bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of grapevine SEPALLATA‐related MADS‐box gene VvMADS39 in flower and ovule development
Authors: Zhang Songlin , Yao Jin , Wang Li , Wu Na , van Nocker Steve , Li Zhi , Gao Min , Wang Xiping
Published: July 2022

Seedlessness is one of the most important breeding goals for table grapes; thus, understanding the molecular genetic regulation of seed development and abortion is critical for the development of seedless cultivars. In the present study, we characterized VvMADS39, a class E MADS‐box gene of grapevine (Vitis vinifera) orthologous to Arabidopsis SEP2. Heterologous overexpression of VvMADS39 in tomato reduced the fruit and seed size and seed number. Targeted mutagenesis of the homologous SlMADS39 in tomato induced various floral and fruit defects. It could reasonable to suppose that active VvMADS39 expression in “Thompson Seedless” may restrict cellular expansion, resulting in the development of smaller fruits and seeds, VvMADS39 may play a role in the regulation of ovule development in grapevine and contributes to seedless fruit formation. In contrast, VvMADS39 suppression in “Red Globe” was associated with enhanced histone H3 lysine 27 trimethylation in the promoter region of VvMADS39, allowing normal ovule and fruit development; Meanwhile, VvMADS39 interacts with VvAGAMOUS, and the activity of the VvMADS39–VvAGAMOUS dimer to induce integument development requires the activation and maintenance of VvINO expression. The synergistic cooperation between VvMADS39 and related proteins plays an important role in maintaining floral meristem characteristics, and fruit and ovule development.
Human T‐lymphotropic virus in Irish blood donors: Impact on future testing strategy
Authors: Williams Pádraig , O'Flaherty Niamh , Field Stephen , Waters Allison
Published: July 2022

Aim

A risk‐based approach to the testing of blood donations for Human T‐Lymphotropic Virus (HTLV) should include an assessment of blood donation seroepidemiology. The objectives of the present study were to determine the proportion of HTLV positive units in Irish blood donations, and subsequently, to estimate the current risk of transfusion transmitted HTLV (TT‐HTLV).

Methods

Over 3 million donations screened between 1996 and 2020, were included in the study (n = 3,666,253). Factors considered in the assessment of TT‐HTLV risk included: (I) HTLV seropositivity, (ii) probability of a leucodepletion failure, and (iii) the HTLV testing strategy.

Results

Six HTLV positive donations were detected throughout the study period, all of them in previously unscreened blood donors (0.000164%; n = 6/3,666,253), 3 of whom had donated prior to the introduction of HLTV antibody testing. On average 0.11% of manufactured blood components assessed, failed to satisfy the leucodepletion quality assurance criteria of less than 1 × 106 cells/unit. In using these values to model the risk of TT‐HTLV, it was shown that the combination of leucodepletion with either universal screening of all = donors, or selective testing of first‐time donors, a possible HTLV transfusion transmitted infection would be prevented every 468–3776 years.

Conclusions

This is the first report on the proportion of HTLV positive in Irish blood donations (1996–2020) and will be used to inform blood donation screening policy in Ireland. Evidence is provided for recommending a selective HTLV donor screening algorithm in Ireland that is accompanied by a robust framework for continued surveillance of leucodepletion failure rate.
An internet survey of the perceived prevalence of zoological companion animal (ZCA) species being evaluated by ACVECC diplomates and emergency and critical care residents and to gauge potential interest in advanced training opportunities in the emergency treatment of these patients
Authors: Sands Jessica , Cudney Sarah , Graham Jennifer , Bercier Marjorie , Mayer Corrine , Rozanski Elizabeth , Schoeffler Gretchen
Published: July 2022

Objectives

To describe the perceived prevalence of zoological companion animal (ZCA) species being evaluated and treated by American College of Veterinary Emergency and Critical Care (ACVECC) diplomates and Emergency and Critical Care (ECC) residents in an emergency room (ER) setting and to assess potential interest in further training for the ACVECC community in the emergency treatment and stabilization of these species.

Design

Internet‐based survey.

Subjects

One hundred and thirty‐nine ACVECC diplomates and ECC residents.

Procedure

An online survey was designed and administered to assess the perceived prevalence of ZCA species that were evaluated and treated in the veterinary ER and to gauge potential interest in advanced training opportunities in the emergency treatment of these patients.

Results

One hundred and fifteen (83%) respondents reported that their hospital offered veterinary services to ZCA species during business hours and 120 (86%) reported that they offered veterinary services to ZCA species during off‐hours. Ninety‐one (65%) respondents reported that ZCA patients were evaluated and treated through their ER with small mammals (n = 60/91 [66%]) and small birds (n = 48/91 [53%]) being the most common species presented. In hospitals with an available ZCA specialist (80/139 [56%]), primary case responsibility was maintained by the ZCA specialist 24–7 in 11 of 91 (14%) hospitals. Seventy‐three (53%) ACVECC diplomate and ECC resident survey respondents reported clinical training specific to ZCA species during veterinary school. A total of 84 of 139 (60%) survey respondents expressed interest in further training regarding ZCA species, with 73 of 84 (87%) those individuals specifying interest or potential interest in a formal ACVECC certificate or other type of advanced training.
Use of vasopressors for treatment of vasodilatory hypotension in dogs and cats by Diplomates of the American College of Veterinary Emergency and Critical Care
Authors: Murphy Kellyann M. , Rishniw Mark , Silverstein Deborah C.
Published: July 2022

Objective

To identify the most common practices of Diplomates of the American College of Veterinary Emergency and Critical Care (DACVECCs) as they relate to the recognition and treatment of hypotension in dogs and cats, particularly concerning the use of vasopressors in vasodilatory shock states.

