bluuebunny/crossref_metadata_2025 huggingface dataset:
Trends in keratinocyte skin cancer incidence, mortality and burden of disease in 33 countries between 1990 and 2017
Authors: Yang Dorothy D , Borsky Kim , Jani Chinmay , Crowley Conor , Rodrigues Jeremy N , Matin Rubeta N , Marshall Dominic C , Salciccioli Justin D , Shalhoub Joseph , Goodall Richard
Published: January 2023

Background

Keratinocyte cancers (KCs) are the most common type of cancer in the White population worldwide, with associated high healthcare costs. Understanding the epidemiological trends for KCs, namely basal cell carcinomas (BCCs) and cutaneous squamous cell carcinomas (SCCs), is required to assess burden of disease, project future trends and identify strategies for addressing this pressing global health issue.

Objectives

To report trends in BCC and SCC incidence, and SCC mortality and disability-adjusted life-years (DALYs).

Methods

An observational study of the Global Burden of Disease (GBD) database between 1990 and 2017 was performed. European Union countries and other selected high-income countries, including the UK and the USA, classified as having high-quality mortality data, were included. Annual age-standardized incidence rates (ASIRs), age-standardized death rates (ASDRs) and DALYs for each country were obtained from the GBD database. Trends were described using joinpoint regression analysis.

Results

Overall, 33 countries were included. For both BCC and SCC in 2015–2017, the highest ASIRs were observed in the USA and Australia. Males had higher ASIRs than females at the end of the observation period in all countries for SCC, and in all countries but two for BCC. In contrast, the highest ASDRs for SCC were observed in Australia and Latvia for males, and in Romania and Croatia for females. The highest DALYs for SCC for both sexes were seen in Australia and Romania. Over the observation period, there were more countries demonstrating decreasing trends in mortality than in incidence, and disparities were observed between which countries had comparatively high mortality rates and which had high incidence rates. Overall reductions in SCC DALYs were observed in 24 of 33 countries for males, and 25 countries for females.

Conclusions

Over the past 27 years, although trends in SCC incidence have risen in most countries, there is evidence that mortality rates have been decreasing. Burden of disease as assessed using DALYs has decreased in the majority of countries. Future work will explore potential explanatory factors for the observed disparity in trends in SCC incidence and mortality.
Anatomical contacts between sensory neurons and epidermal cells: an unrecognized anatomical network for neuro-immuno-cutaneous crosstalk
Authors: Talagas Matthieu
Published: January 2023

Sensory neurons innervating the skin are conventionally thought to be the sole transducers of touch, temperature, pain and itch. However, recent studies have shown that keratinocytes – like Merkel cells – act as sensory transducers, whether for innocuous or noxious mechanical, thermal or chemical stimuli, and communicate with intraepidermal free nerve endings via chemical synaptic contacts. This paradigm shift leads to consideration of the whole epidermis as a sensory epithelium. Sensory neurons additionally function as an efferent system. Through the release of neuropeptides in intimate neuroepidermal contact areas, they contribute to epidermal homeostasis and to the pathogenesis of inflammatory skin diseases. To counteract the dogma regarding neurocutaneous interactions, seen exclusively from the perspective of soluble and spreading mediators, this review highlights the essential contribution of the unrecognized anatomical contacts between sensory neurons and epidermal cells (keratinocytes, melanocytes, Langerhans cells and Merkel cells), which take part in the reciprocal dialogue between the skin, nervous system and immune system.
Detection of extensive host–virus DNA hybrids in human polyomavirus 7-associated pruritic rash
Authors: Starrett Gabriel J , Lee Jae W , Chatterjee Subhajit , Jedrych Jaroslaw J
Published: January 2023

Human polyomavirus 7 (HPyV7) is associated with pruritic dermatoses that primarily affect immunocompromised patients. We identified extensive host–virus DNA hybrids in HPyV7-associated rash, highlighting the need for additional studies on long-term consequences of HPyV7 infection, including its oncogenic potential.
Impact of perioperative α1-antagonists on postoperative urinary retention in orthopaedic surgery: meta-analysis
Authors: Huang Yun-Ting , Chang Yu , Kang Yi-No , Huang Chin-Hsuan , Lin Yu-Shiuan , Wu Jeffrey , Chi Kuan-Yu , Chen Wei-Cheng
Published: January 2023

Background

Postoperative urinary retention (POUR) is a common complication following orthopaedic surgery. Previous studies attempted to establish the preventative role of α1-antagonist in POUR in the general surgical population; however, there is still no consensus regarding its use in orthopaedic surgery due to limited evidence.

Methods

Electronic databases of Cochrane Library, Embase, MEDLINE, and ClinicalTrials.gov were searched by two independent investigators from inception to 1 March 2022 to identify relevant randomized clinical trials. Two reviewers independently completed a critical appraisal of included trials by using the Cochrane Risk of Bias tool version 2.0 and extracted data from included articles. Risk of POUR was summarized as risk ratio (RR) with 95 per cent confidence intervals (c.i.). Mean difference (MD) was used for meta-analysis of continuous outcomes.

