the programs, profession, and/or interprofessional level to garner depth of understanding to guide interventions designed to mitigate or prevent these long-term repercussions.
The Global Status and Trends of Enteropeptidase: A Bibliometric Study
Authors: Yang Xiaoli , Yin Hua , Peng Lisi , Zhang Deyu , Li Keliang , Cui Fang , Xia Chuanchao , Huang Haojie , Li Zhaoshen
Published: February 2022

Background

Enteropeptidase (EP) is a type II transmembrane serine protease and a physiological activator of trypsinogen. Extensive studies related to EP have been conducted to date. However, no bibliometric analysis has systematically investigated this theme. Our study aimed to visualize the current landscape and frontier trends of scientific achievements on EP, provide an overview of the past 120 years and insights for researchers and clinicians to facilitate future collaborative research and clinical intervention.

Methods

Quantitative analysis of publications relating to EP from 1900 to 2020 was interpreted and graphed through the Science Citation Index Expanded of Web of Science Core Collection (limited to SCIE). Microsoft office 2019, GraphPad Prism 8, VOSviewer, and R-bibliometrix were used to conduct the bibliometric analysis.

Results

From 1900 to 2020, a total of 1,034 publications were retrieved. The USA had the largest number of publications, making the greatest contribution to the topic (n = 260, 25.15%). Active collaborations between countries/regions were also enrolled. Grant and Hermontaylor were perhaps the most impactful researchers in the landscape of EP. Protein Expression and Purification and the Journal of Biological Chemistry were the most prevalent (79/1,034, 7.64%) and cited journals (n = 2,626), respectively. Using the top 15 citations and co-citations achievements clarified the theoretical basis of the EP research field. Important topics mainly include the structure of EP, the affective factors for activating substrates by EP, EP-related disorders, and inhibitors of EP.

Conclusion

Based on the bibliometric analysis, we have gained a comprehensive analysis of the global status and research frontiers of studies investigating EP, which provides some guidance and reference for researchers and clinicians engaged in EP research.
Podocyte Endocytosis in Regulating the Glomerular Filtration Barrier
Authors: Tian Xuefei , Bunda Patricia , Ishibe Shuta
Published: February 2022

Endocytosis is a mechanism that internalizes and recycles plasma membrane components and transmembrane receptors via vesicle formation, which is mediated by clathrin-dependent and clathrin-independent signaling pathways. Podocytes are specialized, terminally differentiated epithelial cells in the kidney, located on the outermost layer of the glomerulus. These cells play an important role in maintaining the integrity of the glomerular filtration barrier in conjunction with the adjacent basement membrane and endothelial cell layers within the glomerulus. An intact podocyte endocytic machinery appears to be necessary for maintaining podocyte function. De novo pathologic human genetic mutations and loss-of-function studies of critical podocyte endocytosis genes in genetically engineered mouse models suggest that this pathway contributes to the pathophysiology of development and progression of proteinuria in chronic kidney disease. Here, we review the mechanism of cellular endocytosis and its regulation in podocyte injury in the context of glomerular diseases. A thorough understanding of podocyte endocytosis may shed novel insights into its biological function in maintaining a functioning filter and offer potential targeted therapeutic strategies for proteinuric glomerular diseases.
Case Report: Chronic Lymphocytic Leukemia With Recurrent Complement-Mediated Thrombotic Microangiopathy and C3 Glomerulonephritis
Authors: Ma Tiantian , Wang Hui , Su Tao , Wang Suxia
Published: February 2022

