bluuebunny/crossref_metadata_2025 huggingface dataset:
Can we manage the melanocytic lesions with peripheral globules according to the grade of dysplasia?
Authors: Avcı Ceylan , Akın Gülfem , Lebe Banu , Şahin Mustafa Turhan , Fetil Emel
Published: April 2024

Background/Objectives

Although excision of melanocytic nevi with high‐grade dysplasia is recommended by the World Health Organization (WHO), clinical studies investigating the approach based on the grading dysplasia of melanocytic lesions with peripheral globules (PGs) are lacking. We investigated the grades of dysplasia and their distinguishable dermoscopic and clinical features to provide accurate data for managing these lesions.

Methods

We retrospectively classified histologically confirmed melanocytic lesions with PGs according to the 2018 WHO Classification of Skin Tumours criteria in a university hospital in Turkey. Dermoscopic features, lesions, and patient characteristics were recorded.

Results

Sixty‐six lesions of 56 patients were included. After classification, 9.1% (n: 6) of lesions were melanomas, 39.4% (n: 26) were high‐grade dysplastic nevi, and 50% (n: 33) were low‐grade dysplastic nevi (n: 33, 50%). There was one nevus with no dysplasia (n: 1, 1.5%). Univariate analysis revealed that ≥31 years of age, irregular shape of peripheral globules, black colour, total colour count, and maximum diameter of the lesion were associated with high‐grade dysplasia and melanoma. In the multivariate analyses, ≥31 years of age (OR = 3.80, 95% CI, 1.17–12.37), irregular shape of peripheral globules (OR = 3.90, 95% CI, 1.15–13.2), and total colour count (OR = 3.21, 95% CI, 1.2–8.5) were significant predictive factors for the lesions with high‐grade dysplasia and melanomas.

Conclusions

To avoid the underdiagnosis of both melanomas and high‐grade dysplastic nevi with PGs, the irregular shape of peripheral globules and multiple colours after the third decade may be useful in making an excision decision. The risk increases every 1‐year increase in age. Excision is suggested for all melanocytic lesions with PGs for patients 60 years or older because of the high risk of melanoma and melanocytic nevus with high‐grade dysplasia.
Grievance shocks and coordination in protest
Authors: Correa Sofía , Nandong Gaétan , Shadmehr Mehdi
Published: April 2024

When grievance shocks have heavy tails, large sudden increases in grievances coordinate behavior far more effectively into protests than a sequence of small grievance shocks that generate the same final distribution of grievances in society. That is, society as a whole behaves like the legendary boiling frog, even though each individual does not. An implication is a strong form of path‐dependence in collective action. To assess a society's potential for protest, it is not enough to know the current distribution of antiregime sentiments; we also need to know how they came about: suddenly or gradually. The theory also provides a rationale for the classic J‐curve theory of revolution. We provide a quantitative analysis of the relationship between grievance shocks and protests in Chile in 2014–2019. Consistent with the theory, results suggest that, even after controlling for grievance levels, large grievance shocks increased the number of protests.
This is why we are staying: Job satisfaction among Physiotherapists in the Kimberley region of Western Australia
Authors: King Chenae , Timler Amanda , Gill Janelle , Loh Negin , Morgan Maria , Nolan Jessica , Sturdy Robyn , Debenham James Robert
Published: April 2024

Introduction

The Kimberley region of Western Australia (WA) is classified by the Modified Monash Model as MM6 & 7 (‘Remote/Very Remote’). Many physiotherapists in the Kimberley are considered ‘rural generalists’ and require a diverse set of clinical and non‐clinical skills to work successfully within this setting.

Objective

To understand physiotherapists’ perspectives regarding job satisfaction within the Kimberley region a ‘rural and remote’ areas of Australia.

Design

An exploratory case study approach examined physiotherapists' job satisfaction in the Kimberley. Each participant completed a demographic survey and a one‐on‐one face‐to‐face interview lasting for approximately 60 minutes. Transcriptions were analysed and presented thematically. Eleven physiotherapists (nine women, two men, median age = 32 [27–60] years) participated in the study. Participants' median time working in the Kimberley was 2 (1–15) years; eight participants completed a rural placement, and eight participants had a rural background.

Findings and Discussion

Two overarching themes relating to job satisfaction emerged: ‘personal factors’ and ‘workplace factors’. Furthermore, several sub‐themes illustrated high levels of job satisfaction. Positive sub‐themes relating to personal factors included ‘belonging to the community and a rural lifestyle’. ‘Diversity in caseloads’ and ‘workplace culture’ were examples of positive workplace sub‐themes. Subthemes that challenged the participants personally were ‘family arrangements’ including schooling, ‘spousal employment and family separation’ and the ‘transiency and social issues’ within these remote communities. Workplace challenges comprised of ‘barriers to providing best practice’ and the ‘workforce and clinical experience’ found within the Kimberley physiotherapy community and the wider health care workforce. The primary challenge of job satisfaction that encompassed both personal and workplace factors was ‘accommodation’, with ‘cost’, ‘lack of availability’, and ‘perceived unsafe location’ challenging physiotherapists’ decisions to remain in the Kimberley.

