bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of defensive cadinenes and a novel sesquiterpene synthase responsible for their biosynthesis from the invasive Eupatorium adenophorum
Authors: Liu Yan , Luo Shi‐Hong , Hua Juan , Li De‐Sen , Ling Yi , Luo Qian , Li Sheng‐Hong
Published: September 2020

Eupatorium adenophorum is a malignant invasive plant possessing extraordinary defense potency, but its chemical weaponry and formation mechanism have not yet been extensively investigated.

We identified six cadinene sesquiterpenes, including two volatiles (amorpha‐4,7(11)‐diene and (–)‐amorph‐4‐en‐7‐ol) and four nonvolatiles (9‐oxo‐10,11‐dehydroageraphorone, muurol‐4‐en‐3,8‐dione, 9‐oxo‐ageraphorone and 9β‐hydroxy‐ageraphorone), as the major constitutive and inducible chemicals of E. adenophorum. All cadinenes showed potent antifeedant activity against a generalist insect Spodoptera exigua, indicating that they have significant defensive roles.

We cloned and functionally characterized a sesquiterpene synthase from E. adenophorum (EaTPS1), catalyzing the conversion of farnesyl diphosphate to amorpha‐4,7(11)‐diene and (–)‐amorph‐4‐en‐7‐ol, which were purified from engineered Escherichia coli and identified by extensive nuclear magnetic resonance (NMR) spectroscopy. EaTPS1 was highly expressed in the aboveground organs, which was congruent with the dominant distribution of cadinenes, suggesting that EaTPS1 is likely involved in cadinene biosynthesis. Mechanical wounding and methyl jasmonate negatively regulated EaTPS1 expression but caused the release of amorpha‐4,7(11)‐diene and (–)‐amorph‐4‐en‐7‐ol. Nicotiana benthamiana transiently expressing EaTPS1 also produced amorpha‐4,7(11)‐diene and (–)‐amorph‐4‐en‐7‐ol, and showed enhanced defense function.

The findings presented here uncover the role and formation of the chemical defense mechanism of E. adenophorum – which probably contributes to the invasive success of this plant – and provide a tool for manipulating the biosynthesis of biologically active cadinene natural products.
OsWRKY21 and OsWRKY108 function redundantly to promote phosphate accumulation through maintaining the constitutive expression of OsPHT1;1 under phosphate‐replete conditions
Authors: Zhang Jun , Gu Mian , Liang Ruisuhua , Shi Xinyu , Chen Lingling , Hu Xu , Wang Shichao , Dai Xiaoli , Qu Hongye , Li Huanhuan , Xu Guohua
Published: September 2020

Plant Phosphate Transporter 1 (PHT1) proteins, probably the only influx transporters for phosphate (Pi) uptake, are partially degraded on sufficient Pi levels to prevent excessive Pi accumulation. Therefore, the basal/constitutive expression level of PHT1 genes is vital for maintaining Pi uptake under Pi‐replete conditions.

Rice (Oryza sativa) OsPHT1;1 is a unique gene as it is highly expressed and not responsive to Pi, however the mechanism for maintaining its basal/constitutive expression remains unknown. Using biochemical and genetic approaches, we identified and functionally characterised the transcription factors maintaining the basal/constitutive expression of OsPHT1;1.

OsWRKY21 and OsWRKY108 interact within the nucleus and both bind to the W‐box in the OsPHT1;1 promoter. Overexpression of OsWRKY21 or OsWRKY108 led to increased Pi accumulation, resulting from elevated expression of OsPHT1;1. By contrast, oswrky21 oswrky108 double mutants showed decreased Pi accumulation and OsPHT1;1 expression in a Pi‐dependent manner. Moreover, similar to ospht1;1 mutants, plants expressing the OsWRKY21–SRDX fusion protein (a chimeric dominant suppressor) were impaired in Pi accumulation in Pi‐replete roots, accompanied by downregulation of OsPHT1;1 expression.

Our findings demonstrated that rice WRKY transcription factors function redundantly to promote Pi uptake by activating OsPHT1;1 expression under Pi‐replete conditions, and represent a novel pathway independent of the central Pi signalling system.
Dietetic management of obesity and severe obesity in children and adolescents: A scoping review of guidelines
Authors: Alman Kim L. , Lister Natalie B. , Garnett Sarah P. , Gow Megan L. , Aldwell Katharine , Jebeile Hiba
Published: September 2020

This scoping review describes current guidelines for the dietary management of pediatric obesity and severe obesity. Guidelines were identified via electronic searches of six databases, grey literature, and reference lists and included international clinical practice guidelines (n = 21), position papers (n = 5), and scientific/consensus statements (n = 2) produced by professional bodies and/or expert panels. All recommend multicomponent lifestyle interventions including diet, physical activity, and behavior modification as first‐line treatment. Most guidelines (n = 21) recommend weight loss as a treatment goal for children and adolescents with obesity and associated comorbidities or severe obesity; 15 recommend using dietary approaches. Fourteen of 28 guidelines refer to the management of severe obesity, 10 refer to dietary approaches, and seven recommend using intensive dietary approaches. Dietary approaches to weight loss focus on caloric restriction (n = 14) with some guidelines recommending very low‐energy diet (n = 4), protein‐sparing modified fast (n = 2), and very low‐carbohydrate/ketogenic diets (n = 2). A stronger evidence base is required for dietary management of pediatric obesity and severe obesity to improve consistency in future guidelines. Guidance on the use of dietary approaches, beyond caloric restriction, and in line with the growing evidence base on novel dietary approaches is required to facilitate personalized care and optimal patient outcomes.
Do looks constitute our perceptual evidence?
Authors: Ghijsen Harmen
Published: September 2020

