Biomechanical comparison of bone staple fixation methods with suture material for median sternotomy closure using 3D-printed bone models.

AIM: To compare the biomechanical properties of three different sternal closure techniques in a 3D-printed bone model of a sternum from a 30-kg dog. METHODS: Median sternotomy was performed on a total of 90 three-dimensional (3D) copies of a polycarbonate (PC) model of a sternum, generated from the CT images of the sternum of a 30-kg German Shepherd dog. Three different methods were used to repair the sternotomies: polydioxanone suture (group PDS, n = 30), stainless steel bone staples (group SS, n = 30), and nitinol bone staples (group NS, n = 30). Each repair method was tested by applying tensile force in one of three ways (longitudinally, laterally, or torsionally) resulting in a sample size of n = 10 for each repair method-loading combination. In all experiments, the loads at 1-mm and 2-mm gap formation, failure, and the displacement at the failure point were measured. RESULTS: In lateral distraction and longitudinal shear tests, NS and SS staple repairs required application of significantly greater force than PDS across all displacement criteria (1 and 2 mm). NS exhibited significantly greater failure load than PDS. In torsion tests, NS required significantly greater application of force compared to SS or PDS at all displacement criteria (1 and 2 mm) and exhibited a greater failure load than PDS. In terms of displacement at failure point, PDS suture showed more displacement than SS or NS across all experiments (laterally, longitudinally, torsionally). CONCLUSIONS: In this study, bone staples were mechanically superior to PDS suture in median sternotomy closure using 3D-printed bone model in terms of 1-mm, 2-mm displacement loads, and displacement at failure. NS had a higher failure load than PDS under lateral, longitudinal, and torsional distraction. CLINICAL RELEVANCE: These study results imply that bone staples can be considered as an alternative surgical method for median sternotomy closure in dogs.

Improving digital partner notification for sexually transmitted infections and HIV through a systematic review and application of the Behaviour Change Wheel approach.

BACKGROUND: Partner notification (PN) is key to controlling sexually transmitted infections (STIs) and human immunodeficiency virus (HIV). Digital PN options (e.g. social media, short message service (SMS), emails) are promising in increasing PN behaviour. However, their implementation is often challenging and studies report varied levels of acceptability and uptake of PN, highlighting the need to optimise digital PN interventions. METHODS: A systematic review of barriers and facilitators to digital PN interventions for STIs, including HIV, across eight research databases (from 2010 to 2023) identified eight relevant studies, two of which addressed HIV. Data extraction identified 98 barriers and 54 facilitators to the use of digital PN interventions. These were synthesised into 18 key barriers and 17 key facilitators that were each deemed amenable to change. We then used the Behaviour Change Wheel approach, the Acceptability, Practicability, Effectiveness, Affordability, Side-effects and Equity criteria, and multidisciplinary expert input, to systematically develop practical recommendations to optimise digital PN. RESULTS: Thirty-two specific recommendations clustered around three themes. Digital PN interventions should: (1) empower and support the index patient by providing a range of notification options, accompanied by clear instructions; (2) integrate into users' existing habits and the digital landscape, meeting contemporary standards and expectations of usability; and (3) address the social context of PN both online and offline through normalising the act of PN, combating STI-related stigma and stressing the altruistic aspects of PN through consistent messaging to service users and the public. CONCLUSIONS: Our evidence-based recommendations should be used to optimise existing digital PN interventions and inform the co-production of new ones.

Search for Boosted Dark Matter in COSINE-100.

We search for energetic electron recoil signals induced by boosted dark matter (BDM) from the galactic center using the COSINE-100 array of NaI(Tl) crystal detectors at the Yangyang Underground Laboratory. The signal would be an excess of events with energies above 4 MeV over the well-understood background. Because no excess of events are observed in a 97.7 kg·yr exposure, we set limits on BDM interactions under a variety of hypotheses. Notably, we explored the dark photon parameter space, leading to competitive limits compared to direct dark photon search experiments, particularly for dark photon masses below 4 MeV and considering the invisible decay mode. Furthermore, by comparing our results with a previous BDM search conducted by the Super-Kamionkande experiment, we found that the COSINE-100 detector has advantages in searching for low-mass dark matter. This analysis demonstrates the potential of the COSINE-100 detector to search for MeV electron recoil signals produced by the dark sector particle interactions.

