bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of a fully automated surgical site infection detection algorithm for use in cardiac and orthopedic surgery research
Authors: Suzuki Hiroyuki , Clore Gosia S. , Perencevich Eli N. , Hockett-Sherlock Stacey M. , Goto Michihiko , Nair Rajeshwari , Branch-Elliman Westyn , Richardson Kelly K. , Gupta Kalpana , Beck Brice F. , Alexander Bruce , Balkenende Erin C. , Schweizer Marin L.
Published: February 2021

Objective:

To develop a fully automated algorithm using data from the Veterans’ Affairs (VA) electrical medical record (EMR) to identify deep-incisional surgical site infections (SSIs) after cardiac surgeries and total joint arthroplasties (TJAs) to be used for research studies.

Design:

Retrospective cohort study.

Setting:

This study was conducted in 11 VA hospitals.

Participants:

Patients who underwent coronary artery bypass grafting or valve replacement between January 1, 2010, and March 31, 2018 (cardiac cohort) and patients who underwent total hip arthroplasty or total knee arthroplasty between January 1, 2007, and March 31, 2018 (TJA cohort).

Methods:

Relevant clinical information and administrative code data were extracted from the EMR. The outcomes of interest were mediastinitis, endocarditis, or deep-incisional or organ-space SSI within 30 days after surgery. Multiple logistic regression analysis with a repeated regular bootstrap procedure was used to select variables and to assign points in the models. Sensitivities, specificities, positive predictive values (PPVs) and negative predictive values were calculated with comparison to outcomes collected by the Veterans’ Affairs Surgical Quality Improvement Program (VASQIP).

Results:

Overall, 49 (0.5%) of the 13,341 cardiac surgeries were classified as mediastinitis or endocarditis, and 83 (0.6%) of the 12,992 TJAs were classified as deep-incisional or organ-space SSIs. With at least 60% sensitivity, the PPVs of the SSI detection algorithms after cardiac surgeries and TJAs were 52.5% and 62.0%, respectively.

Conclusions:

Considering the low prevalence rate of SSIs, our algorithms were successful in identifying a majority of patients with a true SSI while simultaneously reducing false-positive cases. As a next step, validation of these algorithms in different hospital systems with EMR will be needed.
Individual differences and emotional labor: the effects of core self-evaluations on depersonalization
Authors: Pujol-Cols Lucas , Dabos Guillermo E. , Lazzaro-Salazar Mariana
Published: February 2021

This paper examines the role of core self-evaluations (CSEs) in the relationships among emotional demands, emotional dissonance, and depersonalization. Data were collected from a non-random sample of 423 teachers who worked in primary, secondary, and higher education institutions. Results from structural equation modeling analysis showed that CSEs displayed both direct and indirect effects on depersonalization through employees' perceptions and reactions to emotional labor. Specifically, those individuals with more positive CSEs tended to perceive the emotional aspects of their job as less demanding, thus being less likely to experience emotional dissonance and, in turn, depersonalization. This research demonstrated that CSEs play a vital role in explaining employees' reactions to emotional labor and, therefore, their effects should be properly accounted for in future studies. Implications for practice and future lines of research are discussed in this paper.
Nitrogen fertilizer value of animal slurries with different proportions of liquid and solid fractions: A 3-year study under field conditions
Authors: Pedersen Betina Nørgaard , Christensen Bent T. , Bechini Luca , Cavalli Daniele , Eriksen Jørgen , Sørensen Peter
Published: February 2021

The plant availability of manure nitrogen (N) is influenced by manure composition in the year of application whereas some studies indicate that the legacy effect in following years is independent of the composition. The plant availability of N in pig and cattle slurries with variable contents of particulate matter was determined in a 3-year field study. We separated cattle and a pig slurry into liquid and solid fractions by centrifugation. Slurry mixtures with varying proportions of solid and liquid fraction were applied to a loamy sand soil at similar NH4+-N rates in the first year. Yields and N offtake of spring barley and undersown perennial ryegrass were compared to plots receiving mineral N fertilizer. The first year N fertilizer replacement value (NFRV) of total N in slurry mixtures decreased with increasing proportion of solid fraction. The second and third season NFRV averaged 6.5% and 3.8% of total N, respectively, for cattle slurries, and 18% and 7.5% for pig slurries and was not related to the proportion of solid fraction. The estimated net N mineralization of residual organic N increased nearly linearly with growing degree days (GDD) with a rate of 0.0058%/GDD for cattle and 0.0116%/GDD for pig slurries at 2000–5000 GDD after application. In conclusion NFRV of slurry decreased with increasing proportion of solid fraction in the first year. In the second year, NFRV of pig slurry N was significantly higher than that of cattle slurry N and unaffected by proportion between solid and liquid fraction.
Relevance of level IIb neck dissection in patients with papillary thyroid carcinoma
Authors: Hosokawa S , Takahashi G , Okamura J , Imai A , Mochizuki D , Ishikawa R , Takizawa Y , Misawa K , Shinmura K , Mineta H
Published: February 2021

Background

Cervical nodal metastasis is a key prognostic factor in patients with papillary thyroid carcinoma. The role of lymph nodes in papillary thyroid carcinoma management and prognosis remains controversial.

Methods

Level IIb lymph nodes obtained from 44 patients with papillary thyroid carcinoma were histopathologically examined retrospectively. Specimens were classified as ipsilateral or contralateral. The number of dissected nodes and prevalence of level IIb metastasis were compared according to pre-operative clinical nodal stage.

