bluuebunny/crossref_metadata_2025 huggingface dataset:
What constitutes brilliant aged care? A qualitative study of practices that exceed expectation
Authors: Dadich Ann , Kearns Rachael , Harris‐Roxas Ben , Ni Chroinin Danielle , Boydell Katherine , Ní Shé Éidín , Lim David , Gonski Peter , Kohler Friedbert
Published: June 2023

Aim

This study aimed to explore what constitutes brilliant aged care.

Background

Although many aged care services do not offer the care that older people and carers need and want, some perform better. Rather than focus on problems with aged care, this study examined brilliant aged care—practices that exceeded expectation.

Design

The methodology for this study was informed by grounded theory, underpinned by constructionism to socially construct meaning.

Methods

This study invited nominations for a Brilliant Award via a survey, and interviews with the nominees via web conference. After receiving survey responses from 10 nominators, interviews were conducted with 12 nominees. Data were analysed using reflexive thematic analysis and documented according to COREQ guidelines to optimise rigour and transparency.

Results

According to participants, brilliant aged care involved being relationally attuned to older people, a deep understanding of the older person, recognition of aged care as more than a job, innovative practices and permission to reprioritise.

Conclusions

This study suggests that, in aged care, brilliance happens. It emphasises the importance of meaningful connections and relationships in aged care, where thoughtful acts acknowledge an older person's value and humanity as well as creativity and innovation.

Relevance to Clinical Practice

For those who manage and deliver aged care, the findings suggest that small practice changes can make a positive difference to older people. Brilliant aged care can involve acts of empathy; enthusiasm for aged care; innovative practices, even those that are small scale; and reprioritising workplace tasks to spend time with older people. For policymakers, this study highlights the need to recognise and raise the profile of the pockets of brilliance within the aged care sector. This might be achieved via awards and other initiatives that serve to celebrate and learn from brilliance in its myriad forms.

Patient or Public Contribution

The nominees, who included carers, were invited to participate in workshops with other carers and older people to co‐design a model of brilliant aged care, during which workshop participants discussed and critiqued the findings constructed from the data.
The Dent in the Floor: Ecological Knowing in the Skilful Performance of Work
Authors: Butler Michael J. R. , Cunliffe Ann L.
Published: June 2023

This paper draws on a phenomenological perspective to explore how people develop and enact skill in work at throughecological knowing– a sensuous form of knowing in one's being embedded in and across place and time. In doing so, we abductively interweave the work of Finnish architect Juhani Pallasmaa and British anthropologist Tim Ingold with an empirical study of two industrial museums and two contemporary illustrations of choral conducting and motion capture performance. Our contribution is threefold: first, we expand theories of knowledge and corporeality by theorizing ecological knowing as encompassing emplaced wisdom and embodied skill – thus elevating embedded and embodied human agency in contrast to studies that focus on the body, skill, and knowledge as objects. Secondly, we present an alternative way of understanding how expertise develops and is enacted in work activities. Finally, we offer methodological resources, currently underutilized in management studies, for studying this sensorial form of knowing in a way that is consistent with its underlying phenomenological commitments.
How does it feel to be greedy? The role of pride in avaricious acquisition
Authors: Mercadante Eric J. , Tracy Jessica L.
Published: June 2023

Background

Psychologists define greed as a desire to acquire more and the dissatisfaction of never having enough, but studies have not examined the psychological processes that underlie and sustain this disposition. We propose that a desire to attain pride might be one emotional mechanism that promotes greedy acquisition. In this account, greedy people experience a boost of pride from acquisition but these feelings are short‐lived, potentially leading to the perpetual acquisitiveness characteristic of dispositional greed.

Method

Four studies (including one reported in the SOM due to space limitations) using correlational, longitudinal, and daily‐diary methods (N = 1778) test hypotheses about how individuals high in dispositional greed respond emotionally to new acquisitions, both when they occur and several weeks later.

Results

Greedy people experience heightened feelings of authentic pride in response to new acquisitions, but these feelings quickly fade. This pattern is distinct to authentic pride and not attributable to shared variance with positive affect. Greedy people also feel elevated hubristic pride in response to acquisitions, but this seems to be part of a dispositional tendency observed in response to a range of events.

Conclusions

These studies provide a new understanding of a psychological process that is associated with, and could partially explain, greedy acquisition.
Associations between higher plasma ferritin and hepcidin levels with liver stiffness in patients with type 2 diabetes: An exploratory study
Authors: Mantovani Alessandro , Csermely Alessandro , Castagna Annalisa , Antinori Elisa , Danese Elisa , Zusi Chiara , Sani Elena , Ravaioli Federico , Colecchia Antonio , Maffeis Claudio , Valenti Luca , Girelli Domenico , Targher Giovanni
Published: June 2023

Background

Currently, there is no information about the association between circulating levels of ferritin and hepcidin and liver fibrosis in patients with type 2 diabetes mellitus (T2DM) and non‐alcoholic fatty liver disease (NAFLD).

Methods

We enrolled 153 patients with T2DM with no known liver diseases, who consecutively attended our diabetes outpatient service and who underwent liver ultrasonography and liver stiffness measurement (LSM) by vibration‐controlled transient elastography (Fibroscan® for the non‐invasive assessment of liver fibrosis). Plasma ferritin and hepcidin concentrations were measured with an electrochemiluminescence immunoassay and mass spectrometry‐based assay, respectively.