Results

Five randomized clinical trials involving 878 patients (α1-antagonist, 434; placebo, 444) undergoing hip/knee arthroplasty and spine surgeries were included. One study was assessed as high risk of bias from the randomization process and was excluded from the final meta-analysis. There was no difference in the risk of POUR between patients taking α1-antagonist and the placebo in arthroplasty (RR, 0.64; 95 per cent c.i., 0.36 to 1.14) and in spine surgeries (RR, 1.03; 95 per cent c.i., 0.69 to 1.55). There was no difference in length of stay (MD, −0.14 days; 95 per cent c.i., −0.33 to 0.05). Use of α1-antagonist was associated with a higher risk of adverse events (RR, 1.97; 95 per cent c.i., 1.27 to 3.06), with a composite of dizziness, light-headedness, fatigue, altered mental status, and syncope being the most commonly reported symptoms.

Conclusion

In patients undergoing spinal surgery and joint arthroplasty, routine administration of perioperative α1-antagonist does not decrease risk of POUR but does increase perioperative dizziness, light-headedness, and syncope.
Polyploidization was not involved in the origin of five endemic species from southern Europe but is otherwise frequent inEuphorbiasectionEsula(Euphorbiaceae)
Authors: Heimer Valentin , Frajman Božo
Published: January 2023

Polyploidization is a key factor in the diversification of flowering plants, but appears to be of only minor importance in the evolution of Euphorbia subgenus Esula. An exception is Euphorbia section Esula, including c. 100 species, many of which are widespread, but several have restricted distribution areas. We used ITS sequencing and relative genome size estimation to explore the evolutionary origin of E. gayi, E. graminifolia, E. tommasiniana, E. valliniana and E. variabilis, which are endemic to disjunct areas along the southern and western margins of the Alps, Corsica and Sardinia. In addition, we explored the incidence of polyploidy across different lineages of E. section Esula. Our phylogenetic results revealed several lineages with unresolved relationships that probably diverged in the Late Miocene, but only one (the Eurasian Group) underwent considerable diversification, probably due to numerous polyploidization events. Several polyploid species or mixed ploidy species in this group are distributed across large areas of Eurasia. All other lineages remained mostly diploid and species-poor, but dispersed to various continents, where most of the species have restricted distribution areas. The five focal species are diploid, but they do not share a common ancestor. Euphorbia graminifolia and E. tommasiniana belong to the Eurasian Group, whereas E. gayi, E. valliniana and E. variabilis belong to the Cosmopolitan Group and are thus not closely related to other European members of the section. Phylogenetic analyses recovered E. valliniana and E. variabilis as genetically distinct, although closely related. This, in combination with a clear morphological differentiation as revealed by morphometric analyses, supports their recognition as independent species. Our study highlights the important role polyploidization had for plant diversification as well as the effects of other factors such as vicariance in disjunct refugia, which probably led to the origin of the five endemic species from Euphorbia section Esula.
Double vision
Authors: Popkirov Stoyan
Published: January 2023

The legitimacy of an illness is often determined by our understanding of the underlying disorder. In this essay, Stoyan Popkirov considers what this means for our approach to functional neurological disorders such as dissociative seizures.
Quantitative approaches to guide epilepsy surgery from intracranial EEG
Authors: Bernabei John M , Li Adam , Revell Andrew Y , Smith Rachel J , Gunnarsdottir Kristin M , Ong Ian Z , Davis Kathryn A , Sinha Nishant , Sarma Sridevi , Litt Brian
Published: January 2023

Over the past 10 years, the drive to improve outcomes from epilepsy surgery has stimulated widespread interest in methods to quantitatively guide epilepsy surgery from intracranial EEG (iEEG). Many patients fail to achieve seizure freedom, in part due to the challenges in subjective iEEG interpretation. To address this clinical need, quantitative iEEG analytics have been developed using a variety of approaches, spanning studies of seizures, interictal periods, and their transitions, and encompass a range of techniques including electrographic signal analysis, dynamical systems modeling, machine learning and graph theory. Unfortunately, many methods fail to generalize to new data and are sensitive to differences in pathology and electrode placement.

Here, we critically review selected literature on computational methods of identifying the epileptogenic zone from iEEG. We highlight shared methodological challenges common to many studies in this field and propose ways that they can be addressed. One fundamental common pitfall is a lack of open-source, high-quality data, which we specifically address by sharing a centralized high-quality, well-annotated, multicentre dataset consisting of >100 patients to support larger and more rigorous studies. Ultimately, we provide a road map to help these tools reach clinical trials and hope to improve the lives of future patients.
A survey of Irish dermatologists’ confidence in caring for people who identify as transgender patients in dermatology settings
Authors: Quigley Claire , Victory Liana , Bowe Stephanie , Deveney Ciara , Brady Ronan , Yoo Helena , Lenane Patsy
Published: January 2023

We surveyed Irish dermatologists’ confidence in caring for people who identify as transgender patients. The majority of respondents had not previously received education around the care of transgender people in dermatology, and most agreed they would benefit from this.
Cryosurgery as adjuvant treatment for cutaneous sporotrichosis in two patients with diabetes mellitus type 2
Authors: Robles-Tenorio Arturo , Rocha-Mendez Leslie Elizabeth , Tarango-Martinez Victor Manuel
Published: January 2023

Sporotrichosis is a subacute or chronic fungal disease caused by the Sporothrix schenckii complex. We report two patients with diabetes mellitus type 2 who developed sporotrichosis. Cryosurgery was used successfully in both patients.
Oral ivermectin to treat scabies: a comparison of two different regimens
Authors: Balestri Riccardo , Magnano Michela , Infusino Salvatore Domenico , Girardelli Carlo R , Ioris Tommaso , Rech Giulia
Published: January 2023

