bluuebunny/crossref_metadata_2025 huggingface dataset:
Stargardt disease-associated missense and synonymous ABCA4 variants result in aberrant splicing
Authors: Kaltak Melita , Corradi Zelia , Collin Rob W J , Swildens Jim , Cremers Frans P M
Published: August 2023

Missense variants in ABCA4 constitute ~50% of causal variants in Stargardt disease (STGD1). Their pathogenicity is attributed to their direct effect on protein function, whilst their potential impact on pre-mRNA splicing disruption remains poorly understood. Interestingly, synonymous ABCA4 variants have previously been classified as ‘severe’ variants based on in silico analyses. Here, we systemically investigated the role of synonymous and missense variants in ABCA4 splicing by combining computational predictions and experimental assays. To identify variants of interest, we used SpliceAI to ascribe defective splice predictions on a dataset of 5579 biallelic STGD1 probands. We selected those variants with predicted delta scores for acceptor/donor gain > 0.20, and no previous reports on their effect on splicing. Fifteen ABCA4 variants were selected, 4 of which were predicted to create a new splice acceptor site and 11 to create a new splice donor site. In addition, three variants of interest with delta scores < 0.20 were included. The variants were introduced in wild-type midigenes that contained 4–12 kb of ABCA4 genomic sequence, which were subsequently expressed in HEK293T cells. By using RT-PCR and Sanger sequencing, we identified splice aberrations for 16 of 18 analyzed variants. SpliceAI correctly predicted the outcomes for 15 out of 18 variants, illustrating its reliability in predicting the impact of coding ABCA4 variants on splicing. Our findings highlight a causal role for coding ABCA4 variants in splicing aberrations, improving the severity assessment of missense and synonymous ABCA4 variants, and guiding to new treatment strategies for STGD1.
Overestimating management progress—modelled vs. monitored silver eel escapement in a North Sea draining river
Authors: Höhne Leander , Freese Marko , Pohlmann Jan-Dag , Diekmann Markus , Fladung Erik , Huisman Jeroen B J , Hanel Reinhold , Marohn Lasse
Published: August 2023

The success of European efforts towards the recovery of the European eel (Anguilla anguilla) population will rely on accurate assessments of local stock status for the implementation of conservation measures. Yet, direct and continuous monitoring of the escapement of potential spawners (“silver eels”) is unfeasible in most habitats. Therefore, population models are widely used to estimate local silver eel escapement, but require input information on recruitment, demographic characteristics, and mortalities that are often estimated with great uncertainties. We conducted a combined mark–recapture and acoustic telemetry study across two migration seasons to quantify the actual silver eel escapement in a sub-catchment of the German river Ems. Results were compared with predictions from the demographic model used to provide stock parameters in Germany according to the EU eel-regulation. Mark–recapture results suggested an annual female silver eel escapement of ∼15–17 tons, while the demographic model predicted 90–98 tons, indicating a considerable overestimation. Our results suggest that realistic prediction of silver eel escapement is hardly feasible without high-quality input information and highlight the need for site-specific model calibrations against monitoring data. Overestimations of local stock sizes are problematic if they obscure the necessity for adequate conservation measures, hindering their implementation.
(S)-Ketamine but Not (R)-Ketamine Shows Acute Effects on Depression-Like Behavior and Sleep-Wake Architecture in Rats
Authors: Koncz Szabolcs , Papp Noémi , Pothorszki Dóra , Bagdy György
Published: August 2023

Background

Racemic ketamine consists of two enantiomers, namely (R)-ketamine and (S)-ketamine, with distinguishable pharmacological properties. Both enantiomers have been reported to show rapid antidepressant effects in rodents. Currently, the (S)-enantiomer has been approved for the treatment of major depression, whereas (R)-ketamine failed to show antidepressant effect in recent clinical studies. Major depressive disorder is frequently characterized by disinhibition of rapid eye movement (REM) sleep and disruption of non-REM (NREM) sleep. Racemic ketamine and most conventional antidepressants affect these parameters. However, it remains largely unknown which enantiomer is responsible for these effects.

Methods

Here, we compared acute effects of the two ketamine enantiomers (15 mg/kg i.p.) on different sleep-wake stages in freely moving, EEG-equipped rats. We also evaluated the antidepressant-like activity of the enantiomers in a chronic restraint stress model of depression.

Results

(S)-ketamine but not (R)-ketamine increased REM sleep latency and decreased REM sleep time at 2 and 3 hours, and increased electroencephalogram delta power during NREM sleep. In addition, only (S)-ketamine increased wakefulness and decreased NREM sleep in the first 2 hours. In the forced swimming test, only (S)-ketamine decreased the immobility time of chronically stressed rats.

