bluuebunny/crossref_metadata_2025 huggingface dataset:
Decoy engineering of the receptor‐like cytoplasmic kinase StPBS1 to defend against virus infection in potato
Authors: Bai Runyao , Li Huanhuan , Du Wenjia , Niu Niu , Li Wenxia , Gao Qican , Yao Chongyang , Zhou Zikai , Bao Wenhua , Che Mingjia , Zhao Yongxiu , Zhou Bin , Wang Yaohui , Wuriyanghan Hada
Published: April 2022

Potato virus Y (PVY) is an important pathogen of potato (Solanum tuberosum). Although the PBS1–RPS5 immune system is well documented in Arabidopsis thaliana, it has not been reported in potato. In Arabidopsis, the bacterial effector AvrPphB cleaves AtPBS1 to trigger an immune response. Here, we show that the AvrPphB‐triggered immune response is mediated by StPBS1, a close homologue of AtPBS1 in potato. However, downstream signalling of StPBS1 was mediated by unknown resistance (R) proteins other than potato orthologues of AtRPS5 and HvPBR1, which is important for HvPBS1 signalling in barley. Immune signalling of StPBS1 is mediated by the AvrPphB C‐terminal cleavage domain and an STKPQ motif, in contrast to AtPBS1‐mediated immunity in which both AvrPphB cleavage fragments and an SEMPH motif are essential. The cleavage sequence of AvrPphB in StPBS1 was replaced with that of the PVY NIa‐Pro protease to obtain StPBS1NIa. StPBS1NIa overexpression potato displayed stronger immunity to PVY infection than did the StPBS1 transgenic lines. StPBS1NIa was cleaved at the expected target site by NIa‐Pro protease from PVY. Thus, we characterized the function of StPBS1 in potato immunity and provide a biotechnology control method for PVY via transformation of decoy‐engineered StPBS1NIa.
Digital display use and contact lens wear: Effects on dry eye signs and symptoms
Authors: Talens‐Estarelles Cristian , García‐Marqués José Vicente , Cerviño Alejandro , García‐Lázaro Santiago
Published: April 2022

Purpose

To assess the potential additive effects of short‐term display use and contact lens (CL) wear on the ocular surface and tear film.

Methods

Thirty‐four healthy volunteers (20.87 ± 2.33 years old) participated in this study. Participants' dry eye symptoms, ocular surface, tear film and pupil size were assessed before and after executing a 20‐min reading task on a computer and a smartphone with and without CL wear, or with CL wear and artificial tear instillation. Measurements included the Ocular Surface Disease Index (OSDI) questionnaire; 5‐item Dry Eye Questionnaire (DEQ‐5); tear meniscus height (TMH); noninvasive keratograph break‐up time (NIKBUT); bulbar conjunctival redness (BR) and pupil size.

Results

Higher symptoms were reported after reading on both displays with and without CLs (p ≤ 0.001) for short periods. BR was higher and NIKBUT shorter after reading on the computer regardless of wearing CLs (p ≤ 0.02 and p ≤ 0.02, respectively), while TMH increased for all conditions (p ≤ 0.02) except for CL computer reading (p = 0.23). Reading with CLs did not lead to greater signs of dry eye (BR, NIKBUT) and symptoms compared with reading unaided (p > 0.05), although a smaller increase in TMH was observed when reading on the computer with CLs (p = 0.005). Artificial tear instillation during CL wear led to a smaller increase in symptoms (p ≤ 0.02), a smaller increase in BR (p ≤ 0.04) and a decrease in NIKBUT (p = 0.02) compared to reading without correction.

Conclusions

Disposable CL wear had no additive effects on signs and symptoms of dry eye when using digital devices for short periods. The instillation of artificial tears is an effective strategy for reducing the impact of display use in CL wearers.
Comprehensive transcriptomic analysis of two RIL parents with contrasting salt responsiveness identifies polyadenylated and non‐polyadenylated flower lncRNAs in chickpea
Authors: Kaashyap Mayank , Kaur Sukhjiwan , Ford Rebecca , Edwards David , Siddique Kadambot H.M. , Varshney Rajeev K. , Mantri Nitin
Published: April 2022

Salinity severely affects the yield of chickpea. Understanding the role of lncRNAs can shed light on chickpea salt tolerance mechanisms. However, because lncRNAs are encoded by multiple sites within the genome, their classification to reveal functional versatility at the transcriptional and the post‐transcriptional levels is challenging. To address this, we deep sequenced 24 salt‐challenged flower transcriptomes from two parental genotypes of a RIL population that significantly differ in salt tolerance ability. The transcriptomes for the first time included 12 polyadenylated and 12 non‐polyadenylated RNA libraries to a sequencing depth of ~50 million reads. The ab initio transcriptome assembly comprised ~34 082 transcripts from three biological replicates of salt‐tolerant (JG11) and salt‐sensitive (ICCV2) flowers. A total of 9419 lncRNAs responding to salt stress were identified, 2345 of which were novel lncRNAs specific to chickpea. The expression of poly(A+) lncRNAs and naturally antisense transcribed RNAs suggest their role in post‐transcriptional modification and gene silencing. Notably, 178 differentially expressed lncRNAs were induced in the tolerant genotype but repressed in the sensitive genotype. Co‐expression network analysis revealed that the induced lncRNAs interacted with the FLOWERING LOCUS (FLC), chromatin remodelling and DNA methylation genes, thus inducing flowering during salt stress. Furthermore, 26 lncRNAs showed homology with reported lncRNAs such as COOLAIR, IPS1 and AT4, thus confirming the role of chickpea lncRNAs in controlling flowering time as a crucial salt tolerance mechanism in tolerant chickpea genotype. These robust set of differentially expressed lncRNAs provide a deeper insight into the regulatory mechanisms controlled by lncRNAs under salt stress.
Bifidobacterium breve during infancy attenuates mobility in low birthweight rats
Authors: Itoh Ayaka , Tanaka Nao , Fukunaga Sachiko , Nakano‐Doi Akiko , Matsuyama Tomohiro , Nakagomi Takayuki , Tsuji Masahiro
Published: April 2022