Results

In the node-negative neck, the prevalence of contralateral and ipsilateral IIb nodes was 0 out of 20 and 0 out of 3, respectively. In the node-positive neck, the prevalence of contralateral and ipsilateral IIb nodes was 1 out of 13 (7.70 per cent) and 3 out of 41 (7.32 per cent), respectively. Clinically determined and pathologically confirmed level IIb node negativity were significantly associated. Thirty-four patients (77.3 per cent) developed accessory nerve complications from level IIb dissection.

Conclusion

Level IIb neck dissection for papillary thyroid carcinoma may be required if pre-operative examination reveals multilevel, level IIa or suspicious level IIb metastasis.
Poverty transitions in severe mental illness: longitudinal analysis of social drift in China, 1994–2015
Authors: Yu Yue-Hui , Luo Wei , Liu Bo , Kuang Wei-Hong , Davidson Larry , Wan Chan Cecilia Lai , Lu Lin , Xiang Meng-Ze , Ran Mao-Sheng
Published: February 2021

Background

Although poverty associated with severe mental illness (SMI) has been documented in many studies, little long-term evidence of social drift exists. This study aimed to unravel the poverty transitions among persons with SMI in a fast change community in China.

Methods

Two mental health surveys, using the International Classification of Disease (ICD-10), were conducted in the same six townships of Xinjin county, Chengdu, China in 1994 and 2015. A total of 308 persons with SMI identified in 1994 were followed up in 2015. The profiles of poverty transitions were identified and regression modelling methods were applied to determine the predictive factors of poverty transitions.

Results

The poverty rate of persons with SMI increased from 39.9% to 49.4% in 1994 and 2015. A larger proportion of them had fallen into poverty (27.3%) rather than moved out of it (17.8%). Those persons with SMI who had lost work ability, had physical illness and more severe mental disabilities in 1994, as well as those who had experienced negative changes on these factors were more likely to live in persistent poverty or fall into poverty. Higher education level and medical treatment were major protective factors of falling into poverty.

Conclusions

This study shows long-term evidence on the social drift of persons with SMI during the period of rapid social development in China. Further targeted poverty alleviation interventions should be crucial for improving treatment and mental recovery and alleviating poverty related to SMI.
The development of a measure of orthographic knowledge in the Arabic language: A psychometric evaluation
Authors: Tibi Sana , Fitton Lisa , McIlraith Autumn L.
Published: February 2021

Although Arabic is an official language in 27 countries, standardized measures to assess Arabic literacy are scarce. The purpose of this research was to examine the item functioning of an assessment of Arabic orthographic knowledge. Sixty novel items were piloted with 201 third grade Arabic-speaking students. Participants were asked to identify the correctly spelled word from a pair of two words. Although the assessment was designed to be unidimensional, competing models were tested to determine whether item performance was attributable to multidimensionality. No multidimensional structure fit the data significantly better than the unidimensional model. The 60 original items were evaluated through item fit statistics and comparing performance against theoretical expectations. Twenty-eight items were identified as functioning poorly and were iteratively removed from the scale, resulting in a 32-item set. A value of 0.987 was obtained for McDonald’s coefficient ω from this final scale. Participants’ scores on the measure correlated with an external word reading accuracy measure at 0.79 (p < .001), suggesting that the tool may measure skills important to word reading in Arabic. The task is simple to score and can discriminate among children with below-average orthographic knowledge. This work provides a foundation to develop Arabic literacy assessments.
Food security and food practices in later life: a new model of vulnerability
Authors: Dickinson Angela , Wills Wendy , Kapetanaki Ariadne Beatrice , Ikioda Faith , Godfrey-Smythe Amy , Halliday Sue Vaux
Published: February 2021

The older population is particularly susceptible to malnutrition, which currently affects 1.3 million people aged 65+ in the United Kingdom. Malnutrition is an outcome of food insecurity and despite demographic changes that have led to a rise in numbers of older people, we know very little about how older people become vulnerable to food insecurity. The aim of this study was therefore to explore older people's everyday food practices in order to expose the strengths and challenges within local and national food systems, and better understand how food insecurity might arise in later life. This empirical study operationalised practice theory using a multi-method ethnographic approach with 25 households aged 60–94 years, comprising interviews, observation, visual methods and food logs. A model of vulnerability developed by Schröder-Butterfill and Marianti framed data collection and analysis. Analysis revealed the assets and adaptations older households used to protect themselves from threats to food security. Factors ranging from changes to physical and mental health, and structural factors such as supermarket design, moved households towards food insecurity. Smaller everyday ‘trivia’, e.g. lack of seating and accessible toilets in supermarkets, accumulated to shift people towards vulnerability. Vulnerability is structured by the habitus but is a fluid, relational, temporal and socially constructed state, and people moved towards and away from vulnerability. We have developed a model that accommodates this fluidity, incorporates the concept of ‘cumulative trivia’ and suggests how the ‘aggregation of marginal gains’ could counter-balance and address trivial threats. This model demonstrates to policy makers and those working in public health how vulnerability to food insecurity operates and where interventions could be applied to support households to achieve food security and avoid becoming malnourished.
Stent compression during resuscitation of a neonate with complex heart disease: fatal outcome
Authors: Krasemann Thomas , Verdijk Robert M. , Bartelds Beatrijs
Published: February 2021

A newborn with hypoplastic left heart underwent a Norwood operation. Obstruction of the Blalock–Thomas–Taussig shunt was treated with a stent. During resuscitation, this was compressed, which contributed to a fatal outcome.
Terrorism in Australia: A Decade of Escalating Deaths and Injuries Supporting the Need for Counter-Terrorism Medicine
Authors: Tin Derrick , Hart Alexander , Hertelendy Attila J. , Ciottone Gregory R.
Published: February 2021

Background:

Australia is ranked 71st on the Global Terrorism Index (GTI; 2019), a scoring system of terrorist activities. While it has a relatively low terrorist risk, events globally have wide-ranging repercussions putting first responders and emergency health workers at risk. Counter-Terrorism Medicine (CTM) is rapidly emerging as a sub-specialty needed to address these threats on the front line. This study aims to provide the epidemiological context for the past decade, detailing the unique injury types responders are likely to encounter, and to develop training programs utilizing these data.

