bluuebunny/crossref_metadata_2025 huggingface dataset:
Drug survival und klinische Wirksamkeit von Secukinumab, Ixekizumab, Brodalumab, Guselkumab, Risankizumab und Tildrakizumab in der Behandlung der Psoriasis
Authors: Mastorino Luca , Dapavo Paolo , Susca Sara , Cariti Caterina , Siliquini Niccolò , Verrone Anna , Stroppiana Elena , Ortoncelli Michela , Quaglino Pietro , Ribero Simone
Published: January 2024

Hintergrund

Biologika, die die Interleukine IL‐23 and IL‐17 hemmen, haben sich in der Behandlung der mittelschweren bis schweren Psoriasis als sicher und wirksam erwiesen.

Studienziel

Medikamenten‐Überleben bei Patienten mit Psoriasis zu untersuchen, die mit Biologika behandelt werden.

Patienten und Methoden

Wir haben die Erreichung des PASI 90 und PASI ≤3 nach 16, 28, and 52 Wochen im Vergleich der IL‐17‐ und IL‐23‐Inhibitoren Brodalumab, Ixekizumab, Secukinumab, Risankizumab, Tildrakizumab und Guselkumab bei insgesamt 1057 Patienten untersucht sowie eine Drug Survival‐Analyse durchgeführt.

Ergebnisse

Unter IL‐17‐Inhibitoren wurden PASI 90 und PASI ≤3 schneller erreicht; nach 16 Wochen waren sie den IL‐23‐Inhibitoren signifikant überlegen (p <0,001; 56% vs. 42% beziehungsweise 70% vs. 59%). Im Drug Survival zeigte sich allerdings ein Vorteil für die IL‐23‐Inhibitoren; dieses betrug nach 24 Monaten 88% im Gegensatz zu 75% für die IL‐17‐Inhibitoren (p <0,001). In der multivariaten Analyse waren die IL‐23‐Inhibitoren (HR 0,54 CI 0,37–0,78, p =  0,001) sowie männliches Geschlecht (HR 0,57 CI 0,42–0,76, p <0,001) mit einer geringeren Wahrscheinlichkeit des Absetzens der Medikation assoziiert. Risankizumab (HR 0,42 CI 0,26‐0,69, p =  0,001), Guselkumab (HR 0,49 CI 0,24–0,99, p =  0,046) und männliches Geschlecht (HR 0,57 CI 0,43–0,77, p <0,001) waren mit geringerer Wahrscheinlichkeit des Absetzens der Medikation assoziiert als Secukinumab.

Schlussfolgerung

IL‐23‐Inhibitoren zeigten bezüglich des Drug Survival die besten Ergebnisse. Auf kürzere Sicht waren die IL‐17‐Inhibitoren wirksamer, aber die Langzeitergebnisse sprechen eher für die IL‐23‐Inhibitoren.
Pockenvirusinfektionen in der Dermatologie
Authors: Obermeier Patrick E. , Buder Susanne C. , Hillen Uwe
Published: January 2024

Die FamiliePoxviridaeumfasst derzeit 22 Gattungen, die Wirbeltiere infizieren können. Humanpathogene Pockenviren gehören den GattungenOrtho‐,Para‐,Mollusci‐undYatapoxvirusan. Bis zur Eradikation der Variola vera im Jahr 1979 waren die Pocken, im Volksmund auch Blattern genannt, eine schwerwiegende Gesundheitsbedrohung für die Bevölkerung. Noch heute sind Dermatologen mit zahlreichen Pockenvirusinfektionen konfrontiert, wie den Bauernhofpocken, die als Zoonosen nach Tierkontakten in ländlichen Gebieten oder nach Massenversammlungen auftreten können. In den Tropen können Erkrankungen durch Tanapox‐ oder Vaccinia‐Viren zu den Differenzialdiagnosen gehören. Dellwarzen sind weltweit verbreitet und werden in bestimmten Fällen als sexuell übertragbare Pockenvirusinfektion angesehen. In jüngster Zeit hatten sich Mpox (Affenpocken) zu einer gesundheitlichen Notlage von internationaler Tragweite entwickelt, die eine rasche Identifizierung und angemessene Behandlung durch Dermatologen und Infektiologen erfordert. Fortschritte und neue Erkenntnisse über Epidemiologie, Diagnose, klinische Manifestationen und Komplikationen sowie Behandlung und Prävention von Pockenvirusinfektionen erfordern ein hohes Maß an Fachwissen und interdisziplinärer Zusammenarbeit in den Bereichen Virologie, Infektiologie und Dermatologie. Dieser CME‐Artikel bietet einen aktualisierten systematischen Überblick, um praktizierende Dermatologen bei der Identifizierung, Differenzialdiagnose und Behandlung klinisch relevanter Pockenvirusinfektionen zu unterstützen.
PREP interventions during COVID‐19: Fixing the environment rather than the person
Authors: Mortenson W. Ben
Published: January 2024