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is a monoclonal B cell lymphocytosis that produces nephrotoxic monoclonal immunoglobulin (MIg). However, the role of MIg in CLL and how it affects CLL patient survival are still unknown. Here, we report a case of MIg with renal significance (MGRS) associated with CLL. A 59-year-old Chinese woman complaining of abdominal pain, skin purpura, and typical soy-colored urine was admitted to the hospital for investigation. Laboratory tests revealed that she had microangiopathic hemolytic anemia, thrombocytopenia, acute kidney injury (AKI), and hypocomplementemia. She also reported cryoglobulinemia, thrombotic microangiopathy (TMA), and AKI 2 years previously. Peripheral blood smears at that time showed 4% schistocytes, a negative Coombs' test, and elevated lactate dehydrogenase (LDH). Based on a diagnosis of complement-mediated TMA, the patient was treated by plasmapheresis and achieved clinical disease remission. However, the serum hypocomplement 4 and cryoglobulinemia persisted. Further investigation showed elevated B lymphocytes and monoclonal serum IgMκ; however, the cryoprecipitate contained monoclonal IgMκ and polyclonal IgG, as well as immunoglobulins κ and λ. After plasmapheresis, her LDH, platelets, and complement 3 (C3) levels returned to normal. Biopsies of the bone marrow and an enlarged subclavicular lymph node revealed CLL/SLL. Renal pathological findings indicated significant arteriolar endothelial cells myxoid edema and glomerular endothelial cells swelling, however no thromboli, cryoglobulin formation and vasculitis were observed. We also found mild mesangial proliferative C3 glomerulonephritis and renal interstitial CLL cells infiltration. Collectively, these clinical and pathological manifestations were attributed to monoclonal IgMκ, which triggered C3 activation. MGRS associated with CLL was finally confirmed. Six cycles of rituximab, cyclophosphamide, verodoxin, and dexamethasone therapy were administered, after which she received ibrutinib. The patient experienced disease remission, and her serum C4 level returned to normal. Cryoglobulin and IgMκ were not detected. This is a special presentation of CLL/SLL with monoclonal IgMκ, which is a type of MGRS. Activation of the complement system by MIg led to TMA with C3 glomerulonephritis. Treatment for TMA and CLL/SLL should be initiated in a timely manner to improve patient prognosis.
Protective Role of Rheumatic Diseases Against Hepatitis B Virus Infection and Human Leukocyte Antigen B27 Highlighted
Authors: Ye Junna , Xie Peilin , Zhou Zhuochao , Sun Yue , Wang Fan , You Yijun , Teng Jialin , Yang Chengde , Zhang Xinxin , Han Yue
Published: February 2022

Background

By determining the hepatitis B virus (HBV) surface antigen (HBsAg) positive rate postexposure and HBV-specific antigen/antibody (Ag/Ab) level in patients with rheumatic diseases, we aimed at exploring the rheumatic link to HBV control.

Methods

Patients who underwent HBV screening in the Ruijin Hospital from 2020 to 2021 were enrolled for the exposure rate estimation. Among antibody to HBV core antigen (HBcAb)-positive patients, we adopted propensity score matching (PSM) to study the impact of rheumatism on HBsAg seroprevalence after exposure. A second PSM evaluated the Ag/Ab differences. We also had HBsAg prevalence in human leukocyte antigen B2 (HLA-B27) tested patients studied.

Results

With 33,989 screened patients, exposure rates remained comparable between rheumatic and non-rheumatic patients: 48.94 vs. 49.86%. PSM first yielded 2,618 balanced pairs. We observed significantly fewer patients with rheumatic diseases in HBsAg positive cases than negative ones (p< 0.001). In the second round, PSM matched 279 pairs, HBsAg (p< 0.001) and HBeAg (p< 0.05) positivity rates were significantly lower in the rheumatic patients, whereas HBsAb positivity rate (p< 0.001) and level (p< 0.01) were significantly higher. Though the value of HBcAb was overall significantly lower (p< 0.001) within the realm of rheumatic diseases, patients with ankylosing spondylitis (AS) demonstrated a significantly higher value than other rheumatic diseases. We saw significantly fewer HBV infections in HLA-B27 positive subjects than in the negative ones (p< 0.001).