Many philosophers take experience to be an essential aspect of perceptual justification. I argue against a specific variety of such an experientialist view, namely, the Looks View of perceptual justification, according to which our visual beliefs are mediately justified by beliefs about the way things look. I describe three types of cases that put pressure on the idea that perceptual justification is always related to looks‐related reasons: unsophisticated cognizers, multimodal identification, and amodal completion. I then provide a tentative diagnosis of what goes wrong in the Looks View: it ascribes a specific epistemic role to beliefs about looks that is actually fulfilled by subpersonal perceptual processes.
Reasoning with heuristics
Authors: Karlan Brett
Published: September 2020

Which rules should guide our reasoning? Human reasoners often use reasoning shortcuts, called heuristics, which function well in some contexts but lack the universality of reasoning rules like deductive implication or inference to the best explanation. Does it follow that human reasoning is hopelessly irrational? I argue: no. Heuristic reasoning often represents human reasoners reaching a local rational maximum, reasoning more accurately than if they try to implement more ‘ideal’ rules of reasoning. I argue this is a genuine rational achievement. Our ideal rational advisors would advise us to reason with heuristic rules, not more complicated ideal rules. I argue we do not need a radical new account of epistemic norms to make sense of the success of heuristic reasoning.
Fifty years of deleterious external engagement with sub‐Saharan African states
Authors: Feinberg Seth L. , Dalquest Delaney , Myers Rachel
Published: September 2020

Since the end of the colonial era the majority of sub‐Saharan African nations have stagnated or declined on key measures of stability and well‐being. Despite numerous foreign interventions in the form of aid, trade, technical assistance, and military support, students and scholars of modern Africa must recognize that foreign powers have consistently failed in their efforts to prop up, stabilize, and maintain independent nation states. A holistic view of more than 50 years of support for dictatorships, inequitable trade deals, resource extraction, conflict intervention, debt entrapment, and attempts at regime change raises the question as to whether foreign interventions were intentionally disruptive. Modern African nations struggle at the bottom of demographic health and well‐being indicators, and conflicting foreign involvements have often stymied the growth of institutions that serve the majority of citizens' democratic, legal, and financial needs for promoting equitable and sustainable growth.
Characterization of two new HLA alleles, HLA‐A*02:942 and HLA‐DQB1*06:02:47
Authors: Loginova Maria , Makhova Olga , Paramonov Igor
Published: September 2020

Two novel alleles, HLA‐A*02:942 and HLA‐DQB1*06:02:47, are characterized.
Association of the areas over and under the lymphocyte curve with cytomegalovirus reactivation after allogeneic hematopoietic stem cell transplantation
Authors: Kimura Shun‐ichi , Nakamura Yuhei , Kawamura Masakatsu , Takeshita Junko , Kawamura Shunto , Yoshino Nozomu , Misaki Yukiko , Yoshimura Kazuki , Matsumi Shimpei , Gomyo Ayumi , Akahoshi Yu , Tamaki Masaharu , Kusuda Machiko , Kameda Kazuaki , Wada Hidenori , Sato Miki , Tanihara Aki , Nakasone Hideki , Kako Shinichi , Kanda Yoshinobu
Published: September 2020

Background

We retrospectively compared the impact of the areas over and under the lymphocyte curve (L_AOC vs L_AUC) on cytomegalovirus (CMV) reactivation after allogeneic hematopoietic stem cell transplantation (HSCT).

Methods

Among 394 consecutive patients who underwent their first allogeneic HSCT at our center between 2007 and 2018, 301 patients met the inclusion criteria. L_AOC was calculated as the area over the lymphocyte curve during lymphopenia (absolute lymphocyte count [ALC] <700/μL). We calculated L_AOC and L_AUC from day 0 to day 15 (L_AOC15, L_AUC15) and from day 0 to day 30 (L_AOC30, L_AUC30).

Results

CMV antigenemia was defined as more than 3 cells/2 slides by the C10/11 method and detected in 204 cases (CMV reactivation) at a median of 39 days after HSCT. Although there were significant differences in L_AOC15, L_AOC30, L_AUC15, and L_AUC30 between patients with and without CMV reactivation, there was no difference in accuracy for predicting CMV reactivation between L_AOC and L_AUC. In a multivariate analysis, L_AOC15 and L_AUC15 were each identified as independent predictive factors for CMV reactivation, along with advanced age and CMV serostatus. However, ALC at day 14 or day 21 was as accurate as area‐based indexes such as L_AOC15 and L_AUC15. L_AOC15 and L_AUC15 were significantly associated with longer duration of anti‐CMV antiviral therapy while ALC was not.

Conclusions

L_AOC15 and L_AUC15 had similar impacts on CMV reactivation. Although these area‐based indexes were not superior to ALC for predicting CMV reactivation, they might predict patients who need longer duration of antiviral therapy more accurately.
A split strategy to prevent cytomegalovirus after kidney transplantation using prophylaxis in serological high‐risk patients and a pre‐emptive strategy in intermediate‐risk patients: Combining the best of two options?
Authors: Hellemans Rachel , Wijtvliet Veerle , Bergs Kristof , Philipse Ester , Vleut Rowena , Massart Annick , Couttenye Marie‐Madeleine , Matheeussen Veerle , Abramowicz Daniel
Published: September 2020

Background

Cytomegalovirus (CMV) remains an important challenge after kidney transplantation. Current Transplantation Society International Consensus Guidelines recommend antiviral prophylaxis or pre‐emptive therapy for high‐risk CMV‐seronegative recipients with a CMV‐seropositive donor (D+/R−) and moderate‐risk CMV‐seropositive recipients (R+). However, a split strategy according to CMV serostatus is not specifically mentioned.