Background

Children with low birthweight (LBW) have a higher risk for developing attention‐deficit/hyperactivity disorder, for which no prophylactic measure exists. The gut microbiota in infants with LBW is different from that in infants with normal birthweight and is associated with attention‐deficit/hyperactivity disorder. Oral supplementation with Bifidobacterium has several health benefits, such as suppressing inflammation.

Methods

We examined the effect of gavage supplementation with Bifidobacterium breve M‐16V from postnatal days 1–21 in a rat model of intrauterine hypoperfusion.

Results

The open‐field test at 5 weeks of age (equivalent to human pubertal age) showed that rats in the LBW‐vehicle group were marginally hyperactive compared with rats in the sham group, while rats in the LBW‐B.breve group were significantly hypoactive compared with rats in the LBW‐vehicle group. The gut microbiota in the LBW‐vehicle group exhibited a profile significantly different from that in the sham group, whereas the gut microbiota in the LBW‐B.breve group did not exhibit a significant difference from that in the sham group. Anatomical/histological evaluation at 6 weeks of age demonstrated that the brain weight and the cerebral areas on coronal sections were reduced in the LBW groups compared with the sham group. Probiotic supplementation did not ameliorate these morphological brain anomalies in LBW animals. The percentage of Iba‐1+ cells in the brain was not different among the LBW‐B.breve, LBW‐vehicle, and sham groups.

Conclusion

Bifidobacterium breve supplementation during early life is suggested to have the potential to help children with LBW attenuate hypermobility in adolescence.
A Sisyphean task: Developing and revising public health nursing competencies
Authors: Canales Mary K. , Drevdahl Denise J.
Published: April 2022

Background

Competencies are intended to enhance the public health workforce's skills. Competencies used to evaluate public health nursing (PHN) practice and education have been promoted by several nursing organizations. Having multiple sets of competencies raises questions about redundancies and their usefulness in evaluating PHN, as well as the central question about the value of the competencies themselves.

Methods

A literature review of psychometric evaluation research of the competencies was performed. Qualitative content analyses were conducted of seven documents: Association of Community Health Nursing Educators’, 2000 and 2010 essentials; Quad Council Coalition's 2004, 2011, and 2018 competencies; and the American Nurses Association's, 2013 and the 2021 draft of PHN scope and standards of practice with respect to competency definition, conceptual basis, and use of an established taxonomy.

Results

No psychometric evaluations of the competency sets were found. Textual content analysis revealed inconsistent and or missing competency definitions and theoretical frameworks with competencies proliferating over time. Taxonomy analysis identified minimal competencies at higher complexity levels according to Bloom's revised taxonomy.

Conclusions

Analyzed competencies lack reliability and validity testing, making assessment difficult for PHN educators and practitioners. Multiple and competing competencies further erode PHN's visibility, even among public health nurses. With unending revisions of PHN competencies and lack of supporting evidence regarding their effect and their integration into education or practice, recommendations for future efforts are offered.
Racially Conditioned Partisans: Exploring How Racial Attitudes Influence Presidential Approval, Issue Competencies, and Vote Choice
Authors: Wright Jamie M.
Published: April 2022

Even in the age of polarization existent today, there are still some partisans that are willing to acknowledge that the out‐party “owns” a subset of issues. But what role does race play in shaping these perceptions? This study posits that racially‐conditioned issue ownership is at play where racial attitudes permeate one's perceptions of which parties can best handle issues where Whites often credit Republicans on racialized issues while non‐Whites often credit Democrats. This study finds that racial attitudes among racially‐conditioned partisans influence perceptions of party's owned issues and shape attitudes toward presidents and vote choice as a result.
Frequency‐domain analysis of fNIRS fluctuations induced by rhythmic mental arithmetic
Authors: Molina‐Rodríguez Sergio , Mirete‐Fructuoso Marcos , Martínez Luis M. , Ibañez‐Ballesteros Joaquín
Published: April 2022