Conclusion

In this propensity score-matched study, rheumatic patients had an advantage in HBV control. In rheumatic patients, HBcAb levels, together with the beneficial role of HLA-B27, were highlighted.
Dietary Vitamins A, C, and Potassium Intake Is Associated With Narrower Retinal Venular Caliber
Authors: Edo Ayaka , Ibrahim Diah Gemala , Hirooka Kazuyuki , Toda Rie , Kamaruddin Muhammad Irfan , Kawano Reo , Nagao Akiko , Ohno Haruya , Yoneda Masayasu , Kiuchi Yoshiaki
Published: February 2022

Introduction

The retinal vasculature, a surrogate for the systemic microvasculature, can be observed non-invasively, providing an opportunity to examine the effects of modifiable factors, such as nutrient intake, on microcirculation. We aimed to investigate the possible associations of dietary nutrient intake with the retinal vessel caliber.

Methods

In this cross-sectional study, a total of 584 participants in a medical survey of Japanese descendants living in Los Angeles in 2015 underwent a dietary assessment, fundus photographic examination, and comprehensive physical and blood examinations. Retinal vessel caliber was measured using fundus photographs with a semi-automated computer system and summarized as central retinal artery and vein equivalents (CRAE and CRVE). The association between dietary nutrient intake and retinal vessel caliber was analyzed using a multivariate linear regression model adjusted for two models including potential confounders. The first model was adjusted for age and sex. The second model was adjusted for age, sex, smoking status, body mass index, hypertension, diabetes, dyslipidemia, history of coronary heart disease, and history of stroke.

Results

After adjustment of potential confounders, compared to the quartile with the lowest intake, the difference in CRVE for the highest quartile was −5.33 μm [95% confidence interval (CI): −9.91 to −0.76, P for trend = 0.02] for vitamin A, −4.93 μm (95% CI: −9.54 to −0.32, P for trend = 0.02) for vitamin C and −3.90 μm (95% CI: −8.48 to 0.69, P for trend = 0.04) for potassium.

Conclusions

A significant association was observed between higher vitamins A, C and potassium intakes and narrower retinal venular caliber.
Proteomic Signatures of Antimicrobial Resistance in Yersinia pestis and Francisella tularensis
Authors: Deatherage Kaiser Brooke L. , Birdsell Dawn N. , Hutchison Janine R. , Thelaus Johanna , Jenson Sarah C. , Andrianaivoarimanana Voahangy , Byström Mona , Myrtennäs Kerstin , McDonough Ryelan F. , Nottingham Roxanne D. , Sahl Jason W. , Schweizer Herbert P. , Rajerison Minoarisoa , Forsman Mats , Wunschel David S. , Wagner David M.
Published: February 2022

Antimicrobial resistance (AMR) is a well-recognized, widespread, and growing issue of concern. With increasing incidence of AMR, the ability to respond quickly to infection with or exposure to an AMR pathogen is critical. Approaches that could accurately and more quickly identify whether a pathogen is AMR also are needed to more rapidly respond to existing and emerging biological threats. We examined proteins associated with paired AMR and antimicrobial susceptible (AMS) strains of Yersinia pestis and Francisella tularensis, causative agents of the diseases plague and tularemia, respectively, to identify whether potential existed to use proteins as signatures of AMR. We found that protein expression was significantly impacted by AMR status. Antimicrobial resistance-conferring proteins were expressed even in the absence of antibiotics in growth media, and the abundance of 10–20% of cellular proteins beyond those that directly confer AMR also were significantly changed in both Y. pestis and F. tularensis. Most strikingly, the abundance of proteins involved in specific metabolic pathways and biological functions was altered in all AMR strains examined, independent of species, resistance mechanism, and affected cellular antimicrobial target. We have identified features that distinguish between AMR and AMS strains, including a subset of features shared across species with different resistance mechanisms, which suggest shared biological signatures of resistance. These features could form the basis of novel approaches to identify AMR phenotypes in unknown strains.
Estrogen-Induced Extracellular Calcium Influx Promotes Endometrial Cancer Progress by Regulating Lysosomal Activity and Mitochondrial ROS
Authors: Shen Boqiang , Hao Juan , Lin Yanying , Li Xingchen , Yang Xiao , Huang Ting , Wang Jiaqi , Jia Yuanyuan , Zhou Jingyi , Wang Jianliu
Published: February 2022

Objective

Calcium is present in serum mainly in filterable and bound forms, and Ca2+ is a major key to modulate signaling pathways that control oncogenesis and oncochannels associated with several types of cancer. However, the biological significance of serum calcium and its related mechanism with estrogen in endometrial cancer (EC) still remains elusive. This study aims to ascertain the relationship between serum calcium and clinicopathology in EC.