Identification of Inhibitors of the Schistosoma mansoni VKR2 Kinase Domain.

Schistosomiasis is a neglected tropical disease caused by parasitic flatworms. Current treatment relies on just one partially effective drug, praziquantel (PZQ). Schistosoma mansoni Venus Kinase Receptors 1 and 2 (SmVKR1 and SmVKR2) are important for parasite growth and egg production, and are potential targets for combating schistosomiasis. VKRs consist of an extracellular Venus Flytrap Module (VFTM) linked via a transmembrane helix to a kinase domain. Here, we initiated a drug discovery effort to inhibit the activity of the SmVKR2 kinase domain (SmVKR2KD) by screening the GSK published kinase inhibitor set 2 (PKIS2). We identified several inhibitors, of which four were able to inhibit its enzymatic activity and induced phenotypic changes in ex vivo S. mansoni. Our crystal structure of the SmVKR2KD displays an active-like state that sheds light on the activation process of VKRs. Our data provide a basis for the further exploration of SmVKR2 as a possible drug target.

A novel blended placement model improves dietitian students' work-readiness and wellbeing and has a positive impact on rural communities: a qualitative study.

BACKGROUND: Clinical placement models that require students to relocate frequently can cause stress, which may impact the student experience and development of work-readiness skills. A blended placement, where placements are undertaken concurrently at one location has potential to address these issues by providing a positive placement experience. Blended long-stay placements undertaken in rural communities increase consistent service provision and may help encourage students to work rurally, with potential to reduce workforce shortages. The aim of this study was to pilot test the feasibility of blended placement models and explore the student experience and skills development. A secondary aim was to explore a fully blended long-stay rural placement and the benefits to the rural community. METHODS: An exploratory qualitative design was used. Focus groups were conducted with dietitian student who participated in usual placements (n = 14) or blended placements (n = 9). Individual semi-structured interviews were conducted with five student supervisors who participated in blended placements. Focus groups and interviews were recorded, transcribed verbatim and analysed together using inductive thematic analyses. RESULTS: The overarching theme across all blended model placements was 'enhanced work-readiness', including increased flexibility, organisational skills and better preparedness for mixed roles. Enhanced work-readiness was influenced by three themes: stress and wellbeing impacts learning, working in two areas of practice concurrently allows for deeper learning, and blended placements meet supervisor needs. Fully blended long-stay rural placements revealed additional benefits. Firstly, in relation to the overarching theme 'enhanced work-readiness': students on these placements also developed extra skills in innovation, social accountability, interprofessional collaboration, conflict resolution and teamwork. Secondly, a new overarching theme emerged for fully blended long-stay rural placements: 'increased community connections' which included additional health services delivery, deeper personal experience and more rewarding student-supervisor relationships. Thirdly, two extra themes emerged that influenced work-readiness and community impact: 'local organisational support and resources' and 'enhanced innovative and interprofessional learning opportunities'. CONCLUSIONS: Blended placements enhance work-readiness skills by providing an alternative model to that commonly applied, and providing flexibility in education programs. Additionally, fully blended long-stay rural placements positively influence the local community through impacting the student experience as well as providing more dietetics services and may therefore assist in reducing dietetics workforce shortages and health inequity.

Electrocatalytic Behavior of PtCu Clusters Produced by Nanoparticle Beam Deposition.