Functional near‐infrared spectroscopy (fNIRS) is an increasingly used technology for imaging neural correlates of cognitive processes. However, fNIRS signals are commonly impaired by task‐evoked and spontaneous hemodynamic oscillations of non‐cerebral origin, a major challenge in fNIRS research. In an attempt to isolate the task‐evoked cortical response, we investigated the coupling between hemodynamic changes arising from superficial and deep layers during mental effort. For this aim, we applied a rhythmic mental arithmetic task to induce cyclic hemodynamic fluctuations suitable for effective frequency‐resolved measurements. Twenty university students aged 18–25 years (eight males) underwent the task while hemodynamic changes were monitored in the forehead using a newly developed NIRS device, capable of multi‐channel and multi‐distance recordings. We found significant task‐related fluctuations for oxy‐ and deoxy‐hemoglobin, highly coherent across shallow and deep tissue layers, corroborating the strong influence of surface hemodynamics on deep fNIRS signals. Importantly, after removing such surface contamination by linear regression, we show that the frontopolar cortex response to a mental math task follows an unusual inverse oxygenation pattern. We confirm this finding by applying for the first time an alternative method to estimate the neural signal, based on transfer function analysis and phasor algebra. Altogether, our results demonstrate the feasibility of using a rhythmic mental task to impose an oscillatory state useful to separate true brain functional responses from those of non‐cerebral origin. This separation appears to be essential for a better understanding of fNIRS data and to assess more precisely the dynamics of the neuro‐visceral link.
Increased phosphorus availability from sewage sludge ashes to maize in a crop rotation with clover
Authors: Wollmann Iris , Möller Kurt
Published: April 2022

A recycling of Phosphorus (P) from the human food chain is mandatory to secure the future P supply for food production. However, many available recycled P fertilizers from sewage sludge do not have an adequate P bioavailability and, thus, are not suitable for their application in soils with pH >5.5–6.0, unless being combined with efficient mobilization measures. The aim of the study was to test the P mobilization ability of red clover (Trifolium pratense L.) from two thermally recycled P fertilizers for a subsequently grown maize. Two sewage sludge ashes (SSA) were investigated in a pot experiment at soil pH 7.5 with red clover differing in its nitrogen (N) supply (added N fertilizer or biological N2 fixation (BNF)), followed by maize (Zea maize L.). Shoot dry matter of maize was almost doubled when N supply of previous grown clover was covered by BNF, instead of receiving added N fertilizer. Similarly, shoot P removal of maize following clover with BNF was significantly increased. It is suggested that the P mobilization is related to the BNF, and a proton release of N2 fixing clover roots led to the measured decrease in soil pH and thereby increased P availability of the tested fertilizers.
MaMYB4 is a negative regulator and a substrate of RING‐type E3 ligases MaBRG2/3 in controlling banana fruit ripening
Authors: Yang Ying‐Ying , Shan Wei , Yang Tian‐Wei , Wu Chao‐Jie , Liu Xun‐Cheng , Chen Jian‐Ye , Lu Wang‐Jin , Li Zheng‐Guo , Deng Wei , Kuang Jian‐Fei
Published: April 2022

Fruit ripening is a complex developmental process, which is modulated by both transcriptional and post‐translational events. Control of fruit ripening is important in maintaining moderate quality traits and minimizing postharvest deterioration. In this study, we discovered that the transcription factor MaMYB4 acts as a negative regulator of fruit ripening in banana. The protein levels of MaMYB4 decreased gradually with banana fruit ripening, paralleling ethylene production, and decline in firmness. DNA affinity purification sequencing combined with RNA‐sequencing analyses showed that MaMYB4 preferentially binds to the promoters of various ripening‐associated genes including ethylene biosynthetic and cell wall modifying genes. Furthermore, ectopic expression of MaMYB4 in tomato delayed tomato fruit ripening, which was accompanied by downregulation of ethylene biosynthetic and cell wall modifying genes. Importantly, two RING finger E3 ligases MaBRG2/3, whose protein accumulation increased progressively with fruit ripening, were found to interact with and ubiquitinate MaMYB4, contributing to decreased accumulation of MaMYB4 during fruit ripening. Transient overexpression of MaMYB4 and MaBRG2/3 in banana fruit ripening delayed or promoted fruit ripening by inhibiting or stimulating ethylene biosynthesis, respectively. Taken together, we demonstrate that MaMYB4 negatively modulates banana fruit ripening, and that MaMYB4 abundance could be regulated by protein ubiquitination, thus providing insights into the role of MaMYB4 in controlling fruit ripening at both transcriptional and post‐translational levels.
Thecellulose synthase‐like F3(CslF3) gene mediates cell wall polysaccharide synthesis and affects root growth and differentiation in barley
Authors: Lou Haoyu , Tucker Matthew R. , Shirley Neil J. , Lahnstein Jelle , Yang Xiujuan , Ma Chao , Schwerdt Julian , Fusi Riccardo , Burton Rachel A. , Band Leah R. , Bennett Malcolm J. , Bulone Vincent
Published: April 2022

The barleycellulose synthase‐like F(CslF) genes encode putative cell wall polysaccharide synthases. They are related to thecellulose synthase(CesA) genes involved in cellulose biosynthesis, and theCslDgenes that influence root hair development. AlthoughCslDgenes are implicated in callose, mannan and cellulose biosynthesis, and are found in both monocots and eudicots,CslFgenes are specific to the Poaceae. Recently the barleyCslF3(HvCslF3) gene was shown to be involved in the synthesis of a novel (1,4)‐β‐linked glucoxylan, but it remains unclear whether this gene contributes to plant growth and development. Here, expression profiling using qRT‐PCR and mRNAin situhybridization revealed thatHvCslF3accumulates in the root elongation zone. SilencingHvCslF3by RNAi was accompanied by slower root growth, linked with a shorter elongation zone and a significant reduction in root system size. Polymer profiling of theRNAilines revealed a significant reduction in (1,4)‐β‐linked glucoxylan levels. Remarkably, the heterologous expression ofHvCslF3in wild‐type (Col‐0) and root hair‐deficient Arabidopsis mutants (csld3andcsld5) complemented thecsld5mutant phenotype, in addition to altering epidermal cell fate. Our results reveal a key role forHvCslF3during barley root development and suggest that members of theCslDandCslFgene families have similar functions during root growth regulation.
Lack of alloimmunization to the D antigen in D‐negative orthotopic liver transplant recipients receiving D‐positive red blood cells perioperatively
Authors: Vijayanarayanan Anjanaa , Wlosinski Lindsey , El‐Bashir Jaber , Galusca Dragos , Nagai Shunji , Yoshida Atsushi , Abouljoud Marwan S. , Otrock Zaher K.
Published: April 2022

