bluuebunny/crossref_metadata_2025 huggingface dataset:
To test or to not test: A retrospective cross-sectional study on potentially inappropriate use of pathology testing in South Australian hospitals
Authors: Banker Twisha R , Gillam Marianne H , O’Loughlin Peter , Rankin Wayne , Ryan Richard , Caruso Connie , Roughead Elizabeth E
Published: November 2023

Objectives

To measure rates of potentially inappropriate pathology testing in the hospital setting.

Methods

Retrospective cross-sectional study in hospital setting from July 2021 to December 2021. We examined 3 potentially inappropriate uses: overordering, selection errors, and unnecessary repeat testing. Overordering included vitamin D and lipids (rarely required in acute hospital care). Selection error was the ratio of iron studies to standalone ferritin requests. Unnecessary repeats included any repeat vitamin D, lipids, iron, or ferritin in an episode of care or C-reactive protein (CRP) repeated within 3 days and N-terminal pro–brain natriuretic peptide (NT-proBNP) within 7 days and repeated previously abnormal CRP and NT-proBNP tests. Costs of inappropriate tests were estimated using the Australian Medicare Benefits Schedules.

Results

Among 55,904 test requests, 15% (n = 8120) were potentially inappropriate. Vitamin D was frequently ordered (n = 4498), as were lipids (n = 2872). Ratio of iron studies to standalone ferritin was 36. Of 19,233 repeat CRPs, 36% (n = 6947) were within 3 days and 62% (n = 179) of repeat NT-proBNPs were within 7 days of the first test. For initially abnormal tests, 89% of CRPs and 97% of NT-proBNPs remained abnormal. Inappropriate test costs accounted for 12% to 30% of costs.

Conclusions

Frequent potential inappropriate use and selection of pathology tests was observed in South Australian hospitals.
Benchmarking of local genetic correlation estimation methods using summary statistics from genome-wide association studies
Authors: Zhang Chi , Zhang Yiliang , Zhang Yunxuan , Zhao Hongyu
Published: November 2023

Local genetic correlation evaluates the correlation of additive genetic effects between different traits across the same genetic variants at a genomic locus. It has been proven informative for understanding the genetic similarities of complex traits beyond that captured by global genetic correlation calculated across the whole genome. Several summary-statistics-based approaches have been developed for estimating local genetic correlation, including $\rho$-hess, SUPERGNOVA and LAVA. However, there has not been a comprehensive evaluation of these methods to offer practical guidelines on the choices of these methods. In this study, we conduct benchmark comparisons of the performance of these three methods through extensive simulation and real data analyses. We focus on two technical difficulties in estimating local genetic correlation: sample overlaps across traits and local linkage disequilibrium (LD) estimates when only the external reference panels are available. Our simulations suggest the likelihood of incorrectly identifying correlated regions and local correlation estimation accuracy are highly dependent on the estimation of the local LD matrix. These observations are corroborated by real data analyses of 31 complex traits. Overall, our findings illuminate the distinct results yielded by different methods applied in post-genome-wide association studies (post-GWAS) local correlation studies. We underscore the sensitivity of local genetic correlation estimates and inferences to the precision of local LD estimation. These observations accentuate the vital need for ongoing refinement in methodologies.
Autophagy core protein BECN1 is vital for spermatogenesis and male fertility in mice
Authors: Ke Lu , Lin Xinyi , Luo Yuchuan , Tao Siming , Yan Chang , He Yifeilong , Wu Yingjie , Liu Ning , Qin Yinghe
Published: November 2023

Mammalian spermatogenesis is a highly complex multi-step biological process, and autophagy has been demonstrated to be involved in the process of spermatogenesis. Beclin-1/BECN1, a core autophagy factor, plays a critical role in many biological processes and diseases. However, its function in spermatogenesis remains largely unclear. In the present study, germ cell–specific Beclin 1 (Becn1) knockout mice were generated and were conducted to determine the role of Becn1 in spermatogenesis and fertility of mice. Results indicate that Becn1 deficiency leads to reduced sperm motility and quantity, partial failure of spermiation, actin network disruption, excessive residual cytoplasm, acrosome malformation, and aberrant mitochondrial accumulation of sperm, ultimately resulting in reduced fertility in male mice. Furthermore, inhibition of autophagy was observed in the testes of germ cell–specific Becn1 knockout mice, which may contribute to impaired spermiogenesis and reduced fertility. Collectively, our results reveal that Becn1 is essential for fertility and spermiogenesis in mice.
Is there a growing global threat of scabies treatment failure? An opportunity to discuss health inequity within UK dermatology
Authors: Khan Sidra S , Fuller L Claire
Published: November 2023

This editorial addresses the rising number of scabies cases seen globally, including within Europe. The authors address scabies treatment failure as a potential contributing factor and the reasons behind this. The authors go on to address the wider social and economic detriments of health in the UK and how these need to be addressed if we are to successfully tackle the rising number of scabies cases.
The pathobiology of psychomotor slowing in psychosis: altered cortical excitability and connectivity
Authors: Lefebvre Stephanie , Gehrig Gwendolyn , Nadesalingam Niluja , Nuoffer Melanie G , Kyrou Alexandra , Wüthrich Florian , Walther Sebastian
Published: November 2023

Psychomotor slowing is a frequent symptom of schizophrenia. Short-interval intracortical inhibition assessed by transcranial magnetic stimulation demonstrated inhibitory dysfunction in schizophrenia. The inhibitory deficit results from additional noise during information processing in the motor system in psychosis. Here, we tested whether cortical inhibitory dysfunction was linked to psychomotor slowing and motor network alterations.