Methods

We evaluated a split strategy to prevent CMV infection after kidney transplantation in which D+/R− patients received valganciclovir (VGC) prophylaxis for 200 days, and R + patients were treated pre‐emptively according to CMV DNAemia. Patients were followed until 1‐year post‐transplant.

Results

Between April 2014 and March 2018, 40 D+/R− and 92 R + patients underwent kidney transplantation. Forty‐six percent received antithymocyte globulin (ATG) induction, and 98% was treated with calcineurin inhibitors, mycophenolic acid (MPA), and steroids. No D+/R− patient developed CMV disease during prophylaxis (median 200 days), but 15% developed post‐prophylaxis or late‐onset disease. Fifty‐three percent developed neutropenia during prophylaxis, including 16/40 (40%) grade 3 or 4 neutropenia requiring reduction/discontinuation of MPA (30%) and/or VGC (35%), and an occasional need for granulocyte colony‐stimulating factor (5%). In the R + group, 40% received antiviral therapy for a median duration of 21 days; 5% developed early‐onset CMV disease. Only 5% developed neutropenia. D+/R + status (hazard ratio (HR) 2.09,P = .004) and ATG use (HR 2.81, P < .0001) were risk factors for CMV reactivation.

Conclusions

Prophylaxis leads to acceptable CMV control in high‐risk patients but comes with a high risk of neutropenia. Pre‐emptive therapy is effective and limits drug exposure in those at lower risk of CMV.
Gene co‐expression analysis reveals transcriptome divergence between wild and cultivated chickpea under drought stress
Authors: Moenga Susan M. , Gai Yunpeng , Carrasquilla‐Garcia Noelia , Perilla‐Henao Laura M. , Cook Douglas R.
Published: September 2020

Ancestral adaptations in crop wild relatives can provide a genetic reservoir for crop improvement. Here we document physiological changes to mild and severe drought stress, and the associated transcriptome dynamics in both wild and cultivated chickpea. Over 60% of transcriptional changes were related to metabolism, indicating that metabolic plasticity is a core and conserved drought response. In addition, changes in RNA processing and protein turnover were predominant in the data, suggestive of broad restructuring of the chickpea proteome in response to drought. While 12% of the drought‐responsive transcripts have similar dynamics in cultivated and wild accessions, numerous transcripts had expression patterns unique to particular genotypes, or that distinguished wild from cultivated genotypes and whose divergence may be a consequence of domestication. These and other comparisons provide a transcriptional correlate of previously described species' genetic diversity, with wild accessions well differentiated from each other and from cultivars, and cultivars essentially indistinguishable at the broad transcriptome level. We identified metabolic pathways such as phenylpropanoid metabolism, and biological processes such as stomatal development, which are differentially regulated across genotypes with potential consequences on drought tolerance. These data indicate that wild Cicer reticulatum may provide both conserved and divergent mechanisms as a resource in breeding for drought tolerance in cultivated chickpea.
Mechanism and prevention of facial pressure injuries: A novel emergent strategy supported by a multicenter controlled study in frontline healthcare professionals fighting COVID‐19
Authors: Zhang Wen , Liu Xinzhu , Wang Shujun , Cai Jianhua , Niu Yuezeng , Shen Chuan'an
Published: September 2020

Numerous healthcare professionals fighting COVID‐19 worldwide are suffering from the protective respirators related facial pressure injuries. This study explored the mechanism and prevention of such injuries and devised a novel emergent strategy, which was supported by a multicenter self‐controlled study in 1161 frontline healthcare professionals. In this study, according to the anatomy of the face and the characteristics of facial pressure injuries, a respirator liner was designed using a polyurethane foam to redistribute the pressure across the face. A preclinical crossover trial was performed on eight participants to evaluate its efficacy. The strategy was then widely applied among 11  100 healthcare workers in seven frontline hospitals, and 1161 of them were sampled for a questionnaire investigation. The preclinical crossover trial showed that the novel strategy was very effective in preventing facial pressure injuries. The questionnaire investigation showed that pain score, wearing disturbance, and the incidence of pressure injury in the healthcare professionals were significantly correlated with wearing time (all ρ = 0.986). The new strategy significantly reduced the incidence of pressure injury from 84.7% to 11.1%, pain score IQR from 5 (2) to 1 (2), and wearing disturbance rate from 91.6% to 6.3%, and the results analyzed according to individual hospitals or different wearing time showed similar trends (all P < .0005). The protective respirators related facial pressure injuries can be effectively mitigated with this emergent strategy, which has also been applied in some European hospitals and can be popularized to help more healthcare professionals who are combating COVID‐19 on the frontlines.
Synergistic effect of vascular endothelial growth factor gene inactivation in endothelial cells and skeletal myofibres on muscle enzyme activity, capillary supply and endurance exercise in mice
Authors: Sulaeman Alexis , Fine Janelle , de Vargas‐Machuca Aleix , Vitorino Steven A. , Wagner Peter D. , Fruttiger Marcus , Breen Ellen C.
Published: September 2020

New Findings

What is the central question of this study?