Methods

Retrospective assessment of a total of 502 patients diagnosed with EC after surgery in Peking University People's Hospital from 2010 to 2018. Preoperative serum ionized calcium and the albumin corrected calcium was calculated in quartiles for various postoperative clinicopathological characteristics, logistic regression adjusted for potential confounders. Intracellular calcium homeostasis change induced by estrogen was detected by confocal analysis. Downstream pathways were analyzed by transcriptome and proteomics. Mitochondrial Ca2+ and ROS (reactive oxygen species) level was detected by confocal and flow cytometry. Lysosomal morphological and membrane changes were verified by confocal or Western blot assays.

Results

High level of albumin-corrected serum calcium was significantly correlated with EC clinicopathological characteristics progression include lymph vascular space invasion, lymph nodes metastasis, myometrial invasion, and cervical invasion. Calcium homeostasis regulated by estrogen in EC cells derived from extracellular calcium influx but not the release of the endoplasmic reticulum. Proteomic and bioinformatic analysis revealed the calcium influx might be involved in the regulation of autophagy and mitochondrial-related pathways. Mechanistic investigation demonstrated that calcium influx acted on the function of mitochondrial ROS and lysosomal activity.

Conclusion

Our findings revealed that serum calcium level was significantly related to poor outcomes. The extracellular calcium influx induced by estrogen was targeted to mitochondrial ROS and lysosome activity, which should be oriented to improve EC therapeutic strategies.
Altered Ecology of the Respiratory Tract Microbiome and Nosocomial Pneumonia
Authors: Pérez-Cobas Ana Elena , Baquero Fernando , de Pablo Raúl , Soriano María Cruz , Coque Teresa M.
Published: February 2022

Nosocomial pneumonia is one of the most frequent infections in critical patients. It is primarily associated with mechanical ventilation leading to severe illness, high mortality, and prolonged hospitalization. The risk of mortality has increased over time due to the rise in multidrug-resistant (MDR) bacterial infections, which represent a global public health threat. Respiratory tract microbiome (RTM) research is growing, and recent studies suggest that a healthy RTM positively stimulates the immune system and, like the gut microbiome, can protect against pathogen infection through colonization resistance (CR). Physiological conditions of critical patients and interventions as antibiotics administration and mechanical ventilation dramatically alter the RTM, leading to dysbiosis. The dysbiosis of the RTM of ICU patients favors the colonization by opportunistic and resistant pathogens that can be part of the microbiota or acquired from the hospital environments (biotic or built ones). Despite recent evidence demonstrating the significance of RTM in nosocomial infections, most of the host-RTM interactions remain unknown. In this context, we present our perspective regarding research in RTM altered ecology in the clinical environment, particularly as a risk for acquisition of nosocomial pneumonia. We also reflect on the gaps in the field and suggest future research directions. Moreover, expected microbiome-based interventions together with the tools to study the RTM highlighting the “omics” approaches are discussed.
Accessory Genome Dynamics of Local and Global Staphylococcus pseudintermedius Populations
Authors: Bruce Spencer A. , Smith Joshua T. , Mydosh Jennifer L. , Ball John , Needle David B. , Gibson Robert , Andam Cheryl P.
Published: February 2022