In this cross-sectional study, we included 60 patients with schizophrenia and psychomotor slowing determined by the Salpêtrière Retardation Rating Scale, 23 patients without slowing and 40 healthy control participants. We acquired single and double-pulse transcranial magnetic stimulation effects from the left primary motor cortex, resting-state functional connectivity and diffusion imaging on the same day. Groups were compared on resting motor threshold, amplitude of the motor evoked potentials, as well as short-interval intracortical inhibition. Regression analyses calculated the association between motor evoked potential amplitudes or cortical inhibition with seed-based resting-state functional connectivity from the left primary motor cortex and fractional anisotropy at whole brain level and within major motor tracts.

In patients with schizophrenia and psychomotor slowing, we observed lower amplitudes of motor evoked potentials, while the short-interval intracortical inhibition/motor evoked potentials amplitude ratio was higher than in healthy controls, suggesting lower cortical inhibition in these patients. Patients without slowing also had lower amplitudes of motor evoked potentials. Across the combined patient sample, cortical inhibition deficits were linked to more motor coordination impairments. In patients with schizophrenia and psychomotor slowing, lower amplitudes of motor evoked potentials were associated with lower fractional anisotropy in motor tracts. Moreover, resting-state functional connectivity between the primary motor cortex, the anterior cingulate cortex and the cerebellum increased with stronger cortical inhibition. In contrast, in healthy controls and patients without slowing, stronger cortical inhibition was linked to lower resting-state functional connectivity between the left primary motor cortex and premotor or parietal cortices.

Psychomotor slowing in psychosis is linked to less cortical inhibition and aberrant functional connectivity of the primary motor cortex. Higher neural noise in the motor system may drive psychomotor slowing and thus may become a treatment target.
Syntax intervention in American Sign Language: an exploratory case study
Authors: Ofori-Sanzo Kimberly , Geer Leah , Embry Kinya
Published: November 2023

This case study describes the use of a syntax intervention with two deaf children who did not acquire a complete first language (L1) from birth. It looks specifically at their ability to produce subject–verb–object (SVO) sentence structure in American Sign Language (ASL) after receiving intervention. This was an exploratory case study in which investigators utilized an intervention that contained visuals to help teach SVO word order to young deaf children. Baseline data were collected over three sessions before implementation of a targeted syntax intervention and two follow-up sessions over 3–4 weeks. Both participants demonstrated improvements in their ability to produce SVO structure in ASL in 6–10 sessions. Visual analysis revealed a positive therapeutic trend that was maintained in follow-up sessions. These data provide preliminary evidence that a targeted intervention may help young deaf children with an incomplete L1 learn to produce basic word order in ASL. Results from this case study can help inform the practice of professionals working with signing deaf children who did not acquire a complete L1 from birth (e.g., speech-language pathologists, deaf mentors/coaches, ASL specialists, etc.). Future research should investigate the use of this intervention with a larger sample of deaf children.
NLRP12 Senses the SARS-CoV-2 Membrane Protein and Promotes an Inflammatory Response
Authors: Li Xingyu , Zhou Guangde , Sun Xingzi , Qu Siying , Lai Hongzhi , Wu Yongjian , Li Dechang , Liu Lei , Zhang Guoliang , Yang Jingwen , Huang Xi
Published: November 2023

COVID-19 is an acute respiratory disorder that is caused by SARS-CoV-2, in which excessive systemic inflammation is associated with adverse patient clinical outcomes. Here, we observed elevated expression levels of NLRP12 (nucleotide-binding leucine-rich repeat–containing receptor 12) in human peripheral monocytes and lung tissue during infection with SARS-CoV-2. Co-immunoprecipitation analysis revealed that NLRP12 directly interacted with the M protein through its leucine-rich repeat domain. Moreover, in vitro studies demonstrated that NLRP12 interacted with TRAF3 and promoted its ubiquitination and degradation, which counteracted the inhibitory effect of TRAF3 on the NF-κB/MAPK signaling pathway and promoted the production of inflammatory cytokines. Furthermore, an in vivo study revealed that NLRP12 knockout mice displayed attenuated tissue injury and ameliorated inflammatory responses in the lungs when infected with a SARS-CoV-2 M protein–reconstituted pseudovirus and mouse coronavirus. Taken together, these findings suggest that NLRP12 mediates the inflammatory responses during coronavirus infection.
Inactivation ofSalmonellaTyphimurium andListeria monocytogeneson buckwheat seeds through combination treatment with plasma, vacuum packaging, and hot water
Authors: Park Ye-Jin , Kim Su-Yeon , Song Won-Jae
Published: November 2023

Aims

The objectives of this study were to evaluate the effect of combination treatment with cold plasma (CP), vacuum packaging (VP), and hot water (HW) on the inactivation of foodborne pathogens on buckwheat seeds, and determined the germination rates of seeds and the quality of sprouts following combination treatment.

Methods and Results

Buckwheat seeds inoculated with Salmonella Typhimurium and Listeria monocytogenes were treated with CP, HW, CP + HW, VP + HW, or CP + VP + HW. The germination rates of the HW-, CP + HW-, VP + HW-, and CP + VP + HW-treated seeds and the antioxidant activities and rutin contents of the CP + HW- and CP + VP + HW-treated sprouts were determined. HW, CP + HW, and CP + VP + HW were found to reduce the levels of the two pathogens to below the detection limit (1.0 log CFU g−1) at 70°C. However, HW and CP + HW significantly reduced the germination rate of buckwheat seeds. CP + VP + HW did not affect the germination rate of seeds nor the antioxidant activities and rutin content of buckwheat sprouts.