Does vascular endothelial growth factor (VEGF) expressed by both endothelial cells and skeletal myofibres maintain the number of skeletal muscle capillaries and regulate endurance exercise?

What is the main finding and its importance?

VEGF expressed by both endothelial cells and skeletal myofibres is not essential for maintaining capillary number but does contribute to exercise performance.

Many chronic diseases lead to exercise intolerance, with loss of skeletal muscle capillaries. While many muscle cell types (myofibres, satellite cells, endothelial cells, macrophages and fibroblasts) express vascular endothelial growth factor (VEGF), most muscle VEGF is stored in myofibre vesicles which can release VEGF to signal VEGF receptor‐expressing cells. VEGF gene ablation in myofibres or endothelial cells alone does not cause capillary regression. We hypothesized that simultaneously deleting the endothelial cell (EC) and skeletal myofibre (Skm) VEGF gene would cause capillary regression and impair exercise performance. This was tested in adult mice by simultaneous conditional deletion of the VEGF gene (Skm/EC‐VEGF−/− mice) through the use of VEGFLoxP, HSA‐Cre‐ERT2 and PDGFb‐iCre‐ERT2 transgenes. These double‐deletion mice were compared to three control groups – WT, EC VEGF gene deletion alone and myofibre VEGF gene deletion alone. Three weeks after initiating gene deletion, Skm/EC‐VEGF−/− mice, but not SkmVEGF−/− or EC‐VEGF−/− mice, reached exhaustion 40 min sooner than WT mice in treadmill tests (P = 0.002). WT, SkmVEGF−/− and EC‐VEGF−/−, but not Skm/EC‐VEGF−/−, mice gained weight over the 3 weeks. Capillary density, fibre area and capillary: fibre ratio in soleus, plantaris, gastrocnemius and cardiac papillary muscle were similar across the groups. Phosphofructokinase and pyruvate dehydrogenase activities increased only in Skm/EC‐VEGF−/− mice. These data suggest that deletion of the VEGF gene simultaneously in endothelial cells and myofibres, while reducing treadmill endurance and despite compensatory augmentation of glycolysis, is not required for muscle capillary maintenance. Reduced endurance remains unexplained, but may possibly be related to a role for VEGF in controlling perfusion of contracting muscle.
Truncating the Pekeris problem
Authors: Evans Richard B.
Published: September 2020

The exact expression for the difference between the acoustic field in an attenuating Pekeris waveguide and the corresponding truncated waveguide is presented. The derivation replaces an earlier version [Evans, J. Acoust. Soc. Am. 74, 193–194 (1983)] that yielded only an approximate estimate of the same difference. The theoretical simplification resulting from the finite truncation is stressed, in contrast to the infinite half-space.
Effect of presentation level and age on release from masking: Behavioral measures
Authors: Faucette Sarah P. , Stuart Andrew
Published: September 2020

The effect of presentation level and age on release from masking (RFM) was examined. Two speech-in-noise paradigms [i.e., fixed speech with varying signal-to-noise ratios (SNRs) and fixed noise with varying speech levels] were employed with competing continuous and interrupted noises. Young and older normal-hearing adults participated (N = 36). Word recognition was assessed at three presentation levels (i.e., 20, 30, and 40 dB sensation level) in SNRs of −10, 0, and 10 dB. Reception thresholds for sentences (RTSs) were determined at three presentation levels (i.e., 55, 65, and 75 dB sound pressure level). RTS SNRs were determined in both noises. RFM was computed by subtracting word recognition scores in continuous noise from interrupted noise and RTS SNRs in interrupted noise from continuous noise. Significant effects of presentation level, group, and SNR were seen with word recognition performance. RFM increased with increasing sensation level, was greater in younger adults, and was superior at −10 dB SNR. With RTS SNRs, significant effects of presentation level and group were found. The findings support the notion that RFM is a level dependent auditory temporal resolution phenomenon and older listeners display a deficit relative to younger listeners.
An Intervention to Support Collegiate Student-Athletes in the Transition to Meaningful Lifetime Physical Activity
Authors: Smith Melinda B. , Gill Diane L. , Reifsteck Erin J.
Published: September 2020

Former student-athletes (SAs) experience unique barriers to maintaining their physical activity, such as loss of team support, less motivation without specific goals, and identity-related changes. Informed by a self-determination theory framework, the authors developed a 6-week Pilates-based intervention to support the physical and psychological wellness of SAs by fostering self-determined motivation and basic psychological needs satisfaction as they make the transition to physically active alumni. In this case study, the authors outline the development and implementation of the program with final-year SAs (N = 12) at a Division III institution. Feasibility was demonstrated through high adherence and positive participant feedback suggesting they valued their experiences in the program and felt more confident in pursuing new forms of physical activity beyond college sports. To extend this type of programming at other institutions, the authors recommend that sport psychology professionals consider unique institutional barriers and opportunities for supporting SAs in their transition to meaningful lifetime activity.
The gene expression network regulating queen brain remodeling after insemination and its parallel use in ants with reproductive workers
Authors: Nagel Manuel , Qiu Bitao , Brandenborg Lisa Eigil , Larsen Rasmus Stenbak , Ning Dongdong , Boomsma Jacobus Jan , Zhang Guojie
Published: September 2020

Ant queen insemination induces brain anatomical and gene regulatory network changes that ants with reproductive workers co-opted.
Polysaccharide length affects mycobacterial cell shape and antibiotic susceptibility
Authors: Justen Alexander M. , Hodges Heather L. , Kim Lili M. , Sadecki Patric W. , Porfirio Sara , Ultee Eveline , Black Ian , Chung Grace S. , Briegel Ariane , Azadi Parastoo , Kiessling Laura L.
Published: September 2020