As Sarcoptes scabiei is becoming less sensitive to permethrin, clinicians have started to prescribe oral ivermectin (OI) as a first-line treatment. Guidelines suggest OI 200 µg kg–1 as two doses, 1 week apart. However, the black box of the ivermectin registered in Italy recommends a single dose. To compare these two regimens, we collected 71 cases of scabies and treated them according to this protocol [single-dose group (SDG)]. This population was compared to 68 patients who received two doses 1 week apart [double-dose group (DDG)]. Clearance of the disease was achieved in 98% of DDG patients. In the SDG, treatment was successful in only 58% of patients. This study confirms that the absence of a second intake of OI is one of the main predictors of treatment failure (P < 0.001), which may also increase the likelihood of emerging resistance in S. scabiei.
Mucocutaneous infections in a patient who is immunocompromised
Authors: Flor Duarte , Xará Joana , Pereira Sofia , Brandão Sara , Brites Maria M , Cardoso José C
Published: January 2023

We report the case of a 74-year-old man who was immunosuppressed and presented with multiple skin lesions on the right upper limb. Histological examination revealed epidermal pseudocarcinomatous hyperplasia and dermal granulomatous suppurative infiltrate with aggregates of Gram-positive microorganisms compatible with a grain-forming infection.
Learning dermatology in medical school: analysis of dermatology topics tested in popular question banks
Authors: Ahmad Maham , Perkins Sara H , Perkins Sara H
Published: January 2023

Given the lack of formal dermatology education in medical schools, dermatology principles covered in board exam preparatory resources remain the only standardized concepts that all medical students across the USA universally learn. The primary objective of this study was to quantify the dermatology topics represented in UWorld and AMBOSS Step 1 and Step 2CK question banks. Our study found that 49% of the 655 questions on dermatology assessed the top 10 most prevalent skin diseases encountered in clinical practice with a variety of rare conditions also tested. Step 2CK question banks had a higher proportion of questions that assessed management of dermatological conditions. Furthermore, there was a large variability in the proportion of questions that included images of the condition. This study highlights the need and opportunity for standardization of dermatology teaching in medical school curricula to optimally prepare graduating physicians for future practice.
Readability of medication guides for Food and Drug Administration-approved biologics in dermatology
Authors: Lau Charles B , Smith Gideon P
Published: January 2023

There is limited available information for patients about biologics. Medication guides are an important resource for patients, so we assessed the readability of medication guides for Food and Drug administration-approved biologics for dermatological conditions. The most important information within medication guides was written at a level more complex than recommended guidelines, highlighting health disparities and opportunities for improvement.
Characterizing the burden of calciphylaxis: a qualitative analysis
Authors: Singh Rohan , McCain Sarah , Feldman Steven R , Strowd Lindsay C
Published: January 2023

Calciphylaxis is a debilitating disease associated with high mortality and morbidity secondary to pain, nonhealing wounds and frequent hospital admissions. We qualitatively assessed the burden of calciphylaxis on patient quality of life through semi-structured interviews with nine adult participants. Participants identified an inability to complete activities of daily living because of mobility impairment and decreased strength, although most denied complete dependence on others. All participants described pain as the worst aspect of disease, citing a variable course, unpredictability in severity and poor control despite medical therapy. Calciphylaxis also caused feelings of sadness and anger, having a negative impact on self-confidence. Supportive care needs to address the pervasive and severe nature of pain, mobility impairment and psychiatric comorbidities; such interventions may decrease the overall burden for patients with calciphylaxis.
Switching from adalimumab originator to biosimilar: a 3-year retrospective cohort analysis
Authors: Killion Lisa , Alsharqi Ali , Kirby Brian
Published: January 2023

Our three year retrospective cohort study demonstrated that the vast majority of patients tolerated the switch from adalimumab originator to adalimumab biosimilar, with a 19% switchback rate. All patients who switched back to originator from biosimilar recovered from loss of efficiency and reported adverse events.

Physicians therefore should be confident in switching patients with well controlled psoriasis to adalimumab biosimilars.
Portrait of an old man with facial vitiligo by Adolph von Menzel
Authors: Maghia Rémi , Kluger Nicolas
Published: January 2023

Adolph von Menzel (1815–1905) is a very important German realism painter from the 19th century. In 1861 he painted, with great precision, a portrait of a sitter who we hypothesize had facial vitiligo.
Intralymphatic histiocytosis-like changes in orofacial granulomatosis
Authors: Honda Aki , Yamamoto Toshiyuki
Published: January 2023

This report provides rare histopathological findings of intralymphatic histiocytosis in orofacial granulomatosis involving the lower lip and unilateral upper eyelid. The number of patients with findings of intralymphatic histiocytosis in the periorbital regions is small. Here, the underlying pathogenesis of intralymphatic histiocytosis is discussed.
Unexplained bruising in an infant: Glanzmann thrombasthenia
Authors: Doolan Brent J , Pelidis Maria , Semkova Kristina
Published: January 2023

Glanzmann thrombasthenia is a rare clotting disorder caused by impaired platelet function that can present with unexplained bruising. We present the case of a 4-month-old girl and outline the assessment and management of this condition, as well as an algorithm for the evaluation of abnormal bleeding and bruising.
Human B-cell subset identification and changes in inflammatory diseases
Authors: Velounias Rebekah L , Tull Thomas J
Published: January 2023