Background and Objectives

D‐negative patients undergoing orthotopic liver transplantation (OLT) might require a large number of red blood cell (RBC) units, which can impact the inventory of D‐negative blood. The blood bank might need to supply these patients with D‐positive RBCs because of inventory constraints. This study evaluates the prevalence of anti‐D formation in D‐negative OLT patients who received D‐positive RBCs perioperatively, as this will assist in successful patient blood management.

Materials and Methods

This was a retrospective study performed at a single academic medical centre. Electronic medical records for all 1052 consecutive patients who underwent OLT from January 2007 through December 2017 were reviewed. D‐negative patients who were transfused perioperatively with D‐positive RBCs and had antibody screening at least 30 days after transfusion were included.

Results

Of a total of 155 D‐negative patients, 23 (14.8%) received D‐positive RBCs perioperatively. Seventeen patients were included in the study. The median age was 54 years (range 36–67 years); 13 (76.5%) were male. The median number of D‐positive RBC units transfused perioperatively was 7 (range 1–66 units). There was no evidence of D alloimmunization in any patient after a median serologic follow‐up of 49.5 months (range 31 days to 127.7 months). The average number of antibody screening post OLT was 7.29.

Conclusion

Our study showed that transfusion of D‐positive RBCs in D‐negative OLT recipients is a safe and acceptable practice in the setting of immunosuppression. This practice allows the conservation of D‐negative RBC inventory.
Compression generated by cortical screws in an artificial bone model of an equine medial femoral condylar cyst
Authors: Moreno Caitlin R. , Santschi Elizabeth M. , Janes Jennifer , Liu Jie , Kim Do‐Gyoon , Litsky Alan S.
Published: April 2022

Objective

Determine compression generated by lag and neutral screws over 12 h using two bone analogs.

Study design

Experimental study.

Sample population

Bone analogs were made of composite synthetic bone (CSB) or three‐dimensional printed polylactic acid (PLA). Analogs had a 2 mm exterior shell with a 10 mm thick internal layer of open‐cell material.

Methods

Bone analogs were opposed, making a 4‐sided box with open ends. A central channel contained the sensor and the screws passed through it to engage both paired analogs. Four screw/analog conditions were tested: neutral and lag screw with bicortical engagement, neutral and lag screw with unicortical engagement. All screws were tightened to 2 Nm torque and compression values recorded at 0, 0.5, 1, 2, 6, and 12 h (six trials per condition). Medians were compared across groups for statistical significance.

Results

There was no difference in median compression between lag and neutral bicortical screws. For PLA, greater median compression was generated by neutral (median 437 N) and lag (median 379 N) bicortical screws compared to neutral unicortical screws (median 208 N, p < .001); lag bicortical screws generated greater median compression than lag unicortical screws (median 265 N, p = .012). For CSB, lag bicortical screws (median 293 N) generated greater median compression than neutral unicortical screws (median 228 N, p = .008).

Conclusion

Lag and neutral screws generated similar compression. Bicortical screws had higher median compression than unicortical screws in bone analogs.

Clinical significance

Neutral screws generate compression in cancellous bone analogs that can be increased with bicortical bone engagement.
Tribo-Erosion Performance of GFRP Composite Panels in Both Offshore and Onshore Environmental Conditions
Authors: Singh Amanpreet , Singh Gurmeet , Kumar Satish , Sehgal Satbir S.
Published: April 2022

The erosion wear due to raindrop plays a vital role in the service life of wind turbine components, especially blades. Furthermore, the rain impact angle and the environmental conditions have a major impact on erosion wear. In the present work, the rain erosion performance of glass fiber reinforced polyester (GFRP) blade material in offshore and onshore environmental conditions has been studied. A whirling arm test rig was created and used to conduct the erosion tests on both offshore and onshore conditions. To simulate the offshore and onshore environmental conditions, experiments were carried out using both fresh and saltwater. The trail runs were carried out for time duration (30–90 min) at different impact angles (0—90 deg) by running the whirling arm tester at different impact velocities (30–70 m/s). During the experimentation, the impact velocity varied from 30 to 70 m/s. The impact angle was taken as 0 deg, 30 deg, 45 deg, 60 deg, and 90 deg, respectively. The results showed that erosion wear in the offshore conditions was more in all the cases as compared to onshore conditions. Furthermore, the maximum mass loss was at 45-deg impact angles for both conditions, which was further endorsed by Scanning Electron Microscope (SEM) analysis. Very little work has been reported on the optimization of erosion wear response of Offshore and Onshore wind turbines by using different design of experiment techniques. The erosion testing reveals that the GFRP blades exhibit a ductile erosion mechanism, which was further explained by using three-dimensional surface plots with the help of Image J software.
Wear Analysis and Tool Life Modeling in Micro Drilling of Inconel 718 Superalloy
Authors: Agrawal Vipul , Gajrani Kishor Kumar , Mote Rakesh G. , Barshilia Harish C. , Joshi Suhas S.
Published: April 2022