This commentary is on the original article by Anaby et al. on pages 931–938
Parents may prefer prognostic uncertainty about their child's genetic neurodevelopmental condition
Authors: Tyynismaa Henna
Published: January 2024

This commentary is on the original article by Turbitt et al. on pages 872–881 of this issue.
Comparison of telomere length in patients with bone marrow failure syndromes and healthy controls
Authors: Barade Aruna , Lakshmi Kavitha M. , Korula Anu , Abubacker Fouzia N. , Kulkarni Uday P. , Abraham Aby , Mathews Vikram , George Biju , Edison Eunice S.
Published: January 2024

Introduction

During normal aging, telomeric DNA is gradually lost in dividing somatic cells, and critically short telomeres lead to replicative senescence, apoptosis, or chromosomal instability. We studied telomere length in bone marrow failure syndromes (BMFS) compared to normal healthy population.

Methods

Peripheral blood was collected from the participants, and genomic DNA was extracted. Relative telomere length was measured using a quantitative polymerase chain reaction. Statistical analysis was performed using SPSS and GraphPad Prism 8.2 software.

Results

The median age of normal Indian population was 31 (0–60) years. As expected, telomere length (TL) showed a decline with age and no difference in TL between males and females. The median age of 650 patients with aplastic anemia (AA) was 30 (1–60) years. TL was significantly shorter in patients with AA compared to healthy controls (p < .001). In FA and MDS patients, TL was significantly shorter than age‐matched healthy controls (p = .028; p < .001), respectively. There was no difference between the median TL in age‐matched AA and FA patients (p = .727). However, patients with MDS had shorter TL than age‐matched AA (p = .031).

Conclusion

TL in BMF syndrome patients was significantly shorter than age‐matched healthy controls.
Extravagance and misery: Hegel on the multiplication and refinement of needs
Authors: García Mills Nicolás
Published: January 2024

The topic of this paper is Hegel's claim in the Philosophy of Right that, within the modern social world, human needs tend to be endlessly expanded. Unlike the role that the system of needs plays in the formation of its participants' psychological makeup and the problem of poverty and the rabble, the topic of the expansion of needs remains underdiscussed in the recent Hegel literature on the virtues and vices of civil society. My discussion of the topic aims to answer the following two sets of questions: How does it come to pass that individuals' needs are endlessly expanded in this way? And is that expansion a phenomenon to be applauded or condemned? In particular, does the endless expansion of needs aid or obstruct the realization of social members' freedom? In answer to the first question, I argue that for Hegel the endless expansion of needs results from the level of specialization and division of labor distinctive of the modern market economy, the human capacity for a certain kind of abstraction, and the desire to be recognized by other participants in the market system. In answer to the second set of questions, and despite Hegel's own apparent ambivalence, I argue on his behalf that the endless expansion of needs represents an obstacle to the realization of freedom, and is on that ground a phenomenon to be condemned, for the following two reasons: First, the endless expansion of needs increases the influence or “pressure” of desire on the members of civil society that are subject to that expansion. Second, that expansion leads to widespread frustration, understood as the inability on the part of the members of civil society to ever fully realize their ends or satisfy their desires. I end by briefly considering two Hegelian solutions to the pernicious effects of the endless expansion of needs.
Kant on race and the radical evil in the human species
Authors: Papish Laura
Published: January 2024

Religion within the Boundaries of Mere Reason remains one of the most opaque of Kant's published writings. Though this opacity belongs, partly, to the text itself, a key claim of this article is that this opacity stems also from the narrow lenses through which his readers view this text. Often read as part of Kant's moral philosophy or his universal history, the literature has thus far neglected a different vantage point on the Religion, one that does not refute the utility of these lenses but complements them. This paper places the Religion alongside parts of Kant's corpus that it is less typically paired with, namely his natural history writings—in particular, his writings on the concept of race and the development of the human races. I argue that by doing so, we can shed much light on Kant's infamous claim that there is a radical evil in the human species. More precisely, we will come to appreciate that this evil is not, as it is usually understood, a static property or fixed characteristic of human beings. Instead, radical evil concerns a dynamic, changing defect in human nature that increasingly threatens our aspirations to collective moral perfection.
Evaluation of oat (Avena sativa L.) populations for autumn sowing production in Southwest China
Authors: Zhang Yongjie , Li Shuchang , Dong Xiaolong , Mou Qiuyu , Li Jiajie , Zhang Xinyi , Lin Min , Yu Kaiquan , Zhou Pingping , Liu Xiaobo , Luo Xiaoling , Yan Honghai , Peng Yuanying
Published: January 2024