Staphylococcus pseudintermediusis a major bacterial colonizer and opportunistic pathogen in dogs. Methicillin-resistantS. pseudintermedius(MRSP) continues to emerge as a significant challenge to maintaining canine health. We sought to determine the phylogenetic relationships ofS. pseudintermediusacross five states in the New England region of the United States and place them in a global context. The New England dataset consisted of 125 previously publishedS. pseudintermediusgenomes supplemented with 45 newly sequenced isolates. The core genome phylogenetic tree revealed many deep branching lineages consisting of 142 multi-locus sequence types (STs).In silicodetection of themecAgene revealed 40 MRSP and 130 methicillin-susceptibleS. pseudintermedius(MSSP) isolates. MRSP were derived from five structural types of SCCmec, the mobile genetic element that carries themecAgene conferring methicillin resistance. Although many genomes were MSSP, they nevertheless harbored genes conferring resistance to many other antibiotic classes, including aminoglycosides, macrolides, tetracyclines and penams. We compared the New England genomes to 297 previously published genomes sampled from five other states in the United States and 13 other countries. Despite the prevalence of the clonally expanding ST71 found worldwide and in other parts of the United States, we did not detect it in New England. We next sought to interrogate the combined New England and global datasets for the presence of coincident gene pairs linked to antibiotic resistance. Analysis revealed a large co-circulating accessory gene cluster, which includedmecAas well as eight other resistance genes [aac (6′)-Ie-aph (2″)-Ia, aad (6), aph (3′)-IIIa, sat4, ermB, cat, blaZ, andtetM]. Furthermore, MRSP isolates carried significantly more accessory genes than their MSSP counterparts. Our results provide important insights to the evolution and geographic spread of high-risk clones that can threaten the health of our canine companions.
Clinical Impact of Colistin Banning in Food Animal on mcr-1-Positive Enterobacteriaceae in Patients From Beijing, China, 2009–2019: A Long-Term Longitudinal Observational Study
Authors: Zhao Qian , Li Yiming , Tian Yingxin , Shen Yueyun , Wang Shaolin , Zhang Ying
Published: February 2022

The colistin resistance gene mcr-1 is emerging as a global public health concern, altering the regulation of colistin usage globally since 2017, especially in China. However, few studies have revealed the impact of policy change on the epidemiology of mcr-positive Enterobacteriaceae (MCRPE) in patients. Here, we describe a molecular epidemiological study to investigate the MCRPE in patients in China from 2009–2019. During the surveillance period, 26,080 non-duplicated Enterobacteriaceae isolates were collected in Beijing. Colistin-resistant isolates were screened by enrichment culture supplemented with colistin, and the presence of the mcr gene was determined by PCR amplification. MCRPE isolates were then analyzed by susceptibility testing, genotyping, and risk factor analysis. Of the 26,080 isolates, mcr-1 was detected in 171 (1.1%) of 15,742 Escherichia coli isolates and 7 (0.1%) of 10,338 Klebsiella pneumoniae isolates. The prevalence of mcr-1-positive E. coli (MCRPEC) showed an increasing trend from 2009 to 2016, while a decreasing trend was observed since 2017. Multi-locus sequence typing analysis showed that MCRPEC isolates had extremely diverse genetic backgrounds, and most of these isolates were non-clonal. The prevalence of MCRPE in China remained at a low level, and even showed a declining trend over the last 3 years after the banning of colistin usage as feed additive in food animal in 2017. However, colistin permission in clinical therapy could still increase the risk of MCRPE transmission and intractable infections, active surveillance and monitoring strategies of MCRPE are recommended to prolong the clinical longevity of colistin.
Association Between CD4/CD8 Ratio Recovery and Chronic Kidney Disease Among Human Immunodeficiency Virus-Infected Patients Receiving Antiretroviral Therapy: A 17-Year Observational Cohort Study
Authors: Qin Fengxiang , Lv Qing , Hong Wen , Wei Di , Huang Kui , Lan Ke , Chen Rongfeng , Liu Jie , Liang Bingyu , Liang Huayue , Liang Hao , Qin Shanfang , Ye Li , Jiang Junjun
Published: February 2022

Background:

CD4/CD8 ratio is considered as an emerging biomarker for human immunodeficiency virus (HIV)-related diseases. However, the relationship of CD4/CD8 ratio recovery and chronic kidney disease (CKD), and whether cumulative antiretroviral therapy (ART) is effective in the CD4/CD8 ratio recovery and in reducing CKD incidence among HIV patients remain unclear.