Conclusion

This study describes the many factors impacting job satisfaction among physiotherapists in a rural and remote location in WA Australia. These factors warrant consideration by organisations interested in improving recruitment and retention in this context. Improving recruitment and retention in physiotherapists in rural and remote Australia has the potential to positively influence health service provision, and therefore improve health outcomes for those living in rural and remote communities.
Model‐based precision dosing and remedial dosing recommendations for delayed or missed doses of isoniazid in Chinese patients with tuberculosis
Authors: Li Jin‐Meng , Zhang Ruo‐Ying , Yang Gao‐Yi , Cai Qing‐Shan , Lang Ya‐Zhen , Zhong Fang‐Ming , Huang Jin‐Peng , Chen Yuan‐Yuan , Qin Yao , Fang Li‐Kui , Ye Bo , Lin Li‐Hua , Lin Hui‐Hong , Cai Xin‐Jun , Xu Kan
Published: April 2024

Aims

Isoniazid (INH) has been used as a first‐line drug to treat tuberculosis (TB) for more than 50 years. However, large interindividual variability was found in its pharmacokinetics, and effects of nonadherence to INH treatment and corresponding remedy regime remain unclear. This study aimed to develop a population pharmacokinetic (PPK) model of INH in Chinese patients with TB to provide model‐informed precision dosing and explore appropriate remedial dosing regimens for nonadherent patients.

Methods

In total, 1012 INH observations from 736 TB patients were included. A nonlinear mixed‐effects modelling was used to analyse the PPK of INH. Using Monte Carlo simulations to determine optimal dosage regimens and design remedial dosing regimens.

Results

A 2‐compartmental model, including first‐order absorption and elimination with allometric scaling, was found to best describe the PK characteristics of INH. A mixture model was used to characterize dual rates of INH elimination. Estimates of apparent clearance in fast and slow eliminators were 28.0 and 11.2 L/h, respectively. The proportion of fast eliminators in the population was estimated to be 40.5%. Monte Carlo simulations determined optimal dosage regimens for slow and fast eliminators with different body weight. For remedial dosing regimens, the missed dose should be taken as soon as possible when the delay does not exceed 12 h, and an additional dose is not needed. delay for an INH dose exceeds 12 h, the patient only needs to take the next single dose normally.

Conclusion

PPK modelling and simulation provide valid evidence on the precision dosing and remedial dosing regimen of INH.
Systematic profiling of Taxol resistance and sensitivity to tubulin missence mutations at molecular and cellular levels
Authors: Zhou Lihua , Ding Xi , Cao Jingjing , Feng Yu , Gu Yuqin , Liu Ling , Chen Rong , Gao Dongyun , Chen Xiaoling
Published: April 2024

Taxol (paclitaxel) is the first approved microtubule‐stabilizing agent (MSA) by binding stoichiometrically to tubulin, which is considered to be one of the most significant advances in first‐line chemotherapy against diverse tumors. However, a large number of residue missence mutations harboring in the tubulin have been observed to cause acquired drug resistance, largely limiting the clinical application of Taxol and its analogs in chemotherapy. A systematic investigation of the intermolecular interactions between the Taxol and various tubulin mutants would help to establish a comprehensive picture of drug response to tubulin mutations in clinical treatment of cancer, and to design new MSA agents with high potency and selectivity to overcome drug resistance. In this study, we described an integration of in silico analysis and in vitro assay (iSiV) to profile Taxol against a panel of 149 clinically observed, cancer‐associated missence mutations in β‐tubulin at molecular and cellular levels, aiming to a systematic understanding of molecular mechanism and biological implication underlying drug resistance and sensitivity conferring from tubulin mutations. It is revealed that the Taxol‐resistant mutations can be classified into three types: (I) nonbonded interaction broken due to mutation, (II) steric hindrance caused by mutation, and (III) conformational change upon mutation. In addition, we identified three new Taxol‐resistant mutations (C239Y, T274I, and R320P) that can largely reduce the binding affinity of Taxol to tubulin at molecular level, in which the T274I and R320P were observed to considerably impair the antitumor activity of Taxol at cellular level. Moreover, a novel drug‐susceptible mutation (M363T) was also identified, which improves Taxol affinity by 2.6‐fold and decreases Taxol antitumor EC50 values from 29.4 to 18.7 μM.
Endocrine, cardiac and neuropsychological aspects of adult congenital adrenal hyperplasia
Authors: Ridder Lukas Ochsner , Balle Camilla Mains , Skakkebæk Anne , Lind‐Holst Marie , Nielsen Mette Mølby , Hermann Pernille , Hansen Stinus , Nielsen Dorte Guldbrand , Knorr Sine , Andersen Niels Holmark , Viuff Mette Hansen , Berglund Agnethe , Gravholt Claus Højbjerg
Published: April 2024

Objective

To investigate the metabolic, cardiovascular, and neuropsychological phenotype, quality of life (QoL), and hormonal regulation in individuals with congenital adrenal hyperplasia (CAH), a group of autosomal recessive disorders characterized by impaired synthesis of cortisol in the adrenal cortex and, if untreated compensatory hyperandrogenism. CAH is associated with an increased cardiovascular and metabolic morbidity, possibly due to overtreatment with glucocorticoids, leading to weight gain, insulin resistance, and metabolic syndrome.

Design, Participants, Measurements

Thirty‐seven individuals with CAH and 33 age‐ and sex‐matched controls were evaluated at a single centre at Aarhus University Hospital with echocardiography, electrocardiogram, 24‐h blood pressure, biochemistry, anthropometrics, and autism spectrum, anxiety, depression, personality, cognitive failures, and QoL were assessed using questionnaires.