Aircraft engine parts, specifically blades, discs, and sheets are primarily made up of Inconel 718, which required drilled holes for assembly. Drilling holes in Inconel 718 is very difficult due to its high hardness, especially microdrilling. The primary studies majorly used uncoated drills for microdrilling Inconel 718, which leads to low tool life due to frequent tool wear. Microdrills bearing different coatings have not been investigated for their efficiency and mechanism of wear in microdrilling of super alloys. Also, time-dependent prediction of cutting tool wear has not been addressed adequately. In this study, a theoretical model to predict tool wear in drilling as a function of time and to evaluate tool life of anti-abrasion-, TiAlSiN-, and TiAlN-coated drills are presented. Considering feed rate and cutting speed as independent variables microdrilling experiments were conducted. In addition, the model estimates the progression of abrasion wear in various sections of the drill and the section with highest wear-rate was considered for calculation of drill life. Life of uncoated and coated drills were also calculated using a failure criterion of 31.3 μm and Taylor’s tool life exponents. Finally, a comparison of the experimental and modelling results was done to validate the model. It was observed that the model and experimental results are in good agreement at low and medium cutting speed. Both the coatings increased the life of the drills compared to uncoated drills. The wear-rate is highest at the corner of the drill. The mode of failure for TiAlSiN-coated drill was noticed to be corner chipping and for TiAlN-coated tool was built-up-edge (BUE) formation followed by flank chipping.
Helmholtz vibrations in bowed strings
Authors: Schwarz R. B.
Published: April 2022

For almost 160 years, it has been known that Helmholtz oscillations, unique to vibrating strings in bowed instruments (violin, cello, etc.), have two distinct regimes: “slip” and “stick.” During the slip regime, the force at the bow-string interaction is attributed to friction between the sliding bow hair and the vibrating string, with a friction coefficient that decreases with increasing relative velocity. Yet the hair-string interaction during the stick regime is less understood. We propose that the interaction force during the stick regime is proportional to the product of the longitudinal acoustic impedance of the bow hair to the relative bow-string velocity. We validate this hypothesis by solving the string's differential equation of motion, including an enhanced formulation to avoid parasitic high-frequency oscillations. This physical model enables us to analyze, in real time, the characteristics of the Helmholtz oscillations, including the string shape, excitation of harmonics, Schelleng ripples, and string energy, showing that the bowed string gains energy during the stick regime and loses energy during the slip regime.
Bioresponsive nano-antibacterials for H
2
S-sensitized hyperthermia and immunomodulation against refractory implant–related infections
Authors: Su Zheng , Kong Lingtong , Dai Yong , Tang Jin , Mei Jiawei , Qian Zhengzheng , Ma Yuanyuan , Li Qianming , Ju Shenghong , Wang Jiaxing , Fan Wenpei , Zhu Chen
Published: April 2022

There is an increasingly growing demand for nonantibiotic strategies to overcome drug resistance in bacterial biofilm infections. Here, a novel “gas-sensitized hyperthermia” strategy is proposed for appreciable bacteria killing by the smart design of a metal-organic framework (MOF)–sealed Prussian blue–based nanocarrier (MSDG). Once the biofilm microenvironment (BME) is reached, the acidity-activated MOF degradation allows the release of diallyl trisulfide and subsequent glutathione-responsive generation of hydrogen sulfide (H
2
S) gas. Upon near-infrared irradiation, H
2
S-sensitized hyperthermia arising from MSDG can efficiently eliminate biofilms through H
2
S-induced extracellular DNA damage and heat-induced bacterial death. The generated H
2
S in the biofilm can stimulate the polarization of macrophages toward M2 phenotype for reshaping immune microenvironment. Subsequently, the secretion of abundant regeneration-related cytokines from M2 macrophages accelerates tissue regeneration by reversing the infection-induced pro-inflammatory environment in an implant-related infection model. Collectively, such BME-responsive nano-antibacterials can achieve biofilm-specific H
2
S-sensitized thermal eradiation and immunomodulatory tissue remodeling, thus realizing the renaissance of precision treatment of refractory implant–related infections.
Delivery of CAR-T cells in a transient injectable stimulatory hydrogel niche improves treatment of solid tumors
Authors: Grosskopf Abigail K. , Labanieh Louai , Klysz Dorota D. , Roth Gillie A. , Xu Peng , Adebowale Omokolade , Gale Emily C. , Jons Carolyn K. , Klich John H. , Yan Jerry , Maikawa Caitlin L. , Correa Santiago , Ou Ben S. , d’Aquino Andrea I. , Cochran Jennifer R. , Chaudhuri Ovijit , Mackall Crystal L. , Appel Eric A.
Published: April 2022