Design

A survey regarding vasopressor use was sent to all active DACVECCs using the Veterinary Information Network. Questions focused on respondent characteristics, method of recognition of hypotension, triggers for initiation of vasopressor therapy, first‐ and second‐line vasopressor choice, and methods of determining response to therapy.

Subjects

A total of 734 DACVECCs were invited to participate, and 203 Diplomates (27.7%) completed the survey.

Results

For both dogs and cats, the most common first‐line vasopressor was norepinephrine (87.9% in dogs and 83.1% in cats). The most common second‐choice vasopressor was vasopressin (44.2% in dogs and 39.0% in cats). Cutoff values for initiating vasopressor therapy varied between species and modality used for blood pressure measurement. In general, most DACVECCs chose to initiate vasopressor therapy at a Doppler blood pressure <90 mm Hg or a mean arterial pressure of <60 or <65 mm Hg when using oscillometric or direct arterial blood pressure measurements in dogs and cats.

Conclusions

Most DACVECCs adhere to published human guidelines when choosing a first‐line vasopressor. However, there is significant variability in blood pressure measurement technique, cutoffs for initiation of vasopressor use, and choice of second‐line vasopressors.
Facilitadores y obstaculizadores de la implementación de un programa de extensión rural chileno
Authors: Keller Santander Karina , Landini Fernando , Rojas-Andrade Rodrigo Miguel , Prosser Bravo Gabriel
Published: July 2022

Los programas de extensión rural son fundamentales para impulsar el desarrollo local en Latinoamérica, sin embargo, pocos estudios abordan su implementación. En este estudio se analizaron las bases técnicas de un programa público chileno y fueron entrevistados trece extensionistas que lo aplican. Se encontró que los profesionales son adherentes a las visitas técnicas así como a las capacitaciones grupales, y que las competencias emocionales y pedagógicas son fundamentales. Los principales facilitadores de estas acciones son la relación entre pares y el compromiso social, mientras que la institucionalidad es el obstáculo más crítico. Se discute la importancia de abordar estos factores para aumentar la calidad de los programas.
Performance Analysis of Corrosion Resistant Electroless Nickel-Plated Impinging Computer Numerical Control Manufactured Liquid Cooling Cold Plate
Authors: Radmard Vahideh , Gharaibeh Ahmad R. , Tradat Mohammad I. , Hoang Cong. H. , Manaserh Yaman Yaseen , Nemati Kourosh , Schiffres Scott N. , Sammakia Bahgat G.
Published: July 2022

More than ever before, data centers must deploy robust thermal solutions to adequately host the high-density and high-performance computing that is in high demand. The newer generation of central processing units (CPUs) and graphics processing units (GPUs) has substantially higher thermal power densities than previous generations. In recent years, more data centers rely on liquid cooling for the high-heat processors inside the servers and air cooling for the remaining low-heat information technology equipment. This hybrid cooling approach creates a smaller and more efficient data center. The deployment of direct-to-chip cold plate liquid cooling is one of the mainstream approaches to providing concentrated cooling to targeted processors. In this study, a processor-level experimental setup was developed to evaluate the cooling performance of a novel computer numerical control (CNC) machined nickel-plated impinging cold plate on a 1 in. × 1 in. mock heater that represents a functional processing unit. The pressure drop and thermal resistance performance curves of the electroless nickel-plated cold plate are compared to those of a pure copper cold plate. A temperature uniformity analysis is done using compuational fluid dynamics and compared to the actual test data. Finally, the CNC machined pure copper one is compared to other reported cold plates to demonstrate its superiority of the design with respect to the cooling performance.
Outgassing rate testbed for in-operation analysis of powered and heated assemblies
Authors: Warner Marvin , Elsen Michael , Wörner Lisa , Braxmaier Claus , Grosse Jens
Published: July 2022

We introduce a new apparatus for measuring the outgassing rate of assemblies and functional units. Outgassing rates given in the literature, if available, are mostly insufficient to plan and set up a vacuum system, more so if commercial parts, preassembled items, or complex electronics with unknown components are deployed. Outgassing rates have a severe impact on the required pumping speed in ultrahigh vacuum systems and they change if the samples are powered or heated. The newly built apparatus uses the throughput method to measure outgassing rates. It can house probes with a size of 0.10×0.10×0.13m3 and supplies electrical currents of up to 5 A. In addition, a heater can establish temperatures of up to 200 °C directly. A procedure is given to identify the main gas inputs and to retrieve data with a lower limit of 1.5×10−8Pam3s−1 after 100 h in vacuum. In this paper, we present the experimental setup and first results for samples of polytetrafluorethylene, polyamide (PA6), Viton (1A), and oxygen-free high thermal conductivity copper at room temperature.
Benefits and Barriers Associated With Intention to Participate in Injury Prevention Programs in Reserve Officers’ Training Corps Cadets
Authors: Gabriel Emily H. , Powden Cameron J.
Published: July 2022

Identification of factors which may influence participation in exercise-related injury prevention programs within Reserve Officers’ Training Corps (ROTC) cadets is an important step in improving adoption and adherence rates. Therefore, the purpose of the study was to identify factors associated with intention to participate in an exercise-related injury prevention program within ROTC cadets. Theory of planned behavior scale perceived benefits (B = 3.65, η2 = .36, p = .001) and Health Belief Model Scale perceived benefits (B = 3.46, η2 = .31, p = .01) had a large positive association with intention to participate. Theory of planned behavior scale perceived barriers (B = −2.28, η2 = .37, p = .001) had a large negative association with intention to participate. Implementation strategies for exercise-related injury prevention programs may need to focus on the benefits and barriers of participation to increase adoption and adherence.
Footwear Type and Testing Environment Do Not Affect Baseline Modified Balance Error Scoring System Performance Among Middle School Athletes
Authors: Erdman Nicholas K. , Kelshaw Patricia M. , Hacherl Samantha L. , Caswell Shane V.
Published: July 2022