Results

After stratification of patients by LSM tertiles [1st tertile median LSM: 3.6 (interquartile range: 3.3–4.0) kPa, 2nd tertile: 5.3 (4.9–5.9) kPa and 3rd tertile: 7.9 (6.7–9.4) kPa], we found that plasma ferritin and hepcidin concentrations increased across LSM tertiles [median ferritin: 68.7 (interquartile range: 25.1–147) vs. 85.8 (48.3–139) vs. 111 (59.3–203) μg/L, p = 0.021; median hepcidin: 2.5 (1.1–5.2) vs. 4.4 (2.5–7.3) vs. 4.1 (1.9–6.8) nmol/L, p = 0.032]. After adjustment for age, sex, diabetes duration, waist circumference, haemoglobin A1c, HOMA‐insulin resistance score, triglycerides, haemoglobin, presence of hepatic steatosis on ultrasonography and patatin‐like phospholipase domain‐containing‐3 (PNPLA3) rs738409 genetic variant, higher plasma ferritin levels were associated with greater LSM values (adjusted‐odds ratio 2.10, 95% confidence interval 1.23–3.57, p = 0.005). Higher plasma hepcidin levels were also associated with greater LSM values (adjusted‐odds ratio 1.90, 95% confidence interval 1.15–3.13, p = 0.013).

Conclusions

Higher levels of plasma ferritin and hepcidin were associated with greater NAFLD‐related liver fibrosis (assessed by LSM) in patients with T2DM, even after adjustment for established cardiometabolic risk factors, diabetes‐related variables and other potential confounders.
The PcMYB44‐mediated miR397‐PcLACs module regulates defence‐induced lignification in pear resistance to fungal disease
Authors: Yang Yuekun , He Ying , Lv Shamei , Zhu Haodong , Wang Tingting , Wang Guoping , Hong Ni , Wang Liping
Published: June 2023

Diseases caused by Alternaria alternata and Botryosphaeria dothidea diminish pear yield and quality, and restrict the pear agricultural industry. Lignification is a conserved mechanism for plant resistance against pathogen invasion. The regulatory mechanisms underlying defence‐induced lignification in pear in response to fungal pathogen infection remain unknown. In this study, analysis of lignification level and lignin content in pear revealed that A. alternata and B. dothidea induced lignification, and transcriptomics showed that lignin biosynthesis was affected. To explore whether laccases (LACs) mediated by miR397 regulate lignification in pear, we investigated the role of PcmiR397 in repressing the expression of PcLACs using 5′‐RNA ligase‐mediated‐RACE and co‐transformation in tobacco. Opposite expression patterns for PcmiR397 and PcLAC target genes were observed in pear in response to pathogens. Transient transformation in pear demonstrated that silencing PcmiR397 and overexpressing a single PcLAC enhanced resistance to pathogens via lignin synthesis. To further reveal the mechanism underpinning the PcMIR397 response of pear to pathogens, the PcMIR397 promoter was analysed, and pMIR397‐1039 was found to be inhibited by pathogen infection. The transcription factor PcMYB44 was up‐regulated, and it bound to the PcMIR397 promoter and inhibited transcription following pathogen infection. The results demonstrate the role of PcmiR397‐PcLACs in broad‐spectrum resistance to fungal disease, and the potential role of PcMYB44 involved in the miR397‐PcLAC module in regulating defence‐induced lignification. The findings provide valuable candidate gene resources and guidance for molecular breeding to improve resistance to fungal disease in pear.
Comparative applicability of MCDM‐SWOT based techniques for developing integrated watershed management framework
Authors: Nasiri Khiavi Ali , Vafakhah Mehdi , Sadeghi Seyed Hamidreza
Published: June 2023

Environmental planning facilitates decision‐making to achieve sustainable development goals and provides a crucial way to achieve integrated watershed management (IWM). However, such systematic planning has not been adequately conducted worldwide. Therefore, this study was conducted to develop an IWM framework using SWOT (i.e., strengths, weaknesses, opportunities, and threats) model for the Cheshmeh–Kileh Watershed, Mazandaran Province, Iran. The input components were comparatively weighted using different multicriteria decision‐making (MCDM) techniques, including Game Theory Algorithm (GTA), Best–Worst Method (BWM), VIekriterijumsko KOmpromisno Rangiranje (VIKOR), Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS), and Simple Additive Weighting (SAW). Semistructured interviews with stakeholders, including watershed residents, executive experts, and policymakers, were used to identify the SWOT factors. The number of interviewees in subgroups of local users, policy‐making institutions and executive organization were 75, 13, and 6 respectively. Five different MCDM techniques were then used to calculate the overall weight of SWOT factors. According to the results, the groups of SWOT factors of abundant water resources, severe floods, promotion of environmental conservation culture, and increasing migration of young age groups with respective weights of 0.298, 0.298, 0.372, and 0.279 scored higher than other factors. Based on the overall weights, it can be said that positive factors scored more points than negative factors. Therefore, according to the opinions of the stakeholders, the Cheshmeh–Kileh Watershed was in a good condition based on strengths and opportunities compared to weaknesses and threats, and for this reason, GTA and SAW, which had included the watershed status in the growth and development strategy, were selected as the best method. BWM and TOPSIS provided relatively acceptable results, and the weakest result was associated with VIKOR, which showed the watershed status in the defensive strategy. The present study results can help managers in optimal decisions for planning and optimal management in the Cheshmeh–Kileh Watershed to create ecological balance and increase the welfare of watershed residents.
Clinical and epidemiological risk factors for infantile hemangioma: A case‐control study
Authors: Chehad Ahmed Samaouel , Hamza Odai , Mansoul Tarek
Published: June 2023