Methods:

The Global Terrorism Database (GTD) was searched for all attacks in Australia from the years 2009-2019. Attacks met inclusion criteria if they fulfilled the following terrorism-related criteria as set by the GTD. Ambiguous events were excluded when there was uncertainty as to whether the incident met all of the criteria for inclusion as a GTD terrorist incident. The grey literature was reviewed, and each event was cross-matched with reputable international and national newspaper sources online to confirm or add details regarding weapon type used, and whenever available, details of victim and perpetrator fatalities and injuries.

Results:

Thirty-seven terrorist events occurred in the study time period. Of the thirty-seven incidents, twenty-six (70.2%) involved incendiary weapons, five (13.5%) involved firearms, four (10.8%) involved melee (bladed weapon/knife) attacks, two (5.4%) were explosive/bombing/dynamite attacks, and one (2.7%) was a mixed attack using both incendiary and melee weapons. All except one firearms-related incident (four out of five) resulted in either a fatality or injury or both. Every melee incident resulted in either a fatality or injury or both.

Conclusions:

In the decade from 2009 to 2019, terrorist attacks on Australian soil have been manageable, small-scale incidents with well-understood modalities. Eleven fatalities and fourteen injuries were sustained as a result of terrorist events during that period. Incendiary weapons were the most commonly chosen methodology, followed by firearms, bladed weapons, and explosive/bombings/dynamite attacks.
Cardiovascular Variability and Reactivity in Major Depressive Disorder
Authors: Duschek Stefan , Bair Angela , Hoffmann Alexandra , Marksteiner Josef , Montoro Casandra I. , Reyes del Paso Gustavo A.
Published: February 2021

Abstract. This study investigated cardiovascular variability and stress reactivity in major depressive disorder (MDD). While previous research has documented reduced heart rate variability, knowledge about blood pressure variability in MDD remains scarce. Regarding reactivity, a particular focus was placed on the time courses of the cardiovascular responses, which may provide insight into the autonomic mechanisms underlying the hypo-reactivity expected in MDD. In 76 MDD patients and 71 healthy controls, blood pressure was continuously recorded at rest and during mental stress induced by a 3-min serial subtraction task. Compared to controls, patients exhibited lower systolic and diastolic blood pressure, heart rate variability, and systolic and diastolic blood pressure variability. Moreover, smaller stress-related changes in heart rate, systolic and diastolic blood pressure, and sensitivity of the cardiac baroreflex arose in patients. Cardiovascular parameters did not differ between patients using antidepressants and unmedicated patients. According to time-course analysis, reduced hemodynamic modulations in MDD mainly occurred after 50 s of the stress period. Low heart rate variability in MDD reflects deficient top-down integration of the brain mechanisms allowing flexible autonomic and behavioral control; diminished blood pressure variability is indicative of poor homeostatic capacity with respect to the regulation of blood pressure and organ perfusion. Moreover, blunted cardiovascular reactivity implies poor adjustment of energetic resources to internal and environmental demands and may be a correlate of deficient motivational dynamics characterizing MDD. While cardiovascular hypo-reactivity in MDD may be mediated by baroreflex and adrenergic mechanisms, the fast-acting parasympathetic system may play a subordinate role.
Filling the Gap in Cascadia: The Emergence of Low‐Amplitude Long‐Term Slow Slip
Authors: Nuyen Carolyn P. , Schmidt David A.
Published: February 2021

Long‐term slow slip events have been observed at several subduction zones around the globe, where they play an integral part in strain release along megathrust faults. Nevertheless, evidence for long‐term slow slip has remained elusive in the Cascadia subduction zone. Here we conduct a systematic analysis of 13 years of GNSS time series data from 2006 to 2019 and present evidence of at least one low‐amplitude long‐term slow slip event on the Cascadia subduction zone, with the possibility of others that are less resolved. Starting in mid‐2012, a 1.5‐year transient is observed in southern Cascadia, with a group of coastal GNSS stations moving ∼2 mm to the west. The data are modeled as a Mw 6.4 slow slip event occurring at 15–35 km depth on the plate interface, just updip of previously recognized short‐term slow slip and tremor. The event shares many characteristics with similar long‐term transient events on the Nankai subduction zone. However, the total fault slip amplitude is an order‐of‐magnitude smaller in Cascadia when compared to large events elsewhere, making long‐term slow slip detection challenging in Cascadia. While there are other westward long‐duration transients in the refined data set, the surface displacements are below the level of the noise or are limited spatially to a few neighboring stations, making interpretation unclear.
Seasonal Variation, Degradation, and Bioavailability of Dissolved Organic Matter in the Changjiang Estuary and its Adjacent East China Sea
Authors: Ji Chong‐Xiao , Chen Yan , Yang Gui‐Peng
Published: February 2021