Context: Limited evidence exists to demonstrate the effect of extrinsic factors, such as footwear worn or the testing environment, on performance of the modified balance error scoring system (mBESS) in the middle school age (10–14 y) population. Therefore, the purpose of our study was to investigate the effect of footwear types and testing environments on performance of the mBESS by middle school athletes. Design: Cross-sectional. Methods: In total, 2667 middle school athletes (55.9% boys and 44.1% girls; age = 12.3 [0.94] y) were administered the mBESS while wearing their self-selected footwear (barefoot, cleats, or shoes) either indoors (basketball court) or outdoors (football field or track). The number of errors committed (range = 0–10) during the double-leg, single-leg, and tandem stances of the mBESS were summed to calculate a total score (range = 0–30). Kruskal–Wallis tests were used to assess for differences among the footwear groups for each mBESS stance and the total score. Mann–Whitney U tests with calculated nonparametric effect sizes (r) were used to assess for differences between the footwear groups and testing environments when appropriate. Results: There were significant differences for the number of committed errors among the footwear groups in the single-leg (P < .001) and tandem (P < .001) stances of the mBESS and mBESS total scores (P < .001). Significantly fewer errors (better) were committed while wearing shoes compared with other footwear in the single-leg and tandem stances of the mBESS (Ps ≤ .032, r = .07–.13). Participants assessed indoors committed significantly fewer errors than those assessed outdoors in each stance of the mBESS (Ps ≤ .022, r = .04–.14). Lower (better) mBESS total scores were observed for participants while wearing shoes (Ps ≤ .002, r = .10–.15) or assessed indoors (P = .001, r = .14). Conclusions: Although our data suggest that the type of footwear worn and the testing environment have a significant effect on mBESS scores of middle school athletes, the magnitudes of these differences are negligible.
A Very Low Volume of Nordic Hamstring Exercise Increases Maximal Eccentric Strength and Reduces Hamstring Injury Rate in Professional Soccer Players
Authors: Cadu Jean-Philippe , Goreau Valentin , Lacourpaille Lilian
Published: July 2022

The aim of this study was to determine whether the inclusion of a very low volume (1 set of 3 maximal repetitions) of eccentric-biased Nordic hamstring program of 21 weeks induced an increase in maximal eccentric strength and whether its magnitude was influenced by the compliance rate. The secondary aim of this study was to determine whether this eccentric-biased Nordic hamstring program was effective at reducing hamstring injury rate. Twenty-three professional soccer players formed the experimental group and undertook regular in-season hamstring strength training and monitoring for 21 weeks. Data from 23 players in the immediately preceding cohort (previous year) were included as a control group. The subdivision of the experimental group revealed that the high compliance subgroup (∼13 d between sessions) exhibited higher changes in maximal eccentric strength compared with the low compliance group (∼24 d between sessions; +26.5%; 95% confidence interval, 7.1%–45.9%; P < .001; g = 1.2). Five hamstring injuries (22%) were recorded in the experimental group and 9 (39%) in the control group, corresponding to a nonsignificant 2.7-fold lower risk (P = .12) of suffering hamstring injury in the experimental group. The current study demonstrates that the inclusion of a very low volume of eccentric-biased Nordic hamstring program for 21 weeks induced an increase in maximal eccentric strength (∼15%) in professional soccer players, the magnitude of which depended on the players’ compliance. We also found that this program was efficient (2.7-fold lower risk), although nonsignificant, at reducing hamstring injury rate in professional soccer players.
Comparison of 4 Different Cooldown Strategies on Lower-Leg Temperature, Blood Lactate Concentration, and Fatigue Perception After Intense Running
Authors: Lim Junhyeong , Park Hyeongjun , Lee Seunghee , Park Jihong
Published: July 2022

Context: Although active recovery (AR) and cold application is recommended, many people take a shower after exercise. Therefore, a direct comparison between a shower and other recommended methods (AR and/or cold-water immersion) is necessary. To compare immediate effects of 4 postexercise cooldown strategies after running. Design: A crossover design. Methods: Seventeen young, healthy males (23 y; 174 cm; 73 kg) visited on 4 different days and performed a 10-minute intense treadmill run (5 km/h at a 1% incline, then a belt speed of 1 km/h, and an incline of 0.5% were increased every minute). Then, subjects randomly experienced 4 different 30-minute cooldown strategies each session—AR (10-min treadmill walk + 10-min static stretch + 10-min shower), cold-water walk (10-min shower + 20-min walk in cold water), cold-water sit (10-min shower + 20-min sit in cold water), and passive recovery (10-min shower + 20-min passive recovery). Across the cooldown conditions, the water temperatures for immersion and shower were set as 18 °C and 25 °C, respectively. Lower-leg muscle temperature, blood lactate concentration, and fatigue perception were statistically compared (P < .001 for all tests) and effect sizes (ES) were calculated. Results: The cold-water walk condition (F135,2928 = 69.29, P < .0001) was the most effective in reducing muscle temperature after running (−11.6 °C, ES = 9.46, P < .0001), followed by the cold-water sit (−8.4 °C, ES = 8.61, P < .0001), passive recovery (−4.5 °C, ES = 4.36, P < .0001), and AR (−4.0 °C, ES = 4.29, P < .0001) conditions. Blood lactate concentration (F6,176 = 0.86, P = .52) and fatigue perception (F6,176 = 0.18, P = .98) did not differ among the 4 conditions. Conclusions: While the effect of lowering the lower-leg temperature was different, the effect of reducing blood lactate concentration and fatigue perception were similar in the 4 cooldown strategies. We suggest selecting the appropriate method while considering the specific goal, available time, facility, and accessibility.
RRM2 enhances MYCN-driven neuroblastoma formation and acts as a synergistic target with CHK1 inhibition
Authors: Nunes Carolina , Depestel Lisa , Mus Liselot , Keller Kaylee M. , Delhaye Louis , Louwagie Amber , Rishfi Muhammad , Whale Alex , Kara Neesha , Andrews Simon R. , Dela Cruz Filemon , You Daoqi , Siddiquee Armaan , Cologna Camila Takeno , De Craemer Sam , Dolman Emmy , Bartenhagen Christoph , De Vloed Fanny , Sanders Ellen , Eggermont Aline , Bekaert Sarah-Lee , Van Loocke Wouter , Bek Jan Willem , Dewyn Givani , Loontiens Siebe , Van Isterdael Gert , Decaesteker Bieke , Tilleman Laurentijn , Van Nieuwerburgh Filip , Vermeirssen Vanessa , Van Neste Christophe , Ghesquiere Bart , Goossens Steven , Eyckerman Sven , De Preter Katleen , Fischer Matthias , Houseley Jon , Molenaar Jan , De Wilde Bram , Roberts Stephen S. , Durinck Kaat , Speleman Frank
Published: July 2022