There is limited data on risk‐factors of infantile hemangioma (IH) in African and Arab countries. One hundred thirty‐two patients with IH were enrolled and compared to 282 healthy controls. Female sex (odds ratios [OR]: 2.2; 95% confidence interval [CI] 1.4–3.6), low birth weight (OR: 4.5; 95% CI 1.9–10.6), and progesterone intake (OR: 38.6; 95% CI 5–296) were the only independent risk factors identified for development of IH, while no associations were found multiple gestation and preeclampsia.
Europe's contribution to the evaluation of the use of systemic antimicrobials in the treatment of periodontitis
Authors: Herrera David , van Winkelhoff Arie Jan , Matesanz Paula , Lauwens Katalina , Teughels Wim
Published: June 2023

This narrative review celebrates Europe's contribution to the current knowledge on systemically administered antimicrobials in periodontal treatment. Periodontitis is the most frequent chronic noncommunicable human disease. It is caused by dysbiotic bacterial biofilms and is commonly treated with subgingival instrumentation. However, some sites/patients do not respond adequately, and its limitations and shortcomings have been recognized. This has led to the development of alternative or adjunctive therapies. One is the use of antimicrobials to target bacteria in subgingival biofilms in the periodontal pocket, which can be targeted directly through the pocket entrance with a locally delivered antibiotic or systemically by oral, intravenous, or intramuscular methods. Since the early 20th century, several studies on systemic antibiotics have been undertaken and published, especially between 1990 and 2010. Europe's latest contribution to this topic is the first European Federation of Periodontology, S3‐level Clinical Practice Guideline, which incorporates recommendations related to the use of adjuncts to treat stage I‐III periodontitis. Understanding the etiopathogenesis of periodontal diseases, specifically periodontitis, has influenced the use of systemic periodontal antibiotic therapy. Randomized clinical trials and systematic reviews with meta‐analyses have demonstrated the clinical advantages of adjunctive systemic antimicrobials. However, current recommendations are restrictive due to concerns about antibiotic misuse and the increase in microbial antibiotic resistance. European researchers have contributed to the use of systemic antimicrobials in the treatment of periodontitis through clinical trials and by providing rational guidelines. Nowadays, European researchers are exploring alternatives and directing clinical practice by providing evidence‐based guidelines to limit the use of systemic antimicrobials.
Monogenean Sparicotyle chrysophrii: The major pathogen of the Mediterranean gilthead seabream aquaculture
Authors: Mladineo Ivona , Volpatti Donatella , Beraldo Paola , Rigos George , Katharios Pantelis , Padros Francesc
Published: June 2023

Following the intensification of the Mediterranean aquaculture over the years, Sparicotyle (syn. Microcotyle) chrysophrii (van Beneden and Hesse, 1863; Microcotylidae, Monogenea) became one of the most pathogenic ectoparasites for the gilthead seabream (Sparus aurata L.) aquaculture. It has demonstrated a remarkable versatility to expand over its known host range, accomplish an efficient transfer between the wild and farmed sparid populations over wide geographic areas, and establish itself as the most detrimental gilthead seabream pathogen. Even though the incidence of S. chrysophrii is closely monitored in marine aquaculture system throughout the Mediterranean, there is a general lack of recent and publicly available data on its epidemiology. Being considered as a parasite whose proliferation is expected to increase under global warming conditions, such lack of data additionally humpers the implementation of integrated pest management strategy at national and Mediterranean level. While EU scientific initiatives greatly contributed to our understanding of S. chrysophrii biology, ecology and sparicotylosis treatment and pathogenesis, there is more ahead to elucidate about the mitigation of the diseases, particularly towards the development of genomic selection breeding programs of parasite‐resilient gilthead seabream, omic‐based screening of novel drug targets and reversed vaccinology.
Effectiveness of fluorides in root caries prevention, Department of Veterans Affairs (2009–2018)
Authors: Jones Judith A. , Gibson Gretchen , Cabral Howard J. , Wehler Carolyn J. , Orner Michelle B. , Jurasic M. Marianne
Published: June 2023

Aims

The aim of this study was to examine the effectiveness of topical fluorides in prevention of root caries‐related treatment in high caries risk Veterans.

Methods

This retrospective analysis of longitudinal data examined the effectiveness of professionally applied or prescription (Rx) fluoride treatment, in VHA clinics from FY 2009–2018. Professional fluoride treatments included 5% Sodium Fluoride (NaF) varnish (22 600 ppm fluoride), 2% NaF gel/rinse (9050 ppm fluoride), and 1.23% APF gel (12 300 ppm fluoride). The Rx for daily home use was 1.1% NaF paste/gel (5000 ppm fluoride). Outcomes studied were new root caries restorations or extractions and percent of patients with treatment over 1 year. Logistic regressions were adjusted for age, gender, race, ethnicity, chronic medical or psychiatric conditions, number of medication classes, anticholinergic drugs, smoking, baseline root caries treatment, preventive care, and time between first‐last restoration in the index year.