Within mycobacteria, polysaccharide chain length determines periplasm size and modulates antibiotic susceptibility.
Medial forebrain bundle structure is linked to human impulsivity
Authors: MacNiven Kelly H. , Leong Josiah K. , Knutson Brian
Published: September 2020

Reduced medial forebrain bundle coherence is associated with greater trait impulsivity, as well as stimulant use disorder.
Water-ion permselectivity of narrow-diameter carbon nanotubes
Authors: Li Yuhao , Li Zhongwu , Aydin Fikret , Quan Jana , Chen Xi , Yao Yun-Chiao , Zhan Cheng , Chen Yunfei , Pham Tuan Anh , Noy Aleksandr
Published: September 2020

Small diameter carbon nanotubes show high water-salt permselectivity and low activation barrier for water transport.
Ancient DNA shows domestic horses were introduced in the southern Caucasus and Anatolia during the Bronze Age
Authors: Guimaraes Silvia , Arbuckle Benjamin S. , Peters Joris , Adcock Sarah E. , Buitenhuis Hijlke , Chazin Hannah , Manaseryan Ninna , Uerpmann Hans-Peter , Grange Thierry , Geigl Eva-Maria
Published: September 2020

Paleogenetics reveals that imported domestic horses replaced native wild ones in Transcaucasia and Anatolia before 2000 BCE.
Annexin A1–dependent tethering promotes extracellular vesicle aggregation revealed with single–extracellular vesicle analysis
Authors: Rogers Maximillian A. , Buffolo Fabrizio , Schlotter Florian , Atkins Samantha K. , Lee Lang H. , Halu Arda , Blaser Mark C. , Tsolaki Elena , Higashi Hideyuki , Luther Kristin , Daaboul George , Bouten Carlijn V.C. , Body Simon C. , Singh Sasha A. , Bertazzo Sergio , Libby Peter , Aikawa Masanori , Aikawa Elena
Published: September 2020

Protein-mediated tethering of vesicles in the extracellular matrix contributes to microcalcification formation.
Electrically driven photon emission from individual atomic defects in monolayer WS
2
Authors: Schuler Bruno , Cochrane Katherine A. , Kastl Christoph , Barnard Edward S. , Wong Edward , Borys Nicholas J. , Schwartzberg Adam M. , Ogletree D. Frank , de Abajo F. Javier García , Weber-Bargioni Alexander
Published: September 2020

Electron-stimulated photon emission from individual point defects in monolayer WS
2
could be visualized with atomic resolution.
Neurotoxic peptides from the venom of the giant Australian stinging tree
Authors: Gilding Edward K. , Jami Sina , Deuis Jennifer R. , Israel Mathilde R. , Harvey Peta J. , Poth Aaron G. , Rehm Fabian B. H. , Stow Jennifer L. , Robinson Samuel D. , Yap Kuok , Brown Darren L. , Hamilton Brett R. , Andersson David , Craik David J. , Vetter Irina , Durek Thomas
Published: September 2020

The pain-inducing components of Australian stinging tree venom are miniproteins that modulate voltage-gated sodium channels.
Photopyroelectric microfluidics
Authors: Li Wei , Tang Xin , Wang Liqiu
Published: September 2020

A “magic” wetting-proof hand is presented to navigate, fuse, pinch, and cleave fluids with a beam of light.
Interleukin-2 signals converge in a lymphoid–dendritic cell pathway that promotes anticancer immunity
Authors: Raeber Miro E. , Rosalia Rodney A. , Schmid Dominic , Karakus Ufuk , Boyman Onur
Published: September 2020

IL-2 immunotherapy expands tumor-infiltrating DCs through a lymphoid pathway, favoring the conversion of poorly immunogenic into immunogenic tumors.
Can eating help treat malaria?
Authors: Hurley Jennifer M.
Published: September 2020

The identification of metabolic control of the
Plasmodium
life cycle may open novel avenues for malaria treatment.
Retrospective Review of Clinical Utility of Shotgun Metagenomic Sequencing Testing of Cerebrospinal Fluid from a U.S. Tertiary Care Medical Center
Authors: Rodino Kyle G. , Toledano Michel , Norgan Andrew P. , Pritt Bobbi S. , Binnicker Matthew J. , Yao Joseph D. , Aksamit Allen J. , Patel Robin
Published: September 2020

Shotgun metagenomic sequencing can detect nucleic acids from bacteria, fungi, viruses, and/or parasites in clinical specimens; however, little data exist to guide its optimal application to clinical practice. We retrospectively reviewed results of shotgun metagenomic sequencing testing requested on cerebrospinal fluid samples submitted to an outside reference laboratory from December 2017 through December 2019. Of the 53 samples from Mayo Clinic patients, 47 were requested by neurologists, with infectious diseases consultation in 23 cases.
Antimicrobial Susceptibility and Phylogenetic Relations in a German Cohort Infected with Mycobacterium abscessus
Authors: Wetzstein Nils , Kohl Thomas A. , Schultze Tilman G. , Andres Sönke , Bellinghausen Carla , Hügel Christian , Kempf Volkhard A. J. , Lehn Annette , Hogardt Michael , Serve Hubert , Vehreschild Maria J. G. T. , Wolf Timo , Niemann Stefan , Maurer Florian P. , Wichelhaus Thomas A.
Published: September 2020