Methods

A 17-year observational cohort study was conducted on all HIV-infected patients receiving ART in Guangxi, China. Kaplan–Meier analysis was used to investigate the cumulative CKD incidence. Cox regression and propensity score matching (PSM) were used to evaluate the association between CD4/CD8 ratio recovery and CKD incidence, and the effect of ART regimens on CD4/CD8 ratio recovery and CKD incidence.

Results

A total of 59,268 eligible individuals contributing 285,143 person-years of follow-up, with an overall CKD incidence of 9.65%. After ART, patients who developed CKD showed higher mortality than those with normal kidney function (12.48 vs. 7.57%, p < 0.001). Patients whose CD4/CD8 ratio did not recover to 0.7 had a higher CKD incidence than the patients who recovered (aHR = 2.84, 95% CI 2.63–3.07), similar to the PSM analysis (aHR = 3.13, 95% CI 2.85–3.45). Compared with the PI-based and INSTI-based regimens, NNRTI-based regimen had a better CD4/CD8 ratio recovery rate (27.04, 16.16, and 29.66%, respectively) and a lower CKD incidence (17.43, 16.16, and 7.31%, respectively).

Conclusion

This large-scale real-world setting provide new evidence that the CD4/CD8 ratio recovery is associated with lower CKD incidence in HIV-infected patients receiving ART. NNRTI-based is a better choice for CD4/CD8 ratio recovery and reducing the risk of CKD.
Identification of Hypericin as a Candidate Repurposed Therapeutic Agent for COVID-19 and Its Potential Anti-SARS-CoV-2 Activity
Authors: Matos Aline da Rocha , Caetano Braulia Costa , de Almeida Filho João Luiz , Martins Jéssica Santa Cruz de Carvalho , de Oliveira Michele Gabrielle Pacheco , Sousa Thiago das Chagas , Horta Marco Aurélio Pereira , Siqueira Marilda Mendonça , Fernandez Jorge Hernandez
Published: February 2022

The COVID-19 pandemic has had an unprecedented impact on the global economy and public health. Its etiologic agent, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly transmissible, pathogenic and has a rapid global spread. Currently, the increase in the number of new confirmed cases has been slowed down due to the increase of vaccination in some regions of the world. Still, the rise of new variants has influenced the detection of additional waves of rising cases that some countries have experienced. Since the virus replication cycle is composed of many distinct stages, some viral proteins related to them, as the main-protease (Mpro) and RNA dependent RNA polymerase (RdRp), constitute individual potential antiviral targets. In this study, we challenged the mentioned enzymes against compounds pre-approved by health regulatory agencies in a virtual screening and later in Molecular Mechanics/Poisson–Bolzmann Surface Area (MM/PBSA) analysis. Our results showed that, among the identified potential drugs with anti-SARS-CoV-2 properties, Hypericin, an important component of the Hypericum perforatum that presents antiviral and antitumoral properties, binds with high affinity to viral Mpro and RdRp. Furthermore, we evaluated the activity of Hypericin anti-SARS-CoV-2 replication in an in vitro model of Vero-E6 infected cells. Therefore, we show that Hypericin inhibited viral replication in a dose dependent manner. Moreover, the cytotoxicity of the compound, in cultured cells, was evaluated, but no significant activity was found. Thus, the results observed in this study indicate that Hypericin is an excellent candidate for repurposing for the treatment of COVID-19, with possible inhibition of two important phases of virus maturation.
Exploration of Diverse Secondary Metabolites From Streptomyces sp. YINM00001, Using Genome Mining and One Strain Many Compounds Approach
Authors: Liu Tao , Ren Zhen , Chunyu Wei-Xun , Li Gui-Ding , Chen Xiu , Zhang Zhou-Tian-Le , Sun Hui-Bing , Wang Mei , Xie Tian-Peng , Wang Meng , Chen Jing-Yuan , Zhou Hao , Ding Zhong-Tao , Yin Min
Published: February 2022