Our understanding of the B-cell subsets found in human blood and their functional significance has advanced greatly in the past decade. This has been aided by the evolution of high dimensional phenotypic tools such as mass cytometry and single-cell RNA sequencing which have revealed heterogeneity in populations that were previously considered homogenous. Despite this, there is still uncertainty and variation between studies as to how B-cell subsets are identified and named. This review will focus on the most commonly encountered subsets of B cells in human blood and will describe gating strategies for their identification by flow and mass cytometry. Important changes to population frequencies and function in common inflammatory and autoimmune diseases will also be described.
Cell-specific switch for epileptiform activity: critical role of interneurons in the mouse subicular network
Authors: Wickham J , Ledri M , Andersson M , Kokaia M
Published: January 2023

During epileptic seizures, neuronal network activity is hyper synchronized whereby GABAergic parvalbumin-interneurons may have a key role. Previous studies have mostly utilized 4-aminopyridine to induce epileptiform discharges in brain slices from healthy animals. However, it is not clear if the seizure-triggering ability of parvalbumin-interneurons also holds true without the use of external convulsive agents. Here, we investigate whether synchronized activation of parvalbumin-interneurons or principal cells can elicit epileptiform discharges in subiculum slices of epileptic mice. We found that selective synchronized activation of parvalbumin-interneurons or principal cells with optogenetics do not result in light-induced epileptiform discharges (LIEDs) neither in epileptic nor in normal brain slices. Adding 4-aminopyridine to slices, activation of parvalbumin-interneurons still failed to trigger LIEDs. In contrast, such activation of principal neurons readily generated LIEDs with features resembling afterdischarges. When GABAA receptor blocker was added to the perfusion medium, the LIEDs were abolished. These results demonstrate that in subiculum, selective synchronized activation of principal excitatory neurons can trigger epileptiform discharges by recruiting a large pool of downstream interneurons. This study also suggests region-specific role of principal neurons and interneurons in ictogenesis, opening towards differential targeting of specific brain areas for future treatment strategies tailored for individual patients with epilepsy.
White-matter degradation and dynamical compensation support age-related functional alterations in human brain
Authors: Petkoski Spase , Ritter Petra , Jirsa Viktor K
Published: January 2023

Structural connectivity of the brain at different ages is analyzed using diffusion-weighted magnetic resonance imaging (MRI) data. The largest decrease of streamlines is found in frontal regions and for long inter-hemispheric links. The average length of the tracts also decreases, but the clustering is unaffected. From functional MRI we identify age-related changes of dynamic functional connectivity (dFC) and spatial covariation features of functional connectivity (FC) links captured by metaconnectivity. They indicate more stable dFC, but wider range and variance of MC, whereas static features of FC did not show any significant differences with age. We implement individual connectivity in whole-brain models and test several hypotheses for the mechanisms of operation among underlying neural system. We demonstrate that age-related functional fingerprints are only supported if the model accounts for: (i) compensation of the individual brains for the overall loss of structural connectivity and (ii) decrease of propagation velocity due to the loss of myelination. We also show that with these 2 conditions, it is sufficient to decompose the time-delays as bimodal distribution that only distinguishes between intra- and inter-hemispheric delays, and that the same working point also captures the static FC the best, and produces the largest variability at slow time-scales.
Novel insights into axon diameter and myelin content in late childhood and adolescence
Authors: Genc Sila , Raven Erika P , Drakesmith Mark , Blakemore Sarah-Jayne , Jones Derek K
Published: January 2023

White matter microstructural development in late childhood and adolescence is driven predominantly by increasing axon density and myelin thickness. Ex vivo studies suggest that the increase in axon diameter drives developmental increases in axon density observed with pubertal onset. In this cross-sectional study, 50 typically developing participants aged 8–18 years were scanned using an ultra-strong gradient magnetic resonance imaging scanner. Microstructural properties, including apparent axon diameter $({d}_a)$, myelin content, and g-ratio, were estimated in regions of the corpus callosum. We observed age-related differences in ${d}_a$, myelin content, and g-ratio. In early puberty, males had larger ${d}_a$ in the splenium and lower myelin content in the genu and body of the corpus callosum, compared with females. Overall, this work provides novel insights into developmental, pubertal, and cognitive correlates of individual differences in apparent axon diameter and myelin content in the developing human brain.
Brain dynamics in triple-network interactions and its relation to multiple cognitive impairments in mild traumatic brain injury
Authors: Li Xuan , Jia Xiaoyan , Liu Yuling , Bai Guanghui , Pan Yizhen , Ji Qiuyu , Mo Zhaoyi , Zhao Wenpu , Wei Yixin , Wang Shan , Yin Bo , Zhang Jie , Bai Lijun
Published: January 2023

Traumatic brain injury (TBI) disrupt the coordinated activity of triple-network and produce impairments across several cognitive domains. The triple-network model posits a key role of the salience network (SN) that regulates interactions with the central executive network (CEN) and default mode network (DMN). However, the aberrant dynamic interactions among triple-network and associations with neurobehavioral symptoms in mild TBI was still unclear. In present study, we used brain network interaction index (NII) and dynamic functional connectivity to examine the time-varying cross-network interactions among the triple-network in 109 acute patients, 41 chronic patients, and 65 healthy controls. Dynamic cross-network interactions were significantly increased and more variable in mild TBI compared to controls. Crucially, mild TBI exhibited an increased NII as enhanced integrations between the SN and CEN while reduced coupling of the SN with DMN. The increased NII also implied much severer and multiple domains of cognitive impairments at both acute and chronic mild TBI. Abnormities in time-varying engagement of triple-network is a clinically relevant neurobiological signature of psychopathology in mild TBI. The findings provided align with and advance an emerging perspective on the importance of aberrant brain dynamics associated with highly disparate cognitive and behavioral outcomes in trauma.
The Prohibition of Prosecution of Child Soldiers: a Desirable Emerging Rule of Customary International Law
Authors: Cataleta Maria Stefania
Published: January 2023