High-risk neuroblastoma, a pediatric tumor originating from the sympathetic nervous system, has a low mutation load but highly recurrent somatic DNA copy number variants. Previously, segmental gains and/or amplifications allowed identification of drivers for neuroblastoma development. Using this approach, combined with gene dosage impact on expression and survival, we identified ribonucleotide reductase subunit M2 (RRM2) as a candidate dependency factor further supported by growth inhibition upon in vitro knockdown and accelerated tumor formation in a neuroblastoma zebrafish model coexpressing human RRM2 with MYCN. Forced RRM2 induction alleviates excessive replicative stress induced by CHK1 inhibition, while high RRM2 expression in human neuroblastomas correlates with high CHK1 activity. MYCN-driven zebrafish tumors with RRM2 co-overexpression exhibit differentially expressed DNA repair genes in keeping with enhanced ATR-CHK1 signaling activity. In vitro, RRM2 inhibition enhances intrinsic replication stress checkpoint addiction. Last, combinatorial RRM2-CHK1 inhibition acts synergistic in high-risk neuroblastoma cell lines and patient-derived xenograft models, illustrating the therapeutic potential.
Experimental and computational understanding of pulsatile release mechanism from biodegradable core-shell microparticles
Authors: Sarmadi Morteza , Ta Christina , VanLonkhuyzen Abigail M. , De Fiesta Dominique C. , Kanelli Maria , Sadeghi Ilin , Behrens Adam M. , Ingalls Bailey , Menon Nandita , Daristotle John L. , Yu Julie , Langer Robert , Jaklenec Ana
Published: July 2022

Next-generation therapeutics require advanced drug delivery platforms with precise control over morphology and release kinetics. A recently developed microfabrication technique enables fabrication of a new class of injectable microparticles with a hollow core-shell structure that displays pulsatile release kinetics, providing such capabilities. Here, we study this technology and the resulting core-shell microstructures. We demonstrated that pulsatile release is governed by a sudden increase in porosity of the polymeric matrix, leading to the formation of a porous path connecting the core to the environment. Moreover, the release kinetics within the range studied remained primarily independent of the particle geometry but highly dependent on its composition. A qualitative technique was developed to study the pattern of pH evolution in the particles. A computational model successfully modeled deformations, indicating sudden expansion of the particle before onset of release. Results of this study contribute to the understanding and design of advanced drug delivery systems.
Structures of atypical chemokine receptor 3 reveal the basis for its promiscuity and signaling bias
Authors: Yen Yu-Chen , Schafer Christopher T. , Gustavsson Martin , Eberle Stefanie A. , Dominik Pawel K. , Deneka Dawid , Zhang Penglie , Schall Thomas J. , Kossiakoff Anthony A. , Tesmer John J. G. , Handel Tracy M.
Published: July 2022

Both CXC chemokine receptor 4 (CXCR4) and atypical chemokine receptor 3 (ACKR3) are activated by the chemokine CXCL12 yet evoke distinct cellular responses. CXCR4 is a canonical G protein–coupled receptor (GPCR), whereas ACKR3 is intrinsically biased for arrestin. The molecular basis for this difference is not understood. Here, we describe cryo-EM structures of ACKR3 in complex with CXCL12, a more potent CXCL12 variant, and a small-molecule agonist. The bound chemokines adopt an unexpected pose relative to those established for CXCR4 and observed in other receptor-chemokine complexes. Along with functional studies, these structures provide insight into the ligand-binding promiscuity of ACKR3, why it fails to couple to G proteins, and its bias toward β-arrestin. The results lay the groundwork for understanding the physiological interplay of ACKR3 with other GPCRs.
Cis-regulatory chromatin loops analysis identifies GRHL3 as a master regulator of surface epithelium commitment
Authors: Huang Huaxing , Liu Jiafeng , Li Mingsen , Guo Huizhen , Zhu Jin , Zhu Liqiong , Wu Siqi , Mo Kunlun , Huang Ying , Tan Jieying , Chen Chaoqun , Wang Bofeng , Yu Yankun , Wang Li , Liu Yizhi , Ouyang Hong
Published: July 2022