State-of-the-art electrocatalysts for electrolyzer and fuel cell applications currently rely on platinum group metals, which are costly and subject to supply risks. In recent years, a vast collection of research has explored the possibility of reducing the Pt content in such catalysts by alloying with earth-abundant and cheap metals, enabling co-optimization of cost and activity. Here, using nanoparticle beam deposition, we explore the electrocatalytic performance of PtCu alloy clusters in the hydrogen evolution reaction (HER). Elemental compositions of the produced bimetallic clusters were shown by X-ray photoelectron spectroscopy (XPS) to range from 2 at. % to 38 at. % Pt, while high-angle annular dark field scanning transmission electron microscopy (HAADF-STEM) combined with energy dispersive X-ray (EDX) spectroscopy indicated that the predominant cluster morphologies could be characterized as either a fully mixed alloy or as a mixed core with a Cu-rich shell. In contrast with previous studies, a monotonic decrease in HER activity with increasing Cu content was observed over the composition range studied, with the current density measured at -0.3 V (vs reversible hydrogen electrode) scaling approximately linearly with Pt at. %. This trend opens up the possibility that PtCu could be used as a reference system for comparing the composition-dependent activity of other bimetallic catalysts.

Fourteen Recommendations to Create a More Inclusive Environment for LGBTQ+ Individuals in Academic Biology.

Individuals who identify as lesbian, gay, bisexual, transgender, queer, and otherwise nonstraight and/or non-cisgender (LGBTQ+) have often not felt welcome or represented in the biology community. Additionally, biology can present unique challenges for LGBTQ+ students because of the relationship between certain biology topics and their LGBTQ+ identities. Currently, there is no centralized set of guidelines to make biology learning environments more inclusive for LGBTQ+ individuals. Rooted in prior literature and the collective expertise of the authors who identify as members and allies of the LGBTQ+ community, we present a set of actionable recommendations to help biologists, biology educators, and biology education researchers be more inclusive of individuals with LGBTQ+ identities. These recommendations are intended to increase awareness of LGBTQ+ identities and spark conversations about transforming biology learning spaces and the broader academic biology community to become more inclusive of LGBTQ+ individuals.

Computational reverse engineering of the lipase from Pseudomonas aeruginosa PAO1: α-helices.

Lipases are important enzymes in many biochemical industries, thus making them attractive targets for protein engineering to improve enzymatic properties. In this work, a ''reverse engineering'' approach was explored: disrupt secondary structures to determine their contribution to enzyme stability and activity. All the α-helices of the lipase from Pseudomonas aeruginosa PAO1 (PAL) were systematically disrupted using computational proline mutagenesis and molecular dynamics (MD) simulations. This method identified the α3 mutant (R89P), located within the vicinity of the active site, to be significantly important for stability and activity. In addition, the α6 system (L159P), part of the ''cap'' domain that regulates substrate entry into the active site, was found to be critical for activity as it pushed the lipase to adopt a completely closed conformation. The perturbation introduced by the proline mutations resulted in increased backbone flexibility that significantly decreased protein stability. Moreover, mutations within the cap domain helices - α4 (A115P), α5 (S132P, G139P), α6 (L159P), and α7 (R169P) - resulted in increased flexibility of the N-terminal region of the α5 helix, the mobile ''lid'' helix, that pushes the gorge into a partially closed conformation. The α6 mutation (L159P) further increased the flexibility of the helix-loop region at the C-terminal end of the α5 helix to push the lid into the fully closed state. Therefore, the α3 and α6 helices could be ''hot spots'' for stabilizing mutations that could improve the overall enzyme stability and activity this lipase. The insights obtained in this work may be validated experimentally in future works.

Search for η

We measured missing mass spectrum of the ^{12}C(γ,p) reaction for the first time in coincidence with potential decay products from η^{'} bound nuclei. We tagged an (η+p) pair associated with the η^{'}N→ηN process in a nucleus. After applying kinematical selections to reduce backgrounds, no signal events were observed in the bound-state region. An upper limit of the signal cross section in the opening angle cosθ_{lab}^{ηp}<-0.9 was obtained to be 2.2 nb/sr at the 90% confidence level. It is compared with theoretical cross sections, whose normalization ambiguity is suppressed by measuring a quasifree η^{'} production rate. Our results indicate a small branching fraction of the η^{'}N→ηN process and/or a shallow η^{'}-nucleus potential.