Conclusions

These results indicate that CP + VP + HW can be used as a novel control method to reduce foodborne pathogens in seeds without causing quality deterioration.
Assessment of a 50:50 mixture of two Bacillus subtilis strains as growth promoters for finishing pigs: productivity improvement and noxious gas reduction
Authors: Song Junho , Jeong Sook-Jung , Lim Chai Bin , Kang Bongseok , Oh Sang Sik , Yun Gilly , Kim In Ho , Cho Yangrae
Published: November 2023

In this study, we aimed to assess the potential of a 50:50 mixture of two Bacillus subtilis strains in improving the productivity and health of finishing pigs and reducing noxious gases in their feces. These strains were found to abundantly secrete surfactin which has been shown to alleviate the effects of lipopolysaccharides in vitro. For the 10-wk experiment, 200 finishing pigs ([Landrace × Yorkshire] × Duroc) with an average body weight of 54.15 ± 1.70 kg were divided into four groups. Each group was fed with a basal diet supplemented with an equal amount of spores from the two B. subtilis strains at different levels: control group, no addition; treatment group 1, 0.5 × 109; treatment group 2, 1.0 × 109; treatment group 3, 1.5 × 109 cfu·kg−1 addition. During the 10-wk feeding period, dietary supplementation of 0.5 × 109, 1.0 × 109, and 1.5 × 109 cfu·kg−1 of the spore cells from these two strains resulted in a 0.9%, 1.9%, and 2.5% increase in body weight, respectively (linear P < 0.095). During the final 5 wk, the average daily gain (ADG) in weight was increased by the strains at amounts of 0.5 × 109, 1.0 × 109, and 1.5 × 109 cfu·kg−1 with a clear dosage effect (linear P < 0.05). However, neither the gain-to-feed ratio, the average daily feed intake, nor nutrient digestibility was affected by the supplementation. In blood, the endotoxin lipopolysaccharides, and two liver toxicity indicator enzymes; aspartate aminotransferase and lactate dehydrogenase were decreased (P < 0.05) in the 1.0 × 109 cfu·kg−1 spores-feeding group. Furthermore, four noxious gases were reduced by 8 to 20% in feces excreted by pigs fed with 1.5 × 109 cfu·kg−1 spores with a linear dosage effect (linear P < 0.001 to 0.05) during the final 5 wk. Our findings suggest that the mixture of B. subtilis strains may enhance the productivity of finishing pigs by reducing the risk of mild endotoxemia, rather than increasing digestibility or daily feed intake. Therefore, these Bacillus strains have the potential to act as growth promoters for pigs, leading to improved animal health and productivity. These results have significant implications for pig farmers seeking to optimize the health and growth of their animals.
Effects of early weaning on productive and reproductive performance of Nelore heifers
Authors: Nishimura Thiago Kan , Goulart Rodrigo Silva , Ramírez-Zamudio Germán Darío , da Silva Amanda Guimarães , de Paula Carlis Matheus Sousa , Abitante Gabriela , Silva Saulo Luz , Dahlen Carl Robertson , Saran Netto Arlindo , Leme Paulo Roberto , Pugliesi Guilherme
Published: November 2023

We aimed to evaluate the effects of early weaning on the productive and reproductive characteristics of Nelore heifer progeny. Ninety-five calves from primiparous (PRI) and multiparous (MUL) dams were assigned to one of two weaning strategies; 1) early weaning at 150 d (149 ± 1.97) of age (EW; n = 16 from PRI and 31 from MUL); or 2) conventional weaning at 240 d (247 ± 2.41) of age (CW; 16 from PRI and 32 from MUL). All heifers received ~5 g/kg of body weight (BW) of creep-feed as fed from 90 d of age until weaning. After weaning, each group of heifers was transferred to a Brachiaria spp. paddock and received 5 g/kg of BW of a protein-energy supplement until 12 mo of age. Then, heifers were confined and fed a diet with a ratio of 79:31 (corn silage: concentrate) for 4 mo, during which they were submitted to a hormonal protocol to induce puberty and timed artificial insemination (TAI). Reproductive tract score (RTS, 1 to 5 scale: 1 being infantile and 5 being cyclic) and endometrial thickness were determined at 12 mo of age, rump fat thickness (RFT), and BW every 28 ± 4 d through the breeding season, and plasma concentrations of IGF-I were evaluated at 12, 14, and 16 mo. At 15.6 mo of age heifers were submitted to a P4/E2 protocol for TAI at day 0 (D0), and a second TAI was performed at D22 in nonpregnant heifers. Ultrasound was used to determine the presence of corpus luteum on D10 and dominant follicle (DF) diameter and blood perfusion on D2 and D0. Data were analyzed using SAS by ANOVA or logistic regression. Though heifers from EW were lighter (P < 0.05) than CW at postweaning time points and CW presented a greater (P = 0.002) RFT than EW heifers from 11 to 15 mo, weaning strategy did not affect (P > 0.1) body condition score at TAI. Concentrations of IGF-I did not differ (P > 0.1) between heifers weaned at 150 and 240 d. The proportion of pubertal heifers, endometrium tone and thickness, and RTS at 16 mo did not differ (P > 0.1) between EW and CW groups. The diameter of DF on D2 and D0 and follicular blood perfusion on D0 were greater (P < 0.05) for heifers in the CW group than EW group, but P/AI at first and second TAI did not differ (P > 0.1) between groups. In conclusion, early weaning in Nelore heifers moderately reduces postweaning growth but does not affect puberty and reproductive performance before the breeding season when submitted to confinement.
Effects of mixtures of arrestants, dislodgers, and phagostimulants with synthetic insecticides on green-belly stink bug: walking behavior assessments, physicochemical interactions, and laboratory and field trials
Authors: Morais Maíra Chagas , Rakes Matheus , Balzan Fabricio , Grützmacher Anderson Dionei , Bernardi Daniel , Ribeiro Leandro do Prado
Published: November 2023