Results

Root caries at baseline was associated with a high risk for new root caries. Veterans without root caries during the index year who received a fluoride gel/rinse intervention were 32–40% less likely to receive caries‐related treatment for root caries during the follow‐up period. Once Veterans had root caries, fluorides did not exhibit a positive effect.

Conclusion

In older adults with high caries risk, early fluoride prevention is key, before root caries requires treatment.
Effects of winter indoor environment on the skin: Unveiling skin condition changes in Korea
Authors: Park Eun Hye , Jo Da Jung , Jeon Hyo Won , Na Seong Jin
Published: June 2023

Background

In Korea, winter can cause skin dryness due to low relative humidity (RH); moreover, indoor heating devices promote moisture loss and air pollution. If dryness persists, dead skin cells accumulate, leading to skin problems; therefore, careful skin care is required. This study aimed to compare changes in skin conditions when exposed to an indoor environment for a short period of 6 h in winter, and to suggest proper winter skin care practices.

Methods

A randomized, split‐face clinical study was conducted in which healthy female participants with normal skin were exposed to an indoor environment with a heater turned on for a short period at least 6 h per day in the winter season, and cream was applied to one side of the face. Skin temperature, hydration, sebum, transepidermal water loss (TEWL), elasticity, texture, pores, redness, and wrinkles were measured at the treated and nontreated sites.

Results

After 6 h of exposure, skin temperature, pores, roughness, redness, and wrinkles significantly increased (p < 0.05) on the face, whereas TEWL significantly increased on the forearm (p < 0.05). However, sebum secretion appeared to function as a barrier to maintain homeostasis in the facial skin. Elasticity, pores, texture, and wrinkles in the cream‐treated ceramide site improved compared to those in the nontreated site (p < 0.05). The moisture content was also significantly higher in the forearm (p < 0.05).

Conclusion

Changes in skin parameters of participants with healthy skin were observed even after short‐term exposure to an indoor environment in winter. Creams containing ceramide maintain skin homeostasis and protect the skin barrier; therefore, it is recommended to use such creams to prevent skin damage and maintain healthy skin, particularly during prolonged exposure to indoor environments during winter.
Post‐hybridization introgression and natural selection promoted genomic divergence of Aegilops speltoides and the four S*‐genome diploid species
Authors: Wang Xin‐Feng , Zhang Yu‐Xin , Niu Yu‐Qian , Sha Yan , Wang Zhen‐Hui , Zhang Zhi‐Bin , Yang Ji , Liu Bao , Li Lin‐Feng
Published: June 2023

Understanding how different driving forces have promoted biological divergence and speciation is one of the central issues in evolutionary biology. The Triticum/Aegilops species complex contains 13 diploid species belonging to the A‐, B‐ and D‐lineages and offers an ideal system to address the evolutionary dynamics of lineage fusion and splitting. Here, we sequenced the whole genomes of one S‐genome species (Aegilops speltoides) of the B‐lineage and four S*‐genome diploid species (Aegilops bicornis, Aegilops longissima, Aegilops sharonensis and Aegilops searsii) of the D‐lineage at the population level. We performed detailed comparisons of the five species and with the other four representative A‐, B‐ and D‐lineage species. Our estimates identified frequent genetic introgressions from A‐ and B‐lineages to the D‐lineage species. A remarkable observation is the contrasting distributions of putative introgressed loci by the A‐ and B‐lineages along all the seven chromosomes to the extant D‐lineage species. These genetic introgressions resulted in high levels of genetic divergence at centromeric regions between Ae. speltoides (B‐lineage) and the other four S*‐genome diploid species (D‐lineage), while natural selection is a potential contributor to divergence among the four S*‐genome species at telomeric regions. Our study provides a genome‐wide view on how genetic introgression and natural selection acted together yet chromosome‐regionally divided to promote genomic divergence among the five S‐ and S*‐genome diploid species, which provides new and nuanced insights into the evolutionary history of the Triticum/Aegilops species complex.
Radiographic measures of the pelvis differ in British shorthair cats with dystocia and eutocia
Authors: Koca Davut , Yilmaz Osman , Avcilar Talha
Published: June 2023

The size of an animal's pelvis can have a substantial impact on the ease or difficulty of giving birth, which can vary depending on the breed. Radiography is a medical imaging technique that is commonly utilized in clinical cases to assess pelvic dimensions. The present retrospective, observational study was designed to evaluate pelvimetric differences in radiographic images of British Shorthair (BS) cats with dystocia and eutocia. Pelvimetric values (linear distance, angle, area, height/width) for ventrodorsal and laterolateral radiographic images were recorded in 15 BS cats with dystocia and 15 BS cats with eutocia. Statistical analysis of the obtained measurement values was performed. When the pelvimetric data were examined overall, it was seen that mean values, except the PL (pelvis length) measurement, were higher in cats with eutocia than in cats with dystocia. Vertical diameter, conjugate vera, coxal tuberosities, transversal diameter, acetabula, pelvic inclination, ischiatic arch, pelvis inlet area (PIA), and pelvic outlet area (POA) values were significantly higher in cats with eutocia than in cats with dystocia (P < 0.05). Mean PIA and POA measurement values in cats with dystocia were 22.89 ± 2.38 cm2 and 19.59 ± 1.90 cm2, respectively; in cats with eutocia, the mean was calculated as 27.16 ± 2.76 cm2 and 23.18 ± 1.88 cm2, respectively. In conclusion, the present study revealed that pelvimetric values, except the PL measurement, were higher in cats with eutocia than in cats with dystocia. Findings can be used to assist veterinarians in future clinical decision‐making for pregnant BS cats.
Successful reconstruction of full‐thickness skin defects in a swine model using simultaneous split‐thickness skin grafting and composite collagen microstructured dermal scaffolds
Authors: Luong Derek , Weisel Adam , Cohen Rachael , Spector Jason A. , Sapir‐Lekhovitser Yulia
Published: June 2023