Results

CAH individuals had lower height than controls (170.5 vs. 182.9 cm in males and 160.2 vs. 170.1 cm in females, p < 0.01). Compared with female controls, females with CAH had higher haemoglobin (8.8 vs. 8.2 mmol/L, p = 0.003) and BMI (29.7 vs. 25.5 kg/m2, p = 0.006), reduced insulin sensitivity (HOMA‐IR): 2.7 vs. 1.9, p = 0.018), prolonged E‐wave deceleration time (193 vs. 174 cm, p = 0.015), and E/é ratios (5.4 vs. 4.5, p = 0.017), and lower self‐reported QoL. Males with CAH had more cognitive complaints (p = 0.034) and higher autistic scores (19.9 vs. 14.9; p = 0.068) compared with male controls. More individuals with CAH than controls reported writing problems.

Conclusion

A sex‐specific comorbidity profile is evident in CAH, with females presenting with decreased metabolic and overall self‐reported health, whereas males with CAH presented with increased cognitive complaints and autistic traits.
Early evolution of Anamorphidae (Coleoptera: Coccinelloidea): the oldest known anamorphid beetles from Upper Cretaceous amber of northern Myanmar and the first report of potential glandular pores in the family
Authors: Arriaga‐Varela Emmanuel , Szawaryn Karol , Zhou Yu‐Lingzi , Bruthansová Jana , Li Yan‐Da , Tomaszewska Wioletta
Published: April 2024

In order to place newly discovered fossil taxa (Palaeosymbius gen. nov. with P. groehni and P. mesozoicus spp. nov.) from the mid‐Cretaceous amber from northern Myanmar, we investigated the relations of extant and extinct lineages of the coccinellid group of Coccinelloidea with emphasis on the family Anamorphidae. We assembled a taxonomic sampling of 34 taxa, including 15 genera and 19 species of Anamorphidae, the most comprehensive sampling of Anamorphidae at the generic level in a phylogenetic analysis. A morphological dataset of 47 characters was built as well as a molecular alignment of 7140 bp including fragments of eight genes (12S, 16S, 18S, 28S, COI, COII, H3 and CAD). Five anamorphid and one endomychid species were sequenced for the first time and added to the dataset. We performed parsimony‐based analysis of the morphological dataset and Bayesian inference analysis of the combined matrix (morphological plus molecular data). Our results confirm that Palaeosymbius belongs to Anamorphidae and represents the oldest known member of this family so far. Among Anamorphidae, Symbiotes (with extant and known Eocene species) was recovered as the most probable closest relative of Palaeosymbius. Our morphological studies additionally revealed the presence of probable glandular openings in the anterolateral corners of the pronotal margins in Asymbius sp. and Anamorphus sp., representing the first report of secretory openings in the family Anamorphidae. Similar openings are found in other cucujiform beetles such as Cryptophagidae and Boganiidae with possible defensive purposes.
Predictors of potential clinically harmful drug–drug interactions at the medical wards in the University of Benin Teaching Hospital, Benin City
Authors: Oriaifo Oseremen Godstime , Opadeyi Abimbola Olubukunola , Oriaifo Tracy Oseremen , Isah Ambrose Ohumagho
Published: April 2024

Drug–drug interactions are preventable causes of adverse events. Different factors have been recognized as important predictors of drug–drug interactions but few studies have addressed these predictors in patients admitted into medical wards of a tertiary hospital in Nigeria hence this study. This was a retrospective study conducted using case records of patients admitted into the medical wards between January 1 and December 31, 2020. Patients were selected using a systematic random sampling method. Socio‐demographic details including age, gender, number of comorbidities, and number of medications prescribed and diagnosis were collected on days 1, 3, and at discharge. Potential drug–drug interactions were checked using Lexi‐interact® software. Analysis was set at p < 0.05. A total of 430 case records were included in this study based on the inclusion criteria. Lexi‐interact recorded a prevalence of (217) 50.5% on day 1, (146) 34.0% on day 3, and (290) 67.4% at discharge. A significant association (p < 0.05) was found between the potential drug–drug interactions (DDI) and an increased number of medicines prescribed on all the days of admission. Also, patients without certain infectious or parasitic diseases have reduced odds of developing DDI. There is a need for continuous monitoring of medications from admission to discharge especially in the elderly, those on multiple medications, certain infectious or parasitic diseases, and comorbidities as these impact on DDIs.
Transforming Assessment: The Impacts and Implications of Large Language Models and Generative AI
Authors: Hao Jiangang , von Davier Alina A. , Yaneva Victoria , Lottridge Susan , von Davier Matthias , Harris Deborah J.
Published: April 2024

The remarkable strides in artificial intelligence (AI), exemplified by ChatGPT, have unveiled a wealth of opportunities and challenges in assessment. Applying cutting‐edge large language models (LLMs) and generative AI to assessment holds great promise in boosting efficiency, mitigating bias, and facilitating customized evaluations. Conversely, these innovations raise significant concerns regarding validity, reliability, transparency, fairness, equity, and test security, necessitating careful thinking when applying them in assessments. In this article, we discuss the impacts and implications of LLMs and generative AI on critical dimensions of assessment with example use cases and call for a community effort to equip assessment professionals with the needed AI literacy to harness the potential effectively.
Tc‐99m‐MIBI SPECT/CT imaging to diagnose secondary hyperparathyroidism after parathyroid forearm transplantation
Authors: Xu Zhenchun , Zheng Chenxi , Rao Maohua , Xiong Yalan , Tian Yan , Yuan Gengbiao
Published: April 2024