Adoptive cell therapy (ACT) has proven to be highly effective in treating blood cancers, but traditional approaches to ACT are poorly effective in treating solid tumors observed clinically. Novel delivery methods for therapeutic cells have shown promise for treatment of solid tumors when compared with standard intravenous administration methods, but the few reported approaches leverage biomaterials that are complex to manufacture and have primarily demonstrated applicability following tumor resection or in immune-privileged tissues. Here, we engineer simple-to-implement injectable hydrogels for the controlled co-delivery of CAR-T cells and stimulatory cytokines that improve treatment of solid tumors. The unique architecture of this material simultaneously inhibits passive diffusion of entrapped cytokines and permits active motility of entrapped cells to enable long-term retention, viability, and activation of CAR-T cells. The generation of a transient inflammatory niche following administration affords sustained exposure of CAR-T cells, induces a tumor-reactive CAR-T phenotype, and improves efficacy of treatment.
New constraints on the timing and character of the Laramide Orogeny and associated gold mineralization in SE California, USA
Authors: Cawood Tarryn K. , Moser Amy , Borsook Ariel , Rooney Alan D.
Published: April 2022

The timing of deformation and associated gold mineralization in SE California, USA, is contentious, partly due to the challenges involved with dating ductile deformation. We therefore combine modern geo- and thermochronology with field and microscopic observations to show that the Cargo Muchacho Mountains preserve evidence of northward thrusting in a kilometer-scale ductile shear zone during the Late Cretaceous Laramide Orogeny, accompanied by hydrothermal fluid flow, gold mineralization, and pegmatite emplacement. Penetrative strain was largely accommodated within the Jurassic metavolcaniclastic Tumco Formation, whereas intrusive Jurassic granitoids behaved as competent bodies. Quartz microstructures suggest deformation at ~500 °C, which is consistent with fabrics defined by amphibolite facies minerals. The timing of thrusting is constrained by dynamically recrystallized titanite with a U-Pb age of 68 ± 1 Ma and late syn-kinematic pegmatites that yield U-Pb zircon ages of 65.0 ± 4.2–63.2 ± 4.8 Ma. Syn-kinematic fluid flow was focused into a lateral thrust ramp where the shear zone foliation was deflected around a relatively rigid pluton, creating zones rich in magnetite-quartz veins and epidote, and precipitating gold associated with pyrite and chalcopyrite. Dating of these sulfides via Re-Os yields an age of 64.7 ± 0.8 Ma, which confirms a Laramide age for the gold mineralization. Together, apatite from the pegmatites and a nearby Jurassic granite yields a U-Pb age of 60.4 ± 3.5 Ma, reflecting cooling to below 530–450 °C. Comparison with published studies suggests that thick-skinned deformation in the Cargo Muchacho Mountains was driven by flat-slab subduction of the conjugate Hess Plateau, which occurred several million years after and to the south of flat-slab subduction of the conjugate Shatsky Rise. This suggests that the conjugate Hess Plateau may have been subducted up to several hundred kilometers farther north than previously thought. Metamorphic devolatilization of underplated Orocopia Schist likely generated the gold-bearing hydrothermal fluids, and anatexis of the schist formed the peraluminous pegmatites, which highlights the importance of schist underplating and devolatilization along much of the Californian and Mexican cordillera.
Trends in diabetic eye disorders and associated comorbidities in Taiwan: a 10-year nationwide population-based cohort study
Authors: Lin Chia-Chen , Lee Chia-Yi , Huang Jing-Yang , Hsu Sheng-Min , Hung Jia-Horung , Yang Shun-Fa
Published: April 2022

Background/aims

In-depth analysis is needed to investigate trends in diabetic retinopathy (DR), diabetic macular oedema (DME) and associated comorbidities in patients with type 2 diabetes mellitus (T2DM) so that we can better understand their prevalence and incidence.

Methods

A retrospective population-based study was conducted using data from Taiwan’s National Health Insurance Research Database from 2005 to 2015, and T2DM, DR and associated comorbidities were identified based on diagnostic codes. We used a standardised incidence rate with age and sex adjustment to estimate the prevalence and incidence of DR, proliferative DR (PDR), advanced PDR (aPDR) and DME, while the difference in each study period was calculated as the annual percentage change. We used the absolute standardised difference to analyse changes in related comorbidities in different periods.

Results

The population of patients with DM increased over 50% between 2005 and 2015, while the prevalence and incidence of DR decreased, as did the incidence of PDR and aPDR. However, the prevalence and incidence of DME increased over the course of 10 years, with an upward trend in all forms of DR. The percentage of patients with hyperlipidaemia in DME and all DR increased, and the percentage of patients with end-stage renal disease (ESRD) was also elevated in DME.

Conclusion

The prevalence and incidence of DR, PDR and aPDR decreased with time in patientsT2DM, while the ratio of DME increased gradually. The incidence of hyperlipidaemia also increased in all forms of diabetic eye disorders, while ESRD increased solely in DME.
Long-term leisure-time physical activity and risk of all-cause and cardiovascular mortality: dose–response associations in a prospective cohort study of 210 327 Taiwanese adults
Authors: Martinez-Gomez David , Cabanas-Sanchez Veronica , Yu Tsung , Rodriguez-Artalejo Fernando , Ding Ding , Lee I-Min , Ekelund Ulf
Published: April 2022

Objectives

We aimed to investigate the dose–response associations of long-term leisure-time physical activity (LTPA) obtained from repeated measures with all-cause and cardiovascular disease (CVD) mortality outcomes in Taiwanese adults.

Methods

We included 210 327 participants with self-reported LTPA at least in two medical examinations (867 968 data points) for up to 20 years (median, IQR: 4.8 years, 2.3–9.0). Dose–response relationships were modelled with restricted cubic spline functions and Cox regressions HRs (95% CIs) adjusted for main covariates.