Understanding the regulatory network of cell fate acquisition remains a major challenge. Using the induction of surface epithelium (SE) from human embryonic stem cells as a paradigm, we show that the dynamic changes in morphology-related genes (MRGs) closely correspond to SE fate transitions. The marked remodeling of cytoskeleton indicates the initiation of SE differentiation. By integrating promoter interactions, epigenomic features, and transcriptome, we delineate an SE-specific cis-regulatory network and identify grainyhead-like 3 (GRHL3) as an initiation factor sufficient to drive SE commitment. Mechanically, GRHL3 primes the SE chromatin accessibility landscape and activates SE-initiating gene expression. In addition, the evaluation of GRHL3-mediated promoter interactions unveils a positive feedback loop of GRHL3 and bone morphogenetic protein 4 on SE fate decisions. Our work proposes a concept that MRGs could be used to identify cell fate transitions and provides insights into regulatory principles of SE lineage development and stem cell–based regenerative medicine.
Overexpression of the scopoletin biosynthetic pathway enhances lignocellulosic biomass processing
Authors: Hoengenaert Lennart , Wouters Marlies , Kim Hoon , De Meester Barbara , Morreel Kris , Vandersyppe Steven , Pollier Jacob , Desmet Sandrien , Goeminne Geert , Ralph John , Boerjan Wout , Vanholme Ruben
Published: July 2022

Lignin is the main factor limiting the enzymatic conversion of lignocellulosic biomass into fermentable sugars. To reduce the recalcitrance engendered by the lignin polymer, the coumarin scopoletin was incorporated into the lignin polymer through the simultaneous expression of
FERULOYL-CoA 6′-HYDROXYLASE 1
(
F6′H1
) and
COUMARIN SYNTHASE
(
COSY
) in lignifying cells in
Arabidopsis
. The transgenic lines overproduced scopoletin and incorporated it into the lignin polymer, without adversely affecting plant growth. About 3.3% of the lignin units in the transgenic lines were derived from scopoletin, thereby exceeding the levels of the traditional
p-
hydroxyphenyl units. Saccharification efficiency of alkali-pretreated scopoletin-overproducing lines was 40% higher than for wild type.
CRISPR interference interrogation of COPD GWAS genes reveals the functional significance of desmoplakin in iPSC-derived alveolar epithelial cells
Authors: Werder Rhiannon B. , Liu Tao , Abo Kristine M. , Lindstrom-Vautrin Jonathan , Villacorta-Martin Carlos , Huang Jessie , Hinds Anne , Boyer Nathan , Bullitt Esther , Liesa Marc , Silverman Edwin K. , Kotton Darrell N. , Cho Michael H. , Zhou Xiaobo , Wilson Andrew A.
Published: July 2022

Genome-wide association studies (GWAS) have identified dozens of loci associated with chronic obstructive pulmonary disease (COPD) susceptibility; however, the function of associated genes in the cell type(s) affected in disease remains poorly understood, partly due to a lack of cell models that recapitulate human alveolar biology. Here, we apply CRISPR interference to interrogate the function of nine genes implicated in COPD by GWAS in induced pluripotent stem cell–derived type 2 alveolar epithelial cells (iAT2s). We find that multiple genes implicated by GWAS affect iAT2 function, including differentiation potential, maturation, and/or proliferation. Detailed characterization of the GWAS gene
DSP
demonstrates that it regulates iAT2 cell-cell junctions, proliferation, mitochondrial function, and response to cigarette smoke–induced injury. Our approach thus elucidates the biological function, as well as disease-relevant consequences of dysfunction, of genes implicated in COPD by GWAS in type 2 alveolar epithelial cells.
Fast constructing polarity-switchable zinc-bromine microbatteries with high areal energy density
Authors: Dai Chunlong , Hu Linyu , Jin Xuting , Wang Ying , Wang Rui , Xiao Yukun , Li Xiangyang , Zhang Xinqun , Song Li , Han Yuyang , Cheng Huhu , Zhao Yang , Zhang Zhipan , Liu Feng , Jiang Lan , Qu Liangti
Published: July 2022

Microbatteries (MBs) are promising candidates to provide power for various miniaturized electronic devices, yet they generally suffer from complicated fabrication procedures and low areal energy density. Besides, all cathodes of current MBs are solid state, and the trade-off between areal capacity and reaction kinetics restricts their wide applications. Here, we propose a dual-plating strategy to facilely prepare zinc-bromine MBs (Zn-Br
2
MBs) with a liquid cathode to achieve both high areal energy density and fast kinetics simultaneously. The Zn-Br
2
MBs deliver a record high areal energy density of 3.6 mWh cm
−2
, almost an order of magnitude higher than available planar MBs. Meanwhile, they show a polarity-switchable feature to tolerate confusion of cathode and anode. This strategy could also be extended to other battery systems, such as Zn-I
2
and Zn-MnO
2
MBs. This work not only proposes an effective construction method for MBs but also enriches categories of microscale energy storage devices.
Fully body visual self-modeling of robot morphologies
Authors: Chen Boyuan , Kwiatkowski Robert , Vondrick Carl , Lipson Hod
Published: July 2022