Much of Chinese animal husbandry relies on the continuous availability of forage crops, but climactic constraints in production regions cause seasonal shortages which threaten the industry. This study compares the major characteristics of different forage oat lines and cultivars to evaluate their suitability for cultivation in the winter fallow fields of southwest China. To achieve this goal, six oat populations (2 cultivars and 4 lines) were sown in autumn in three locations in southwest China. Yield‐related traits such as dry matter yield (DMY) and plant height (PH), as well as nutritional traits such as crude protein (CP), crude ash (ASH), neutral detergent fibre (NDF), acid detergent fibre (ADF), and relative feed value (RFV) were measured during two consecutive growing seasons. Our results indicate that all measured traits, with the exception of CP, were significantly influenced by environment, genotype, year and their interaction (p < .05). Forage yield (DMY) had a positive correlation with PH and RFV, but a strong negative one with nutritional values, suggesting a trade‐off between yield and quality. Among the six oat populations, ‘WC109’ consistently displayed the highest DMY, PH, and CP mean values as well as lower ASH, NDF, and ADF compared to all the other cultivars/lines. Based on these findings, ‘WC109’ was selected as the ideal candidate for autumn‐sown forage oat in southwest China.
Impact of social determinants of health on time to antiretroviral therapy initiation and HIV viral undetectability for migrants enrolled in a multidisciplinary HIV clinic with rapid, free, and onsite B/F/TAF: ‘The ASAP study’
Authors: Arora Anish K. , Vicente Serge , Engler Kim , Lessard David , Huerta Edmundo , Ishak Joel , Routy Jean‐Pierre , Klein Marina , Kronfli Nadine , Cox Joseph , Lemire Benoit , de Pokomandy Alexandra , Del Balso Lina , Sebastiani Giada , Vedel Isabelle , Quesnel‐Vallée Amélie ,   ASAP Migrant Advisory Committee, Lebouché Bertrand
Published: January 2024

Objective

Multidisciplinary care with free, rapid, and on‐site bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) dispensation may improve health outcomes among migrants living with HIV. However, models for rapid B/F/TAF initiation are not well studied among migrants living with HIV, and an understanding of how social determinants of health (SDH) may affect HIV‐related health outcomes for migrants enrolled in such care models is limited.

Methods

Within a 96‐week pilot feasibility prospective cohort study at a multidisciplinary HIV clinic, participants received free B/F/TAF rapidly after care linkage. The effects of SDH (i.e., birth region, sexual orientation, living status, education, employment, French proficiency, health coverage, use of a public health facility outside our clinic for free blood tests, and time in Canada) and other covariates (i.e., age, sex) on median time to antiretroviral therapy (ART) initiation and HIV viral undetectability from care linkage were calculated via survival analyses.

Results

Thirty‐five migrants were enrolled in this study. Median time to ART initiation and HIV undetectability was 5 days (range 0–50) and 57 days (range 5–365), respectively. Those who took significantly longer to initiate ART were aged <35 years, identified as heterosexual, had less than university‐level education, or were unemployed. No factor was found to significantly affect time to undetectability.

Conclusion

Despite the provision of free B/F/TAF, several SDH were linked to delays in ART initiation. However, once initiated and engaged, migrants living with HIV reached HIV undetectability efficiently. Findings provide preliminary support for adopting this care model with migrants living with HIV and suggest that SDH should be considered when designing clinical interventions for more equitable outcomes.
Location and visa‐category determinants of naturalization in Australia
Authors: Tan Yan , Liu Xuchun
Published: January 2024

Immigrants' naturalization is conditioned by demographic, socioeconomic and contextual factors, but little is known about how it is affected by permanent visa category and geographic location at the destination. Using the 2016 Australian Census and Migrants Integrated Dataset (ACMID) and Probit regression analysis, we examined how visa category and location of residence influence naturalization rates for Chinese and Indian migrants arriving in Australia between 2000 and 2016. Chinese migrants were most likely to naturalize if entering under a Humanitarian visa, and Indian migrants if under a Skilled Independent visa. Migrants in the Australian Capital Territory were the most likely to naturalize, and those in Victoria the least likely—a distinction sharpened by metropolitan as opposed to regional location. The transnational perspective, allied with cost–benefit and integration theories, performs well in accounting for these heterogeneities. The differences have clear policy and practice in Australia and for countries of origin.
Fabry‐specific treatment in Australia: time to align eligibility criteria with international best practices
Authors: Nicholls Kathleen , Denaro Charles , Tchan Michel , Ellaway Carolyn , Bratkovic Drago , Campbell Sheridan , Fookes Megan , Thomas Mark
Published: January 2024