Results

During up to 23 years of follow-up (3 655 734 person-years), 10 539 participants died, of which 1919 of CVD. We observed an inverse, non-linear dose–response association between long-term LTPA and all-cause and CVD mortality. Compared with the referent (0 metabolic equivalent of task (MET) hours/week), insufficient (0.01–7.49 MET hours/week), recommended (7.50–15.00 MET hours/week) and additional (>15 MET hours/week) amounts of LTPA had a lower mortality risk of 0.74 (0.69–0.80), 0.64 (0.60–0.70) and 0.59 (0.54–0.64) for all-cause mortality and 0.68 (0.60–0.84), 0.56 (0.47–0.67) and 0.56 (0.47–0.68) for CVD mortality. When using only baseline measures of LTPA, the corresponding mortality risk was 0.88 (0.84–0.93), 0.83 (0.78–0.88) and 0.78 (0.73–0.83) for all-cause and 0.91 (0.81–1.02), 0.78 (0.68–0.89) and 0.80 (0.70–0.92) for CVD mortality.

Conclusion

Long-term LTPA was associated with lower risks of all-cause and CVD mortality. The magnitude of risk reductions was larger when modelling repeated measures of LTPA compared with one measure of LTPA at baseline.
Estimating the contribution of transmission in primary healthcare clinics to community-wide TB disease incidence, and the impact of infection prevention and control interventions, in KwaZulu-Natal, South Africa
Authors: McCreesh Nicky , Karat Aaron S , Govender Indira , Baisley Kathy , Diaconu Karin , Yates Tom A , Houben Rein MGJ , Kielmann Karina , Grant Alison D , White Richard
Published: April 2022

Background

There is a high risk ofMycobacterium tuberculosis(Mtb) transmission in healthcare facilities in high burden settings. WHO guidelines on tuberculosis (TB) infection prevention and control (IPC) recommend a range of measures to reduce transmission in healthcare settings. These were evaluated primarily based on evidence for their effects on transmission to healthcare workers in hospitals. To estimate the overall impact of IPC interventions, it is necessary to also consider their impact on community-wide TB incidence and mortality.

Methods

We developed an individual-based model ofMtbtransmission in households, primary healthcare (PHC) clinics, and all other congregate settings. The model was parameterised using data from a high HIV prevalence community in South Africa, including data on social contact by setting, by sex, age, and HIV/antiretroviral therapy status; and data on TB prevalence in clinic attendees and the general population. We estimated the proportion of disease in adults that resulted from transmission in PHC clinics, and the impact of a range of IPC interventions in clinics on community-wide TB.

Results

We estimate that 7.6% (plausible range 3.9%–13.9%) of non-multidrug resistant and multidrug resistant TB in adults resulted directly from transmission in PHC clinics in the community in 2019. The proportion is higher in HIV-positive people, at 9.3% (4.8%–16.8%), compared with 5.3% (2.7%–10.1%) in HIV-negative people. We estimate that IPC interventions could reduce incident TB cases in the community in 2021–2030 by 3.4%–8.0%, and deaths by 3.0%–7.2%.

Conclusions

A non-trivial proportion of TB results from transmission in clinics in the study community, particularly in HIV-positive people. Implementing IPC interventions could lead to moderate reductions in disease burden. We recommend that IPC measures in clinics should be implemented for their benefits to staff and patients, but also for their likely effects on TB incidence and mortality in the surrounding community.
Followership: an undervalued concept in effective teams within the military and NHS
Authors: Adams Thomas , Gibson A
Published: April 2022

Introduction

Leadership is accepted as a crucial component of effective working within teams. Followership’s contribution to successful performance is increasingly recognised but understudied. This study evaluated followership levels in military doctors at different stages of their careers and made recommendations for how followership concepts can be used to develop the self and better understand the challenges of small team working.

Methods

A self-report study in which Kelley’s followership questionnaire was distributed to 64 military doctors in three cohorts. 53 results were assessed using Kelley’s followership framework. Subgroup analysis was undertaken to look at differences depending on service, age, gender and career stage.

Results

The study demonstrated a predominant exemplary followership style within military doctors. No statistical difference was identified at the 0.05 level in followership by career stage, age, gender or service in the sample group.

Conclusion

This study gives insight into the attributes of doctors within the Defence Medical Services and laid out a methodology for further cohort evaluations of followership. It made recommendations on the areas of the field that require further research and how followership concepts may be included in further development courses and reporting for military medical personnel.
Traumatic brain injury during COVID-19 pandemic—time-series analysis of a natural experiment
Authors: Rajalu Banu Manickam , Indira Devi Bhagavatula , Shukla Dhaval P , Shukla Lekhansh , Jayan Mini , Prasad Krishna , Jayarajan Deepak , Kandasamy Arun , Murthy Pratima
Published: April 2022

Objectives

This study aims to find if the incidence and pattern of traumatic brain injury (TBI) changed during the COVID-19pandemic. We also aim to build an explanatory model for change in TBI incidence using Google community mobility and alcohol sales data.

Design

A retrospective time-series analysis.

Setting

Emergency department of a tertiary level hospital located in a metropolitan city of southern India. This centre is dedicated to neurological, neurosurgical and psychiatric care.