Reconstitution of normal skin anatomy after full‐thickness skin loss may be accomplished using a combination of a dermal regeneration template (DRT) and a split thickness skin graft (STSG). However, because of the relatively low rate of cell infiltration and vascularisation of currently available DRTs, reconstruction is almost always performed in a two‐step procedure over the course of several weeks, resulting in multiple dressing changes, prolonged immobilisation and increased chance of infection. To mitigate the potential complications of this prolonged process, the collagen‐based dermal template DermiSphere™ was developed and tested in a single‐step procedure wherein DermiSphere and STSG were implanted simultaneously. When evaluated in a porcine, full thickness, excisional wound model, DermiSphere successfully supported simultaneous split thickness skin graft take and induced functional neodermal tissue deposition. When compared to a market leading product Integra Bilayer Wound Matrix, which was used in a multistep procedure (STSG placed 14 days after product implantation according to the product IFU), DermiSphere induced a similar moderate and transient inflammatory response that produced similar neodermal tissue maturity, thickness and vascularity, despite being implanted in a single surgical procedure leading to wound closure 2 weeks earlier. These data suggest that DermiSphere may be implanted in a single‐step procedure with an STSG, which would significantly shorten the time course required for the reconstruction of both dermal and epidermal components of skin after full thickness loss.
Experimental Investigations on Effect of Orientation on Thermal Performance of a Novel Phase Change Material-Based Heat Sink
Authors: Ravi Shankar Ch , Naresh Y.
Published: June 2023

As electronic devices generate heat while operating, thermal management is important in view of the reliability and lifespan of the device. Much research is focused on the improvement of charging time for continuous operations of the device. Moreover, for intermittent operation of devices, the reduction in the discharging time is also as essential as the improvement in the charging time. Therefore, the objective of the study is to develop a strategy that improves charging time and reduces discharging time. This paper reports the experimental heat transfer results of a novel phase change material (PCM)-based heat sink coupled with a heat pipe under different orientations. The experiments are conducted at a constant fill ratio of 99% on several heat sink configurations, such as a heat sink (i) with the stem at the center, (ii) with four fins, and (iii) with three longitudinal fins coupled with a heat pipe. The aluminum-made heat sink having an outer diameter of 58 mm and a height of 55 mm with a wall thickness of 4 mm, is used for all the heat sink configurations. The heat pipe with an evaporator length of 60 mm and a condenser length of 40 mm is attached at the center of a three-fin heat sink configuration. Experiments are performed on different heat sinks with n-Eicosane as PCM at different orientations of 0 deg, 45 deg, 90 deg, 135 deg, and 180 deg at various power levels. The heat input is varied between 6 W and 12 W. The condenser section of the heat pipe is cooled under two different conditions, i.e., (i) natural convection and (ii) forced convection. The results show that the finned heat sink coupled with a heat pipe (FHSHP) gives the best charging and discharging performance compared to other configurations. Moreover, it is observed that the performance of an FHSHP is orientation-dependent. Furthermore, the overall effectiveness of FHSHP is high when the condenser section of the heat pipe is cooled using forced convection rather than natural convection.
Monitoring α-synuclein ubiquitination dynamics reveals key endosomal effectors mediating its trafficking and degradation
Authors: Zenko Dmitry , Marsh Jade , Castle Andrew R. , Lewin Rahel , Fischer Roman , Tofaris George K.
Published: June 2023

While defective α-synuclein homeostasis is central to Parkinson’s pathogenesis, fundamental questions about its degradation remain unresolved. We have developed a bimolecular fluorescence complementation assay in living cells to monitor de novo ubiquitination of α-synuclein and identified lysine residues 45, 58, and 60 as critical ubiquitination sites for its degradation. This is mediated by NBR1 binding and entry into endosomes in a process that involves ESCRT I-III for subsequent lysosomal degradation. Autophagy or the autophagic chaperone Hsc70 is dispensable for this pathway. Antibodies against diglycine-modified α-synuclein peptides confirmed that endogenous α-synuclein is similarly ubiquitinated in the brain and targeted to lysosomes in primary and iPSC-derived neurons. Ubiquitinated α-synuclein was detected in Lewy bodies and cellular models of aggregation, suggesting that it may be entrapped with endo/lysosomes in inclusions. Our data elucidate the intracellular trafficking of de novo ubiquitinated α-synuclein and provide tools for investigating the rapidly turned-over fraction of this disease-causing protein.
SMYD2 inhibition–mediated hypomethylation of Ku70 contributes to impaired nonhomologous end joining repair and antitumor immunity
Authors: Tang Ming , Chen Guofang , Tu Bo , Hu Zhiyi , Huang Yujia , DuFort Christopher C. , Wan Xiaoping , Mao Zhiyong , Liu Yongzhong , Zhu Wei-Guo , Lu Wen
Published: June 2023