Children taking part, directly or indirectly, in hostilities commit war crimes. Moreover, in many cases, child soldiers are not in control of their actions when forced under threat of death to commit crimes. In such cases they are drugged against their will and act under duress, which is often the defence to mitigate their responsibility and punishment. Many questions arise in this regard. Is the status of being enlisted in itself a state of duress for a child, even in the absence of explicit violence or threat? Is the condition of being a soldier something unnatural and abnormal for a child, to the point of being considered in any case a justification for his actions? Can a child soldier be responsible in some cases for war crimes, when mainly in control of his actions? This article maintains that, notwithstanding the fact that classic IHL and HRL do not prohibit the prosecution of children for war crimes, there is emerging customary law that follows the approach of the UN and non-governmental organization bodies in prohibiting the prosecution of child soldiers. According to this, States should refrain from prosecuting children responsible for war crimes. This is furthermore the consolidated approach of the international criminal law today, as stated in the Statute of the ICC.
Safety and Immunogenicity of Influenza A/H5N8 Virus Vaccine in Healthy Adults: Durability and Cross-reactivity of Antibody Responses
Authors: Neuzil Kathleen M , Anderson Evan J , Frenck Robert W , Frey Sharon E , Walter Emmanuel B , Rupp Richard , Rotrosen Elizabeth T , Rouphael Nadine G , Brady Rebecca C , Graham Irene , Schmader Kenneth E , Porterfield Laura , Ortiz Justin R , Swamy Geeta K , El Sahly Hana M , Jeevan Trushar , Sitaula Ranjan , Wegel Ashley , Webby Richard J , Bryant Christopher ,   Influenza A/H5N8 Virus Vaccine Group, Chen Wilbur , Sztein Marcelo , Toapanta Franklin , Bernstein David I , Yildirim Inci , Rostad Christina , Kao Carol , Yi Jumi , Raabe Vanessa , Kelley Colleen , Edupuganti Srilatha , Collins Matthew , Phadke Varun , Abate Getahun , Hoft Daniel , Creech Clarence , Crowe James E
Published: January 2023

Background

Influenza A/H5N8 viruses infect poultry and wild birds in many countries. In 2021, the first human A/H5N8 cases were reported.

Methods

We conducted a phase I, cohort-randomized, double-blind, controlled trial of inactivated influenza A/H5N8 vaccine (clade 2.3.4.4c) administered with or without adjuvant. Cohort 1 subjects received either two doses of AS03-adjuvanted vaccine containing 3.75 μg or 15 μg hemagglutinin (HA); two doses of 15 μg HA unadjuvanted vaccine; or one dose of AS03-adjuvanted vaccine (3.75 μg or 15 μg HA), followed by one dose of non-adjuvanted vaccine (same HA content). Cohort 2 subjects received two doses of MF59-adjuvanted vaccine containing 3.75 μg or 15 μg HA, or 15 μg HA of non-adjuvanted vaccine. Subjects were followed for 13 months for safety and immunogenicity.

Results

We enrolled 386 adult subjects in good health. Solicited adverse events were generally mild and more common among subjects who received adjuvanted vaccines. Antibody responses (hemagglutination inhibition or microneutralization assays) were highest in the two-dose AS03 group, followed by the one-dose AS03 group, the MF59 groups, and the non-adjuvanted groups. Antibody levels returned to baseline 12 months after the second vaccination in all groups except the 15 μg AS03-adjuvanted group. Cross-reactive antibodies to clade 2.3.4.4b strains isolated from recent human cases were demonstrated in a subset of both 15 μg adjuvanted groups.

Conclusions

Two doses of influenza A/H5N8 vaccine were well-tolerated. Immunogenicity improved with receipt of two doses of adjuvanted vaccine and higher antigen content. (Funded by the National Institute of Allergy and Infectious Diseases;
Plasma Aβ42/Aβ40 Ratios in Older People With Human Immunodeficiency Virus
Authors: Cooley Sarah A , Nelson Brittany , Boerwinkle Anna , Yarasheski Kevin E , Kirmess Kris M , Meyer Matthew R , Schindler Suzanne E , Morris John C , Fagan Anne , Ances Beau M , O’Halloran Jane A
Published: January 2023

Background

As people with human immunodeficiency virus (HIV) (PWH) age, it remains unclear whether they are at higher risk for age-related neurodegenerative disorders—for example, Alzheimer disease (AD)—and, if so, how to differentiate HIV-associated neurocognitive impairment from AD. We examined a clinically available blood biomarker test for AD (plasma amyloid-β [Aβ] 42/Aβ40 ratio) in PWH who were cognitively normal (PWH_CN) or cognitively impaired (PWH_CI) and people without HIV (PWoH) who were cognitively normal (PWoH_CN) or had symptomatic AD (PWoH_AD).