A talented endophytic bacteria strain YINM00001, which showed strong antimicrobial activity and multiple antibiotic resistances, was isolated from a Chinese medicinal herb Peperomia dindygulensis Miq. Phylogenetic analysis based on 16S rRNA gene sequences demonstrated that strain was closely related to Streptomyces anulatus NRRL B-2000T (99.93%). The complete genome of strain YINM00001 was sequenced. The RAxML phylogenomic tree also revealed that strain YINM00001 was steadily clustered on a branch with strain Streptomyces anulatus NRRL B-2000T under the 100 bootstrap values. The complete genome of strain YINM00001 consists of an 8,372,992 bp linear chromosome (71.72 mol% GC content) and a 317,781 bp circular plasmid (69.14 mol% GC content). Genome mining and OSMAC approach were carried out to investigate the biosynthetic potential of producing secondary metabolites. Fifty-two putative biosynthetic gene clusters of secondary metabolites were found, including the putative cycloheximide, dinactin, warkmycin, and anthracimycin biosynthetic gene clusters which consist with the strong antifungal and antibacterial activities exhibited by strain YINM00001. Two new compounds, peperodione (1) and peperophthalene (2), and 17 known compounds were isolated from different fermentation broth. Large amounts and high diversity of antimicrobial and/or anticancer compounds cycloheximide, dinactin, anthracimycin, and their analogs had been found as predicted before, which highlights strain YINM00001 as an ideal candidate for further biosynthetic studies and production improvement of these valuable compounds. Meanwhile, several gene clusters that were highly conserved in several sequenced actinomycetes but significantly different from known gene clusters might be silent under proceeding fermentation conditions. Further studies, such as heterologous expression and genetic modification, are needed to explore more novel compounds from this talented endophytic Streptomyces strain.
Identification of SNAT Family Genes Suggests GhSNAT3D Functional Reponse to Melatonin Synthesis Under Salinity Stress in Cotton
Authors: Zhang Yuexin , Rui Cun , Fan Yapeng , Xu Nan , Zhang Hong , Wang Jing , Sun Liangqing , Dai Maohua , Ni Kesong , Chen Xiugui , Lu Xuke , Wang Delong , Wang Junjuan , Wang Shuai , Guo Lixue , Zhao Lanjie , Feng Xixian , Chen Chao , Ye Wuwei
Published: February 2022

Serotonin N-acetyltransferase (SNAT) is a key enzyme in the biosynthesis of melatonin, and plays an important role in the regulation of melatonin synthesis. The study of SNAT is of great significance to understand the function of melatonin. In this study, we analyzed the structural characteristics, phylogenetic relationship, gene structure, expression pattern, evolutionary relationship and stress response of the members of the SNAT gene family in upland cotton through bioinformatics. A putative Serotonin n-acetyltransferase gene GhSNAT3D was identified, and preliminarily function of GhSNAT3D was verified by virus-induced gene silencing. We identified a total of 52 SNAT genes in the whole genome of G. hirsutum, and part of the GhSNATs were regulated by exogenous melatonin. The content of melatonin, antioxidant enzyme activity and Ca2+ content of GhSNAT3D gene silenced plants decreased, and the salt tolerance of GhSNAT3D gene silenced plants was reduced. Exogenous melatonin supplementation restored the salt tolerance of GhSNAT3D gene silenced plants. GhSNAT3D may interact with GhSNAT25D and ASMT to regulate melatonin synthesis. This study provided an important basis for further study on the regulation of melatonin in cotton against abiotic stress.
Bidirectional Longitudinal Study of Frailty and Depressive Symptoms Among Older Chinese Adults
Authors: Cao Limin , Zhou Yuhan , Liu Huiyuan , Shi Mengyuan , Wei Yingliang , Xia Yang
Published: February 2022

Objective

Frailty and depression, as two common conditions among older adults in China, have been shown to be closely related to each other. The aim of this study was to investigate the bidirectional effects between frailty and depressive symptoms in Chinese population.