The green-belly stink bug (Diceraeus melacanthus Dallas (Hemiptera: Pentatomidae)) is a key pest of corn-soybean crop systems and the management of this pest is difficult due to behavioral characteristics. However, products that alter its behavior, such as arrestants, dislodgers, and phagostimulants, have been used in an attempt to improve the effectiveness of chemical control. In this study, the effect of these products on the walking behavior of nymphs and adults of D. melacanthus was initially evaluated through computational behavioral tracking (Ethovision system). Adults of D. melacanthus exposed to the dislodgers Creolin Pearson and Quimifol S450 (sulfur) significantly increased the distance covered and the walking speed. On the other hand, the only treatment that significantly affected the walking behavior of nymphs was the treatment with soy milk (phagostimulant). The physical–chemical analyses indicated considerable changes in the pH and electrical conductivity of mixtures of such products with insecticides from different chemical groups, as well as lack of homogeneity (physical incompatibility). Nevertheless, none of the products tested improved the control efficacy of an insecticide based on imidacloprid + beta-cyfluthrin, either in laboratory tests (contact bioassay) or in tests conducted in corn crops during 2 crop harvests. Thus, the association of these products in a tank mixture does not increase the control levels of D. melacanthus in post-emergence of maize and may have an antagonistic effect in some associations.
Climate change and oil and gas production regulation: an impossible reconciliation?
Authors: Shapovalova Daria
Published: November 2023

Fossil fuel combustion is undeniably the largest source of greenhouse gas emissions worldwide. In order to meet the Paris Agreement target of keeping global warming below 2°C, globally, a third of oil and half of gas reserves should remain unused from 2010 to 2050. In 2021, the International Energy Agency estimated that in the net-zero emissions scenario there is no need for fossil fuel exploration, new oil and natural gas fields beyond those already been approved for development, or new coal mines or mine extensions. While greenhouse gas emissions from the actual exploration and production activities (upstream emissions) are increasingly regulated, the emissions from the final combustion of the produces oil and gas are not taken into account when new projects are approved. This paper argues that there is a significant lack of integration between climate and energy regulation which, if not corrected, may result in challenges to achieve the global climate targets. It analyses the mechanisms for better inclusion of climate considerations at the oil and gas development approval stage. It starts with a review of international initiatives examining the lack of engagement with the climate regime and fossil fuel production. It further analyses the oil and gas development approval regime in the UK with a view to highlighting the lack of integration of climate concerns in the licensing and environmental assessment processes.
Travel and tourism to the Kingdom of Saudi Arabia: what are the health risks?
Authors: Memish Ziad A , Memish Tariq Z , Kattan Rana F
Published: November 2023

Tourism in Saudi Arabia has been rapidly growing and evolving in recent years as part of the Saudi government’s efforts to diversify its economy away from oil dependence and promote the country as a tourist destination. The country aims to invest $800 billion in the next decade, particularly targeting international travellers.
Dynamics of hemoglobins during nodule development, nitrate response, and dark stress in Lotus japonicus
Authors: Minguillón Samuel , Román Ángela , Pérez-Rontomé Carmen , Wang Longlong , Xu Ping , Murray Jeremy D , Duanmu Deqiang , Rubio Maria C , Becana Manuel
Published: November 2023

Legume nodules express multiple leghemoglobins (Lbs) and non-symbiotic hemoglobins (Glbs), but how they are regulated is unclear. Here, we study the regulation of all Lbs and Glbs of Lotus japonicus in different physiologically relevant conditions and mutant backgrounds. We quantified hemoglobin expression, localized reactive oxygen species (ROS) and nitric oxide (NO) in nodules, and deployed mutants deficient in Lbs and in the transcription factors NLP4 (associated with nitrate sensitivity) and NAC094 (associated with senescence). Expression of Lbs and class 2 Glbs was suppressed by nitrate, whereas expression of class 1 and 3 Glbs was positively correlated with external nitrate concentrations. Nitrate-responsive elements were found in the promoters of several hemoglobin genes. Mutant nodules without Lbs showed accumulation of ROS and NO and alterations of antioxidants and senescence markers. NO accumulation occurred by a nitrate-independent pathway, probably due to the virtual disappearance of Glb1-1 and the deficiency of Lbs. We conclude that hemoglobins are regulated in a gene-specific manner during nodule development and in response to nitrate and dark stress. Mutant analyses reveal that nodules lacking Lbs experience nitro-oxidative stress and that there is compensation of expression between Lb1 and Lb2. They also show modulation of hemoglobin expression by NLP4 and NAC094.
New insights into plant autophagy: molecular mechanisms and roles in development and stress responses
Authors: Yagyu Mako , Yoshimoto Kohki
Published: November 2023