Mycobacterium abscessus
is a highly antibiotic-resistant opportunistic pathogen causing clinically challenging infections in patients with preexisting lung diseases or under immunosuppression. Hence, reliable antibiotic susceptibility data are required for effective treatment. Aims of this study were to investigate (i) the congruence of genotypic and phenotypic antimicrobial susceptibility testing, (ii) the relationship between resistance profile and clinical course, and (iii) the phylogenetic relations of
M. abscessus
in a German patient cohort.
Acidic pH-Induced Conformational Changes in Chikungunya Virus Fusion Protein E1: a Spring-Twisted Region in the Domain I-III Linker Acts as a Hinge Point for Swiveling Motion of Domains
Authors: Sahoo Bibekananda , Gudigamolla Naresh Kumar , Chowdary Tirumala Kumar
Published: September 2020

Aedes
mosquito-transmitted viruses such as the Zika, dengue, and chikungunya viruses have spread globally. CHIKV, similar to many other enveloped viruses, enters cells in sequential steps: step 1 involves receptor binding followed by endocytosis, and step 2 involves viral-cell membrane fusion in the endocytic vesicle. The viral envelope surface protein, E1, performs membrane fusion. E1 is triggered to undergo conformational changes by acidic pH of the maturing endosome. Different domains of E1 rearrange during the pre- to postfusion conformation change. Using
in silico
analysis of the E1 structure and different biochemical experiments, we explained a structural mechanism of key conformational changes in E1 triggered by acidic pH. We noted two important structural changes in E1 at acidic pH. In the first, a spring-twisted region in a loop connecting two domains (I and III) untwists, bringing a swiveling motion of domains on each other. In the second, breaking of interactions between domains I and III and domain separation are required for membrane fusion. This knowledge will help devise new therapeutic strategies to block conformation changes in E1 and thus viral entry.
Covalent Modifications of the Bacteriophage Genome Confer a Degree of Resistance to Bacterial CRISPR Systems
Authors: Liu Yuepeng , Dai Li , Dong Junhua , Chen Cen , Zhu Jingen , Rao Venigalla B. , Tao Pan
Published: September 2020

Restriction-modification (R-M) and CRISPR-Cas systems are two well-known defense mechanisms of bacteria. Both recognize and cleave phage DNA at specific sites while protecting their own genomes. It is well accepted that T4 and other phages have evolved counterdefense mechanisms to protect their genomes from R-M cleavage by covalent modifications, such as the hydroxymethylation and glucosylation of cytosine. However, it is unclear whether such genome modifications also provide broad protection against the CRISPR-Cas systems. Our results suggest that genome modifications indeed afford resistance against CRISPR systems. However, the resistance is not complete, and it is also variable, allowing rapid evolution of mutant phages that escape CRISPR pressure. Bacteria in turn could target more than one site on the phage genome to more effectively restrict the infection of ghmC-modified phage. Such defense-counterdefense strategies seem to confer survival advantages to both the organisms, one of the possible reasons for their great diversity.
Complete Genome Sequence of Shewanella chilikensis Strain DC57, Isolated from Corroded Seal Rings at a Floating Oil Production System in Australia
Authors: Salgar-Chaparro Silvia J. , Castillo-Villamizar Genis , Poehlein Anja , Daniel Rolf , Machuca Laura L.
Published: September 2020

Here, we describe the genome of
Shewanella chilikensis
strain DC57, a facultatively anaerobic bacterium isolated from corroded seal rings at a floating oil production system in Australia. The genome of strain DC57 has a size of 4.91 Mbp and harbors 4,178 predicted protein-encoding genes.
Draft Genome Sequences of 171 Listeria monocytogenes Isolates from Food-Related Listeriosis Outbreaks in California from 2007 to 2017
Authors: Wu Cindy H. , Ng Jenny , Kiang David
Published: September 2020

This publication reports the availability of draft genome sequences of 171
Listeria monocytogenes
strains isolated from various food-related sources from California between 2007 and 2017. All isolates contain at least two antimicrobial resistance genes.
Genomic Characterization of Invasive Meningococcal Serogroup B Isolates and Estimation of 4CMenB Vaccine Coverage in Finland
Authors: Bodini Margherita , Brozzi Alessandro , Giuliani Maria , Nohynek Hanna , Vainio Anni , Kuusi Markku , De Paola Rosita , Pizza Mariagrazia , Medini Duccio , Toropainen Maija , Serino Laura , Muzzi Alessandro
Published: September 2020

4CMenB is a 4-component vaccine used against invasive meningococcal disease (IMD) caused by
Neisseria meningitidis
serogroup B (MenB). We investigated the genetic variability of MenB in Finland and evaluated 4CMenB strain coverage by 2 different methods: MATS (meningococcal antigen typing system) and gMATS (genetic MATS). In a set of MenB isolates, 78% (MATS) and 86% (gMATS) were predicted as covered by 4CMenB, suggesting that use of 4CMenB would help reduce IMD incidence in Finland. MATS has been used in 13 countries worldwide, generating information on phenotypic characteristics that could infer protection by 4CMenB. Based on these data and genetic information, gMATS coverage predictions can be made. gMATS predicts coverage consistent with MATS for about 94% of tested strains. Unlike MATS, gMATS does not require live isolates, thus allowing the analysis also of noncultivable strains, making the coverage predictions more accurate. Therefore, gMATS can replace MATS to assess 4CMenB coverage, including in regions with no prior MATS data.
Competitive SARS-CoV-2 Serology Reveals Most Antibodies Targeting the Spike Receptor-Binding Domain Compete for ACE2 Binding
Authors: Byrnes James R. , Zhou Xin X. , Lui Irene , Elledge Susanna K. , Glasgow Jeff E. , Lim Shion A. , Loudermilk Rita P. , Chiu Charles Y. , Wang Taia T. , Wilson Michael R. , Leung Kevin K. , Wells James A.
Published: September 2020