Methods

A total of 66 PWH (age >40 years) (HIV RNA <50 copies/mL) and 195 PWoH provided blood samples, underwent magnetic resonance imaging, and completed a neuropsychological battery or clinical dementia rating scale. Participants were categorized by impairment (PWH_CN, n = 43; PWH_CI, n = 23; PWoH_CN, n = 138; PWoH_AD, n = 57). Plasma Aβ42 and Aβ40 concentrations were obtained using a liquid chromatography–tandem mass spectrometry method to calculate the PrecivityAD amyloid probability score (APS). The APS incorporates age and apolipoprotein E proteotype into a risk score for brain amyloidosis. Plasma Aβ42/Aβ40 ratios and APSs were compared between groups and assessed for relationships with hippocampal volumes or cognition and HIV clinical characteristics (PWH only).

Results

The plasma Aβ42/Aβ40 ratio was significantly lower, and the APS higher, in PWoH_AD than in other groups. A lower Aβ42/Aβ40 ratio and higher APS was associated with smaller hippocampal volumes for PWoH_AD. The Aβ42/Aβ40 ratio and APS were not associated with cognition or HIV clinical measures for PWH.

Conclusions

The plasma Aβ42/Aβ40 ratio can serve as a screening tool for AD and may help differentiate effects of HIV from AD within PWH, but larger studies with older PWH are needed.
New Antifungals for Vulvovaginal Candidiasis: What Is Their Role?
Authors: Sobel Jack D
Published: January 2023

New antifungals, ibrexafungerp and oteseconazole, are now available for treatment of vulvovaginal candidiasis. Both have novel antimicrobial and pharmacokinetic properties and advantages over fluconazole, although comparative trials have involved only placebo. In the absence of allergy, intolerance, and resistance, it is unclear whether these antifungals will replace fluconazole.
Relationships Between Social Vulnerability and Coronavirus Disease 2019 Vaccination Coverage and Vaccine Effectiveness
Authors: Dalton Alexandra F , Weber Zachary A , Allen Katie S , Stenehjem Edward , Irving Stephanie A , Spark Talia L , Adams Katherine , Zerbo Ousseny , Lazariu Victoria , Dixon Brian E , Dascomb Kristin , Hartmann Emily , Kharbanda Anupam B , Ong Toan C , DeSilva Malini B , Beaton Maura , Gaglani Manjusha , Patel Palak , Naleway Allison L , Kish Magdalene N S , Grannis Shaun J , Grisel Nancy , Sloan-Aagard Chantel , Rao Suchitra , Raiyani Chandni , Dickerson Monica , Bassett Elizabeth , Fadel William F , Arndorfer Julie , Nanez Juan , Barron Michelle A , Vazquez-Benitez Gabriela , Liao I Chia , Griggs Eric P , Reese Sarah E , Valvi Nimish R , Murthy Kempapura , Rowley Elizabeth A K , Embi Peter J , Ball Sarah , Link-Gelles Ruth , Tenforde Mark W
Published: January 2023

Background

Coronavirus disease 2019 (COVID-19) vaccination coverage remains lower in communities with higher social vulnerability. Factors such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure risk and access to healthcare are often correlated with social vulnerability and may therefore contribute to a relationship between vulnerability and observed vaccine effectiveness (VE). Understanding whether these factors impact VE could contribute to our understanding of real-world VE.

Methods

We used electronic health record data from 7 health systems to assess vaccination coverage among patients with medically attended COVID-19-like illness. We then used a test-negative design to assess VE for 2- and 3-dose messenger RNA (mRNA) adult (≥18 years) vaccine recipients across Social Vulnerability Index (SVI) quartiles. SVI rankings were determined by geocoding patient addresses to census tracts; rankings were grouped into quartiles for analysis.

Results

In July 2021, primary series vaccination coverage was higher in the least vulnerable quartile than in the most vulnerable quartile (56% vs 36%, respectively). In February 2022, booster dose coverage among persons who had completed a primary series was higher in the least vulnerable quartile than in the most vulnerable quartile (43% vs 30%). VE among 2-dose and 3-dose recipients during the Delta and Omicron BA.1 periods of predominance was similar across SVI quartiles.

Conclusions

COVID-19 vaccination coverage varied substantially by SVI. Differences in VE estimates by SVI were minimal across groups after adjusting for baseline patient factors. However, lower vaccination coverage among more socially vulnerable groups means that the burden of illness is still disproportionately borne by the most socially vulnerable populations.
Classifying social media bots as malicious or benign using semi-supervised machine learning
Authors: Mbona Innocent , Eloff Jan H P
Published: January 2023

Users of online social network (OSN) platforms, e.g. Twitter, are not always humans, and social bots (referred to as bots) are highly prevalent. State-of-the-art research demonstrates that bots can be broadly categorized as either malicious or benign. From a cybersecurity perspective, the behaviors of malicious and benign bots differ. Malicious bots are often controlled by a botmaster who monitors their activities and can perform social engineering and web scraping attacks to collect user information. Consequently, it is imperative to classify bots as either malicious or benign on the basis of features found on OSNs. Most scholars have focused on identifying features that assist in distinguishing between humans and malicious bots; the research on differentiating malicious and benign bots is inadequate. In this study, we focus on identifying meaningful features indicative of anomalous behavior between benign and malicious bots. The effectiveness of our approach is demonstrated by evaluating various semi-supervised machine learning models on Twitter datasets. Among them, a semi-supervised support vector machine achieved the best results in classifying malicious and benign bots.
Developing a disease-specific annotation protocol for VHL gene curation using Hypothes.is
Authors: Salehipour Dena , Farncombe Kirsten M , Andric Veronica , Ansar Safa , Delong Sean , Li Eric , Macpherson Samantha , Ridd Sarah , Ritter Deborah I , Thaxton Courtney , Kim Raymond H
Published: January 2023