Autophagy is an evolutionarily conserved eukaryotic intracellular degradation process. Although the molecular mechanisms of plant autophagy share similarities with those in yeast and mammals, certain unique mechanisms have been identified. Recent studies have highlighted the importance of autophagy during vegetative growth stages as well as in plant-specific developmental processes, such as seed development, germination, flowering, and somatic reprogramming. Autophagy enables plants to adapt to and manage severe environmental conditions, such as nutrient starvation, high-intensity light stress, and heat stress, leading to intracellular remodeling and physiological changes in response to stress. In the past, plant autophagy research lagged behind similar studies in yeast and mammals; however, recent advances have greatly expanded our understanding of plant-specific autophagy mechanisms and functions. This review summarizes current knowledge and latest research findings on the mechanisms and roles of plant autophagy with the objective of improving our understanding of this vital process in plants.
The PEPSI Exoplanet Transit Survey (PETS) – IV. Assessing the atmospheric chemistry of KELT-20b
Authors: Petz Sydney , Johnson Marshall C , Asnodkar Anusha Pai , Wang Ji , Gaudi B Scott , Henning Thomas , Keles Engin , Molaverdikhani Karan , Poppenhaeger Katja , Scandariato Gaetano , Shkolnik Evgenya K , Sicilia Daniela , Strassmeier Klaus G , Yan Fei
Published: November 2023

Most ultra-hot Jupiters (UHJs) show evidence of temperature inversions, in which temperature increases with altitude over a range of pressures. Temperature inversions can occur when there is a species that absorbs the stellar irradiation at a relatively high level of the atmospheres. However, the species responsible for this absorption remains unidentified. In particular, the UHJ KELT-20b is known to have a temperature inversion. Using high resolution emission spectroscopy from LBT/PEPSI we investigate the atomic and molecular opacity sources that may cause the inversion in KELT-20b, as well as explore its atmospheric chemistry. We confirm the presence of Fe i with a significance of 17σ. We also report a tentative 4.3σ detection of Ni i. A nominally 4.5σ detection of Mg i emission in the PEPSI blue arm is likely in fact due to aliasing between the Mg i cross-correlation template and the Fe i lines present in the spectrum. We cannot reproduce a recent detection of Cr i, while we do not have the wavelength coverage to robustly test past detections of Fe ii and Si i. Together with non-detections of molecular species like TiO, this suggests that Fe i is likely to be the dominant optical opacity source in the dayside atmosphere of KELT-20b and may be responsible for the temperature inversion. We explore ways to reconcile the differences between our results and those in literature and point to future paths to understand atmospheric variability.
Gertsenshtein–Zel’dovich effect: a plausible explanation for fast radio bursts?
Authors: Kushwaha Ashu , Malik Sunil , Shankaranarayanan S
Published: November 2023

We present a novel model that may provide an interpretation for a class of non-repeating fast radio bursts (FRBs) – short ($\lt 1~\rm {s}$), bright ($0.1 - 1000~\rm {Jy}$) bursts of MHz–GHz frequency radio waves. The model has three ingredients – compact object, a progenitor with effective magnetic field strength around 1010 Gauss, and high-frequency (MHz–GHz) gravitational waves (GWs). At resonance, the energy conversion from GWs to electromagnetic waves occurs when GWs pass through the magnetosphere of such compact objects due to the Gertsenshtein–Zel’dovich effect. This conversion produces bursts of electromagnetic waves in the MHz–GHz range, leading to FRBs. Our model has three key features: (i) predict peak flux, (ii) can naturally explain the pulse width, and (iii) coherent nature of FRB. We thus conclude that the neutron star/magnetar could be the progenitor of FRBs. Further, our model offers a novel perspective on the indirection detection of GWs at high-frequency beyond detection capabilities. Thus, transient events like FRBs are a rich source for the current era of multi-messenger astronomy.
Characterization and decontamination of background noise in droplet-based single-cell protein expression data with DecontPro
Authors: Yin Yuan , Yajima Masanao , Campbell Joshua D
Published: November 2023

Assays such as CITE-seq can measure the abundance of cell surface proteins on individual cells using antibody derived tags (ADTs). However, many ADTs have high levels of background noise that can obfuscate down-stream analyses. In an exploratory analysis of PBMC datasets, we find that some droplets that were originally called ‘empty’ due to low levels of RNA contained high levels of ADTs and likely corresponded to neutrophils. We identified a novel type of artifact in the empty droplets called a ‘spongelet’ which has medium levels of ADT expression and is distinct from ambient noise. ADT expression levels in the spongelets correlate to ADT expression levels in the background peak of true cells in several datasets suggesting that they can contribute to background noise along with ambient ADTs. We then developed DecontPro, a novel Bayesian hierarchical model that can decontaminate ADT data by estimating and removing contamination from these sources. DecontPro outperforms other decontamination tools in removing aberrantly expressed ADTs while retaining native ADTs and in improving clustering specificity. Overall, these results suggest that identification of empty drops should be performed separately for RNA and ADT data and that DecontPro can be incorporated into CITE-seq workflows to improve the quality of downstream analyses.
More specific feedback: why “confidence” in feedback is too ambiguous
Authors: Uetz Maxwell , Ananthakrishnan Sonia , Tulsky Asher , Demers Lindsay B , Noronha Craig
Published: November 2023