This article report a 40‐year‐old male patient who underwent total thyroidectomy and forearm auto‐transplantation in another hospital for secondary hyperparathyroidism. After 4 years of follow‐up, the level of parathyroid hormone continued to increase, and ultrasound showed nodules in the neck and right forearm, which were considered to be of parathyroid origin. Technetium 99m sestamibi single photon emission computed tomography and computed tomography (Tc‐99m‐MIBI SPECT/CT) imaging showed increased radioactive uptake in the submuscular soft tissue nodule of the right medial forearm, maximum standardized uptake value (SUVmax) is 0.98, which was identified as transplanted functioning parathyroid tissue. No parathyroid imaging activity was found in the neck. The patient then underwent partial removal of ectopic parathyroid tissue from the right forearm. Pathological examination confirmed parathyroid tissue, and removal was followed by a rapid decline in serum parathyroid hormone levels.
Outcomes of immune checkpoint inhibitor‐induced liver toxicity managed by hepatologists in a multidisciplinary toxicity team
Authors: Ito Takanori , Mizuno Kazuyuki , Yamamoto Takafumi , Yasuda Tsukasa , Yokoyama Shinya , Yamamoto Kenta , Imai Norihiro , Ishizu Yoji , Honda Takashi , Hama Masayo , Kataoka Tomomi , Shimokata Tomoya , Ando Yuichi , Kawashima Hiroki
Published: April 2024

Aim

To detect immune‐related adverse events (irAEs) early and treat them appropriately, our institute established an irAE‐focused multidisciplinary toxicity team in cooperation with various departments. This study aimed to evaluate a consultation system involving a team of hepatologists in terms of its utility for the management of severe immune checkpoint inhibitor (ICI)‐induced liver toxicity.

Methods

To analyze the diagnosis and treatment of severe ICI‐induced liver toxicity (Grade 2 requiring corticosteroid therapy and Grade 3 or higher), we examined patients' clinical courses before and after the hepatologist consultation system was established (pre‐period, September 2014 to February 2019; post‐period, March 2019 to March 2023).

Results

The median follow‐up period was 392 days. Of the 1247 patients with advanced malignancies treated with ICIs, 66 developed severe ICI‐induced liver toxicity (n = 22 and 44 in the pre‐ and post‐periods, respectively). In the pre‐period, hepatologist consultations were sought for 15/22 patients, whereas in the post‐period, 42/44 patients were referred to and treated by hepatologists. The time from the onset of liver toxicity to the consultation was significantly shorter in the post‐period than in the pre‐period (mean 1.9 vs. 6.5 days, respectively; p = 0.012). The number of patients with a biopsy‐confirmed diagnosis of ICI‐induced liver toxicity was significantly higher in the post‐period than in the pre‐period (n = 22 vs. n = 3, respectively; p = 0.006). Finally, there were no cases of immune‐related cholangitis in the pre‐period, compared to five cases in the post‐period.

Conclusion

A hepatologist consultation system in an irAE‐focused multidisciplinary toxicity team is useful for managing severe ICI‐induced liver toxicity.
Effects of a nurse‐led therapeutic conversations intervention in stroke patient–family caregiver dyads: A randomized control trial
Authors: Tsai Su‐Ju , Li Chia‐Chi , Pai Hsiang‐Chu
Published: April 2024

Background

Few studies have evaluated the effectiveness of family functional care interventions among stroke caregiver dyads. This study aimed to examine the effect of a nurse‐led therapeutic conversation intervention on resilience, family function, self‐efficacy in managing the disease, and quality of life (QoL) in stroke family caregiver dyads.

Aims

This study aimed to examine the effect of a nurse‐led therapeutic conversation intervention on resilience, family function, self‐efficacy in managing the disease, and QoL in stroke–family caregiver dyads.

Design

This study was a single‐blind (evaluator) randomized controlled trial. The planned execution time was from August 2021 to December 2022, in the rehabilitation ward of a medical university hospital.

Methods

A total of 82 dyads were included in this analysis. Dyads randomized to the intervention group received nurse‐led therapeutic conversations intervention one at four weeks after the patient's hospitalization for a stroke. The family caregiver dyads of stroke survivors in the control group received routine care. An effectiveness analysis that included patients' resilience, self‐efficacy, and patient–family caregiver dyads' family function and QoL was conducted at one month. We used the CONSORT Checklist for reporting parallel group randomized trials in this study.

Results

The patients in the intervention group showed improvement in resilience and self‐efficacy after one month. Furthermore, the effects on resilience (Cohen's d = 0.49) and self‐efficacy (Cohen's d = 0.46) were significantly higher than in the control group. Family functioning was significantly higher in patient–family caregiver dyads in the intervention group than in the control group (Cohen's d = 0.55; Cohen's d = 0.50). However, no significant difference in QoL was found between patients and caregivers in either group.