Internal computational models of physical bodies are fundamental to the ability of robots and animals alike to plan and control their actions. These “self-models” allow robots to consider outcomes of multiple possible future actions without trying them out in physical reality. Recent progress in fully data-driven self-modeling has enabled machines to learn their own forward kinematics directly from task-agnostic interaction data. However, forward kinematic models can only predict limited aspects of the morphology, such as the position of end effectors or velocity of joints and masses. A key challenge is to model the entire morphology and kinematics without prior knowledge of what aspects of the morphology will be relevant to future tasks. Here, we propose that instead of directly modeling forward kinematics, a more useful form of self-modeling is one that could answer space occupancy queries, conditioned on the robot’s state. Such query-driven self-models are continuous in the spatial domain, memory efficient, fully differentiable, and kinematic aware and can be used across a broader range of tasks. In physical experiments, we demonstrate how a visual self-model is accurate to about 1% of the workspace, enabling the robot to perform various motion planning and control tasks. Visual self-modeling can also allow the robot to detect, localize, and recover from real-world damage, leading to improved machine resiliency.
Targeting KDM4 for treating PAX3-FOXO1–driven alveolar rhabdomyosarcoma
Authors: Singh Shivendra , Abu-Zaid Ahmed , Jin Hongjian , Fang Jie , Wu Qiong , Wang Tingting , Feng Helin , Quarni Waise , Shao Ying , Maxham Lily , Abdolvahabi Alireza , Yun Mi-Kyung , Vaithiyalingam Sivaraja , Tan Haiyan , Bowling John , Honnell Victoria , Young Brandon , Guo Yian , Bajpai Richa , Pruett-Miller Shondra M. , Grosveld Gerard C. , Hatley Mark , Xu Beisi , Fan Yiping , Wu Gang , Chen Eleanor Y. , Chen Taosheng , Lewis Peter W. , Rankovic Zoran , Li Yimei , Murphy Andrew J. , Easton John , Peng Junmin , Chen Xiang , Wang Ruoning , White Stephen W. , Davidoff Andrew M. , Yang Jun
Published: July 2022

Chimeric transcription factors drive lineage-specific oncogenesis but are notoriously difficult to target. Alveolar rhabdomyosarcoma (RMS) is an aggressive childhood soft tissue sarcoma transformed by the pathognomonic Paired Box 3–Forkhead Box O1 (PAX3-FOXO1) fusion protein, which governs a core regulatory circuitry transcription factor network. Here, we show that the histone lysine demethylase 4B (KDM4B) is a therapeutic vulnerability for PAX3-FOXO1
+
RMS. Genetic and pharmacologic inhibition of KDM4B substantially delayed tumor growth. Suppression of KDM4 proteins inhibited the expression of core oncogenic transcription factors and caused epigenetic alterations of PAX3-FOXO1–governed superenhancers. Combining KDM4 inhibition with cytotoxic chemotherapy led to tumor regression in preclinical PAX3-FOXO1
+
RMS subcutaneous xenograft models. In summary, we identified a targetable mechanism required for maintenance of the PAX3-FOXO1–related transcription factor network, which may translate to a therapeutic approach for fusion-positive RMS.
Retrospective Cohort Study of the Incidence of Acute Kidney Injury with Vancomycin Area under the Curve-Based Dosing with Concomitant Piperacillin-Tazobactam Compared to Meropenem or Cefepime
Authors: Kiley Patrick S. , Pearston Aaron P. , Hodge Laura A. , Kaplan Marcus C. , Baczek Stephanie M. , Stanley James S. , Wilson Tyler J. , Soriano Kristina M. , Yao Andrew , Shaeffer Zachary A. , Talt Irene E. , Cohen Joshua A. , Ingemi Amanda I.
Published: July 2022

Acute kidney injury (AKI) is a complication associated with vancomycin. Previous studies demonstrated that the combination of vancomycin and piperacillin-tazobactam increases the risk of AKI compared to vancomycin with meropenem or cefepime.
Relationship between Vancomycin Trough Serum Concentrations and Clinical Outcomes in Children: a Systematic Review and Meta-Analysis
Authors: Cao Lu , Li Zhuo , Zhang Peng , Yong Suyun
Published: July 2022

To systematically evaluate the relationships between vancomycin trough serum concentrations and clinical outcomes in children using meta-analysis. Several databases, including PubMed, Elsevier, Web of Science, EMBASE, Medline,
clinicaltrials.gov
, the Cochrane Library, and three Chinese databases (Wanfang Data, China National Knowledge Infrastructure, and SINOMED), were comprehensively searched to obtain research articles on vancomycin use in children from inception through December 2021.
Sensing Host Health: Insights from Sensory Protein Signature of the Metagenome
Authors: Bhar Subhrajit , Singh Rashmi , Pinna Nishal Kumar , Bose Tungadri , Dutta Anirban , Mande Sharmila S.
Published: July 2022

The composition of the human microbiota, a collection of host-associated microbes, has been shown to differ among healthy and diseased individuals. Recent studies have investigated whether tracking these variations could be exploited for disease diagnostics.
The α- and β-Subunit Boundary at the Stem of the Mushroom-Like α
3
β
3
-Type Oxygenase Component of Rieske Non-Heme Iron Oxygenases Is the Rieske-Type Ferredoxin-Binding Site
Authors: Tsai Pi-Cheng , Chakraborty Joydeep , Suzuki-Minakuchi Chiho , Terada Tohru , Kotake Tatsurou , Matsuzawa Jun , Okada Kazunori , Nojiri Hideaki
Published: July 2022

We clarified the critical amino acid residues of the oxygenase component (Oxy) of Rieske non-heme iron oxygenase (RO) for binding with Rieske-type ferredoxin (Fd). Our results showed that Rieske-type Fd-binding site is commonly located at the stem (side-wise site) of the mushroom-like α
3
β
3
quaternary structure in many ROs.
Primary Infection by E. multilocularis Induces Distinct Patterns of Cross Talk between Hepatic Natural Killer T Cells and Regulatory T Cells in Mice
Authors: Yarahmadov Tural , Wang Junhua , Sanchez-Taltavull Daniel , Rojas Cristian A. Alvarez , Brodie Tess , Büchi Isabel , Keogh Adrian , Gottstein Bruno , Stroka Deborah , Beldi Guido
Published: July 2022