With the emergence and continued spread of the SARS-CoV-2 virus, and of the associated disease, coronavirus disease 2019 (COVID-19), there is an urgent need for improved understanding of how the body mounts an immune response to the virus. Here, we developed a competitive SARS-CoV-2 serological assay that can simultaneously determine whether an individual has developed antibodies against the SARS-CoV-2 Spike protein receptor-binding domain (RBD) and measure the proportion of these antibodies that block interaction with the human angiotensin-converting enzyme 2 (ACE2) required for viral entry. Using this assay and 144 SARS-CoV-2 patient serum samples, we found that a majority of anti-RBD antibodies compete for ACE2 binding. These results not only highlight the need to design vaccines to generate such blocking antibodies but also demonstrate the utility of this assay to rapidly screen patient sera for potentially neutralizing antibodies.
Supplemental Material: Deglacial Kankakee Torrent, source to sink
Authors: Curry B. Brandon , al. et
Published: September 2020

Report for the optically stimulated luminescence dating (OSL) of four samples
Laparoscopic bowel resection in the presence of a lumbo-peritoneal shunt: a rare case
Authors: Neagle Gregg , Bhatti Emma , Hawkins Martyn , Rodger Chris
Published: September 2020

The presence of a cerebrospinal fluid (CSF) shunt was previously considered a contra-indication to laparoscopic surgery, however, case reports appeared that describe laparoscopic surgery proceeding with no adverse outcomes in such patients. The majority of these reports relate to laparoscopic cholecystectomy. Here we present what we believe to be only the second report of a patient undergoing laparoscopic bowel resection in the presence of a lumbo-peritoneal shunt. With this case we aim to add to the evidence that more major laparoscopic procedures can be performed safely in the presence of CSF shunts and with a brief review of the current evidence, have suggested appropriate monitoring and precautionary measures for approaching these procedures.
Opportunistic screening versus usual care for detection of atrial fibrillation in primary care: cluster randomised controlled trial
Authors: Uittenbogaart Steven B , Verbiest-van Gurp Nicole , Lucassen Wim A M , Winkens Bjorn , Nielen Mark , Erkens Petra M G , Knottnerus J André , van Weert Henk C P M , Stoffers Henri E J H
Published: September 2020

Objective

To investigate whether opportunistic screening in primary care increases the detection of atrial fibrillation compared with usual care.

Design

Cluster randomised controlled trial.

Setting

47 intention-to-screen and 49 usual care primary care practices in the Netherlands, not blinded for allocation; the study was carried out from September 2015 to August 2018.

Participants

In each practice, a fixed sample of 200 eligible patients, aged 65 or older, with no known history of atrial fibrillation in the electronic medical record system, were randomly selected. In the intention-to-screen group, 9218 patients eligible for screening were included, 55.0% women, mean age 75.2 years. In the usual care group, 9526 patients were eligible for screening, 54.3% women, mean age 75.0 years.

Interventions

Opportunistic screening (that is, screening in patients visiting their general practice) consisted of three index tests: pulse palpation, electronic blood pressure measurement with an atrial fibrillation algorithm, and electrocardiography (ECG) with a handheld single lead electrocardiographic device. The reference standard was 12 lead ECG, performed in patients with at least one positive index test and in a sample of patients (10%) with three negative tests. If 12 lead ECG showed no atrial fibrillation, patients were invited for more screening by continuous monitoring with a Holter electrocardiograph for two weeks.

Main outcome measures

Difference in the detection rate of newly diagnosed atrial fibrillation over one year in intention-to-screen versus usual care practices.

Results

Follow-up was complete for 8874 patients in the intention-to-screen practices and for 9102 patients in the usual care practices. 144 (1.62%) new diagnoses of atrial fibrillation in the intention-to-screen group versus 139 (1.53%) in the usual care group were found (adjusted odds ratio 1.06 (95% confidence interval 0.84 to 1.35)). Of 9218 eligible patients in the intention-to-screen group, 4106 (44.5%) participated in the screening protocol. In these patients, 12 lead ECG detected newly diagnosed atrial fibrillation in 26 patients (0.63%). In the 266 patients who continued with Holter monitoring, four more diagnoses of atrial fibrillation were found.

Conclusions

Opportunistic screening for atrial fibrillation in primary care patients, aged 65 and over, did not increase the detection rate of atrial fibrillation, which implies that opportunistic screening for atrial fibrillation is not useful in this setting.

Trial registration

Netherlands Trial Register No NL4776 (old NTR4914).
Living with Ulcerative Colitis Study (LUCY) in England: a retrospective study evaluating healthcare resource utilisation and direct healthcare costs of postoperative care in ulcerative colitis
Authors: Brookes Matthew J , Waller John , Cappelleri Joseph C , Modesto Irene , DiBonaventura Marco D , Bohm Natalie , Mokgokong Ruth , Massey Olivia , Wood Robert , Bargo Danielle
Published: September 2020

Objective

Ulcerative colitis (UC) is a lifelong, relapsing-remitting disease. Patients non-responsive to pharmacological treatment may require a colectomy. We estimated pre-colectomy and post-colectomy healthcare resource utilisation (HCRU) and costs in England.