Conclusions

The intervention was effective in promoting family functioning and can also promote patient resilience and self‐efficacy in disease management. However, the intervention did not have a significant effect on the QoL of patient–family caregiver dyads.
Effect of quality nursing care on wound pain and anxiety in burn patients: A meta‐analysis
Authors: Yang Ling , Yuan Bo‐Qin , Ju Yang‐Yang , Liu Wei , Wang Yang‐Ping
Published: April 2024

To systematically evaluate the effects of quality nursing care on wound pain and anxiety in burn patients. Computerised searches of PubMed, Google Scholar, Cochrane Library, Embase, Wanfang, China Biomedical Literature Database and China National Knowledge Infrastructure databases randomised controlled trials (RCTs) on the application of quality nursing care to burn patients were carried out from database inception to October 2023. Literature was screened and evaluated by two researchers based on inclusion and exclusion criteria, and data were extracted from the final included literature. Stata 17.0 software was employed for data analysis. Overall, 15 RCTs and 1115 burn patients were included, including 563 and 552 in the quality care and routine care groups. It was found that, compared with routine care, burn patients who implemented quality care had significantly less wound pain (SMD: −1.79, 95% CI: −2.22 to −1.36, p < 0.001), anxiety (SMD: −2.71. 95% CI: −3.49 to −1.92, p < 0.001) and depression (SMD: −1.74, 95% CI: −2.35 to −1.14, p < 0.001) levels were significantly reduced post‐trauma.
Australian nursing students' experiences of workplace violence during clinical placement: A cross‐sectional study
Authors: Johnston Sandra , Fox Amanda , Patterson Susan , Jones Rikki , Dafny Hila , Pich Jacqueline , Duff Jed
Published: April 2024

Aim

To identify the nature, degree and contributing factors of workplace violence (WPV) incidents experienced by Australian nursing students during clinical placement.

Design

Descriptive cross‐sectional study.

Methods

Data were collected from 13 September to 25 November 2022. Eligible participants included all nursing students enrolled in nursing degrees at any Australian university who had completed at least one clinical placement. An adapted version of the WPV in the Health Sector Country Case Study survey was used.

Results

A total of 381 nursing students across eight states of Australia completed the survey. More than half of the students had experienced an episode of WPV; patients were the most frequent perpetrators. Personal factors of patients, staff and students, organizational factors and cultural norms within the workplace supported acts of WPV.

Conclusion

Student nurses (SNs) most often experience violence from patients during direct care. Patient encounters are the core component of clinical placement. Education providers have a responsibility to effectively prepare students to be able to identify escalating situations and manage potentially violent situations. Registered nurses who supervise students during clinical placement require support to balance their clinical role with student supervision.

Implications for The Profession

Experiencing WPV can negatively impact relationships between students, healthcare professionals and care recipients. This results in personal distress, decreased job satisfaction and potentially the decision to leave the nursing profession.

Impact

What already is known: SNs are exposed to WPV during clinical placement.

What this paper adds: More than half the SNs in this study experienced violence inclusive of physical, verbal, racial and sexual harassment. Patients were the predominant perpetrators.

Implications for practice/policy: Interventions at individual and systemic levels are required to mitigate WPV.

Reporting Method

This study is reported using the STROBE guidelines.
Dermoscopy and reflectance confocal microscopy of solitary flat pink lesions: A new combined score to diagnose amelanotic melanoma
Authors: Spadafora M. , Megna A. , Lippolis N. , Cavicchi M. , Borsari S. , Piana S. , Guida S. , Kaleci S. , Chester J. , Pellacani G. , Longo C.
Published: April 2024

Background

Differential diagnosis of amelanotic/hypomelanotic melanoma among solitary flat pink lesions is challenging, due to limited clinical and dermoscopic clues. Dermoscopy and reflectance confocal microscopy assessments improve diagnostic accuracy, but their combined capacity among solitary flat pink lesions is yet to be defined.

Objectives

To determine (i) whether diagnostic accuracy is improved with combined dermoscopy and reflectance confocal microscopy, (ii) a model to estimate probability of flat amelanotic/hypomelanotic melanoma among solitary flat pink lesions.

Methods

A retrospective single‐centre study of solitary flat pink lesions, excised for suspected malignancy between 2011 and 2022 was performed. Images were independently evaluated by two dermatologists, blinded to histopathological diagnosis. Diagnostic performance was evaluated on the receiver operating characteristic curve and the area under the curve. Predictive features were identified by univariate and multivariate logistic regression analyses. A final predictive nomogram of independent risk factors was calculated by backward likelihood ratio. Hypothesis being tested was formulated before data collection.

Results

A total of 184 patients (87 females, 47.3%) were included; mean age was 57.6 years (19–95). Combined dermoscopy and reflectance confocal microscopy was more sensitive (83%, CI 69.2–92.4 and 91.5%, CI 79.6–97.6) than dermoscopy alone (76.6%, CI 62.0–87.7 and 85.1%, CI 71.7–93.8). Predictive features defined the new model, including linear irregular vessels (4.26‐folds, CI 1.5–12.1), peripheral pigment network (6.07‐folds, CI 1.83–20.15), remnants of pigmentation (4.3‐folds, CI 1.27–14.55) at dermoscopy and atypical honeycomb (9.98‐folds, CI 1.91–51.96), disarranged epidermal pattern (15.22‐folds, CI 2.18–106.23), dendritic pagetoid cells in the epidermis (3.77‐folds, CI 1.25–11.26), hypopigmented pagetoid cells (27.05‐folds, CI 1.57–465.5), and dense and sparse nests (3.68‐folds, CI 1.24–10.96) in reflectance confocal microscopy. Diagnostic accuracy of the model was high (AUC 0.91).

Conclusions

Adjunctive reflectance confocal microscopy increases diagnostic sensitivity of flat amelanotic/hypomelanotic melanoma differential diagnosis. The proposed model requires validation.
Does salivary pH affect postoperative sore throat in the head‐down position of general anesthesia?
Authors: Koike Masayoshi , Abukawa Yukako , Kaji Keiko , Satou Kazuki , Takahashi Kazunari , Nakamura Makoto , Hasunuma Jun , Imura Hideto , Natsume Nagato , Abukawa Harutsugi
Published: April 2024

Background

Tracheal intubation sometimes causes postoperative sore throat (POST) due to laryngeal damage. However, clinical observations suggest that the environment of the oral cavity may also affect POST.