Background

Disease‐specific therapy aims to improve symptoms, stabilise current disease and delay progression in patients with Fabry disease. In Australia, treatment access is subject to eligibility criteria initially established in 2004. Patients and their clinicians question why these criteria have remained unchanged despite significant progress in disease understanding.

Aims

Appraise the clinical quality of the Australian treatment access criteria.

Methods

The Fabry Australia Medical Advisory Committee (N = 6) used the Appraisal of Guidelines for REsearch and Evaluation Global Rating Scale (AGREE II GRS) to assess the clinical quality of the current treatment eligibility criteria. They reviewed the literature, developed 17 clinical statements to help guide reforms of the eligibility criteria and achieved consensus (achievement of ≥75% agreement in the range 5–7 on a 7‐point Likert scale) through anonymous voting. The findings were applied to develop proposals for revised classification and treatment initiation criteria.

Results

The current treatment eligibility criteria underperformed on the AGREE II GRS. They are pragmatic but out‐of‐step with contemporary data. Consensus was achieved on all 17 proposed clinical statements. There was strong agreement to differentiate classical male Fabry patients to facilitate timelier access to Fabry‐specific treatment. There was also agreement on the value of adopting relevant organ involvement criteria in classical female patients and patients with non‐classical disease.

Conclusions

Australian access criteria are misaligned with current clinical evidence. The clinical statements and proposed classification and initiation criteria should prompt discussions to support more equitable access to treatment and better align Australian practice with contemporary evidence and international guidelines.
What's the point? Infants' and adults' perception of different pointing gestures
Authors: Ger Ebru , Wermelinger Stephanie , de Ven Maxine , Daum Moritz M.
Published: January 2024

Adults and infants as young as 4 months old orient to pointing gestures. Although adults are shown to orient faster to index‐finger pointing than other hand shapes, it is unknown whether hand shapes influence infants' perception of pointing. In this study, we used a spatial cueing paradigm on an eye tracker to investigate whether and to what extent adults and 12‐month‐old infants orient their attention in the direction of pointing gestures with different hand shapes: index finger, whole hand, and pinky finger. Furthermore, we assessed infants' and their parents' pointing production. Results revealed that adults showed a reliable cueing effect: shorter saccadic reaction times (SRTs) to congruent than incongruent targets, for all hand shapes. However, they did not show a larger cueing effect triggered by the index or any other finger. This contradicts previous findings and is discussed with respect to the differences in methodology. Infants showed a cueing effect only for the whole hand but not for the index or pinky fingers. The current results suggest that infants' orienting to pointing may be more robust for the whole hand shape in the first year, and tuning in to the social‐communicative relevance of the canonical index finger shape may develop later or require additional social‐communicative cues.
Do competitive bonuses ruin cooperation in heterogeneous teams?
Authors: Glenn Dutcher E. , Oexl Regine , Ryvkin Dmitry , Salmon Timothy C.
Published: January 2024

A debate among practicing managers is whether to use cooperative or competitive incentives for team production. While competitive incentives may drive individual effort higher, they may also lead to less help and more sabotage, with unclear consequences overall, especially when team members' abilities differ. Using a lab experiment, we examine how increasing competitive incentives affects performance as team composition changes. We find that competitive incentives generally under‐perform noncompetitive incentives and a larger bonus does not generate enough effort to compensate for a loss in help. Our results help understand better how to balance out individual versus team rewards and how firms could structure teams when employees have heterogeneous abilities.
Association of metabolic dysfunction‐associated fatty liver disease with gallstone development: A longitudinal study
Authors: Sogabe Masahiro , Okahisa Toshiya , Kagawa Miwako , Sei Motoko , Kagemoto Kaizo , Tanaka Hironori , Kida Yoshifumi , Nakamura Fumika , Tomonari Tetsu , Okamoto Koichi , Miyamoto Hiroshi , Sato Yasushi , Nakasono Masahiko , Takayama Tetsuji
Published: January 2024

Background and Aim

The influence of metabolic dysfunction‐associated fatty liver disease on gallstone development remains unclear. We aimed to investigate the longitudinal association between metabolic dysfunction‐associated fatty liver disease and gallstone development in both men and women.