Conclusion

Effects of the two ketamine enantiomers on rat sleep-wake architecture and behavior are markedly different when administered in the same dose. (S)-ketamine remarkably affects the sleep-wake cycle and very likely sleep-related neuroplasticity, which may be relevant for its antidepressant efficacy. Our results regarding (R)-ketamine’s lack of effect on vigilance and behavior are in line with recent clinical studies.
The Higher Education (Freedom of Speech) Act 2023: An Employment Focused Overview
Authors: Murray James
Published: August 2023

This article considers the provisions of the new Higher Education (Freedom of Speech) Act 2023 and focuses on its employment impact for registered higher education providers in England with respect to the management (in particular, discipline and dismissal) of their staff generally and their academic staff more specifically. Overall, it concludes that the impact on the employment relationship in this context will be significant. Alongside introducing specific provisions related to recruitment, dismissal and discipline of academic staff which will be enforceable through a statutory tort and a complaints scheme, the Act will influence how key aspects of the Employment Rights Act 1996 and the Equality Act 2010 are interpreted.
Counting Security in the Vernacular: Quantification Rhetoric in “Everyday” (In)Security Discourse
Authors: Jarvis Lee
Published: August 2023

Recent years have witnessed a “vernacular turn” in critical security scholarship centered on everyday constructions of (in)security. In this article, I advance this turn by arguing for greater attention to the role of numbers in non-elite discourse on (in)security. Doing so deepens understanding of the mechanisms and registers through which (in)securities are constructed in the vernacular while conceptually strengthening work on vernacular security through insight from literature on the rhetorical, sociological, and political functions of numbers. To pursue this claim, the article develops a new methodological framework through which to explore the work of numbers in vernacular security discourse before applying it to original focus group data on (counter-)radicalization. From this, I highlight the importance of numerical arguments in vernacular constructions of threat, evaluation of security policies, contestation of dominant security discourses, and performances of security literacy.
Future advancement of health care through standardized nursing terminologies: reflections from a Friends of the National Library of Medicine workshop honoring Virginia K. Saba
Authors: Dunn Lopez Karen , Heermann Langford Laura , Kennedy Rosemary , McCormick Kathleen , Delaney Connie White , Alexander Greg , Englebright Jane , Carroll Whende M , Monsen Karen A
Published: August 2023

Objective

To honor the legacy of nursing informatics pioneer and visionary, Dr. Virginia Saba, the Friends of the National Library of Medicine convened a group of international experts to reflect on Dr. Saba’s contributions to nursing standardized nursing terminologies.

Process

Experts led a day-and-a-half virtual update on nursing’s sustained and rigorous efforts to develop and use valid, reliable, and computable standardized nursing terminologies over the past 5 decades. Over the course of the workshop, policymakers, industry leaders, and scholars discussed the successful use of standardized nursing terminologies, the potential for expanded use of these vetted tools to advance healthcare, and future needs and opportunities. In this article, we elaborate on this vision and key recommendations for continued and expanded adoption and use of standardized nursing terminologies across settings and systems with the goal of generating new knowledge that improves health.

Conclusion

Much of the promise that the original creators of standardized nursing terminologies envisioned has been achieved. Secondary analysis of clinical data using these terminologies has repeatedly demonstrated the value of nursing and nursing’s data. With increased and widespread adoption, these achievements can be replicated across settings and systems.
Predicting dry matter intake in beef cattle
Authors: Blake Nathan E , Walker Matthew , Plum Shane , Hubbart Jason A , Hatton Joseph , Mata-Padrino Domingo , Holásková Ida , Wilson Matthew E
Published: August 2023

Technology that facilitates estimations of individual animal dry matter intake (DMI) rates in group-housed settings will improve production and management efficiencies. Estimating DMI in pasture settings or facilities where feed intake cannot be monitored may benefit from predictive algorithms that use other variables as proxies. This study examined the relationships between DMI, animal performance, and environmental variables. Here we determined whether a machine learning approach can predict DMI from measured water intake variables, age, sex, full body weight, and average daily gain (ADG). Two hundred and five animals were studied in a drylot setting (152 bulls for 88 d and 53 steers for 50 d). Collected data included daily DMI, water intake, daily predicted full body weights, and ADG using In-Pen-Weighing Positions and Feed Intake Nodes. After exclusion of 26 bulls of low-frequency breeds and one severe (>3 standard deviations) outlier, the final number of animals used for modeling was 178 (125 bulls, 53 steers). Climate data were recorded at 30-min intervals throughout the study period. Random Forest Regression (RFR) and Repeated Measures Random Forest (RMRF) were used as machine learning approaches to develop a predictive algorithm. Repeated Measures ANOVA (RMANOVA) was used as the traditional approach. Using the RMRF method, an algorithm was constructed that predicts an animal’s DMI within 0.75 kg. Evaluation and refining of algorithms used to predict DMI in drylot by adding more representative data will allow for future extrapolation to controlled small plot grazing and, ultimately, more extensive group field settings.
War Crimes Involving Autonomous Weapons
Authors: Lewis Dustin A
Published: August 2023

This article identifies and evaluates key international legal aspects concerning three notions that have figured in debates on war crimes involving an autonomous weapon system (AWS): responsibility, liability and accountability. It focuses on the general contours of the existing international law of armed conflict, also known as international humanitarian law (IHL), and related fields, concepts and institutions. Regarding responsibility, this article examines, on one hand, the international responsibility of a state for an internationally wrongful act related to a breach of a rule of IHL involving an AWS that may form the basis of a war crime and, on the other hand, individual criminal responsibility for a war crime involving an AWS. As for liability, this article outlines three international legal concepts of state liability potentially related to a war crime involving an AWS. Finally, this article sets out an, at least, legally adjacent concept of accountability that involves an explanation of the conduct related to a war crime involving an AWS and imposing political, legal, social or other consequences where such an explanation is absent or insufficient.
Gut microbial diversity and function analysis of the final-instar larvae of Protohermes xanthodes (Megaloptera: Corydalidae)
Authors: Shen Zaiyun , Cao Chengquan , Xia Xiaofeng
Published: August 2023