Objective

The purpose of this study was to investigate whether salivary pH in the oral cavity affects POST.

Methods

After obtaining ethical approval, informed consent was obtained from all patients. Patients who underwent surgery in the supine position were enrolled as the control group. Patients who underwent laparoscopic surgery in the head‐down position were enrolled as the intervention group. Immediately before both groups of patients were anaesthetised, expelled saliva was collected, and salivary pH was measured. Immediately postoperatively, the same measurement was carried out before the patient regained consciousness. The primary outcome was the change in salivary pH. The secondary outcome was POST. In our study, POST was defined as pharyngeal and swallowing pain in the glossopharyngeal and superior laryngeal nerves. The normal distribution of pH was tested using the Shapiro–Wilk test followed by analysis using repeated‐measurements and one‐way analysis of variance. Statistical significance was set at p < .05.

Results

A total of 62 patients were enrolled, of whom two were excluded based on the exclusion criteria. Salivary pH in the intervention group was significantly lower than that in the control group. Five patients had POST in the intervention group, whereas none had POST in the control group had POST.

Conclusion

Acidotic‐shifted saliva is considered one of the causes of POST.
Melatonin in the mammalian retina: Synthesis, mechanisms of action and neuroprotection
Authors: Felder‐Schmittbuhl Marie Paule , Hicks David , Ribelayga Christophe P. , Tosini Gianluca
Published: April 2024

Melatonin is an important player in the regulation of many physiological functions within the body and in the retina. Melatonin synthesis in the retina primarily occurs during the night and its levels are low during the day. Retinal melatonin is primarily synthesized by the photoreceptors, but whether the synthesis occurs in the rods and/or cones is still unclear. Melatonin exerts its influence by binding to G protein‐coupled receptors named melatonin receptor type 1 (MT1) and type 2 (MT2). MT1 and MT2 receptors activate a wide variety of signaling pathways and both receptors are present in the vertebrate photoreceptors where they may form MT1/MT2 heteromers (MT1/2h). Studies in rodents have shown that melatonin signaling plays an important role in the regulation of retinal dopamine levels, rod/cone coupling as well as the photopic and scotopic electroretinogram. In addition, melatonin may play an important role in protecting photoreceptors from oxidative stress and can protect photoreceptors from apoptosis. Critically, melatonin signaling is involved in the modulation of photoreceptor viability during aging and other studies have implicated melatonin in the pathogenesis of age‐related macular degeneration. Hence melatonin may represent a useful tool in the fight to protect photoreceptors—and other retinal cells—against degeneration due to aging or diseases.
Longitudinal associations of meeting the WHO physical activity guidelines and physical fitness, from preschool to childhood
Authors: Tigerstrand Grevnerts Hanna , Delisle Nyström Christine , Migueles Jairo Hidalgo , Löf Marie
Published: April 2024

There is a well‐established relationship between physical activity (PA) and physical fitness in children, being the latter an important marker for present and future health; however, there is still insufficient knowledge for the transition from the preschool age to early childhood. Therefore, this study in Swedish children aimed to investigate the estimated effect of meeting the aerobic component of the PA guidelines at 4 and/or 9 years of age on physical fitness measured at 9 years of age. PA was assessed using a wrist‐worn ActiGraph accelerometer and identical data processing in 217 healthy children in Sweden (114 boys and 103 girls). Physical fitness test included cardiorespiratory (20 m shuttle run test), motor (4 × 10 m shuttle run), and muscular fitness (hand grip strength and long jump). A linear mixed model was run, investigating the interaction between meeting the PA guidelines and time (either 4 or 9 years of age) and each fitness component (at 4 and 9). Interactions by sex were also checked. Meeting the PA guidelines consistently (at 4 and 9 years) was significantly associated to better performance in physical fitness parameters for motor fitness (−0.76 s, p < 0.001) and lower body muscular fitness (+4.6 cm; p < 0.001) at 9 years. There was an interaction between meeting the PA guidelines and time point, for cardiorespiratory fitness (+4.58 laps; p < 0.001). This study shows that meeting the PA guidelines at 4 and 9 years of age is associated to higher physical fitness at 9 years of age.
Since you put it that way… Gender norms and interruptions at Supreme Court oral arguments
Authors: Gleason Shane A.
Published: April 2024

Objective

At U.S. Supreme Court oral arguments, female attorneys are more likely to be interrupted than their male counterparts under some conditions. This makes it difficult for women to effectively construct a narrative and substantively impact case law. While existing work conceptualizes gender as a binary, I draw on recent work stressing gender is performative to deesentialize gender and explore how attorneys’ compliance with gender norms and subtle expectations about men's and women's behavior in a host of contexts, predicts interruptions at oral arguments.

Methods

Via quantitative textual analysis of all oral arguments from 2004 to 2019 where one attorney argues for the petitioner and one for the respondent, I examine the extent to which gender norm compliance predicts interruptions.

Results

I find both male and female attorneys are interrupted more frequently when their oral arguments are not gender normative. Thus, an argument that is successful for a male attorney is not necessarily successful for a female attorney, and vice versa.