DNA damage repair (DDR) is a double-edged sword with different roles in cancer susceptibility and drug resistance. Recent studies suggest that DDR inhibitors affect immune surveillance. However, this phenomenon is poorly understood. We report that methyltransferase SMYD2 plays an essential role in nonhomologous end joining repair (NHEJ), driving tumor cells adaptive to radiotherapy. Mechanically, in response to DNA damage, SMYD2 is mobilized onto chromatin and methylates Ku70 at lysine-74, lysine-516, and lysine-539, leading to increased recruitment of Ku70/Ku80/DNA-PKcs complex. Knockdown of SMYD2 or its inhibitor AZ505 results in persistent DNA damage and improper repair, which sequentially leads to accumulation of cytosolic DNA, and activation of cGAS-STING pathway and triggers antitumor immunity via infiltration and activation of cytotoxic CD8
+
T cells. Our study reveals an unidentified role of SMYD2 in regulating NHEJ pathway and innate immune responses, suggesting that SMYD2 is a promising therapeutic target for cancer treatment.
Super-resolution vibrational imaging based on photoswitchable Raman probe
Authors: Shou Jingwen , Komazawa Ayumi , Wachi Yuusaku , Kawatani Minoru , Fujioka Hiroyoshi , Spratt Spencer John , Mizuguchi Takaha , Oguchi Kenichi , Akaboshi Hikaru , Obata Fumiaki , Tachibana Ryo , Yasunaga Shun , Mita Yoshio , Misawa Yoshihiro , Kojima Ryosuke , Urano Yasuteru , Kamiya Mako , Ozeki Yasuyuki
Published: June 2023

Super-resolution vibrational microscopy is promising to increase the degree of multiplexing of nanometer-scale biological imaging because of the narrower spectral linewidth of molecular vibration compared to fluorescence. However, current techniques of super-resolution vibrational microscopy suffer from various limitations including the need for cell fixation, high power loading, or complicated detection schemes. Here, we present reversible saturable optical Raman transitions (RESORT) microscopy, which overcomes these limitations by using photoswitchable stimulated Raman scattering (SRS). We first describe a bright photoswitchable Raman probe (DAE620) and validate its signal activation and depletion characteristics when exposed to low-power (microwatt level) continuous-wave laser light. By harnessing the SRS signal depletion of DAE620 through a donut-shaped beam, we demonstrate super-resolution vibrational imaging of mammalian cells with excellent chemical specificity and spatial resolution beyond the optical diffraction limit. Our results indicate RESORT microscopy to be an effective tool with high potential for multiplexed super-resolution imaging of live cells.
Somitic positional information guides self-organized patterning of snake scales
Authors: Tzika Athanasia C. , Ullate-Agote Asier , Zakany Szabolcs , Kummrow Maya , Milinkovitch Michel C.
Published: June 2023

Two influential concepts in tissue patterning are Wolpert’s positional information and Turing’s self-organized reaction–diffusion (RD). The latter establishes the patterning of hair and feathers. Here, our morphological, genetic, and functional—by CRISPR-Cas9–mediated gene disruption—characterization of wild-type versus “scaleless” snakes reveals that the near-perfect hexagonal pattern of snake scales is established through interactions between RD in the skin and somitic positional information. First, we show that ventral scale development is guided by hypaxial somites and, second, that ventral scales and epaxial somites guide the sequential RD patterning of the dorsolateral scales. The RD intrinsic length scale evolved to match somite periodicity, ensuring the alignment of ribs and scales, both of which play a critical role in snake locomotion.
Cell competition for neuron-derived trophic factor controls the turnover and lifespan of microglia
Authors: Yu Tao , Kuang Haoyue , Wu Xiaohai , Huang Ying , Wang Jianzhong , Wen Zilong
Published: June 2023

Microglia are brain-resident macrophages capable of long-term maintenance through self-renewal. Yet the mechanism governing the turnover and lifespan of microglia remains unknown. In zebrafish, microglia arise from two sources, rostral blood island (RBI) and aorta-gonad-mesonephros (AGM). The RBI-derived microglia are born early but have a short lifespan and diminish in adulthood, while the AGM-derived microglia emerge later and are capable of long-term maintenance in adulthood. Here, we show that the attenuation of RBI microglia is due to their less competitiveness for neuron-derived interleukin-34 (Il34) caused by age-dependent decline of colony-stimulating factor-1 receptor a (
csf1ra
). Alterations of Il34/Csf1ra levels and removal of AGM microglia revamp the proportion and lifespan of RBI microglia. The
csf1ra/CSF1R
expression in zebrafish AGM-derived microglia and murine adult microglia also undergo age-dependent decline, leading to the elimination of aged microglia. Our study reveals cell competition as a general mechanism controlling the turnover and lifespan of microglia.
Heat-driven molecule gatekeepers in MOF membrane for record-high H
2
selectivity
Authors: Zhao Meng , Zhou Dong-Dong , Chen Pin , Ban Yujie , Wang Yuecheng , Hu Ziyi , Lu Yutong , Zhou Mu-Yang , Chen Xiao-Ming , Yang Weishen
Published: June 2023