Protohermes xanthodes (Megaloptera, Corydalidae, Protohermes), widespread species in China, is an important insects treated as food and medicine for aquaculture. In this study, the gut microbiota was investigated by 16S rRNA microbial profiling. A total of 600 Amplicon Sequence Variants (ASV) were identified, Proteobacteria and Firmicutes were the main dominant phyla, and 27 genera ran through the entire digestive tract, mainly Hafnia-Obesumbacterium (Proteobacteria), Lactobacillus and Lactococcus (Firmicutes). The PICRUSt2 functional prediction of gut microbiota showed that the foregut abundant pathways related to metabolism, environmental information processing, and genetic information processing. while the midgut had the most abundant metabolic and environmental information processing pathways, including the prominent phosphotransferase system (PTS), propionate metabolism, and β-lactam resistance. The hindgut had the weakest metabolic function, but its genetic information processing was more abundant than the foregut and midgut. Additionally, 26 strains of bacteria were isolated from the midgut microorganisms, with Firmicutes being the dominant bacteria, and some of the purified bacteria had potential probiotic and anti-pathogen functions. These findings suggest that there are differences in the microorganisms of the different gut floras of the larvae, and each flora has specific metabolic functions. This research could be used to further understand the function of gut microorganisms, explore the co-evolution of P. xanthodes and gut microorganisms, and promote healthy breeding based on gut microorganisms.
Non-operative management involving chemoradiation therapy combined with high-dose-rate brachytherapy for T3 rectal cancer using a vaginal shielded cylindrical applicator: a technical report
Authors: Murakami Naoya , Kojima Kanako , Okuma Kae , Kashihara Tairo , Nakamura Satoshi , Shimizu Wakako , Suda Ryuichiro , Igaki Hiroshi , Shikama Naoto
Published: August 2023

It has been shown that a group of rectal cancer patients will achieve a pathological complete response following preoperative chemoradiotherapy, and non-operative management has recently gained attention. To escalate the tumour dose and increase the likelihood of pathological complete response, brachytherapy can play an important role in safely increasing the total dose. However, at the time this report was published, an applicator dedicated to rectal brachytherapy was unaffordable in Japan. Here, we report two T3 rectal cancer patients who were inoperable or refused surgery and treated by chemoradiotherapy following intracavitary brachytherapy involving a vaginal cylinder applicator with lead shielding.
Hume on Modal Projection
Authors: Ehli Bridger
Published: August 2023

Hume’s claim that we project necessity onto objects we take to be causally related has been influential in contemporary discussions of modality, inspiring deflationary accounts of our modal commitments. Hume is commonly understood as holding that modal projection explains our judging that an effect must follow its cause. This misunderstands the role of projection in Hume’s discussions of causation and causal judgement. Projection is a diagnosis of a distinctively philosophical confusion: the commitment to mind-independent necessary connections. In arguing for this, I provide an account of the psychological process that, in Hume’s view, underlies projection. This account resolves problems with Hume’s projectivism identified by his commentators.
Explanationism versus Modalism in Debunking (and Theory Choice)
Authors: Bhogal Harjit
Published: August 2023

At the core of the recent debate over moral debunking arguments is a disagreement between explanationist and modalist approaches. Explanationists think that the lack of an explanatory connection between our moral beliefs and the moral truths, given a non-naturalist realist conception of morality, is a reason to reject non-naturalism. Modalists disagree. They say that, given non-naturalism, our beliefs have the appropriate modal features with respect to truth – in particular they are safe and sensitive – so there is no problem. There is a stand-off here. I argue, though, that by looking at the role explanatory and modal factors have to play in theory choice more generally, and, in particular, by considering the practice of theory choice in science, we can see that the explanationist is right. The lack of an explanatory connection between our moral beliefs and the moral truths is a reason to reject non-naturalist realism about morality.
Improving health literacy of antifungal use—Comparison of the readability of antifungal medicines information from Australia, EU, UK, and US of 16 antifungal agents across 5 classes (allylamines, azoles, echinocandins, polyenes, and others)
Authors: Moore John E , Tang Ka Wah Kelly , Millar Beverley C
Published: August 2023