Design/Method

A retrospective, longitudinal cohort study indexing adult patients with UC undergoing colectomy (2009–2015), using linked Clinical Practice Research Datalink/Hospital Episode Statistics data, was conducted. HCRU, healthcare costs and pharmacological treatments were evaluated during 12 months prior to and including colectomy (baseline) and 24 months post-colectomy (follow-up; F-U), comparing baseline/F-U, emergency/elective colectomy and subtotal/full colectomy using descriptive statistics and paired/unpaired tests.

Results

249 patients from 26 165 identified were analysed including 145 (58%) elective and 184 (74%) full colectomies. Number/cost of general practitioner consultations increased post-colectomy (p<0.001), and then decreased at 13–24 months (p<0.05). From baseline to F-U, the number of outpatient visits, number/cost of hospitalisations and total direct healthcare costs decreased (all p<0.01). Postoperative HCRU was similar between elective and emergency colectomies, except for the costs of colectomy-related hospitalisations and medication, which were lower in the elective group (p<0.05). Postoperative costs were higher for subtotal versus full colectomies (p<0.001). At 1–12 month F-U, 30%, 19% and 5% of patients received aminosalicylates, steroids and immunosuppressants, respectively.

Conclusion

HCRU/costs increased for primary care in the first year post-colectomy but decreased for secondary care, and varied according to the colectomy type. Ongoing and potentially unnecessary pharmacological therapy was seen in up to 30% of patients. These findings can inform patients and decision-makers of potential benefits and burdens of colectomy in UC.
Health system resilience in managing the COVID-19 pandemic: lessons from Singapore
Authors: Chua Alvin Qijia , Tan Melisa Mei Jin , Verma Monica , Han Emeline Kai Lin , Hsu Li Yang , Cook Alex Richard , Teo Yik Ying , Lee Vernon J , Legido-Quigley Helena
Published: September 2020

Singapore, one of the first countries affected by COVID-19, adopted a national strategy for the pandemic which emphasised preparedness through a whole-of-nation approach. The pandemic was well contained initially until early April 2020, when there was a surge in cases, attributed to Singapore residents returning from hotspots overseas, and more significantly, rapid transmission locally within migrant worker dormitories. In this paper, we present the response of Singapore to the COVID-19 pandemic based on core dimensions of health system resilience during outbreaks. We also discussed on the surge in cases in April 2020, highlighting efforts to mitigate it. There was: (1) clear leadership and governance which adopted flexible plans appropriate to the situation; (2) timely, accurate and transparent communication from the government; (3) public health measures to reduce imported cases, and detect as well as isolate cases early; (4) maintenance of health service delivery; (5) access to crisis financing; and (6) legal foundation to complement policy measures. Areas for improvement include understanding reasons for poor uptake of government initiatives, such as the mobile application for contact tracing and adopting a more inclusive response that protects all individuals, including at-risk populations. The experience in Singapore and lessons learnt will contribute to pandemic preparedness and mitigation in the future.
Antibiotic overuse in the primary health care setting: a secondary data analysis of standardised patient studies from India, China and Kenya
Authors: Sulis Giorgia , Daniels Benjamin , Kwan Ada , Gandra Sumanth , Daftary Amrita , Das Jishnu , Pai Madhukar
Published: September 2020

Introduction

Determining whether antibiotic prescriptions are inappropriate requires knowledge of patients’ underlying conditions. In low-income and middle-income countries (LMICs), where misdiagnoses are frequent, this is challenging. Additionally, such details are often unavailable for prescription audits. Recent studies using standardised patients (SPs) offer a unique opportunity to generate unbiased prevalence estimates of antibiotic overuse, as the research design involves patients with predefined conditions.

Methods

Secondary analyses of data from nine SP studies were performed to estimate the proportion of SP–provider interactions resulting in inappropriate antibiotic prescribing across primary care settings in three LMICs (China, India and Kenya). In all studies, SPs portrayed conditions for which antibiotics are unnecessary (watery diarrhoea, presumptive tuberculosis (TB), angina and asthma). We conducted descriptive analyses reporting overall prevalence of antibiotic overprescribing by healthcare sector, location, provider qualification and case. The WHO Access–Watch–Reserve framework was used to categorise antibiotics based on their potential for selecting resistance. As richer data were available from India, we examined factors associated with antibiotic overuse in that country through hierarchical Poisson models.

Results

Across health facilities, antibiotics were given inappropriately in 2392/4798 (49.9%, 95% CI 40.8% to 54.5%) interactions in India, 83/166 (50.0%, 95% CI 42.2% to 57.8%) in Kenya and 259/899 (28.8%, 95% CI 17.8% to 50.8%) in China. Prevalence ratios of antibiotic overuse in India were significantly lower in urban versus rural areas (adjusted prevalence ratio (aPR) 0.70, 95% CI 0.52 to 0.96) and higher for qualified versus non-qualified providers (aPR 1.55, 95% CI 1.42 to 1.70), and for presumptive TB cases versus other conditions (aPR 1.19, 95% CI 1.07 to 1.33). Access antibiotics were predominantly used in Kenya (85%), but Watch antibiotics (mainly quinolones and cephalosporins) were highly prescribed in India (47.6%) and China (32.9%).

Conclusion

Good-quality SP data indicate alarmingly high levels of antibiotic overprescription for key conditions across primary care settings in India, China and Kenya, with broad-spectrum agents being excessively used in India and China.