High quality feedback should be delivered in a timely manner, based on specific direct observation, and formulated to be actionable on the part of the trainee. Utilizing “confidence” as a point of feedback does not meet these criteria given the ambiguity and lack of actionable steps towards improvement. “Confidence”-based feedback makes a judgment about the trainee’s internal state leading to potentially gender or culturally biased feedback. There is a risk of emotional harm for trainees when it is integrated into feedback and it is unclear if there is a role for the use of “confidence” in medical education. We are calling for a moratorium on the utilization of the word “confidence” in feedback in medical education until further studies are performed to assess its potential place. At this time, educators should refrain from “confidence”-based feedback and shift the focus towards more specific, actionable, behavioral-based feedback.
Healthcare apprenticeships: assessing the potential benefits to an acute care provider NHS organization
Authors: Ball Alfred , Brecknell John
Published: November 2023

The introduction of healthcare-based apprenticeships to become both a physician associate and a doctor has been approved for delivery in England. This will revolutionize medical training and it is hoped that medical training would be more accessible. This has generated a mixture of reactions, some enthusiastic and others concerned.

This paper gauges interest among staff at Barking, Havering, and Redbridge University Hospitals NHS Trust in pursuing training as a doctor and/or physician associate through the apprenticeship route. Applicants were interviewed to discover their motivations for interest, and the potential benefit to the Trust of these new opportunities was also assessed.

This revealed that applicants were primarily driven through intrinsic motivations, such as a lifelong dream to be a doctor and a desire to fulfil a patient-facing role. Many expressed financial and social situations were a barrier to prior application, making the apprenticeship role more attractive.

Healthcare professionals should accurately represent the population that they serve, which is currently not the case. The prospective applicants, with diverse backgrounds and existing healthcare experience, can help to improve patient care through their diverse perspective and understanding of multidisciplinary team working.

This article highlights the potential of medical-based apprenticeships to help address longstanding challenges in medical education and workforce diversity. Furthermore, there could be significant financial and practical benefits to the trust of upskilling enthusiastic staff. However, there is currently a lack of clarity regarding selection processes and entry criteria, which must be addressed.
Basics of the 12-lead ECG
Authors: Day Mercedes , Bruce Kellie , Moore Amy Karen , Mello Inola , Hilliard Tara
Published: November 2023

A 12-lead ECG is a noninvasive diagnostic tool that detects and records cardiac electrical activity and can identify cardiac pathology. This article discusses select ECG abnormalities including myocardial infarction, bundle-branch blocks, and heart blocks. This is part 2 of a two-part series. Part 1 was published in the November 2023 issue of Nursing2023.
County-Level Maternal Vulnerability and Preterm Birth in the US
Authors: Salazar Elizabeth G. , Montoya-Williams Diana , Passarella Molly , McGann Carolyn , Paul Kathryn , Murosko Daria , Peña Michelle-Marie , Ortiz Robin , Burris Heather H. , Lorch Scott A. , Handley Sara C.
Published: November 2023

(Abstracted from JAMA Network Open 2023;6(5):e2315306)

In the United States, approximately 1 in 10 births are considered preterm, or born at <37 weeks of gestation. Historically, studies on preterm birth (PTB) have focused on maternal characteristics. However, an appreciation for the impact of community factors, such as poverty, air pollution, and other measures of neighborhood quality, on PTB is growing.
Treatment of Gestational Diabetes Mellitus Diagnosed Early in Pregnancy
Authors: Simmons D , Immanuel J. , Hague W. M. , Teede H. , Nolan C. J. , Peek M. J. , Flack J. R. , McLean M. , Wong V. , Hibbert E. , Kautzky-Willer A. , Harreiter J. , Backman H. , Gianatti E. , Sweeting A. , Mohan V. , Enticott J. , Cheung N. W. ,   for the TOBOGM Research Group*
Published: November 2023

(Abstracted from N Engl J Med 2023;388(23):2132–2144)

Gestational diabetes mellitus is a common pregnancy complication. It is associated with adverse outcomes, including preeclampsia, obstetrical intervention, large-for-gestational-age neonates, shoulder dystocia, birth trauma, and neonatal hypoglycemia. Cohort studies have found that women with hyperglycemia before 20 weeks of gestation are more likely to experience accelerated fetal growth by 24 to 28 weeks than those diagnosed with GDM later in pregnancy.
A Quality Improvement Initiative to Reduce Adverse Effects of Transitions of Anesthesia Care on Postoperative Outcomes: A Retrospective Cohort Study
Authors: Saha Amit K. , Segal Scott
Published: November 2023

Background

An intraoperative transfer of care from one anesthesia provider to another, or handover, may result in information loss and contribute to adverse patient outcomes. In 2019 the authors undertook a quality improvement effort to increase the use of a structured intraoperative handover tool incorporated in the electronic medical record. The authors hypothesized that intraoperative handovers of anesthesia care would be associated with adverse patient outcomes, and that increased use of a structured tool would attenuate this effect.

Methods

This study included adult patients undergoing noncardiac surgery of at least 1 h duration performed during the period 2016 to 2021. Cases with a handover were identified if either there was a change of attending anesthesiologist or change of nurse anesthetist or resident for more than 35 min. The primary outcome was the occurrence of a composite of postoperative mortality and major postoperative morbidity. The effect of the intervention was analyzed by examining the quarterly change in odds ratio for the primary outcome for cases with and without a handover.