Systematic surveys to examine seasonal variation, degradation, and bioavailability of dissolved organic matter (DOM) in the Changjiang Estuary and the adjacent East China Sea were conducted in July 2016 and February 2017. Concentrations of dissolved organic carbon (DOC) and total hydrolyzable amino acids (THAA) were higher in July than in February. THAA and chlorophyll a (Chl‐a) were positively correlated in July, but not in February. The carbon normalized yields of THAA (THAA‐C%) in surface waters in July and February were not significantly different. However, degradation index (DI) values in the surface water were higher in February than in July. Compared with outer estuary, the inner estuary had lower THAA‐C% and DI values in both surveys. Solar radiation experiments showed that THAA and THAA‐C% values increased with time at station A6‐11 in the oceanic water but declined at C3 in the freshwater, possibly due to the different origins, chemical compositions, or initial degradation states of the DOM at the time of collection. Microbial incubation experiments showed that accumulated DOC and DON in surface waters were bioavailable to the microbial community of the surface layer, but recalcitrant to the microbial fauna from the bottom layer. Leucine (Leu) was selectively consumed, while glycine (Gly), threonine, and alanine appeared to be recalcitrant in summer (July) microbial incubations; and histidine, Gly, and methionine were preferentially consumed, while aspartic acid, serine, phenylalanine, and Leu were recalcitrant in winter (February) incubations.
Danger-associated molecular pattern molecules take unexpectedly a central stage in Nlrp3 inflammasome–caspase-1-mediated trafficking of hematopoietic stem/progenitor cells
Authors: Thapa Arjun , Adamiak Mateusz , Bujko Kamila , Ratajczak Janina , Abdel-Latif Ahmed K. , Kucia Magda , Ratajczak Mariusz Z.
Published: February 2021

Like their homing after transplantation to bone marrow (BM), the mobilization of hematopoietic stem/progenitor cells (HSPCs) is still not fully understood, and several overlapping pathways are involved. Several years ago our group proposed that sterile inflammation in the BM microenvironment induced by pro-mobilizing agents is a driving force in this process. In favor of our proposal, both complement cascade (ComC)-deficient and Nlrp3 inflammasome-deficient mice are poor G-CSF and AMD3100 mobilizers. It is also known that the Nlrp3 inflammasome mediates its effects by activating caspase-1, which is responsible for proteolytic activation of interleukin-1β (IL-1β) and interleukin-18 (IL-18) and their release from cells along with several danger-associated molecular pattern molecules (DAMPs). We observed in the past that IL-1β and IL-18 independently promote mobilization of HSPCs. In the current work we demonstrated that caspase-1-KO mice are poor mobilizers, and, to our surprise, administration of IL-1β or IL-18, as in the case of Nlrp3-KO animals, does not correct this defect. Moreover, neither Caspase-1-KO nor Nlrp3-KO mice properly activated the ComC to execute the mobilization process. Interestingly, mobilization in these animals and activation of the ComC were both restored after injection of the DAMP cocktail eATP+HGMB1+S100A9, the components of which are normally released from cells in an Nlrp3 inflammasome–caspase-1-dependent manner. In addition, we report that caspase-1-deficient HSPCs show a decrease in migration in response to BM homing factors and engraft more poorly after transplantation. These results for the first time identify caspase-1 as an orchestrator of HSPC trafficking.
Organic photovoltaics for simultaneous energy harvesting and high-speed MIMO optical wireless communications
Authors: Tavakkolnia Iman , Jagadamma Lethy K. , Bian Rui , Manousiadis Pavlos P. , Videv Stefan , Turnbull Graham A. , Samuel Ifor D. W. , Haas Harald
Published: February 2021

We show that organic photovoltaics (OPVs) are suitable for high-speed optical wireless data receivers that can also harvest power. In addition, these OPVs are of particular interest for indoor applications, as their bandgap is larger than that of silicon, leading to better matching to the spectrum of artificial light. By selecting a suitable combination of a narrow bandgap donor polymer and a nonfullerene acceptor, stable OPVs are fabricated with a power conversion efficiency of 8.8% under 1 Sun and 14% under indoor lighting conditions. In an optical wireless communication experiment, a data rate of 363 Mb/s and a simultaneous harvested power of 10.9 mW are achieved in a 4-by-4 multiple-input multiple-output (MIMO) setup that consists of four laser diodes, each transmitting 56 mW optical power and four OPV cells on a single panel as receivers at a distance of 40 cm. This result is the highest reported data rate using OPVs as data receivers and energy harvesters. This finding may be relevant to future mobile communication applications because it enables enhanced wireless data communication performance while prolonging the battery life in a mobile device.
Facilitative lysosomal transport of bile acids alleviates ER stress in mouse hematopoietic precursors
Authors: Persaud Avinash K. , Nair Sreenath , Rahman Md Fazlur , Raj Radhika , Weadick Brenna , Nayak Debasis , McElroy Craig , Shanmugam Muruganandan , Knoblaugh Sue , Cheng Xiaolin , Govindarajan Rajgopal
Published: February 2021