Adherence to antifungals is poor in high endemic regions where antifungal resistance is high. Poor readability of prescription/over-the-counter (OTC) antifungals may contribute to poor adherence, due to the patient not fully understanding the purpose, importance, and dosage of their antifungal medicine. As there are no reports on the readability of antifungals, this study examined the readability of patient-facing antifungal information. Antifungals (n = 16; five classes [allylamines, azoles, echinocandins, polyenes, and others—flucytosine and griseofulvin]) were selected. Readability of four sources of information, (i) summary of product characteristics, (ii) patient information leaflets (PILs), (iii) OTC patient information, and (iv) patient web-based information, was calculated using Readable software, to obtain readability scores [(i) Flesch Reading Ease [FRE], (ii) Flesch–Kinkaid Grade Level [FKGL], (iii) Gunning Fog Index, and (iv) Simple Measure of Gobbledygook (SMOG) Index) and text metrics [word count, sentence count, words/sentence, and syllables/word]. PILs, web-based resources, and OTC patient information had good readability (FRE mean ± sd = 52.8 ± 6.7, 58.6 ± 6.9, and 57.3 ± 7.4, respectively), just falling short of the ≥ 60 target. For FKGL (target ≤ 8.0), PILs, web-based resources, and OTC patient information also had good readability (mean ± sd = 8.5 ± 1.0, 7.2 ± 0.86, and 7.8 ± 0.1, respectively). Improved readability scores observed correlate with reduced words, words/sentence and syllables/word. Improving readability may lead to improved patient health literacy. Healthcare professionals, academics, and publishers preparing written materials regarding antifungals for the lay/patient community are encouraged to employ readability calculators to check the readability of their work, so that the final material is within recommended readability reference parameters, to support the health literacy of their patients/readers.
Exploring the diversity and similarity of radially anisotropic Milky Way-like stellar haloes: implications for disrupted dwarf galaxy searches
Authors: Orkney Matthew D A , Laporte Chervin F P , Grand Robert J J , Gómez Facundo A , van de Voort Freeke , Fattahi Azadeh , Marinacci Federico , Pakmor Rüdiger , Fragkoudi Francesca , Springel Volker
Published: August 2023

We investigate the properties of mergers comparable to the Gaia–Sausage–Enceladus (GSE) using cosmological hydrodynamical simulations of Milky Way-like galaxies. The merger progenitors span an order of magnitude in their peak stellar mass ($3\times 10^8\lt M_{\star }/\rm {M}_{\odot }\lt 4\times 10^9$) and include both rotation and pressure-supported galaxies (0.10 < D/T < 0.77). In a minority of cases, the GSE-like debris is comprised of stars from more than one merger progenitor. However, there is a close similarity in their chemodynamical properties and the triaxial shapes of their debris, and so it is not always possible to distinguish them. The merger progenitors host a variety of luminous satellites (0 and 8 with $M_{\star }\gt 10^6\, \rm {M}_{\odot }$), but most of these do not follow the merger to low orbital energies. Between 0 and 1 of these satellites may survive to z = 0, but with no clear signatures of their past association. We show that the fraction of stars originating from GSE-like mergers is reduced for lower metallicities (reaching a minimum around [Fe/H] = −2), and also within 5 kpc of the Galactic Centre. Whilst these central regions are dominated by in-situ stars, the ex-situ fraction trends towards a 100 per cent asymptote when considering the most metal-poor stars ([Fe/H] ≪ −2.5). Considering this, its near proximity, and its small volume on the sky, the Galactic Centre lends itself as a prime environment in the search for the stars from the earliest galaxies, whilst avoiding contamination from GSE stars.
Postgraduate Selection in Medical Education: A Scoping Review of Current Priorities and Values
Authors: Caretta-Weyer Holly A. , Eva Kevin W. , Schumacher Daniel J. , Yarris Lalena M. , Teunissen Pim W.
Published: August 2023

Purpose

The process of screening and selecting trainees for postgraduate training has evolved significantly in recent years, yet remains a daunting task. Postgraduate training directors seek ways to feasibly and defensibly select candidates, which has resulted in an explosion of literature seeking to identify root causes for the problems observed in postgraduate selection and generate viable solutions. The authors therefore conducted a scoping review to analyze the problems and priorities presented within the postgraduate selection literature to explore practical implications and present a research agenda.

Method

Between May 2021 and February 2022, the authors searched PubMed, EMBASE, Web of Science, ERIC, and Google Scholar for English language literature published after 2000. Articles that described postgraduate selection were eligible for inclusion. 2,273 articles were ultimately eligible for inclusion. Thematic analysis was performed on a subset of 100 articles examining priorities and problems within postgraduate selection. Articles were sampled to ensure broad thematic and geographical variation across the breadth of articles that were eligible for inclusion.

Results

Five distinct perspectives or value statements were identified in the thematic analysis: (1) Using available metrics to predict performance in postgraduate training; (2) identifying the best applicants via competitive comparison; (3) seeking alignment between applicant and program in the selection process; (4) ensuring diversity, mitigation of bias, and equity in the selection process; and (5) optimizing the logistics or mechanics of the selection process.

Conclusions

This review provides insight into the framing and value statements authors use to describe postgraduate selection within the literature. The identified value statements provide a window into the assumptions and subsequent implications of viewing postgraduate selection through each of these lenses. Future research must consider the outcomes and consequences of the value statement chosen and the impact on current and future approaches to postgraduate selection.
Evaluating Educational Outcomes Using Patient Outcomes of New Surgeons Performing Partial Colectomy Compared to Cholecystectomy
Authors: George Brian C. , Thelen Angela E. , Howard Ryan A. , Kendrick Daniel E. , Chen Xilin , Clark Michael J. , Gupta Tanvi , Brown Craig S. , Bandeh-Ahmadi Hoda , Luckoski John L. , Wnuk Greg M. , Fan Zhaohui , Krumm Andrew E. , Ryan Andrew M. , Buyske Jo , Mukherjee Bhramar , Dimick Justin B.
Published: August 2023

Purpose

Despite ongoing efforts to improve surgical education, surgical residents face gaps in their training. However, it is unknown if differences in the training of surgeons are reflected in the patient outcomes of those surgeons once they enter practice. This study aimed to compare the patient outcomes among new surgeons performing partial colectomy—a common procedure for which training is limited—and cholecystectomy—a common procedure for which training is robust.