Conclusion

My results underscore female attorneys are not less successful as a matter of course; attorney success is driven by attorney compliance with gender norms. This work also raises a number of normative questions I encourage future scholars to explore.
Nonspherical oscillations of an encapsulated microbubble with interface energy under the acoustic field
Authors: Dash Nehal , Tamadapu Ganesh
Published: April 2024

Spherical instability in acoustically driven encapsulated microbubbles (EBs) suspended in a fluid can trigger nonspherical oscillations within them. We apply the interface energy model [N. Dash and G. Tamadapu, J. Fluid Mech. 932, A26 (2022b)] to investigate nonspherical oscillations of smaller radius microbubbles encapsulated with a viscoelastic shell membrane under acoustic field. Using the Lagrangian energy formulation, coupled governing equations for spherical and nonspherical modes are derived, incorporating interface energy effects, shell elasticity, and viscosity. Numerical simulations of governing equations revealed that the parametrically forced even mode excites even modes, while the odd modes excite both even and odd modes. The model demonstrates that finite amplitude nonspherical oscillations are identifiable in smaller radius EBs only when the interface parameters are introduced into the model; otherwise, they are not. Realizing that nonlinear mode coupling is responsible for saturation of instability resulting in stable nonspherical oscillations, we perform a steady-state and stability analysis using the slow-time equations obtained from Krylov–Bogoliubov perturbation method. Analytical expressions for modal amplitudes and stability thresholds are derived in terms of interface and material parameters. The stability curves are invaluable in determining the precise range of excitation pressure and frequency values required for the EB to exhibit finite amplitude nonspherical oscillations.
Time-resolved measurement of acoustic density fluctuations using a phase-shifting Mach-Zehnder interferometer
Authors: Shoji Eita , Maddi Anis , Penelet Guillaume , Biwa Tetsushi
Published: April 2024

Phase-shifting interferometry is one of the optical measurement techniques that improves accuracy and resolution by incorporating a controlled phase shift into conventional optical interferometry. In this study, a four-step phase-shifting interferometer is developed to measure the spatiotemporal distribution of acoustic density oscillations of the gas next to a rigid plate. The experimental apparatus consists of a polarizing Mach–Zehnder interferometer with a polarization camera capable of capturing four polarization directions in one shot image and it is used to measure the magnitude and the phase of density fluctuations through a duct of rectangular cross section connected to a loudspeaker. The results are compared with the well-established thermoacoustic theory describing the thermal coupling between acoustic oscillations and rigid boundaries, and the results show a very good agreement for various ratios of the (frequency-dependent) thermal boundary layer thickness to the plate spacing. This measurement technique could be advantageously employed to analyze more complex heat transfer processes involving the coupling of acoustic oscillations with rigid boundaries.
English vowel recognition in multi-talker babbles mixed with different numbers of talkers
Authors: Wang Xianhui , Xu Li
Published: April 2024

The present study examined English vowel recognition in multi-talker babbles (MTBs) in 20 normal-hearing, native-English-speaking adult listeners. Twelve vowels, embedded in the h-V-d structure, were presented in MTBs consisting of 1, 2, 4, 6, 8, 10, and 12 talkers (numbers of talkers [N]) and a speech-shaped noise at signal-to-noise ratios of −12, −6, and 0 dB. Results showed that vowel recognition performance was a non-monotonic function of N when signal-to-noise ratios were less favorable. The masking effects of MTBs on vowel recognition were most similar to consonant recognition but less so to word and sentence recognition reported in previous studies.
Perceived Barriers to Physical Activity Among Youth Living in Rural and Urban Canadian Communities: A Nationally Representative Cross-Sectional Study
Authors: Manyanga Taru , White Nicole , Sluggett Larine , Duchesne Annie , Anekwe David , Pelletier Chelsea
Published: April 2024

Background: We used nationally representative data to explore associations among location of residence (rural/urban) and perceived barriers to physical activity (PA) in Canadian youth. Methods: We analyzed the 2017 Canadian Community Health Survey, Barriers to Physical Activity Rapid Response data for 12- to 17-year-old youth. Nine items from the survey assessing perceived barriers to PA were combined into 3 barrier domains: resources, motivational, and socioenvironmental. The likelihood of reporting barriers to PA based on rural–urban location was examined using survey-weighted binary logistic regression following a model fitting approach. Sociodemographic factors were modeled as covariates and tested in interaction with location. For each barrier domain, we derived the best-fitting model with fewest terms. Results: There were no location-specific effects related to reporting any barrier or motivation-related PA barriers. We found a sex by location interaction predicting the likelihood of reporting resource-related barriers. Rural boys were less likely to report resource-related barriers compared with urban boys (odds ratio [OR] = 0.42 [0.20, 0.88]). Rural girls were more likely to report resource-related barriers compared with boys (OR = 3.72 [1.66, 8.30]). Regarding socioenvironmental barriers, we observed a significant body mass index by location interaction demonstrating that rural youth with body mass index outside the “normal range” showed a higher likelihood of reporting socioenvironmental barriers compared with urban youth (OR = 2.38 [1.32, 4.30]). For urban youth, body mass index was unrelated to reporting socioenvironmental barriers (OR = 1.07 [0.67, 1.71]). Conclusion: PA barriers are not universal among Canadian youth. Our analyses highlight the importance of testing interactions in similar studies as well as considering key sociodemographic characteristics when designing interventions.
Sexual dimorphism in skin immunity is mediated by an androgen-ILC2-dendritic cell axis
Authors: Chi Liang , Liu Can , Gribonika Inta , Gschwend Julia , Corral Dan , Han Seong-Ji , Lim Ai Ing , Rivera Claudia A. , Link Verena M. , Wells Alexandria C. , Bouladoux Nicolas , Collins Nicholas , Lima-Junior Djalma S. , Enamorado Michel , Rehermann Barbara , Laffont Sophie , Guéry Jean-Charles , Tussiwand Roxane , Schneider Christoph , Belkaid Yasmine
Published: April 2024