Catalytic cleavage of HEAT and subsequent covalent binding of the tetralone moiety by the SARS-CoV-2 main protease

Here we present the crystal structure of SARS-CoV-2 main protease (Mpro) covalently bound to 2-methyl-1-tetralone. This complex was obtained by co-crystallization of Mpro with HEAT (2-(((4-hydroxyphenethyl)amino)methyl)-3,4-dihydronaphthalen-1(2H)-one) in the framework of a large X-ray crystallographic screening project of Mpro against a drug repurposing library, consisting of 5632 approved drugs or compounds in clinical phase trials. Further investigations showed that HEAT is cleaved by Mpro in an E1cB-like reaction mechanism into 2-methylene-1-tetralone and tyramine. The catalytic Cys145 subsequently binds covalently in a Michael addition to the methylene carbon atom of 2-methylene-1-tetralone. According to this postulated model HEAT is acting in a pro-drug-like fashion. It is metabolized by Mpro, followed by covalent binding of one metabolite to the active site. The structure of the covalent adduct elucidated in this study opens up a new path for developing non-peptidic inhibitors.

Active site manipulation in MoS2 cluster electrocatalysts by transition metal doping.

The development of non-platinum group metal catalysts for the hydrogen evolution reaction (HER) in water electrolyser devices is essential for their widespread and sustainable deployment. In recent years, molybdenum disulfide (MoS2) catalysts have received significant attention as they not only exhibit good electrocatalytic HER activity but also, crucially, acid-stability. However, further performance enhancement is required for these materials to be competitive with Pt and to that end transition metal doping of MoS2 has been explored as a route to further increasing its catalytic activity. In this work, cluster beam deposition was employed to produce controlled cobalt-doped MoS2 clusters (MoS2-Co). We demonstrate that, in contrast to previous observations of performance enhancement in MoS2 resulting from nickel doping (MoS2-Ni), the introduction of Co has a detrimental effect on HER activity. The contrasting behaviours of Ni and Co doping are rationalized by density functional theory (DFT) calculations, which suggest that HER-active surface vacancies are deactivated by combination with Co dopant atoms, whilst their activity is retained, or even partially enhanced, by combination with Ni dopant atoms. Furthermore, the adatom dopant-vacancy combination kinetics appear to be more than three orders of magnitude faster in MoS2-Co than for MoS2-Ni. These findings highlight a fundamental difference in the influence of transition metal dopants on the HER performance of MoS2 electrocatalysts and stress the importance of considering surface atomic defects when predicting their behaviour.

Identification of heat shock protein gene expression in hair follicles as a novel indicator of heat stress in beef calves.

Heat shock proteins (HSPs) consist of highly preserved stress proteins that are expressed in response to stress. Two studies were carried out to investigate whether HSP genes in hair follicles from beef calves can be suggested as indicators of heat stress (HS). In study 1, hair follicles were harvested from three male Hanwoo calves (aged 172.2 ± 7.20 days) on six dates over the period of 10 April to 9 August 2017. These days provided varying temperature-humidity indices (THIs). In study 2, 16 Hanwoo male calves (aged 169.6 ± 4.60 days, with a BW of 136.9 ± 6.23 kg) were maintained (4 calves per experiment) in environmentally controlled chambers. A completely randomized design with a 2 × 4 factorial arrangement involving two periods (thermoneutral: TN; HS) and four THI treatment groups (threshold: THI = 68 to 70; mild: THI = 74 to 76; moderate THI = 81 to 83; severe: THI = 88 to 90). The calves in the different group were subjected to ambient temperature (22°C) for 7 days (TN) and subsequently to the temperature and humidity corresponding to the target THI level for 21 days (HS). Every three days (at 1400 h) during both the TN and HS periods, the heart rate (HR) and rectal temperature (RT) of each individual were measured, and hair follicles were subsequently collected from the tails of each individual. In study 1, the high variation (P < 0.0001) in THI indicated that the external environment influenced the HS to different extents. The expression levels of the HSP70 and HSP90 genes at the high-THI level were higher (P = 0.0120, P = 0.0002) than those at the low-THI level. In study 2, no differences in the THI (P = 0.2638), HR (P = 0.2181) or RT (P = 0.3846) were found among the groups during the TN period, whereas differences in these indices (P < 0.0001, P < 0.0001 and P < 0.0001, respectively) were observed during the HS period. The expression levels of the HSP70 (P = 0.0010, moderate; P = 0.0065, severe) and HSP90 (P = 0.0040, severe) genes were increased after rapid exposure to heat-stress conditions (moderate and severe levels). We conclude that HSP gene expression in hair follicles provides precise and accurate data for evaluating HS and can be considered a novel indicator of HS in Hanwoo calves maintained in both external and climatic chambers.