Results

A total of 121,077 cases, 40.4% of which had a handover, were included. After weighting, the composite outcome was statistically associated with handovers (3,517 of 48,986 [7.2%] in handover cases vs. 4,470 of 72,091 [6.2%] in nonhandover cases; odds ratio, 1.08; 95% CI, 1.04 to 1.12). Time series analysis showed a marked increase in usage of the structured tool after the initial intervention. The odds ratio for the composite outcome showed a significant decrease over time after the initial intervention (t = –3.97; P < 0.001), with the slope of the odds ratio versus time curve decreasing from 0.002 (95% CI, 0.001 to 0.004; P = 0.018) to –0.011 (95% CI, –0.01 to –0.018; P < 0.001).

Conclusions

Intraoperative handovers are significantly associated with adverse outcomes even after controlling for multiple confounding variables. Use of a structured handover tool during anesthesia care may attenuate the adverse effect.

Editor’s Perspective

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Hybrid Press-fit and Adjustable Button Femoral Fixation of Anterior Cruciate Ligament Semitendinosus and Bone-patellar Tendon-bone Autografts—A Technical Note
Authors: Aldawoudy Akram , Alajwani Mahmoud , Hirschmann Michael , Badr Ahmad , Waly Ahmed H. , Soliman Eiman
Published: November 2023

Introduction:

Many fixation methods are available for anterior cruciate ligament (ACL) grafts. Adjustable buttons (ABs) are characterized by their high fixation strength but have the disadvantage of potential stretching of their linking suture material. Press-fit bone plugs provide fixation at the joint line and enhance biological graft healing. Using both is thought to result in a higher fixation strength, enhancing graft biology and transferring the fixation point to the joint line.

Materials and Methods:

It is the aim of this technical note to describe a certain technique of ACL graft hybrid fixation for hamstrings or bone-tendon-bone grafts, using AB combined with bone grafting of the femoral and tibial tunnels with press-fit bone plugs or bone chips.

Discussion:

ABs are commonly used fixation devices for ACL grafts. AB also allows the surgeon to tighten the ACL graft in full or near full extension. The ultimate load to failure of AB has the potential disadvantage of rendering the ACL graft progressively slack. AB augmented with press-fitting bone plugs enhances biological potentials, adds to fixation strength, and transfers the fixation level of the graft from the outer femoral cortex to the joint line.

Conclusion:

Hybrid AB and bone plug fixation of ACL autografts, whether hamstrings or bone-tendon bone, optimizes ACL graft fixation by gaining advantages and omitting the disadvantages of both techniques.
Duration of analgesia after forefoot surgery compared between an ankle and a sciatic nerve block at the popliteal crease
Authors: Olofsson Magnus , Nguyen Alexandre , Rossel Jean-Benoit , Albrecht Eric
Published: November 2023

BACKGROUND

Forefoot surgery is associated with severe postoperative pain. Ankle and sciatic nerve blocks provide satisfactory postoperative analgesia after forefoot surgery, but little is known on their respective duration of analgesia.

OBJECTIVE

This randomised controlled, single-blinded trial tested the hypothesis that after forefoot surgery in the setting of multimodal analgesia, an ankle block provides analgesia superior to that of a sciatic nerve block at the popliteal crease.

DESIGN

A randomised controlled study.

SETTING

A single centre study in a university hospital in Switzerland, from September 2018 to November 2022.

PATIENTS

From 91 patients scheduled for forefoot surgery, 60 met the inclusion criteria of which 56 completed the protocol and their data were available for analysis. Exclusion criteria were existing sciatic nerve deficit, pre-existing peripheral neuropathy, chronic pain diagnosis, pregnancy, or identified contraindications to peripheral nerve block.

INTERVENTION

Patients undergoing forefoot surgery were randomly allocated to either a multi-injection ankle block (partly under ultrasound guidance) or a sciatic nerve block at the popliteal crease (under ultrasound guidance) combined with a saphenous nerve block at the ankle. Patients in each group received a total of 30 ml of ropivacaine 0.5% and a multimodal analgesic regimen inclusive of dexamethasone, paracetamol, ketorolac then ibuprofen.

MAIN OUTCOME MEASURE

The primary outcome was duration of analgesia, defined as time to first morphine request.

RESULTS

Mean ± SD duration of analgesia was 15.4 ± 8.0 h in the ankle block group and 20.0 ± 10.3 h in the sciatic nerve block group (P = 0.32). Of note, 15 of 26 (58%) and 24 of 30 (80%) patients of the ankle and sciatic nerve block groups did not request any morphine (P = 0.09). Other secondary outcomes were similar between groups.

CONCLUSION

Compared with the ankle block, the sciatic nerve block at the popliteal crease does not provide a longer duration of analgesia in patients undergoing forefoot surgery in the setting of multimodal analgesia.

TRIAL REGISTRATION

Clinicaltrials.com identifier: NCT03683342.
Peri-operative night-time work of anaesthesiologists
Authors: Ippolito Mariachiara , Noto Alberto , Lakbar Ines , Chalkias Athanasios , Afshari Arash , Kranke Peter , Garcia Carolina Soledad Romero , Myatra Sheila Nainan , Schultz Marcus J. , Giarratano Antonino , Bilotta Federico , De Robertis Edoardo , Einav Sharon , Cortegiani Andrea
Published: November 2023

BACKGROUND

Qualitative data on the opinions of anaesthesiologists regarding the impact of peri-operative night-time working conditions on patient safety are lacking.