Mutations in human equilibrative nucleoside transporter 3 (ENT3) encoded by SLC29A3 results in anemia and erythroid hypoplasia, suggesting that ENT3 may regulate erythropoiesis. Here, we demonstrate that lysosomal ENT3 transport of taurine-conjugated bile acids (TBA) facilitates TBA chemical chaperone function and alleviates endoplasmic reticulum (ER) stress in expanding mouse hematopoietic stem and progenitor cells (HSPCs). Slc29a3−/− HSPCs accumulate less TBA despite elevated levels of TBA in Slc29a3−/− mouse plasma and have elevated basal ER stress, reactive oxygen species (ROS), and radiation-induced apoptosis. Reintroduction of ENT3 allows for increased accumulation of TBA into HSPCs, which results in TBA-mediated alleviation of ER stress and erythroid apoptosis. Transplanting TBA-preconditioned HSPCs expressing ENT3 into Slc29a3−/− mice increase bone marrow repopulation capacity and erythroid pool size and prevent early mortalities. Together, these findings suggest a putative role for a facilitative lysosomal transporter in the bile acid regulation of ER stress in mouse HSPCs which may have implications in erythroid biology, the treatment of anemia observed in ENT3-mutated human genetic disorders, and nucleoside analog drug therapy.
The lytic polysaccharide monooxygenase CbpD promotes Pseudomonas aeruginosa virulence in systemic infection
Authors: Askarian Fatemeh , Uchiyama Satoshi , Masson Helen , Sørensen Henrik Vinther , Golten Ole , Bunæs Anne Cathrine , Mekasha Sophanit , Røhr Åsmund Kjendseth , Kommedal Eirik , Ludviksen Judith Anita , Arntzen Magnus Ø. , Schmidt Benjamin , Zurich Raymond H. , van Sorge Nina M. , Eijsink Vincent G. H. , Krengel Ute , Mollnes Tom Eirik , Lewis Nathan E. , Nizet Victor , Vaaje-Kolstad Gustav
Published: February 2021

The recently discovered lytic polysaccharide monooxygenases (LPMOs), which cleave polysaccharides by oxidation, have been associated with bacterial virulence, but supporting functional data is scarce. Here we show that CbpD, the LPMO of Pseudomonas aeruginosa, is a chitin-oxidizing virulence factor that promotes survival of the bacterium in human blood. The catalytic activity of CbpD was promoted by azurin and pyocyanin, two redox-active virulence factors also secreted by P. aeruginosa. Homology modeling, molecular dynamics simulations, and small angle X-ray scattering indicated that CbpD is a monomeric tri-modular enzyme with flexible linkers. Deletion of cbpD rendered P. aeruginosa unable to establish a lethal systemic infection, associated with enhanced bacterial clearance in vivo. CbpD-dependent survival of the wild-type bacterium was not attributable to dampening of pro-inflammatory responses by CbpD ex vivo or in vivo. Rather, we found that CbpD attenuates the terminal complement cascade in human serum. Studies with an active site mutant of CbpD indicated that catalytic activity is crucial for virulence function. Finally, profiling of the bacterial and splenic proteomes showed that the lack of this single enzyme resulted in substantial re-organization of the bacterial and host proteomes. LPMOs similar to CbpD occur in other pathogens and may have similar immune evasive functions.
Enantioselective construction of six- and seven-membered triorgano-substituted silicon-stereogenic heterocycles
Authors: Chen Shuyou , Mu Delong , Mai Pei-Lin , Ke Jie , Li Yingzi , He Chuan
Published: February 2021

The exploitation of chirality at silicon in asymmetric catalysis is one of the most intriguing and challenging tasks in synthetic chemistry. In particular, construction of enantioenriched mediem-sized silicon-stereogenic heterocycles is highly attractive, given the increasing demand for the synthesis of novel functional-materials-oriented silicon-bridged compounds. Here, we report a rhodium-catalyzed enantioselective construction of six- and seven-membered triorgano-substituted silicon-stereogenic heterocycles. This process undergoes a direct dehydrogenative C−H silylation, giving access to a wide range of triorgano-substituted silicon-stereogenic heterocycles in good to excellent yields and enantioselectivities, that significantly enlarge the chemical space of the silicon-centered chiral molecules. Further elaboration of the chiral monohydrosilane product delivers various corresponding tetraorgano-substituted silicon-stereogenic heterocycles without the loss of enantiopurity. These silicon-bridged heterocycles exhibit bright blue fluorescence, which would have potential application prospects in organic optoelectronic materials.
Control of oviductal fluid flow by the G-protein coupled receptor Adgrd1 is essential for murine embryo transit
Authors: Bianchi Enrica , Sun Yi , Almansa-Ordonez Alexandra , Woods Michael , Goulding David , Martinez-Martin Nadia , Wright Gavin J.
Published: February 2021

Dysfunction of embryo transport causes ectopic pregnancy which affects approximately 2% of conceptions in the US and Europe, and is the most common cause of pregnancy-related death in the first trimester. Embryo transit involves a valve-like tubal-locking phenomenon that temporarily arrests oocytes at the ampullary-isthmic junction (AIJ) where fertilisation occurs, but the mechanisms involved are unknown. Here we show that female mice lacking the orphan adhesion G-protein coupled receptor Adgrd1 are sterile because they do not relieve the AIJ restraining mechanism, inappropriately retaining embryos within the oviduct. Adgrd1 is expressed on the oviductal epithelium and the post-ovulatory attenuation of tubal fluid flow is dysregulated in Adgrd1-deficient mice. Using a large-scale extracellular protein interaction screen, we identified Plxdc2 as an activating ligand for Adgrd1 displayed on cumulus cells. Our findings demonstrate that regulating oviductal fluid flow by Adgrd1 controls embryo transit and we present a model where embryo arrest at the AIJ is due to the balance of abovarial ciliary action and the force of adovarial tubal fluid flow, and in wild-type oviducts, fluid flow is gradually attenuated through Adgrd1 activation to enable embryo release. Our findings provide important insights into the molecular mechanisms involved in embryo transport in mice.
Triptonide is a reversible non-hormonal male contraceptive agent in mice and non-human primates
Authors: Chang Zongliang , Qin Weibing , Zheng Huili , Schegg Kathleen , Han Lu , Liu Xiaohua , Wang Yue , Wang Zhuqing , McSwiggin Hayden , Peng Hongying , Yuan Shuiqiao , Wu Jiabao , Wang Yongxia , Zhu Shenghui , Jiang Yanjia , Nie Hua , Tang Yuan , Zhou Yu , Hitchcock Michael J. M. , Tang Yunge , Yan Wei
Published: February 2021