Von Hippel–Lindau (VHL) disease is a rare, autosomal dominant disorder that predisposes individuals to developing tumors in many organs. There is significant phenotypic variability and genetic variants encountered within this syndrome, posing a considerable challenge to patient care. The lack of VHL variant data sharing paired with the absence of aggregated genotype–phenotype information results in an arduous process, when characterizing genetic variants and predicting patient prognosis. To address these gaps in knowledge, the Clinical Genome Resource (ClinGen) VHL Variant Curation Expert Panel (VCEP) has been resolving a list of variants of uncertain significance within the VHL gene. Through community curation, we crowdsourced the laborious task of variant annotation by modifying the ClinGen Community Curation (C3)-developed Baseline Annotation protocol and annotating all published VHL cases with the reported genotype–phenotype information in Hypothes.is, an open-access web annotation tool. This process, incorporated into the ClinGen VCEP’s workflow, will aid in their curation efforts. To facilitate the curation at all levels of genetics expertise, our team developed a 4-day biocuration training protocol and resource guide. To date, 91.3% of annotations have been completed by undergraduate and high-school students without formal academic genetics specialization. Here, we present our VHL-specific annotation protocol utilizing Hypothes.is, which offers a standardized method to present case-resolution data, and our biocuration training protocol, which can be adapted for other rare disease platforms. By facilitating training for community curation of VHL disease, we increased student engagement with clinical genetics while enhancing knowledge translation in the field of hereditary cancer.

Database URL: https://hypothes.is/groups/dKymJJpZ/vhl-hypothesis-annotation
Home Literacy Experiences and Shared Reading Practices: Preschoolers With Hearing Loss
Authors: DesJardin Jean L , Stika Carren J , Eisenberg Laurie S , Johnson Karen C , Ganguly Dianne Hammes , Henning Shirley C
Published: January 2023

Home literacy experiences and observed parent and child behaviors during shared book reading were investigated in preschool-age children with hearing loss and with typical hearing to examine the relationships between those factors and children’s language skills. The methods involved parent-reported home literacy experiences and videotaped parent–child dyads during shared book reading. Children’s language skills were tested using the Preschool Language Scale-4. The results indicated significant differences between groups for home literacy experiences and observed parent and child behaviors. Parents of children with hearing loss were found to read more frequently to their children than parents of children with typical hearing, yet scored lower for literacy strategies and teaching techniques compared to parents of children with typical hearing. Children with hearing loss scored lower in interactive reading behaviors compared to children with typical hearing. For children with hearing loss, frequency of book reading and child interactive reading behaviors were strong predictive factors for children’s language skills. These results suggest that families of children with hearing loss would benefit from professional support as they read storybooks to their children. Similarly, children with hearing loss should be encouraged to be more interactive during shared book reading.
The genome ofLyophyllum shimejiprovides insight into the initial evolution of ectomycorrhizal fungal genomes
Authors: Kobayashi Yuuki , Shibata Tomoko F , Hirakawa Hideki , Nishiyama Tomoaki , Yamada Akiyoshi , Hasebe Mitsuyasu , Shigenobu Shuji , Kawaguchi Masayoshi
Published: January 2023

Mycorrhizae are one of the most fundamental symbioses between plants and fungi, with ectomycorrhizae being the most widespread in boreal forest ecosystems. Ectomycorrhizal fungi are hypothesized to have evolved convergently from saprotrophic ancestors in several fungal clades, especially members of the subdivision Agaricomycotina. Studies on fungal genomes have identified several typical characteristics of mycorrhizal fungi, such as genome size expansion and decreases in plant cell-wall degrading enzymes (PCWDEs). However, genomic changes concerning the evolutionary transition to the ectomycorrhizal lifestyle are largely unknown. In this study, we sequenced the genome of Lyophyllum shimeji, an ectomycorrhizal fungus that is phylogenetically related to saprotrophic species and retains some saprotroph-like traits. We found that the genome of Ly. shimeji strain AT787 lacks both incremental increases in genome size and reduced numbers of PCWDEs. Our findings suggest that the previously reported common genomic traits of mycorrhizal fungi are not essential for the ectomycorrhizal lifestyle, but are a result of abolishing saprotrophic activity. Since Ly. shimeji is commercially consumed as an edible mushroom, the newly available genomic information may also impact research designed to enhance the cultivation of this mushroom.
Survival after Ivor Lewis versus McKeown esophagectomy for cancer: propensity score matched analysis
Authors: Luijten J C H B M , Verstegen M H P , van Workum F , Nieuwenhuijzen G A P , van Berge Henegouwen M I , Gisbertz S S , Wijnhoven B P L , Verhoeven R H A , Rosman C
Published: January 2023