OBJECTIVE(S)

This study aimed to achieve in-depth understanding of anaesthesiologists’ perceptions regarding the impact of night-time working conditions on peri-operative patient safety and actions that may be undertaken to mitigate perceived risks.

DESIGN

Qualitative analysis of responses to two open-ended questions.

SETTING

Online platform questionnaire promoted by the European Society of Anaesthesiology and Intensive Care (ESAIC).

PARTICIPANTS

The survey sample consisted of an international cohort of anaesthesiologists.

MAIN OUTCOME MEASURES

We identified and classified recurrent themes in the responses to questions addressing perceptions regarding (Q1) peri-operative night-time working conditions, which may affect patient safety and (Q2) potential solutions.

RESULTS

We analysed 2112 and 2113 responses to Q1 and Q2, respectively. The most frequently reported themes in relation to Q1 were a perceived reduction in professional performance accompanied by concerns regarding the possible consequences of work with fatigue (27%), and poor working conditions at night-time (35%). The most frequently proposed solutions in response to Q2 were a reduction of working hours and avoidance of 24-h shifts (21%), an increase in human resources (14%) and performance of only urgent or emergency surgeries at night (14%).

CONCLUSION

Overall, the surveyed anaesthesiologists believe that workload-to-staff imbalance and excessive working hours were potential bases for increased peri-operative risk for their patients, partly because of fatigue-related medical errors during night-time work. The performance of nonemergency elective surgical cases at night and lack of facilities were among the reported issues and potential targets for improvement measures. Further studies should investigate whether countermeasures can improve patient safety as well as the quality of life of anaesthesia professionals. Regulations to improve homogeneity, safety, and quality of anaesthesia practice at night seem to be urgently needed.
LRH-1 agonist DLPC through STAT6 promotes macrophage polarization and prevents parenteral nutrition-associated cholestasis in mice
Authors: Ghosh Swati , Devereaux Michael W. , Liu Cuining , Sokol Ronald J.
Published: November 2023

Background and Aims:

Parenteral nutrition-associated cholestasis (PNAC) is an important complication in patients with intestinal failure with reduced LRH-1 expression. Here, we hypothesized that LRH-1 activation by its agonist, dilauroylphosphatidylcholine (DLPC), would trigger signal transducer and activator of transcription 6 (STAT6) signaling and hepatic macrophage polarization that would mediate hepatic protection in PNAC.

Approach and Results:

PNAC mouse model (oral DSSx4d followed by PNx14d; DSS-PN) was treated with LRH-1 agonist DLPC (30 mg/kg/day) intravenously. DLPC treatment prevented liver injury and cholestasis while inducing hepatic mRNA expression of Nr5a2 (nuclear receptor subfamily 5 group A member 2), Abcb11 (ATP binding cassette subfamily B member 11), Abcg5 (ATP-binding cassette [ABC] transporters subfamily G member 5), Abcg8 (ATP-binding cassette [ABC] transporters subfamily G member 8), nuclear receptor subfamily 0, and ATP-binding cassette subfamily C member 2 (Abcc2) mRNA, all of which were reduced in PNAC mice. To determine the mechanism of the DLPC effect, we performed RNA-sequencing analysis of the liver from Chow, DSS-PN, and DSS-PN/DLPC mice, which revealed DLPC upregulation of the anti-inflammatory STAT6 pathway. In intrahepatic mononuclear cells or bone-marrow derived macrophages (BMDM) from PNAC mice, DLPC treatment prevented upregulation of pro-inflammatory (M1) genes, suppressed activation of NFκB and induced phosphorylation of STAT6 and its target genes, indicating M2 macrophage polarization. In vitro, incubation of DLPC with cultured macrophages showed that the increased Il-1b and Tnf induced by exposure to lipopolysaccharides or phytosterols was reduced significantly, which was associated with increased STAT6 binding to promoters of its target genes. Suppression of STAT6 expression by siRNA in THP-1 cells exposed to lipopolysaccharides, phytosterols, or both resulted in enhanced elevation of IL-1B mRNA expression. Furthermore, the protective effect of DLPC in THP-1 cells was abrogated by STAT6 siRNA.

Conclusions:

These results indicate that activation of LRH-1 by DLPC may protect from PNAC liver injury through STAT6-mediated macrophage polarization.
Modulated partial associating liver partition and portal vein ligation for staged hepatectomy for colorectal liver disease: a case report
Authors: Macone Lorenzo , Costa Jessica , Granieri Stefano , Sileo Annaclara , Roncaccia Valerio , Germini Alessandro , Gjoni Elson , Paleino Sissi , Cotsoglou Christian
Published: November 2023

Postoperative liver failure remains one of the most common causes of mortality after liver surgery. Many techniques have been developed to induce parenchymal increase to reduce the incidence of postoperative liver failure. In our video [online] we showed our technique, which we called “modulated partial associating liver partition and portal vein ligation for staged hepatectomy (ALPPS),” which aimed to minimize the surgical stress between the two phases of a two-stage hepatectomy. Our patient was a 49-year-old man affected by colorectal liver metastases who underwent a two-stage right hepatectomy through the modulated partial ALPPS technique. Postoperative CT scans revealed an increase in future liver remnants, that resulted sufficient for the patient to sustain liver resection. Although further studies would be necessary and true randomization is hard to obtain, in relation to the complexity of these cases, we propose a feasible technique that reduces the surgical stress between the two phases of a two-stage hepatectomy, improving the prognosis for patients affected by colorectal liver metastases.