Hydrogen/carbon dioxide (H
2
/CO
2
) separation for sustainable energy is in desperate need of reliable membranes at high temperatures. Molecular sieve membranes take their nanopores to differentiate sizes between H
2
and CO
2
but have compromised at a marked loss of selectivity at high temperatures owing to diffusion activation of CO
2
. We used molecule gatekeepers that were locked in the cavities of the metal-organic framework membrane to meet this challenge. Ab initio calculations and in situ characterizations demonstrate that the molecule gatekeepers make a notable move at high temperatures to dynamically reshape the sieving apertures as being extremely tight for CO
2
and restitute with cool conditions. The H
2
/CO
2
selectivity was improved by an order of magnitude at 513 kelvin (K) relative to that at the ambient temperature.
Exploring alternative pathways for the in vitro establishment of the HOPAC cycle for synthetic CO
2
fixation
Authors: McLean Richard , Schwander Thomas , Diehl Christoph , Cortina Niña Socorro , Paczia Nicole , Zarzycki Jan , Erb Tobias J.
Published: June 2023

Nature has evolved eight different pathways for the capture and conversion of CO
2
, including the Calvin-Benson-Bassham cycle of photosynthesis. Yet, these pathways underlie constrains and only represent a fraction of the thousands of theoretically possible solutions. To overcome the limitations of natural evolution, we introduce the HydrOxyPropionyl-CoA/Acrylyl-CoA (HOPAC) cycle, a new-to-nature CO
2
-fixation pathway that was designed through metabolic retrosynthesis around the reductive carboxylation of acrylyl-CoA, a highly efficient principle of CO
2
fixation. We realized the HOPAC cycle in a step-wise fashion and used rational engineering approaches and machine learning–guided workflows to further optimize its output by more than one order of magnitude. Version 4.0 of the HOPAC cycle encompasses 11 enzymes from six different organisms, converting ~3.0 mM CO
2
into glycolate within 2 hours. Our work moves the hypothetical HOPAC cycle from a theoretical design into an established in vitro system that forms the basis for different potential applications.
Using Dynamic Oral Dosing of Rifapentine and Rifabutin to Simulate Exposure Profiles of Long-Acting Formulations in a Mouse Model of Tuberculosis Preventive Therapy
Authors: Chang Yong S. , Li Si-Yang , Pertinez Henry , Betoudji Fabrice , Lee Jin , Rannard Steven P. , Owen Andrew , Nuermberger Eric L. , Ammerman Nicole C.
Published: June 2023

Administration of tuberculosis preventive therapy (TPT) to individuals with latent tuberculosis infection is an important facet of global tuberculosis control. The use of long-acting injectable (LAI) drug formulations may simplify and shorten regimens for this indication.
High Lethality of
Mycobacterium tuberculosis
Infection in Mice Lacking the Phagocyte Oxidase and Caspase1/11
Authors: Thomas Sean M. , Olive Andrew J.
Published: June 2023

Immune networks that control antimicrobial and inflammatory mechanisms have overlapping regulation and functions to ensure effective host responses. Genetic interaction studies of immune pathways that compare host responses in single and combined knockout backgrounds are a useful tool to identify new mechanisms of immune control during infection.
Transcription Factor PecS Mediates
Agrobacterium fabrum
Fitness and Survival
Authors: Nwokocha George C. , Adhikari Prava , Iqbal Asif , Elkholy Hannah , Doerrler William T. , Larkin John C. , Grove Anne
Published: June 2023

PecS is a transcription factor that is conserved in several pathogenic bacteria, where it regulates virulence genes. The plant pathogen
Agrobacterium fabrum
is important not only for its induction of crown galls in susceptible plants but also for its role as a tool in the genetic manipulation of host plants.
Bilateral post-LASIK exacerbation of granular corneal dystrophy with epithelial ingrowth
Authors: Mandal Sohini , Namdev Vaibhav , Sen Seema , Sinha Rajesh
Published: June 2023

A male patient in his 30s, with a history of bilateral microkeratome-assisted myopic laser-assisted in situ keratomileusis (LASIK) 8 years ago at another centre, presented to us with gradually progressive diminution of vision and glare in both eyes for the last 4 years. On presentation, uncorrected distance visual acuity (UDVA) was 6/24 and 6/15 in the right eye and left eye, respectively, with normal intraocular pressures. Slit-lamp examination and anterior segment optical coherence tomography revealed well-defined white deposits, limited to an area within the LASIK flap. The deposits were confluent, at the level of the LASIK flap interface, and few discrete opacities were present in the posterior stroma. His father also had a similar clinical picture in both eyes. A diagnosis of both eyes post-LASIK exacerbation of granular corneal dystrophy with epithelial ingrowth was made. He underwent right eye femtosecond laser-assisted sutureless superficial anterior lamellar keratoplasty. At 6-month follow-up, UDVA improved to 6/12 with graft clarity of 4+ and coexistent grade 1 epithelial ingrowth.
Effect of different visual presentations on the public’s comprehension of prognostic information using acute and chronic condition scenarios: two online randomised controlled trials
Authors: Abukmail Eman , Bakhit Mina , Jones Mark , Del Mar Chris , Hoffmann Tammy
Published: June 2023

Objectives

To assess the effectiveness of bar graph, pictograph and line graph compared with text-only, and to each other, for communicating prognosis to the public.