Methods

This observational cohort study included 5398 patients without gallstones who underwent > 2 health check‐ups between April 1, 2014, and March 31, 2020. A generalized estimation equation model was used to analyze the association between metabolic dysfunction‐associated fatty liver disease and gallstone development according to repeated measures at baseline and most recent stage.

Results

After adjustment, the odds ratios of metabolic dysfunction‐associated fatty liver disease for gallstone development in men and women were 3.019 (95% confidence interval [CI]: 1.901–4.794) and 2.201 (95% CI: 1.321–3.667), respectively. Among patients aged ≥ 50 years, the odds ratio for gallstone development was significantly enhanced with increasing metabolic dysfunction‐associated fatty liver disease component numbers in both sexes; however, no significance was observed in those aged < 50 years. Other significant risk factors for gallstone development were age (odds ratio: 1.093, 95% CI: 1.060–1.126) and waist circumference (odds ratio: 1.048, 95% CI: 1.018–1.079) in men and age (odds ratio: 1.035, 95% CI: 1.003–1.067) and current smoking (odd ratio: 5.465, 95% CI: 1.881–15.88) in women.

Conclusion

Although the risk factors for gallstone development differed between sexes, metabolic dysfunction‐associated fatty liver disease was common. Paying attention to an increase in the number of metabolic dysfunction‐associated fatty liver disease components in patients aged ≥ 50 years is important for gallstone prevention.
ArUco‐based stylus reliability for reproductible 3D digitalisation of shoulder cartilage contours
Authors: Moissenet Florent , Elmo Kulanesan Christian , Co Kevin , Rodriguez Pablo , Vacher Pierre , Beaulieu Jean‐Yves , Holzer Nicolas
Published: January 2024

Imaging techniques in anatomy have developed rapidly over the last decades through the emergence of various 3D scanning systems. Depending on the dissection level, non‐contact or tactile contact methods can be applied on the targeted structure. The aim of this study was to assess the inter and intra‐observer reproducibility of an ArUco‐based localisation stylus, that is, a manual technique on a hand‐held stylus. Ten fresh–frozen, unembalmed adult arms were used to digitalise the glenoid cartilage related to the glenohumeral joint and the contour of the clavicle cartilage related to the acromioclavicular joint. Three operators performed consecutive digitalisations of each cartilage contour using an ArUco‐based localisation stylus recorded by a single monocular camera. The shape of each cartilage was defined by nine shape parameters. Intra‐observer repeatability and inter‐observer reproducibility were computed using an intra‐class correlation (ICC) for each of these parameters. Overall, 35.2 ± 2.4 s and 26.6 ± 10.2 s were required by each examiner to digitalise the contour of a glenoid and acromioclavicular cartilage, respectively. For most parameters, good‐to‐excellent agreements were observed concerning intra‐observer (ICC ranging between 0.81 and 1.00) and inter‐observer (ICC ranging between 0.75 and 0.99) reproducibility. To conclude, through a fast and versatile process, the use of an ArUco‐based localisation stylus can be a reliable low‐cost alternative to conventional imaging methods to digitalise shoulder cartilage contours.
An upcycled fraction of Melaleuca alternifolia essential oil regenerates the skin through the skin melatonin pathway and improves sleep quality
Authors: Duroux Romain , Jain Anshul , Tabert Matthias , Attia Joan
Published: January 2024

Background

Sleep is one of the most important factors affecting overall health. During the night, the skin repairs damage caused by daily stresses. Melatonin plays a key role in this process. Toxins are removed, and cellular repair and growth hormone production are increased. Inter alia, this also decreases signs of intrinsic aging.

Aims

The current study was intended to demonstrate the impact of a unique fraction of Melaleuca alternifolia (FMA) essential oil, on sleep and skin quality.

Methods

The effect of FMA was investigated in vitro on skin cells, evaluating its antioxidant and anti‐inflammatory properties, and in an ex‐vivo study on human skin biopsies treated with FMA following stress induction. In addition, two clinical studies were performed on volunteers with life‐style‐related sleep complaints. In one study, sleep was measured using a noncontact monitoring device (SleepScore Labs, Max). A second study was conducted to assess skin anti‐aging effects.

Results

In vitro application of FMA reduced IL‐8 and reactive oxygen species (ROS) generation in skin cells. This was confirmed ex vivo through a decrease in inflammatory markers and an increase in antioxidant enzymes after stress induction. Interestingly, FMA also upregulated melatonin‐associated genes. Real‐world sleep tracking revealed that FMA significantly improved sleep quality, relative to unscented control. In vivo applications also showed a reduction in signs of aging.