Method

The authors retrospectively analyzed all adult Medicare claims data for patients undergoing inpatient partial colectomy and inpatient cholecystectomy between 2007 and 2018. Generalized additive mixed models were used to investigate the associations between surgeon years in practice and risk-adjusted rates of 30-day serious complications and death for patients undergoing partial colectomy and cholecystectomy.

Results

A total of 14,449 surgeons at 4,011 hospitals performed 340,114 partial colectomy and 355,923 cholecystectomy inpatient operations during the study period. Patients undergoing a partial colectomy by a surgeon in their 1st vs 15th year of practice had higher rates of serious complications (5.22% [95% CI, 4.85%–5.60%] vs 4.37% [95% CI, 4.22%–4.52%]; P < .01) and death (3.05% [95% CI, 2.92%–3.17%] vs 2.83% [95% CI, 2.75%–2.91%]; P < .01). Patients undergoing a cholecystectomy by a surgeon in their 1st vs 15th year of practice had similar rates of 30-day serious complications (4.11% vs 3.89%; P = .11) and death (1.71% vs 1.70%; P = .93).

Conclusions

Patients undergoing partial colectomy faced a higher risk of serious complications and death when the operation was performed by a new surgeon compared to an experienced surgeon. Conversely, patient outcomes following cholecystectomy were similar for new and experienced surgeons. More attention to partial colectomy during residency training may benefit patients.
Bile acids promote the development of HCC by activating the inflammasome
Authors: Chen Wenbo , Ding Ming , Ji Liyan , Yao Jingjing , Guo Yajuan , Yan Wenxin , Yu Shaofang , Shen Qinghong , Huang Min , Zheng Yaqiu , Lin Yuefang , Wang Ying , Liu Zhongqiu , Lu Linlin , Jin Xin
Published: August 2023

Background:

Hepatocellular carcinoma (HCC) is associated with chronic inflammation caused by different factors; especially, the interaction of inflammatory pathways and bile acids (BAs) can affect hepatocyte proliferation, death, and regeneration, but whether BAs promote HCC progression through inflammatory pathways and the mechanisms is still unclear.

Methods and results:

By examining cancer and tumor-adjacent tissue BA levels and genes associated with BA homeostasis in 37 HCC patients, we found that total bile acids (TBAs) were decreased by 36% and varying degrees of changes in factors regulating BA homeostasis (p < 0.05). In addition, we found that BA homeostasis was disturbed in diethylnitrosamine-induced HCC mouse models, and TBA was correlated with inflammasome activation during HCC progression (6–24 W) (p < 0.05). Similarly, the inflammasome and chenodeoxycholic acid (CDCA) content were suppressed in cholestasis model mice (Mrp2-deficient mice) (p < 0.05). In vitro, CDCA significantly promoted the malignant transformation of hepatocytes (p < 0.001), activated the inflammasome by triggering the release of mitochondrial reactive oxygen species and mitochondrial DNA, and ultimately induced pyroptosis. Furthermore, we found that CDCA has a targeted binding effect with HO-1 through molecular docking and Cellular Thermal Shift Assay experiments.

Conclusions:

In conclusion, we found that CDCA can trigger the excessive accumulation of mitochondrial reactive oxygen species by targeting HO-1 to promote the activation of the inflammasome and ultimately promote the progression of HCC. Our study provides a novel mechanism by which BAs promote HCC by activating the inflammasome and establishes the important role of BA homeostasis imbalance in the progression of HCC from the aspect of inflammation.
Broad-spectrum neuroprotection exerted by DDD-028 in a mouse model of chemotherapy-induced neuropathy
Authors: Lucarini Elena , Micheli Laura , Rajagopalan Raghavan , Ciampi Clara , Branca Jacopo J.V. , Pacini Alessandra , Leandri Massimo , Rajagopalan Parthasarathi , Ghelardini Carla , Di Cesare Mannelli Lorenzo
Published: August 2023

Neurotoxicity of chemotherapeutics involves peculiar alterations in the structure and function, including abnormal nerve signal transmission, of both the peripheral and central nervous system. The lack of effective pharmacological approaches to prevent chemotherapy-induced neurotoxicity necessitates the identification of innovative therapies. Recent evidence suggests that repeated treatment with the pentacyclic pyridoindole derivative DDD-028 can exert both pain-relieving and glial modulatory effects in mice with paclitaxel-induced neuropathy. This work is aimed at assessing whether DDD-028 is a disease-modifying agent by protecting the peripheral nervous tissues from chemotherapy-induced damage. Neuropathy was induced in animals by paclitaxel injection (2.0 mg kg−1 i.p). DDD-028 (10 mg kg−1) and the reference drug, pregabalin (30 mg kg−1), were administered per os daily starting concomitantly with the first injection of paclitaxel and continuing 10 days after the end of paclitaxel treatment. The behavioural tests confirmed the antihyperalgesic efficacy of DDD-028 on paclitaxel-induced neuropathic pain. Furthermore, the electrophysiological analysis revealed the capacity of DDD-028 to restore near-normal sensory nerve conduction in paclitaxel-treated animals. Histopathology evidence indicated that DDD-028 was able to counteract effectively paclitaxel-induced peripheral neurotoxicity by protecting against the loss of intraepidermal nerve fibers, restoring physiological levels of neurofilament in nerve tissue and plasma, and preventing morphological alterations occurring in the sciatic nerves and dorsal root ganglia. Overall, DDD-028 is more effective than pregabalin in preventing chemotherapy-induced neurotoxicity. Thus, based on its potent antihyperalgesic and neuroprotective efficacy, DDD-028 seems to be a viable prophylactic medication to limit the development of neuropathies consequent to chemotherapy.
Comparing the prevalence of chronic pain in school-aged children in the United States from 2019 to 2020: a nationally representative study examining differences associated with the COVID-19 pandemic
Authors: Kapos Flavia P. , Vandeleur Daron M. , Tham See Wan , Palermo Tonya M. , Groenewald Cornelius B.
Published: August 2023