There are no non-hormonal male contraceptives currently on the market despite decades of efforts toward the development of “male pills”. Here, we report that triptonide, a natural compound purified from the Chinese herbTripterygium Wilfordii Hook Fdisplays reversible male contraceptive effects in both mice and monkeys. Single daily oral doses of triptonide induces deformed sperm with minimal or no forward motility (close to 100% penetrance) and consequently male infertility in 3–4 and 5–6 weeks in mice and cynomolgus monkeys, respectively. Male fertility is regained in ~4–6 weeks after cessation of triptonide intake in both species. Either short- or long-term triptonide treatment causes no discernable systematic toxic side effects based on histological examination of vital organs in mice and hematological and serum biochemical analyses in monkeys. Triptonide appears to target junction plakoglobin and disrupts its interactions with SPEM1 during spermiogenesis. Our data further prove that targeting late spermiogenesis represents an effective strategy for developing non-hormonal male contraceptives.
A rotary mechanism for allostery in bacterial hybrid malic enzymes
Authors: Harding Christopher John , Cadby Ian Thomas , Moynihan Patrick Joseph , Lovering Andrew Lee
Published: February 2021

Bacterial hybrid malic enzymes (MaeB grouping, multidomain) catalyse the transformation of malate to pyruvate, and are a major contributor to cellular reducing power and carbon flux. Distinct from other malic enzyme subtypes, the hybrid enzymes are regulated by acetyl-CoA, a molecular indicator of the metabolic state of the cell. Here we solve the structure of a MaeB protein, which reveals hybrid enzymes use the appended phosphotransacetylase (PTA) domain to form a hexameric sensor that communicates acetyl-CoA occupancy to the malic enzyme active site, 60 Å away. We demonstrate that allostery is governed by a large-scale rearrangement that rotates the catalytic subunits 70° between the two states, identifying MaeB as a new model enzyme for the study of ligand-induced conformational change. Our work provides the mechanistic basis for metabolic control of hybrid malic enzymes, and identifies inhibition-insensitive variants that may find utility in synthetic biology.
Publisher Correction: Rapid 14C excursion at 3372-3371 BCE not observed at two different locations
Authors: Jull A. J. Timothy , Panyushkina Irina P. , Molnár Mihály , Varga Tamás , Wacker Lukas , Brehm Nicolas , Laszló Elemér , Baisan Chris , Salzer Matthew W. , Tegel Willy
Published: February 2021

A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-21647-w
Automating parameter selection to avoid implausible biological pathway models
Authors: Magnano Chris S. , Gitter Anthony
Published: February 2021

A common way to integrate and analyze large amounts of biological “omic” data is through pathway reconstruction: using condition-specific omic data to create a subnetwork of a generic background network that represents some process or cellular state. A challenge in pathway reconstruction is that adjusting pathway reconstruction algorithms’ parameters produces pathways with drastically different topological properties and biological interpretations. Due to the exploratory nature of pathway reconstruction, there is no ground truth for direct evaluation, so parameter tuning methods typically used in statistics and machine learning are inapplicable. We developed the pathway parameter advising algorithm to tune pathway reconstruction algorithms to minimize biologically implausible predictions. We leverage background knowledge in pathway databases to select pathways whose high-level structure resembles that of manually curated biological pathways. At the core of this method is a graphlet decomposition metric, which measures topological similarity to curated biological pathways. In order to evaluate pathway parameter advising, we compare its performance in avoiding implausible networks and reconstructing pathways from the NetPath database with other parameter selection methods across four pathway reconstruction algorithms. We also demonstrate how pathway parameter advising can guide reconstruction of an influenza host factor network. Pathway parameter advising is method agnostic; it is applicable to any pathway reconstruction algorithm with tunable parameters.
Effects of antithrombotic drugs on the results of fecal immunochemical test in colorectal neoplasms screening
Authors: Ibuka Takashi , Adachi Seiji , Horibe Yohei , Ohno Tomohiko , Mabuchi Masatoshi , Suzuki Yusuke , Yamauchi Osamu , Takada Eri , Iwama Midori , Saito Koshiro , Arao Masamichi , Takai Koji , Araki Hiroshi , Shimizu Masahito
Published: February 2021