It is unknown whether Ivor Lewis (IL) or McKeown (McK) esophagectomy is preferred in patients with potentially curable esophageal or gastro-esophageal junction (GEJ) cancer. Patients with mid- and distal esophageal and GEJ cancer without distant metastases who underwent IL or McK esophagectomy in the Netherlands between 2015 and 2017, were selected from the Netherlands Cancer Registry. Patients were propensity score matched for sex, age, American Society of Anesthesiologist classification, comorbidity, tumor type, tumor location, clinical stage, neoadjuvant treatment and year of diagnosis. The primary outcome was a 3-year relative survival (RS). Secondary outcome parameters were number of lymph nodes examined, number of positive lymph nodes, radical resection rate, tumor regression grade, post-operative complications and mortality. A total of 1627 patients who underwent IL (n = 1094) or McK (n = 533) esophagectomy were included. Patient and tumor characteristics were balanced after propensity score matching, leaving 658 patients to be compared. The 3-year RS was 54% after IL and 50% after McK esophagectomy, P = 0.140. The median number of lymph nodes examined, median number of positive lymph nodes, radical resection rate and tumor regression grade were comparable between both groups. Recurrent laryngeal nerve palsy (2 vs. 5%, P = 0.006) occurred less frequently after IL esophagectomy. No differences were observed in post-operative anastomotic leakage rate, pulmonary complication rate and mortality rates. There was no statistically significant difference in the 3-year RS between IL and McK esophagectomy. Based on these results, both IL and McK esophagectomy can be performed in patients with mid to distal esophageal and GEJ cancer.
Cerambycid Pheromones Attract PredatorsTemnoscheila virescens(Coleoptera: Trogossitidae),Chariessa pilosa(Coleoptera: Cleridae), andApiomerus crassipes(Hemiptera: Reduviidae)
Authors: Miller D R , Mayo P D , Sweeney J D
Published: January 2023

In 2011–2013, we determined the interactive effects of the cerambycid pheromones racemic syn-2,3-hexanediol, racemic 3-hydroxyhexan-2-one, and racemic 3-hydroxyoctan-2-one on trap catches of predators associated with bark and woodboring beetles in north Georgia and South Carolina. Temnoscheila virescens (F.) (Coleoptera: Trogossitidae) was attracted to traps baited with 3-hydroxyhexan-2-one; ethanol enhanced attraction. Traps baited with syn-2,3-hexanediol attracted Chariessa pilosa (Forster) (Coleoptera: Cleridae); attraction was interrupted by 3-hydroxyhexan-2-one. An assassin bug Apiomerus crassipes (F.) (Hemiptera: Reduviidae) was attracted to traps baited with 3-hydroxyhexan-2-one and/or 3-hydroxyoctan-2-one. Ethanol had no effect on trap catches of C. pilosa and A. crassipes. We compared response profiles of these predators to those of longhorn beetles captured in these same studies to provide insights on possible ecological interactions between these species.
Additional left ventricular septal lead facilitates R-wave sensing of implantable cardioverter-defibrillator in arrhythmogenic right ventricular cardiomyopathy: a case report
Authors: Lu Wenzhao , Chen Keping , Dai Yan , Zhang Shu
Published: January 2023

Background

Implantable cardioverter-defibrillator (ICD) implantation is a key therapeutic option in arrhythmogenic right ventricular cardiomyopathy (ARVC) to prevent sudden cardiac death due to ventricular tachycardia (VT) and fibrillation (VF). However, sub-optimized R-wave sensing due to myocardium loss interferes with VT/VF identification and appropriate therapy. We tried to implant a 3830 lead to the left ventricular septum (LVS) to facilitate ICD sensing in an ARVC patient.

Case summary

A 68-year-old woman diagnosed with ARVC was scheduled to undergo ICD implantation. Initially, no sites with suitable R-wave amplitudes were found in the right ventricle (RV) to deploy the defibrillation lead (<3.0 mV). It was likely due to severe RV involvement, but the LVS myocardium was more preserved based on cardiac magnetic resonance imaging. Therefore, we implanted a 3830 lead into the deep area of the septum to facilitate R-wave sensing. During the procedure from the right to left septum, the R-wave amplitude significantly increased (2.6 to 4.3–7.1 mV). Left ventricular septum pacing was finally achieved with favourable R-wave sensing (9.9 mV 24 h post-operation). The 3830 lead was plugged into the IS-1 port, while the defibrillation lead was plugged into the DF-1 port. After a 4-month follow-up, the R-wave amplitude of the 3830 lead was 11.1 mV.

Discussion

When the R-wave sensing is not acceptable for ICD implantation in ARVC patients, it is critical to assess myocardial conditions comprehensively. If the septal myocardium is preserved, implanting a 3830 lead to the deep or LVS is feasible to improve R-wave sensing.
Percutaneous transluminal septal myocardial ablation was effective in hypertrophic obstructive cardiomyopathy with anomalous mitral papillary muscles: a case report
Authors: Yuzawa-Tsukada Naoko , Tokuda Michifumi , Miyamoto Takashi , Yoshimura Michihiro
Published: January 2023

Background

Abnormalities of the mitral subvalvular apparatus are not uncommon in hypertrophic obstructive cardiomyopathy (HOCM). Where invasive treatment is indicated in these patients to reduce left ventricular outflow tract (LVOT) obstruction, surgical myectomy with mitral valve repair is recommended.

Case summary

In this report, we describe the case of a patient with HOCM and anomalous papillary muscle anatomy, successfully treated by percutaneous transluminal septal myocardial ablation (PTSMA).

Discussion

PTSMA effectively reduced septal myocardial thickness and LVOT gradient, with only mild residual systolic anterior motion and mitral regurgitation despite anomalous papillary muscle anatomy. Upon careful anatomical evaluation, PTSMA may be a suitable therapeutic option for patients with LVOT obstruction and mitral valve abnormalities who are poor surgical candidates.