The coronavirus disease 19 (COVID-19) pandemic negatively affected children's health in the United States (US), with more severe disruption for marginalized groups. However, potential impact on pediatric chronic pain has not been assessed at the population level. This study aimed to (1) estimate differences in the US national prevalence of pediatric chronic pain during the first year of the COVID-19 pandemic (2020), relative to one year earlier (2019); (2) determine whether differences in prevalence varied across sociodemographic groups; and (3) explore changes in child, caregiver, and family factors associated with chronic pain prevalence. Using data of children 6 to 17 years from the National Survey of Children's Health 2019 and 2020 (n = 50,518), we compared weighted percentages of sample characteristics by year and conducted a series of directed-acyclic graph–informed survey-weighted Poisson regressions. The estimated national prevalence (95% CI) of pediatric chronic pain was 10.8% (9.9, 11.9%) in 2019, decreasing to 7.6% (6.9, 8.3%) in 2020. Contrary to hypotheses, the adjusted prevalence of chronic pain was 31% lower in 2020 than in 2019 (aPR = 0.69, 95% CI: 0.61, 0.79), adjusting for child age, sex, race or ethnicity, caregiver education, neighborhood park or playground, and census region. The 2019 to 2020 change in chronic pain prevalence was similar by age (P = 0.34), sex (P = 0.94), race or ethnicity (P = 0.41), caregiver education (P = 0.49), neighborhood park or playground (P = 0.22), and census region (P = 0.20). Exploratory analyses identified 3 potential contributors to the unexpected decrease in the national prevalence of pediatric chronic pain: lower prevalence of bullying, more frequent family meals, and higher family resilience.
From provider to professor: Supporting nurse practitioner faculty through NONPF's Faculty Institute
Authors: Sun Grace , Stanik-Hutt Julie
Published: August 2023

Over the past 15 years, the number of practicing nurse practitioners (NPs) has increased exponentially. This growth has been sustained by an increase in the number of schools offering NP preparation. Experienced NPs have assumed faculty positions in these schools. Although educational curricula prepare NPs to deliver high-quality patient care, it does not prepare graduates for academic roles in teaching, dissemination of scholarship, or service leadership to advance the profession. To address these gaps in NP faculty preparation, faculty development resources specific to NP education are needed. The National Organization of Nurse Practitioner Faculties (NONPF) has stepped forward to fill this gap. The NONPF Faculty Institute was created in 2017, and it includes the annual Fall Conference, the Faculty Leadership Mentoring Program, the Webinar Series, and, most recently, the joint NPACE/NONPF New Faculty Development Program. This comprehensive focus on faculty development aligns with NONPF's mission to promote excellence in NP education and advance the NP role in health care. Programs in the NONPF Faculty Institute are specifically designed to address the distinct learning needs of NP faculty. They use “just in time” presentations and active learning strategies to provide NP faculty with easily accessible and targeted content and opportunities for direct application of new skills. The Institute's goal is to provide NP faculty opportunities to prepare themselves to meet the teaching, scholarship and service leadership expectations of academia, the learning needs of students, and advance the impact of NP practice on patient and health care system outcomes.
Serum lipoprotein(a), and plasminogen activator inhibitor-1 in uncomplicated type 2 diabetes mellitus: a case–control study
Authors: Abdullah Fargeen E. , Ahmed Sardar N.
Published: August 2023

Background:

Increased levels of lipoprotein (a) [Lp(a)] are indicative of coronary artery disease (CAD). Dyslipidemia, which is an established risk factor for CAD, is also an additional adverse effect of uncontrolled type 2 diabetes. Procoagulant and fibrinolytic indicators have been linked to the development of type 2 diabetes. Plasminogen activator inhibitor-1 (PAI-1), plays a significant negative regulatory role in fibrinolysis, through its function as the main inhibitor of tissue plasminogen activator. This study was designed to investigate the levels of Lp(a) and PAI-1 in uncomplicated type 2 diabetic patients and their association with healthy controls.

Materials and methods:

A case–control study designed for the estimation of Lp(a) and PAI-1 in serum after collecting blood samples from type 2 diabetic patients at the Layla Qasim Diabetic Center in Erbil, Iraq. The study included 90 participants, of whom 30 were healthy controls (15 males and 15 females). The remaining 60 cases were patients with type 2 diabetes with a duration of up to 6 years (30 males and 30 females).