Conclusion

These results provide initial data to suggest that this unique FMA delivers skin anti‐aging benefits via a two‐pronged mode of action, improving sleep quality, and reducing skin inflammatory and oxidative stress.
Targeting the FGF19–FGFR4 pathway for cholestatic, metabolic, and cancerous diseases
Authors: Li Xiaokun , Lu Weiqin , Kharitonenkov Alexei , Luo Yongde
Published: January 2024

Human fibroblast growth factor 19 (FGF19, or FGF15 in rodents) plays a central role in controlling bile acid (BA) synthesis through a negative feedback mechanism. This process involves a postprandial crosstalk between the BA‐activated ileal farnesoid X receptor and the hepatic Klotho beta (KLB) coreceptor complexed with fibrobalst growth factor receptor 4 (FGFR4) kinase. Additionally, FGF19 regulates glucose, lipid, and energy metabolism by coordinating responses from functional KLB and FGFR1‐3 receptor complexes on the periphery. Pharmacologically, native FGF19 or its analogs decrease elevated BA levels, fat content, and collateral tissue damage. This makes them effective in treating both cholestatic diseases such as primary biliary or sclerosing cholangitis (PBC or PSC) and metabolic abnormalities such as nonalcoholic steatohepatitis (NASH). However, chronic administration of FGF19 drives oncogenesis in mice by activating the FGFR4‐dependent mitogenic or hepatic regenerative pathway, which could be a concern in humans. Agents that block FGF19 or FGFR4 signaling have shown great potency in preventing FGF19‐responsive hepatocellular carcinoma (HCC) development in animal models. Recent phase 1/2 clinical trials have demonstrated promising results for several FGF19‐based agents in selectively treating patients with PBC, PSC, NASH, or HCC. This review aims to provide an update on the clinical development of both analogs and antagonists targeting the FGF19–FGFR4 signaling pathway for patients with cholestatic, metabolic, and cancer diseases. We will also analyze potential safety and mechanistic concerns that should guide future research and advanced trials.
Role of neuropeptides in orofacial pain: A literature review
Authors: Wang Jian , Liu Xiangtao , Gou Junzhuo , Deng Jing , Li Mujia , Zhu Yafen , Wu Zhifang
Published: January 2024

Background

Neuropeptides play a critical role in regulating pain and inflammation. Despite accumulating evidence has further uncovered the novel functions and mechanisms of different neuropeptides in orofacial pain sensation and transmission, there is deficient systematic description of neuropeptides' pain modulation in the orofacial region, especially in the trigeminal system.

Objectives

The present review aims to summarise several key neuropeptides and gain a better understanding of their major regulatory roles in orofacial inflammation and pain.

Methods

We review and summarise current studies related to calcitonin gene‐related peptide (CGRP), substance P (SP), opioid peptide (OP), galanin (GAL) and other neuropeptides' functions and mechanisms as well as promising targets for orofacial pain control.

Results

A number of neuropeptides are clearly expressed in the trigeminal sensory system and have critical functions in the transduction and pathogenesis of orofacial pain. The functions, possible cellular and molecular mechanisms have been introduced and discussed. Neuropeptides and their agonists or antagonists which are widely studied to be potential treatment options of orofacial pain has been evaluated.

Conclusions

Various neuropeptides play important but distinct (pro‐nociceptive or analgesic) roles in orofacial pain with different mechanisms. In summary, CGRP, SP, NPY, NKA, HK‐1, VIP mainly play proinflammatory and pro‐nociceptive effects while OP, GAL, OXT, OrxA mainly have inhibitory effects on orofacial pain.
Objectively measured prolonged sleep is associated with plasma cytokines in older adults with mild cognitive impairment
Authors: Tokunaga Akari , Kimura Noriyuki , Masuda Teruaki , Hanaoka Takuya , Matsubara Etsuro
Published: January 2024

This study aimed to determine whether objective sleep time is associated with the concentrations of various plasma cytokines in older adults with mild cognitive impairment (MCI). In total, 118 adults with MCI (66 women; mean age: 75.7 years) participated in this prospective cohort study. All participants were required to wear a wristband sensor for 7.8 days, on average, every 3 months for 1 year and undergo measurement of 27 plasma cytokines using multiplex immunoassays. After adjusting for potential confounders, the associations of total sleep time with cytokine concentrations were assessed by multiple linear regression analysis. The total sleep time was significantly correlated with plasma interleukin (IL)‐9 and macrophage inflammatory protein (MIP)‐1β levels (r = 0.239, p = 0.009, and r = 0.242, p = 0.008, respectively). Moreover, these associations remained significant after adjusting for covariates, including demographic characteristics, lifestyle‐related diseases, and apolipoprotein E status (β = 0.272, 95% confidence interval: 0.095–0.448, p = 0.003, and β = 0.27, 95% confidence interval: 0.092–0.449, p = 0.003, respectively). Thus, this study is the first to demonstrate the association between objective prolonged sleep and higher plasma IL‐9 and MIP‐1β levels in older adults with MCI.
Urbanization reduces gut bacterial microbiome diversity in a specialist ground beetle, Carabus convexus
Authors: Magura Tibor , Mizser Szabolcs , Horváth Roland , Tóth Mária , Likó István , Lövei Gábor L.
Published: January 2024