Males and females exhibit profound differences in immune responses and disease susceptibility. However, the factors responsible for sex differences in tissue immunity remain poorly understood. Here, we uncovered a dominant role for type 2 innate lymphoid cells (ILC2s) in shaping sexual immune dimorphism within the skin. Mechanistically, negative regulation of ILC2s by androgens leads to a reduction in dendritic cell accumulation and activation in males, along with reduced tissue immunity. Collectively, our results reveal a role for the androgen-ILC2-dendritic cell axis in controlling sexual immune dimorphism. Moreover, this work proposes that tissue immune set points are defined by the dual action of sex hormones and the microbiota, with sex hormones controlling the strength of local immunity and microbiota calibrating its tone.
Molecularly thin, two-dimensional all-organic perovskites
Authors: Choi Hwa Seob , Lin Jun , Wang Gang , Wong Walter P. D. , Park In-Hyeok , Lin Fang , Yin Jun , Leng Kai , Lin Junhao , Loh Kian Ping
Published: April 2024

Recently, the emergence of all-organic perovskites with three-dimensional (3D) structures has expanded the potential applications of perovskite materials. However, the synthesis and utilization of all-organic perovskites in 2D form remain largely unexplored because the design principle has not been developed. We present the successful synthesis of a metal-free 2D layered perovskite, denoted as the Choi-Loh van der Waals phase (CL-v phase), with the chemical formula A
2
B
2
X
4
, where A represents a larger-sized cation compared to B and X denotes an anion. The CL-v phase exhibits a van der Waals gap enabled by interlayer hydrogen bonding and can be exfoliated or grown as molecularly thin 2D organic crystals. The dielectric constants of the CL-v phase range from 4.8 to 5.5 and we demonstrate their potential as gate dielectrics for thin-film transistors.
Exceptionally long-lived nuclear RNAs
Authors: Lawrence Jeanne , Hall Lisa
Published: April 2024

RNA labeled in young mice is detected 2 years later in adult mouse brains
Gates foundation places bold bet on preprints
Authors: Brainard Jeffrey
Published: April 2024

Funder to mandate preprints and no longer pay open-access publishing fees for grantees
Inhibition of the RLR signaling pathway by SARS-CoV-2 ORF7b is mediated by MAVS and abrogated by ORF7b-homologous interfering peptide
Authors: Xiao Xiao , Fu Yanan , You Wanling , Huang Congcong , Zeng Feng , Gu Xinsheng , Sun Xiaoguang , Li Jian , Zhang Qiwei , Du Weixing , Cheng Gong , Liu Zhixin , Liu Long
Published: April 2024

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and characterized by dysregulated immune response. Studies have shown that the SARS-CoV-2 accessory protein ORF7b induces host cell apoptosis through the tumor necrosis factor alpha (TNF-α) pathway and blocks the production of interferon beta (IFN-β). The underlying mechanism remains to be investigated. In this study, we found that ORF7b facilitated viral infection and production, and inhibited the RIG-I-like receptor (RLR) signaling pathway through selectively interacting with mitochondrial antiviral-signaling protein (MAVS). MAVS
439-466
region and MAVS Lys461 were essential for the physical association between MAVS and ORF7b, and the inhibition of the RLR signaling pathway by ORF7b. MAVS
K461
/K63 ubiquitination was essential for the RLR signaling regulated by the MAVS–ORF7b complex. ORF7b interfered with the recruitment of tumor necrosis factor receptor-related factor 6 (TRAF6) and the activation of the RLR signaling pathway by MAVS. Furthermore, interfering peptides targeting the ORF7b complex reversed the ORF7b-suppressed MAVS-RLR signaling pathway. The most potent interfering peptide V disrupts the formation of ORF7b tetramers, reverses the levels of the ORF7b-inhibited physical association between MAVS and TRAF6, leading to the suppression of viral growth and infection. Overall, this study provides a mechanism for the suppression of innate immunity by SARS-CoV-2 infection and the mechanism-based approach via interfering peptides to potentially prevent SARS-CoV-2 infection.

IMPORTANCE

The pandemic coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and continues to be a threat to public health. It is imperative to understand the biology of SARS-CoV-2 infection and find approaches to prevent SARS-CoV-2 infection and ameliorate COVID-19. Multiple SARS-CoV-2 proteins are known to function on the innate immune response, but the underlying mechanism remains unknown. This study shows that ORF7b inhibits the RIG-I-like receptor (RLR) signaling pathway through the physical association between ORF7b and mitochondrial antiviral-signaling protein (MAVS), impairing the K63-linked MAVS polyubiquitination and its recruitment of tumor necrosis factor receptor-related factor 6 (TRAF6) to MAVS. The most potent interfering peptide V targeting the ORF7b–MAVS complex may reverse the suppression of the MAVS-mediated RLR signaling pathway by ORF7b and prevent viral infection and production. This study may provide new insights into the pathogenic mechanism of SARS-CoV-2 and a strategy to develop new drugs to prevent SARS-CoV-2 infection.