Methods

The bidirectional effect of frailty with depressive symptoms was analyzed among 5,303 adults ≥ 60 years of age from the China Health and Retirement Longitudinal Study (CHARLS). Phenotype and a frailty index were used to measure frailty. Depressive symptoms were evaluated using the Epidemiological Studies Depression Scale (CES-D). Logistic regression and Cox proportional hazard regression models were used to determine the bidirectional effects of frailty and depressive symptoms in cross-sectional and cohort studies, respectively. Subgroup and sensitivity analyses were further used to further verify the associations.

Results

In the cross-sectional study, the multivariate-adjusted ORs (95% CIs) for depressive symptoms among pre-frail and frail adults, as defined by the frailty index and phenotype, were 3.05 (2.68–3.49), and 9.78 (8.02–12.03), respectively. Depressed participants showed higher risks of pre-frailty and frailty [frailty index, 3.07 (2.69–3.50); and phenotypic frailty, 9.95 (8.15–12.24)]. During follow-up, the multivariate-adjusted HRs (95% CIs) for depressive symptoms among pre-frail and frail participants, as defined by the frailty index and phenotype, were 1.38 (1.22–1.57), and 1.30 (1.14–1.48), respectively. No significant relationship existed between baseline depressive symptoms and the incidence of frailty. Moreover, the results from subgroup and sensitivity analyses were consistent with the main results.

Conclusion

Although a cross-sectional bidirectional association between depressive symptom and frailty has been observed in older (≥60 years old) Chinese adults, frailty may be an independent predictor for subsequent depression. Moreover, no effect of depressive symptoms on subsequent frailty was detected. Additional bidirectional studies are warranted in China.
Correlation Between Urine Formaldehyde and Cognitive Abilities in the Clinical Spectrum of Alzheimer’s Disease
Authors: Wang Ying , Pan Fengfeng , Xie Fang , He Rongqiao , Guo Qihao
Published: February 2022

Urine-based formaldehyde has been reported to be a potential biomarker for Alzheimer’s disease (AD). However, there is a lack of research about the correlation between urine formaldehyde and cognitive abilities in the clinical spectrum of AD, especially the preclinical period. The relationship of urine formaldehyde with APOE genotype, brain Aβ status and plasma pathological markers in AD are also not clear. This study intends to explore the correlation between urine formaldehyde and cognitive abilities throughout the AD continuum, to evaluate the role of APOE genotype and Aβ accumulation on urine formaldehyde, and further to clarify the relationship between urine formaldehyde level and AD plasma pathological markers. We recruited 72 cognitively normal controls (NC), 110 subjective cognitive decline (SCD), 140 objectively defined subtle cognitive decline (Obj-SCD), 171 mild cognitive impairment (MCI) and 136 AD dementia participants. Next, we collected the data of clinical materials, neuropsychological examination, APOE genotyping, urine formaldehyde concentration, 18F-florbetapir PET imaging and plasma biomarkers. Compared with NC, Obj-SCD and MCI groups, the level of urine formaldehyde was found to be significantly upregulated in SCD group. In addition, the level of urine formaldehyde was significantly higher in AD group compared to both NC and MCI groups. Further subgroup analysis showed that, the level of urine formaldehyde was higher in APOE ε4+ subgroup compared to APOE ε4– subgroup in both NC and AD groups. There was no difference in urine formaldehyde level between the brain Aβ+ subgroup and Aβ– subgroup in each group. In addition, regression analysis showed urine formaldehyde level was correlated with gender, plasma Aβ42 and p-Tau181/T-tau. The dynamic change of urine formaldehyde in the AD continuum could be used as a potential biomarker, and combined with comprehensive cognitive evaluation could become a useful method to distinguish SCD from NC and Obj-SCD, and to distinguish MCI from AD.