Results:

Serum Lp(a) and PAI-1 levels were significantly lower in type 2 diabetic patients than in controls (P<0.01), this is an opposite result that usually happen in uncontrolled and complicated diabetic patients.

Conclusions:

The results were clearly stated a beneficial effect of Metformin on the levels of Lp(a) and PAI-1 in type 2 diabetes, so lowering their concentrations would help prevention of CAD, a known cause of death in diabetic patients.
SARS-CoV-2 spike protein reduces burst activities in neurons measured by micro-electrode arrays
Authors: Salvador Melanie , Tseng Noah , Park Camdon , Williams Grace , Vethan Arianne , Thomas Grant , Baker John , Hemry Joseph , Hammond Emma , Freeburg Paige , Chou Guan-Wen , Taylor Nick , Lu Yi-Fan
Published: August 2023

Background:

Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) caused a large-scale global pandemic between 2020 and 2022. Despite efforts to understand its biological and pathogenic mechanisms, the viral impact on the neurological systems remains unclear. The main goal of this study was to quantify the neurological phenotypes induced by the SARS-CoV-2 spike protein in neurons, as measured by in-vitro multiwell micro-electrode arrays (MEAs).

Materials and methods:

The authors extracted the whole-brain neurons from the newborn P1 mice and plated them on multiwell MEAs and administered purified recombinant spike proteins (both S1 and S2 subunits) from the SARS-CoV-2 virus. The signals from the MEAs were transmitted from an amplifier to a high-performance computer for recording and analysis using an in-house developed algorithm to quantify neuronal phenotypes.

Results:

Primary among the phenotypic features analyzed, we discovered that neuronal treatment with spike 1 protein (S1) protein from SARS-CoV-2 decreased the mean burst numbers observed on each electrode, an effect that could be rescued with an anti-S1 antibody. Conversely, this mean burst number decrease was not observed with spike 2 protein (S2) treatment. Finally, our data strongly suggest that the receptor binding domain of S1 is responsible for the reduction in neuronal burst activity.

Conclusion:

Overall, our results strongly indicate that spike proteins may play an important role in altering neuronal phenotypes, specifically the burst patterns, when neurons are exposed during early development.
Spontaneous secondary pneumothorax due to cannabis-induced bullous lung disease: a case report
Authors: Zhitny Vladislav Pavlovich , Diaz Jared , Lambert-Swainston Chalette , Abdallah Ala , Gurz Sana , Young Jake , Palma Chriselyn , Chen Cliff , Khan Nazia
Published: August 2023

Introduction and importance:

Marijuana use has grown rapidly in the last decade with a prevalence greater than that of cocaine and opioids. With its increasing recreational and medical use, potential adverse outcomes from heavy use may be associated with bullous lung disease and spontaneous pneumothorax.

This case report has been reported in line with the SCARE Criteria.

Case presentation:

The authors describe a case of an adult male with a past medical history of spontaneous pneumothorax and long-standing marijuana use presenting with dyspnoea who was found to have a secondary spontaneous pneumothorax requiring invasive treatment.

Clinical discussion:

The aetiology of lung injury due to heavy marijuana smoke may be from direct tissue injury from inhaled irritants and the method of which marijuana smoke is inhaled compared with tobacco smoke.

Conclusion:

Chronic marijuana use should be considered when evaluating structural lung disease and pneumothorax in the setting of minimal tobacco use.
Retained surgical item (Gossypiboma): a case report and literature review
Authors: Alsuhaimi Mohammed A. , Alghamdi Hallah S. , Alshaiji Sarah A. , Fayi Mohammed A. , Aldhafeeri Sahar M.
Published: August 2023

Introduction and importance:

Retained surgical item is a known incidental surgical complication that is a mass of a sponge. This cotton matrix is left behind in the body cavity after surgical procedures. It is an incidental, rare medical error.

Case presentation:

Here, the authors present a case of a 30-year-old woman who had undergone a cesarean section 2 months ago and presented with the cardinal symptoms of small bowel obstruction. A computerized abdominal tomography (CT) scan showed a well-defined tubular hyperdense structure adherent to the anterior abdominal wall that exerts a mass effect on the adjacent small bowel loops. Following the computerized abdominal tomography results, an exploratory laparotomy resection and anastomosis of a small segment of the ileum were performed. The postoperative period was uneventful, and the patient has remained disease-free to date.

Clinical discussion:

Because it is not anticipated, and its clinical manifestations are variable, it is frequently misdiagnosed, and often unnecessary radical surgical procedures are performed.

Conclusion:

It should be considered in the differential diagnosis of any postoperative case with an unresolved or unusual presentation.
Pressure sore at an unusual site: the bilateral knee – a case report
Authors: Acharya Pawan , Poudel Bipin , Shrestha Shubham , Maharjan Bunu
Published: August 2023

Introduction and importance:

A pressure ulcer is a skin and soft tissue injury that commonly occur on bony prominences like the ischium, sacrum, heel, malleolus, and occiput but the knee is not the usual site for pressure ulcers. Here, the authors present a case of a pressure ulcer over an unusual site, the knee.