Fecal immunochemical test (FIT) is widely used as a colorectal cancer screening tool. Antithrombotic drugs may affect the screening performance of FIT for colorectal tumors. The aim of this study was to clarify the effect of antithrombotic agents on FIT accuracy in screening for colorectal neoplasms. This retrospective study enrolled a total of 758 patients who underwent both FIT and total colonoscopy. The effect of antithrombotic drugs on FIT accuracy in detecting colorectal neoplasms (CN), including colorectal cancer (CRC), advanced adenoma (AA), and non-advanced adenoma (NAA), was examined. Of the 758 patients, 144 (19%) received antithrombotic drugs (administration group). In administration group, 61/144 (42%) cases had CN [CRC:14, AA:15, NAA:32] and 217/614 (35%) cases had CN (CRC:43, AA:56, NAA:118) in non-administration group. The prevalence of CN was not significantly different between the two groups (p = 0.1157). There was no significant difference in sensitivity or specificity of the detection of all types of CN with or without taking antithrombotic drugs. Neither the positive predictive value nor negative predictive value of FIT was affected by antithrombotic drug administration. Taking antithrombotic drugs may not have a large impact on sensitivity, specificity, positive predictive value, or negative predictive value of FIT in screening for CN.
Simultaneous absolute quantification and sequencing of fish environmental DNA in a mesocosm by quantitative sequencing technique
Authors: Hoshino Tatsuhiko , Nakao Ryohei , Doi Hideyuki , Minamoto Toshifumi
Published: February 2021

The combination of high-throughput sequencing technology and environmental DNA (eDNA) analysis has the potential to be a powerful tool for comprehensive, non-invasive monitoring of species in the environment. To understand the correlation between the abundance of eDNA and that of species in natural environments, we have to obtain quantitative eDNA data, usually via individual assays for each species. The recently developed quantitative sequencing (qSeq) technique enables simultaneous phylogenetic identification and quantification of individual species by counting random tags added to the 5′ end of the target sequence during the first DNA synthesis. Here, we applied qSeq to eDNA analysis to test its effectiveness in biodiversity monitoring. eDNA was extracted from water samples taken over 4 days from aquaria containing five fish species (Hemigrammocypris neglectus, Candidia temminckii, Oryzias latipes, Rhinogobius flumineus, and Misgurnus anguillicaudatus), and quantified by qSeq and microfluidic digital PCR (dPCR) using a TaqMan probe. The eDNA abundance quantified by qSeq was consistent with that quantified by dPCR for each fish species at each sampling time. The correlation coefficients between qSeq and dPCR were 0.643, 0.859, and 0.786 for H. neglectus, O. latipes, and M. anguillicaudatus, respectively, indicating that qSeq accurately quantifies fish eDNA.
C-reactive protein is a predictive factor for complications after incisional hernia repair using a biological mesh
Authors: Janet Julien , Derbal Sophiane , Durand Fontanier Sylvaine , Bouvier Stephane , Christou Niki , Fabre Anne , Fredon Fabien , Rivaille Thibaud , Valleix Denis , Mathonnet Muriel , Taibi Abdelkader
Published: February 2021

The introduction of biological or absorbable synthetic meshes has provided an alternative to conventional repair for incisional hernia. The ability to predict the development of complications after hernia surgery is important, as it guides surgical planning and patient management. This retrospective study assessed whether the postoperative C-reactive protein (CRP) level can predict complications after incisional hernia repair using biological mesh reinforcement. Patients who underwent incisional hernia repair surgery using biological meshes between February 2009 and February 2015 were screened for study inclusion. Patients included in the study were divided into two groups: those with and without postoperative complications. The two groups were analysed based on sex, surgical operation, length of intensive care unit stay (ICU), complications and mortality. Laboratory values, including white blood cell (WBC) count and CRP levels, were determined preoperatively and up to postoperative day (POD) 10. Postoperative complications requiring further management occurred in 32 of the 60 patients (53.3%). Among 47 patients, the mean CRP and WBC levels were 6.6 mg/L and 9.073 G/L in the group without complications vs. 141.0 mg/L, 16.704 G/L in the group with complications (p < 0.001). Patients with complications also had a longer ICU stay (10.1 vs. 0.6 days, p < 0.0001). A cut-off was 101 mg/L and offered 80.00% sensitivity (IC 61.43% to 92.29) and 95.24% specificity (76.18% to 99.88%) for postoperative complication. The rate of postoperative complications before POD10 was 95% in the group with CRP > 100 mg/L vs. 46% in the group with CRP < 100 mg/L (p = 0.000372). A high postoperative CRP level (> 100 mg/L) up to POD10 may serve as a predictor of postoperative complications in patients undergoing incisional hernia using biological meshes.
Shift a laser beam back and forth to exchange heat and work in thermodynamics
Authors: Albay John A. C. , Zhou Zhi-Yi , Chang Cheng-Hung , Jun Yonggun
Published: February 2021

Although the equivalence of heat and work has been unveiled since Joule’s ingenious experiment in 1845, they rarely originate from the same source in experiments. In this study, we theoretically and experimentally demonstrated how to use a high-precision optical feedback trap to combine the generation of virtual temperature and potential to simultaneously manipulate the heat and work of a small system. This idea was applied to a microscopic Stirling engine consisting of a Brownian particle under a time-varying confining potential and temperature. The experimental results justified the position and the velocity equipartition theorem, confirmed several theoretically predicted energetics, and revealed the engine efficiency as well as its trade-off relation with the output power. The small theory–experiment discrepancy and high flexibility of the swift change of the particle condition highlight the advantage of this optical technique and prove it to be an efficient way for exploring heat and work-related issues in the modern thermodynamics for small systems.
Response of soil N2O emission and nitrogen utilization to organic matter in the wheat and maize rotation system
Authors: Shu Xiaoxiao , Wang Yanqun , Wang Yaling , Ma Yang , Men Mingxin , Zheng Yunpu , Xue Cheng , Peng Zhengping , Noulas Christos
Published: February 2021