Urbanization is rapidly shaping and transforming natural environments, creating networks of modified land types. These urbanization‐driven modifications lead to local extinctions of several species, but the surviving ones also face numerous novel selection pressures, including exposure to pollutants, habitat alteration, and shifts in food availability and diversity. Based on the assumption that the environmental pool of microorganisms is reduced in urban habitats due to habitat alteration, biodiversity loss, and pollution, we hypothesized that the diversity of bacterial microbiome in digestive tracts of arthropods would be lower in urban than rural habitats. Investigating the gut bacterial communities of a specialist ground beetle, Carabus convexus, in forested rural versus urban habitats by next generation high‐throughput sequencing of the bacterial 16S rRNA gene, we identified 3839 bacterial amplicon sequence variants. The composition of gut bacterial samples did not significantly differ by habitat (rural vs. urban), sex (female vs. male), sampling date (early vs. late spring), or their interaction. The microbiome diversity (evaluated by the Rényi diversity function), however, was higher in rural than urban adults. Our findings demonstrate that urbanization significantly reduced the diversity of the gut bacterial microbiome in C. convexus.
Assertiveness as a tool to prevent and mitigate inter‐physician conflict
Authors: Amick Ashley E. , Schrepel Caitlin Pearl
Published: January 2024

Amick and Schrepel comment on the value of incorporating assertiveness into best practices for inter‐physician communication and conflict mitigation.
HDA6 modulates Arabidopsis pavement cell morphogenesis through epigenetic suppression of ROP6 GTPase expression and signaling
Authors: Du Xiaojuan , Gao Yingmiao , Zhang Hao , Xu Xiaoyu , Li Ying , Zhao Lifeng , Luo Ming , Wang Hao
Published: January 2024

The transcriptional regulation of Rho‐related GTPase from plants (ROPs), which determine cell polarity formation and maintenance during plant development, still remains enigmatic.

In this study, we elucidated the epigenetic mechanism of histone deacetylase HDA6 in transcriptional repression of ROP6 and its impact on cell polarity and morphogenesis in Arabidopsis leaf epidermal pavement cells (PCs).

We found that the hda6 mutant axe1‐4 exhibited impaired jigsaw‐shaped PCs and convoluted leaves. This correlated with disruptions in the spatial organizations of cortical microtubules and filamentous actin, which is integral to PC indentation and lobe formation. Further transcriptional analyses and chromatin immunoprecipitation assay revealed that HDA6 specifically represses ROP6 expression through histone H3K9K14 deacetylation. Importantly, overexpression of dominant negative‐rop6 in axe1‐4 restored interdigitated cell morphology.

Our study unveils HDA6 as a key regulator in Arabidopsis PC morphogenesis through epigenetic suppression of ROP6. It reveals the pivotal role of HDA6 in the transcriptional regulation of ROP6 and provides compelling evidence for the functional interplay between histone deacetylation and ROP6‐mediated cytoskeletal arrangement in the development of interdigitated PCs.
Polyketides/nonribosomal peptides from Streptococcus mutans and their ecological roles in dental biofilm
Authors: Luo Wenxin , Zhang Mengdie , Zhou Xuedong , Xu Xin , Cheng Xingqun
Published: January 2024