Design

Two online four-arm parallel-group randomised controlled trials. Statistical significance was set at p<0.016 to allow for three-primary comparisons.

Participants and setting

Two Australian samples were recruited from members registered at Dynata online survey company. In trial A: 470 participants were randomised to one of the four arms, 417 were included in the analysis. In trial B: 499 were randomised and 433 were analysed.

Interventions

In each trial four visual presentations were tested: bar graph, pictograph, line graph and text-only. Trial A communicated prognostic information about an acute condition (acute otitis media) and trial B about a chronic condition (lateral epicondylitis). Both conditions are typically managed in primary care where ‘wait and see’ is a legitimate option.

Main outcome

Comprehension of information (scored 0–6).

Secondary outcomes

Decision intention, presentation satisfaction and preferences.

Results

In both trials, the mean comprehension score was 3.7 for the text-only group. None of the visual presentations were superior to text-only. In trial A, the adjusted mean difference (MD) compared with text-only was: 0.19 (95% CI −0.16 to 0.55) for bar graph, 0.4 (0.04 to 0.76) for pictograph and 0.06 (−0.32 to 0.44) for line graph. In trial B, the adjusted MD was: 0.1 (−0.27 to 0.47) for bar graph), 0.38 (0.01 to 0.74) for pictograph and 0.1 (−0.27 to 0.48) for line graph. Pairwise comparisons between the three graphs showed all were clinically equivalent (95% CIs between −1.0 and 1.0). In both trials, bar graph was the most preferred presentation (chosen by 32.9% of trial A participants and 35.6% in trial B).

Conclusions

Any of the four visual presentations tested may be suitable to use when discussing quantitative prognostic information.

Trial registration number

Australian New Zealand Clinical Trials Registry (ACTRN12621001305819).
Neonatal mortality in NHS maternity units by timing and mode of birth: a retrospective linked cohort study
Authors: Carty Lucy , Grollman Christopher , Plachcinski Rachel , Cortina-Borja Mario , Macfarlane Alison
Published: June 2023

Objectives

To compare neonatal mortality in English hospitals by time of day and day of the week according to care pathway.

Design

Retrospective cohort linking birth registration, birth notification and hospital episode data.

Setting

National Health Service (NHS) hospitals in England.

Participants

6 054 536 liveborn singleton births from 2005 to 2014 in NHS maternity units in England.

Main outcome measures

Neonatal mortality.

Results

After adjustment for confounders, there was no significant difference in the odds of neonatal mortality attributed to asphyxia, anoxia or trauma outside of working hours compared with working hours for spontaneous births or instrumental births. Stratification of emergency caesareans by onset of labour showed no difference in mortality by birth timing for emergency caesareans with spontaneous or induced onset of labour. Higher odds of neonatal mortality attributed to asphyxia, anoxia or trauma out of hours for emergency caesareans without labour translated to a small absolute difference in mortality risk.

Conclusions

The apparent ‘weekend effect’ may result from deaths among the relatively small numbers of babies who were coded as born by emergency caesarean section without labour outside normal working hours. Further research should investigate the potential contribution of care-seeking and community-based factors as well as the adequacy of staffing for managing these relatively unusual emergencies.
Health risk assessment of indoor air quality, sociodemographic and kitchen characteristics on respiratory health among women responsible for cooking in urban settings of Oromia region, Ethiopia: a community-based cross-sectional study
Authors: Zewdie Asrat , Degefa Gutama Haile , Donacho Dereje Oljira
Published: June 2023

Objectives

In Ethiopia, where biomass fuel is used by the majority of the population, women who are primarily responsible for cooking are at a higher risk of having respiratory symptoms. However, there is limited information on the respiratory symptoms of exposed women. This study assessed the magnitude of respiratory disease symptoms and associated factors among women responsible for cooking in Mattu and Bedele towns, south-west Ethiopia.

Methods

A community-based cross-sectional study was conducted among 420 randomly selected women in urban settings in south-west Ethiopia. Data were collected through face-to-face interviews using a modified version of the American Thoracic Society Respiratory Questionnaire. The data were cleaned, coded and entered into EpiData V.3.1 and exported into SPSS V.22 for analysis. Bivariable and multivariable logistic regression analyses were used to identify factors associated with respiratory symptoms at a value of p<0.05.

Results

It is found that 34.9% of the study participants have respiratory symptoms (95% CI 30.6% to 39.4%). Unimproved floor (adjusted OR (AOR)=2.4 at 95% CI 1.42 to 4.15), presence of thick black soot in the ceiling (AOR=2.1 at 95% CI 1.2 to 3.6), using fuel wood (AOR=2.3 at 95% CI 1.1 to 4.7), using a traditional stove (AOR=3.37 at 95% CI 1.85 to 6.16), long duration of cooking (AOR=2.52 at 95% CI 1.4 to 4.5) and cooking room without a window (AOR=2.4 at 95% CI 1.5 to 3.9) were significantly associated with women’s respiratory symptoms.

Conclusion

More than two in six women who cook had respiratory symptoms. Floor, fuel and stove type, soot deposits in the ceiling, duration of cooking and cooking in a room without a window were the identified factors. Appropriate ventilation, improved floor and stove design and the switch to high-efficiency, low-emission fuels could help to lessen the effects of wood smoke on women’s respiratory health.