Exploring the Relationship between Teacher Knowledge and Active-Learning Implementation in Large College Biology Courses.

Not all instructors implement active-learning strategies in a way that maximizes student outcomes. One potential explanation for variation in active-learning effectiveness is variation in the teaching knowledge an instructor draws upon. Guided by theoretical frameworks of pedagogical content knowledge and pedagogical knowledge, this study investigated the teaching knowledge instructors used in planning, implementing, and reflecting on active-learning lessons in large courses. We used a preinstruction interview, video footage of a target class session, and a postinstruction interview with stimulated recall to elicit the teaching knowledge participants used. We then conducted qualitative content analysis to describe and contrast teaching knowledge employed by instructors implementing active learning that required students to generate their own understandings (i.e., generative instruction) and active learning largely focused on activity and recall (i.e., active instruction). Participants engaging in generative instruction exhibited teaching knowledge distinct from that of participants focused on activity. Those using generative instruction drew on pedagogical knowledge to design lessons focused on students generating reasoning; integrated pedagogical content knowledge and pedagogical knowledge to plan lessons to target student difficulties; and created opportunities to develop new pedagogical content knowledge while teaching. This work generated hypotheses about the teaching knowledge necessary for effective, generative active-learning instruction.

Search for a Dark Matter-Induced Annual Modulation Signal in NaI(Tl) with the COSINE-100 Experiment.

We present new constraints on the dark matter-induced annual modulation signal using 1.7 years of COSINE-100 data with a total exposure of 97.7 kg yr. The COSINE-100 experiment, consisting of 106 kg of NaI(Tl) target material, is designed to carry out a model-independent test of DAMA/LIBRA's claim of WIMP discovery by searching for the same annual modulation signal using the same NaI(Tl) target. The crystal data show a 2.7 cpd/kg/keV background rate on average in the 2-6 keV energy region of interest. Using a χ-squared minimization method we observe best fit values for modulation amplitude and phase of 0.0092±0.0067 cpd/kg/keV and 127.2±45.9 d, respectively.

Design optimization of a fast-neutron detector with scintillating fibers for triton burnup experiments at fusion experimental devices.

Time-resolved triton burnup studies have been carried out to estimate the behavior of alpha particles in DD fusion experimental devices. In those studies, 14 MeV neutrons emitted through DT reactions in DD plasmas should be measured selectively in the backgrounds of DD neutrons and gamma rays. For this purpose, a scintillating-fiber (Sci-Fi) based fast-neutron detector has been adapted because of its advantages such as fast response, design flexibility in detection efficiency by changing the number of Sci-Fi, and discrimination property against 2.4 MeV neutrons produced through DD reactions and gamma rays. However, its length had conventionally been set to around 10 cm without an optimization study of its design parameters to meet the requirements as 14 MeV neutron detector. In the present study, we tested three types of Sci-Fi detectors with three different lengths and compared with the simulated results of energy deposition, through which we tried to understand the phenomena in the detection process of fast neutrons. From the results, it has been shown that, due to the self-shielding of neutrons by Sci-Fi and the attenuation of scintillation photons during the transmission process to the photomultiplier tube, the optimal length of Sci-Fi is concluded to be about 6 cm.