Participants

Daily counts of TBI patients seen between 1 December 2019 and 3 January 2021 (400 days); n=8893. To compare the profile of TBI cases seen before and during the pandemic, a subset of these cases seen between 1 December 2019 and 31 July 2020 (244 days), n=5259, are studied in detail.

Results

An optimal changepoint is detected on 20 March 2020 following which the mean number of TBI cases seen every day has decreased and variance has increased (mean 1=29.4, variance 1=50.1; mean 2=19.5, variance 2=59.7, loglikelihood ratio test: χ2=130, df=1, p<0.001). Two principal components of community mobility, alcohol sales and weekday explain the change in the number of TBI cases (pseudo R2=58.1). A significant decrease in traffic accidents, falls, mild/moderate injuries and, an increase in assault and severe injuries is seen during the pandemic period.

Conclusions

Decongestion of roads and regulation of alcohol sales can decrease TBI occurrence substantially. An increase in violent trauma during lockdown needs further research in the light of domestic violence. Acute care facilities for TBI should be maintained even during a strict lockdown as the proportion of severe TBI requiring admission increases.
From basic to advanced computerised intravenous to oral switch for paracetamol and antibiotics: an interrupted time series analysis
Authors: Quintens Charlotte , Coenen Marie , Declercq Peter , Casteels Minne , Peetermans Willy E , Spriet Isabel
Published: April 2022

Objectives

Early switch from intravenous to oral therapy of bioequivalent drugs has major advantages but remains challenging. At our hospital, a basic clinical rule was designed to automatically alert the physician to review potential intravenous to oral switch (IVOS). A rather low acceptance rate was observed. In this study, we aimed to develop, validate and investigate the effect of more advanced clinical rules for IVOS, as part of a centralised pharmacist-led medication review service.

Design and setting

A quasi-experimental study was performed in a large teaching hospital in Belgium using an interrupted time series design.

Intervention

A definite set of 13 criteria for IVOS, focusing on the ability of oral absorption and type of infection, was obtained by literature search and validated by a multidisciplinary expert panel. Based on these criteria, we developed a clinical rule for paracetamol and one for ten bioequivalent antibiotics to identify patients with potentially inappropriate intravenous prescriptions (PIVs). Postintervention, the clinical rule alerts were reviewed by pharmacists, who provided recommendations to switch in case of eligibility.

Primary and secondary outcome measures

A regression model was used to assess the impact of the intervention on the number of persistent PIVs between the preintervention and the postintervention period. The total number of recommendations, acceptance rate and financial impact were recorded for the 8-month postintervention period.

Results

At baseline, a median number of 11 (range: 7–16) persistent PIVs per day was observed. After the intervention, the number reduced to 3 (range: 1–7) per day. The advanced IVOS clinical rules showed an immediate relative reduction of 79% (incidence rate ratio=0.21, 95% CI 0.13 to 0.32; p<0.01) in the proportion of persistent PIVs. No significant underlying time trends were observed during the study. Postintervention, 1091 recommendations were provided, of which 74.1% were accepted, resulting in a total 1-day cost saving of €4648.35.

Conclusions

We showed the efficacy of advanced clinical rules combined with a pharmacist-led medication review for IVOS of bioequivalent drugs.
Development of a decision analytical framework to prioritise operating room capacity: lessons learnt from an empirical example on delayed elective surgeries during the COVID-19 pandemic in a hospital in the Netherlands
Authors: Rovers Maroeska M , Wijn Stan RW , Grutters Janneke PC , Metsemakers Sanne JJPM , Vermeulen Robin J , van der Pennen Ron , Berden Bart JJM , Gooszen Hein G , Scholte Mirre , Govers Tim M
Published: April 2022

Objective

To develop a prioritisation framework to support priority setting for elective surgeries after COVID-19 based on the impact on patient well-being and cost.

Design

We developed decision analytical models to estimate the consequences of delayed elective surgical procedures (eg, total hip replacement, bariatric surgery or septoplasty).

Setting

The framework was applied to a large hospital in the Netherlands.

Outcome measures

Quality measures impacts on quality of life and costs were taken into account and combined to calculate net monetary losses per week delay, which quantifies the total loss for society expressed in monetary terms. Net monetary losses were weighted by operating times.

Results

We studied 13 common elective procedures from four specialties. Highest loss in quality of life due to delayed surgery was found for total hip replacement (utility loss of 0.27, ie, 99 days lost in perfect health); the lowest for arthroscopic partial meniscectomy (utility loss of 0.05, ie, 18 days lost in perfect health). Costs of surgical delay per patient were highest for bariatric surgery (€31/pp per week) and lowest for arthroscopic partial meniscectomy (−€2/pp per week). Weighted by operating room (OR) time bariatric surgery provides most value (€1.19/pp per OR minute) and arthroscopic partial meniscectomy provides the least value (€0.34/pp per OR minute). In a large hospital the net monetary loss due to prolonged waiting times was €700 840 after the first COVID-19 wave, an increase of 506% compared with the year before.

Conclusions

This surgical prioritisation framework can be tailored to specific centres and countries to support priority setting for delayed elective operations during and after the COVID-19 pandemic, both in and between surgical disciplines. In the long-term, the framework can contribute to the efficient distribution of OR time and will therefore add to the discussion on appropriate use of healthcare budgets. The online framework can be accessed via:https://stanwijn.shinyapps.io/priORitize/.