The larval stage of the helminthic cestode
Echinococcus multilocularis
can inflict tumor-like hepatic lesions that cause the parasitic disease alveolar echinococcosis in humans, with high mortality in untreated patients. Opportunistic properties of the disease have been established based on the increased incidence in immunocompromised patients and mouse models, indicating that an appropriate adaptive immune response is required for the control of the disease.
Insertional Inactivation and Gene Complementation of Prevotella intermedia Type IX Secretion System Reveals Its Indispensable Roles in Black Pigmentation, Hemagglutination, Protease Activity of Interpain A, and Biofilm Formation
Authors: Naito Mariko , Shoji Mikio , Sato Keiko , Nakayama Koji
Published: July 2022

The virulence factors of periodontal pathogens such as
Prevotella intermedia
have not been elucidated. Using our established procedure, we succeeded in generating type IX secretion system mutants and gene complementation strains that might transfer virulence factors to the bacterial surface.
The NS4A Protein of Classical Swine Fever Virus Suppresses RNA Silencing in Mammalian Cells
Authors: Qian Qi , Xu Ruyi , Wang Yaping , Ma Lixin
Published: July 2022

It is well known that RNAi is an important posttranscriptional gene silencing mechanism that is also involved in the antiviral response in mammalian cells. While numerous viruses have evolved to block this antiviral immunity by encoding VSRs.
Posttranscriptional Regulation by Copper with a New Upstream Open Reading Frame
Authors: Roy Gauthier , Antoine Rudy , Schwartz Annie , Slupek Stéphanie , Rivera-Millot Alex , Boudvillain Marc , Jacob-Dubuisson Françoise
Published: July 2022

Copper is a transition metal necessary for living beings but also extremely toxic. Bacteria thus tightly control its homeostasis with transcriptional regulators.
Complete Genome Sequences of Multidrug-Resistant Campylobacter coli Strains YH501, YH503, and YH504, from Retail Chicken
Authors: He Yiping , Reed Sue , Yan Xianghe , Zhang Dandan , Strobaugh Terence , Capobianco Joseph , Gehring Andrew
Published: July 2022

Campylobacter coli
is an important foodborne pathogen that can cause inflammation of the intestine and diarrhea in humans. The complete genomes, including megaplasmids, of
C. coli
strains YH501, YH503, and YH504 from retail chicken were sequenced and
de novo
assembled. Whole-genome analysis revealed a number of virulence and antibiotic resistance genes, suggesting significant potential for these poultry-originating isolates to cause human disease.
Draft Genome Sequence of Xanthobacter aminoxidans ATCC BAA-299
T
Authors: Siddiqui Fardeen A. , Trudel Shoshana , Goen Abigail E. , Fatima Syeda A. , MacLea Kyle S.
Published: July 2022

Xanthobacter aminoxidans
is a Gram-negative pleomorphic and diazotrophic Knallgas bacillus that undergoes asymmetric budding of V-shaped branched cells during cell division. Like other
Xanthobacter
spp., cells are yellow from production of zeaxanthine dirhamnoside. We sequenced strain 14a
T
(= ATCC BAA-299
T
) and report a genome size of 5,829,486 bp with a G+C content of 67.9%.
Single-Cell Analysis of the Antimicrobial and Bactericidal Activities of the Antimicrobial Peptide Magainin 2
Authors: Hossain Farzana , Billah Md Masum , Yamazaki Masahito
Published: July 2022

To elucidate the activity of antimicrobial peptides (AMPs) against bacterial cells, it is important to estimate the interaction time that is sufficient to induce cell death. We have developed a method to examine the antimicrobial and bactericidal activities of AMPs at the single-cell level (i.e., single-cell analysis).
Emergence and Characterization of Tigecycline Resistance Gene
tet
(X4) in ST609 Escherichia coli Isolates from Wastewater in Turkey
Authors: Kürekci Cemil , Lu Xiaoyu , Celil Büsra Gülay , Disli Hüseyin Burak , Mohsin Mashkoor , Wang Zhiqiang , Li Ruichao
Published: July 2022

Emergence of pathogens harboring tigecycline resistance genes incurs great concerns. Wastewater is recognized as the important reservoir of antimicrobial resistance genes. Here we characterized the phenotypes and genotypes of bacteria carrying
tet
(X4) from wastewater in Turkey for the first time. Four
tet
(X4)-positive
Escherichia coli
isolates were identified and characterized by PCR, Sanger sequencing, antimicrobial susceptibility testing, conjugation assays, Illumina sequencing, nanopore sequencing and bioinformatic analysis. Four
tet
(X4)-harboring isolates were multidrug-resistant (MDR) bacteria and the
tet
(X4) gene was nontransferable in four isolates. Genetic analysis revealed that
tet
(X4) genes in four isolates were located on plasmids co-harboring two replicons IncFIA(HI1) and IncFIB(K). However, none of the four plasmids carried genes associated with horizontal transfer of plasmids. The coexistence of
bla
SHV-12
-bearing IncX3-type plasmid and
tet
(X4)-harboring plasmid was also found in one isolate. These findings indicate that continuous surveillance of the
tet
(X4)-bearing isolates in different environments worldwide should be strengthened.
The Arginine Biosynthesis Pathway of Candida albicans Regulates Its Cross-Kingdom Interaction with Actinomyces viscosus to Promote Root Caries
Authors: Xiong Kaixin , Zhu Hualing , Li Yanyao , Ji Mengzhen , Yan Yujia , Chen Xuan , Chi Yaqi , Yang Xueqin , Deng Ling , Zhou Xuedong , Zou Ling , Ren Biao
Published: July 2022

Root caries is a critical problem that threatens the oral health of the elderly population. Our results identified the essential roles of the
C. albicans
arginine biosynthesis pathway in its cross-kingdom interactions with
A. viscosus
in root caries for the first time and indicated that targeting this pathway was a practical way to treat root caries caused by multiple species.
An Outbreak of Severe Neonatal Pneumonia Caused by Human Respiratory Syncytial Virus BA9 in a Postpartum Care Centre in Shenyang, China
Authors: Wang Bing , Song Jingjing , Song Jinhua , Mao Naiying , Liang Jiayuan , Chen Ye , Qi Ying , Bai Lina , Xie Zhibo , Zhang Yan
Published: July 2022