The appropriate nitrogen (N) fertilizer regulator could increase N utilization of crops and reduce N losses in the North China Plain. We investigated the effects of reduced inorganic-N rate combined with an organic fertilizer on nitrous oxide (N2O) emissions in winter wheat and summer maize rotation system. Simultaneously studied the effect of different treatments on N use efficiency (NUE), N balance and net income. After reducing the amount of nitrogen fertilizer in the wheat-corn rotation system, the results showed that the cumulative emission of soil N2O from the RN40% + HOM [40% of RN (recommended inorganic-N rate) with homemade organic matter] treatment was 41.0% lower than that of the RN treatment. In addition, the N production efficiency, agronomic efficiency, and apparent utilization were significantly increased by 50.2%, 72.4% and 19.5% than RN, respectively. The use of RN40% + HOM resulted in 22.0 and 30.1% lower soil N residual and N losses as compared with RN. After adding organic substances, soil N2O cumulative emission of RN40% + HOM treatment decreased by 20.9% than that of the HAN (zinc and humic acid urea at the same inorganic-N rate of RN) treatment. The N production efficiency, N agronomic efficiency and NUE of RN40% + HOM treatment were 36.6%, 40.9% and 15.3% higher than HAN’s. Moreover, soil residual and apparent loss N were 23.3% and 18.0% less than HAN’s. The RN40% + HOM treatment appears to be the most effective as a fertilizer control method where it reduced N fertilizer input and its loss to the environment and provided the highest grain yield.
Structural changes in brains of patients with disorders of consciousness treated with deep brain stimulation
Authors: Raguž Marina , Predrijevac Nina , Dlaka Domagoj , Orešković Darko , Rotim Ante , Romić Dominik , Almahariq Fadi , Marčinković Petar , Deletis Vedran , Kostović Ivica , Chudy Darko
Published: February 2021

Disorders of consciousness (DOC) are one of the major consequences after anoxic or traumatic brain injury. So far, several studies have described the regaining of consciousness in DOC patients using deep brain stimulation (DBS). However, these studies often lack detailed data on the structural and functional cerebral changes after such treatment. The aim of this study was to conduct a volumetric analysis of specific cortical and subcortical structures to determine the impact of DBS after functional recovery of DOC patients. Five DOC patients underwent unilateral DBS electrode implantation into the centromedian parafascicular complex of the thalamic intralaminar nuclei. Consciousness recovery was confirmed using the Rappaport Disability Rating and the Coma/Near Coma scale. Brain MRI volumetric measurements were done prior to the procedure, then approximately a year after, and finally 7 years after the implementation of the electrode. The volumetric analysis included changes in regional cortical volumes and thickness, as well as in subcortical structures. Limbic cortices (parahippocampal and cingulate gyrus) and paralimbic cortices (insula) regions showed a significant volume increase and presented a trend of regional cortical thickness increase 1 and 7 years after DBS. The volumes of related subcortical structures, namely the caudate, the hippocampus as well as the amygdala, were significantly increased 1 and 7 years after DBS, while the putamen and nucleus accumbens presented with volume increase. Volume increase after DBS could be a result of direct DBS effects, or a result of functional recovery. Our findings are in accordance with the results of very few human studies connecting DBS and brain volume increase. Which mechanisms are behind the observed brain changes and whether structural changes are caused by consciousness recovery or DBS in patients with DOC is still a matter of debate.
Melanocortin receptor activation alleviates amyloid pathology and glial reactivity in an Alzheimer’s disease transgenic mouse model
Authors: Lau Jackie K. Y. , Tian Min , Shen Yang , Lau Shun-Fat , Fu Wing-Yu , Fu Amy K. Y. , Ip Nancy Y.
Published: February 2021

Alzheimer’s disease (AD) is a devastating neurodegenerative disorder with no disease-modifying treatment. AD progression is characterized by cognitive decline, neuroinflammation, and accumulation of amyloid-beta (Aβ) and neurofibrillary tangles in the brain, leading to neuronal and glial dysfunctions. Neuropeptides govern diverse pathophysiological processes and represent key players in AD pathogenesis, regulating synaptic plasticity, glial cell functions and amyloid pathology. Activation of the pro-opiomelanocortin (POMC)-derived neuropeptide and its receptor from the melanocortin receptor (MCR) family have previously been shown to rescue the impairment in hippocampus-dependent synaptic plasticity in the APP/PS1 mouse model of AD. However, the functional roles of MCR signaling in AD conditions, particularly in glial functions, are largely unknown. In this study, we investigated the potential benefits of MCR activation in AD. In APP/PS1 transgenic mice, we demonstrate that MCR activation mediated by the central administration of its agonist D-Tyr MTII substantially reduces Aβ accumulation, while alleviating global inflammation and astrocytic activation, particularly in the hippocampus. MCR activation prominently reduces the A1 subtype of reactive astrocytes, which is considered a key source of astrocytic neurotoxicity in AD. Concordantly, MCR activation suppresses microglial activation, while enhancing their association with amyloid plaques. The blunted activation of microglia may contribute to the reduction in the neurotoxic phenotypes of astrocytes. Importantly, transcriptome analysis reveals that MCR activation restores the impaired homeostatic processes and microglial reactivity in the hippocampus in APP/PS1 mice. Collectively, our findings demonstrate the potential of MCR signaling as therapeutic target for AD.