Case presentation:

The authors reported a case of a 66-year-old male, last seen 5 days ago by his son, who was found on the floor (with the knee on the ground) and was brought to the hospital. The patient had no history of mobility issue. On initial assessment his vitals were unstable but Glasgow Coma Scale 15/15 and CT head and ECG were unremarkable. On knee examination, there was bilateral grazing and bruising diagnosed as grade 3 and grade 4 pressure sore in the right and left knee, respectively. The pressure ulcer was managed adhering to the principles to remove all pressure, keep the ulcer clean, prevent further injury, and regular dressing by tissue viability nurses. On 17 March 2023, the patient was discharged from the hospital to a care home after his condition improved.

Clinical discussion:

A comprehensive review of the medical literature found no other reports of pressure sore at knee. A few published articles showed pressure sore as a complication of prone positioning. It is postulated that fall and long-term lie on the knees have developed this pressure ulcer.

Conclusion:

The Clinicians should be vigilant to check for pressure ulcers especially in all the bony prominences in any patients having an unwitnessed fall.
An unusual site for hydatid cyst on ovary misdiagnosed as an ovarian cyst: a case report
Authors: Bdeiwi Hassan , Sultan Hala , Mezketli Zaher , jouma Al-hejazi Tala , Trissi Mazen , Kellawi Kinda , Zayat Roula , Al-Hammod AbdulMehdi
Published: August 2023

Introduction and importance:

A hydatid cyst is a parasitic infection that can occur in multiple organs of the body, mostly in the liver. The ovary is one of the very rare locations for those cysts.

Case presentation:

The authors report a case of a 43-year-old woman with a primary hydatid cyst, the patient presented with left lower quadrant abdominal pain for 2 months. Ultrasound of the abdomen showed evidence of a multivesicular, fluid-containing cystic lesion in the left adnexa. The mass was excised and a hysterectomy with total left salpingo-oophorectomy was performed. Histopathology confirmed it to be a hydatid cyst.

Clinical discussion:

The clinical presentation of an ovarian hydatid cyst can differ, ranging from asymptomatic for years to dull pain if it compresses on the neighbouring organs or tissues, it may even cause a systemic immunological reaction if it ruptures.

Conclusion:

Cyst excision when possible is the best treatment, percutaneous sterilization techniques, and drug therapy may also be applied in certain cases.
Spontaneous fundal rupture in an unscarred uterus in a female with twin pregnancy after in-vitro fertilization: a case report
Authors: Mainali Sumnima , Devkota Sagar , Elsaghi Marwan Abd Elglil Elsayed , Soloman Badewa Olaitan , Bharati Bishal , Yadav Priyanka
Published: August 2023

Introduction and importance:

Spontaneous uterine rupture in an unscarred uterus is very rare. It is found to be rarer after in-vitro fertilization. It is associated with significant morbidity and mortality if not diagnosed and treated promptly.

Case presentation:

Thirty three years female with twin pregnancy following in-vitro fertilization after 11 years of marriage presented to emergency department with lower abdominal pain at 36 weeks 3 days of gestation and was planned for emergency caesarean section for precious twin pregnancy in labour.

Clinical findings and investigation:

She was vitally stable and on palpation of abdomen, there was generalized tenderness along with guarding. All the investigations were within normal limits.

Intervention and outcome:

Emergency caesarean section was performed under subarachnoid block which revealed a 6×2 cm fundal uterine rupture with no active bleeding which was repaired in layers. The babies were extracted with a lower uterine segment incision. First twin cried immediately after birth while the second one needed resuscitation and mechanical ventilation due to perinatal asphyxia.

Conclusion:

Even though rare in a previously unscarred uterus, uterine rupture can present in different forms and thus, requires vigilant evaluation of the patient and prompt intervention to avoid significant maternal or foetal morbidity and mortality.
Percutaneous management of complicated empyema thoracis using pigtail, report of a case from University Hospital of Nepal: a case report
Authors: Mainali Sumina , Yadav Binay , Koju Naman , Karki Aashish , K.C Narendra , Bista Dhanupa
Published: August 2023

Introduction and importance:

Empyema thoracis is a condition characterized by the accumulation of pus in the pleural cavity of the lungs. Empyema thoracis is a cause of high mortality in man and its occurrence is increasing in both children and adults. Traditionally, chest tube drainage has been a preferred method of treatment, but recent studies have shown that pigtail catheter drainage is a more effective and less invasive alternative. Image-guided drainage is also preferred over blind drainage, and alternative drainage sites are being explored. These management changes have improved patient outcomes and reduced the risk of complications.

Case presentation and clinical discussion:

A 66-year-old female presented with complaints of cough, fever, and chest pain. A clinical examination was done and relevant investigations were sent. She was then treated in the line of left-sided empyema thoracis. A pigtail catheter was inserted into the loculated empyema via the left 9th intercostal space through a posterolateral approach with ultrasonography guidance.

Conclusion:

The main aim of this article is to provide an overview of a rare management approach for empyema, a condition characterized by the accumulation of pus in the pleural cavity of the lungs. In this case report, the authors have focused on pigtail catheter drainage over traditionally performed chest tube drainage, and image-guided drainage has been performed over blind drainage ensuring accurate placement and reducing the risk of damage to surrounding tissues. Another notable change in empyema management is the shift in drainage sites from the safety triangle to other sites based on the site of loculations under ultrasonography guidance.