Human respiratory syncytial virus (HRSV) is one of the leading causes of acute lower respiratory infections (ALRI) worldwide. In this study, we first reported an outbreak of severe neonatal pneumonia caused by HRSVB BA9 at a postpartum care center in mainland China.
Molecular Characterization of
bla
NDM
-Carrying IncX3 Plasmids:
bla
NDM-16b
Likely Emerged from a Mutation of
bla
NDM-5
on IncX3 Plasmid
Authors: Ariyoshi Tsukasa , Aoki Kotaro , Kubota Hiroaki , Sadamasu Kenji , Ishii Yoshikazu , Tateda Kazuhiro
Published: July 2022

bla
NDM
-carrying IncX3 plasmids have been reported worldwide. Harbored
bla
NDM
variants were mainly
bla
NDM-5
, but there were also rare variants like
bla
NDM-17
,
bla
NDM-19
,
bla
NDM-20
,
bla
NDM-21
, and
bla
NDM-33
, including
bla
NDM-16b
detected in this study.
Swiss chiropractic practice-based research network and musculoskeletal pain cohort pilot study: protocol of a nationwide resource to advance musculoskeletal health services research
Authors: Lalji Rahim , Hofstetter Léonie , Kongsted Alice , von Wyl Viktor , Puhan Milo A , Hincapié Cesar A
Published: July 2022

Introduction

Musculoskeletal (MSK) pain conditions, a leading cause of global disability, are usually first managed in primary care settings such as medical, physiotherapy, and chiropractic community-based practices. While chiropractors often treat MSK conditions, there is limited real-world evidence on the topic of health service outcomes among patients receiving this type of care. A nationwide Swiss chiropractic practice-based research network (PBRN) and MSK pain patient cohort study will have potential to monitor the epidemiological trends of MSK pain conditions and contribute to healthcare quality improvement. The primary aims of this protocol are to (1) describe the development of an MSK-focused PBRN within the Swiss chiropractic setting, and (2) describe the methodology of the first nested study to be conducted within the PBRN—an observational prospective patient cohort pilot study.

Methods and analysis

This initiative is conceptualised with two distinct phases. Phase I focuses on the development of the Swiss chiropractic PBRN, and will use a cross-sectional design to collect information from chiropractic clinicians nationwide. Phase II will recruit consecutive patients aged 18 years or older with MSK pain from community-based chiropractic practices participating in the PBRN into a prospective chiropractic cohort pilot study. All data collection will occur through electronic surveys offered in the three Swiss official languages (German, French, Italian) and English. Surveys will be provided to patients prior to their initial consultation in clinics, 1 hour after initial consultation, and at 2, 6 and 12 weeks after initial consultation.

Ethics and dissemination

Ethics approval has been obtained from the independent research ethics committee of Canton Zurich (BASEC-Nr: 2021-01479). Informed consent will be obtained electronically from all participants. Findings will be reported to stakeholders after each study phase, presented at local and international conferences, and disseminated through peer-reviewed publications.

Study pre-registration

Phase I—Swiss chiropractic PBRN (ClinicalTrials.gov identifier: NCT05046249); Phase 2—Swiss chiropractic cohort (Swiss ChiCo) pilot study (ClinicalTrials.gov identifier: NCT05116020).
Improving the Detection, Assessment, Management and Prevention of Delirium in Hospices (the DAMPen-D study): protocol for a co-design and feasibility study of a flexible and scalable implementation strategy to deliver guideline-adherent delirium care
Authors: Pearson Mark , Jackson Gillian , Jackson Catriona , Boland Jason , Featherstone Imogen , Huang Chao , Ogden Margaret , Sartain Kathryn , Siddiqi Najma , Twiddy Maureen , Johnson Miriam
Published: July 2022

Introduction

Delirium is a complex condition in which altered mental state and cognition causes severe distress and poor clinical outcomes for patients and families, anxiety and stress for the health professionals and support staff providing care, and higher care costs. Hospice patients are at high risk of developing delirium, but there is significant variation in care delivery. The primary objective of this study is to demonstrate the feasibility of an implementation strategy (designed to help deliver good practice delirium guidelines), participant recruitment and data collection.

Methods and analysis

Three work packages in three hospices in the UK with public involvement in codesign, study management and stakeholder groups: (1) experience-based codesign to adapt an existing theoretically-informed implementation strategy (Creating Learning Environments for Compassionate Care (CLECC)) to implement delirium guidelines in hospices; (2) feasibility study to explore ability to collect demographic, diagnostic and delirium management data from clinical records (n=300), explanatory process data (number of staff engaged in CLECC activities and reasons for non-engagement) and cost data (staff and volunteer hours and pay-grades engaged in implementation activities) and (3) realist process evaluation to assess the acceptability and flexibility of the implementation strategy (preimplementation and postimplementation surveys with hospice staff and management, n=30 at each time point; interviews with hospice staff and management, n=15). Descriptive statistics, rapid thematic analysis and a realist logic of analysis will be used be used to analyse quantitative and qualitative data, as appropriate.

Ethics and dissemination

Ethical approval obtained: Hull York Medical School Ethics Committee (Ref 21/23), Health Research Authority Research Ethics Committee Wales REC7 (Ref 21/WA/0180) and Health Research Authority Confidentiality Advisory Group (Ref 21/CAG/0071). Written informed consent will be obtained from interview participants. A results paper will be submitted to an open access peer-reviewed journal and a lay summary shared with study site staff and stakeholders.

Trial registration number

ISRCTN55416525.