Streptococcus mutans is the major etiological agent of dental caries in humans. S. mutans overgrowth within dental biofilms can trigger biofilm dysbiosis, ultimately leading to the initiation or progression of dental caries. Polyketides and nonribosomal peptides (PKs/NRPs) are secondary metabolites with complex structures encoded by a cluster of biosynthetic genes. Although not essential for microbial growth, PKs/NRPs play important roles in physiological regulation. Three main classes of hybrid PKs/NRPs in S. mutans have been identified, including mutanobactin, mutanocyclin, and mutanofactin, encoded by the mub, muc, and muf gene clusters, respectively. These three hybrid PKs/NRPs play important roles in environmental adaptation, biofilm formation, and interspecies competition of S. mutans. In this review, we provide an overview of the major hybrid PKs/NRPs of S. mutans, including mutanobactin, mutanocyclin, and mutanofactin and address their ecological roles in dental biofilms. We place specific emphasis on important questions that are yet to be answered to provide novel insights into the cariogenic mechanism of S. mutans and facilitate improved management of dental caries. We highlight that S. mutans PKs/NRPs may be potential novel targets for the prevention and treatment of S. mutans‐induced dental caries. The development of genomics, metabolomics, and mass spectrometry, together with the integration of various databases and bioinformatics tools, will allow the identification and synthesis of other secondary metabolites. Elucidating their physicochemical properties and their ecological roles in oral biofilms is crucial in the identification of novel targets for the ecological management of dental caries.
L4/5 Disc Herniation: Not Unusually Accompanied with L5/S1 Low‐Grade Spondylolytic Spondylolisthesis
Authors: Zhou Haicheng , Zhou Qingshuang , Wang Bin , Qiu Yong , Zhu Zezhang , Liu Zhen , Sun Xu
Published: January 2024

Objective

Isthmic spondylolisthesis (IS) is distinguished by a congenital defect or acquired fracture of the pars interarticularis. Numerous studies on L5 low‐grade IS have been carried out; however, there is a paucity of data regarding the condition of L5 IS concomitant with L4/5 disc herniation. This study aimed to identify the incidence rate and to illustrate the possible risk factors for L4/5 disc herniation in L5 low‐grade IS patients.

Methods

A total of 268 consecutive patients diagnosed as L5/S1 low‐grade IS between May 2017 and May 2022 were retrospectively enrolled in this study. Depending on the presence of L4/5 disc herniation or not, patients were divided into an L4/5 disc herniation group (L4/5 DH) and an L4/5 non‐disc herniation group (L4/5 non‐DH). Radiographic parameters were measured, and the ratios of L4–S1 segmental lordosis (SL) to lumbar lordosis (LDI), L4 inferior endplate (IEP) to L5 superior endplate (SEP) (L4 IEP/L5 SEP), and L5 IEP to S1 SEP (L5 IEP/S1 SEP) were compared between groups. The Pfirrmann grade of the L4/5 disc and the L5/S1 disc, and Roussouly classifications of each patient were also recorded. Univariate analysis (including independent‐samples t‐test and χ2‐test) and multiple logistic regression analysis were performed to analyze the data.

Results

There were 40 patients (14.9%) in the L4/5 DH group. The Roussouly classification differed significantly between groups. As demonstrated by the Pfirrmann grade, the L4/5 DH group showed more advanced disc degeneration at L4/5 than the L4/5 non‐DH group. In contrast to the L4/5 non‐DH group, the L4/5 DH group had a significantly larger L4 IEP, L4 IEP/L5 SEP, S1 SEP, and LDI while smaller L4/5 disc angle, L4/5 disc height, slip percentage, lumbar lordosis, and sacral slope. Multivariate logistic regression analysis revealed that higher L4/5 disc Pfirrmann grade (p = 0.004), decreased L4/5 disc height (p < 0.001), and lower L5 slip percentage (p = 0.022) were significantly associated with the occurrence of L4/5 DH.

Conclusions

L4/5 disc herniation is not unusually accompanied by L5/S1 low‐grade IS. Advanced L4/5 disc degeneration, decreased L4/5 disc height, and lower L5 slip percentage might be significantly associated with L4/5 disc herniation.
Antidemocratic tendencies on the left, the right, and beyond: A critical review of the theory and measurement of left‐wing authoritarianism
Authors: Nilsson Artur
Published: January 2024

A series of new conceptualizations of left‐wing authoritarianism have recently been proposed to counterbalance the traditional focus on right‐wing authoritarianism in political psychology. This article scrutinizes conceptual confusions in the literature on authoritarianism that have been exacerbated by these new conceptualizations, including a pseudo‐debate about the existence of left‐wing authoritarianism; a conflation of the psychological phenomenon of authoritarianism with the more general category of all antidemocratic predispositions; and a number of logical, conceptual, and statistical fallacies that obscure psychological differences between antidemocratic predispositions on the right and the left. It proposes that antidemocratic predispositions on the right typically involve an authoritarian adherence to established norms along with violence and repression directed at perceived threats to, or deviations from, these norms, whereas those that occur on the left more commonly involve a motivation to overthrow the established authority along with violence and repression directed at perceived threats to superordinate ideological values. It concludes with a call for a broadened and reinvigorated program of research that studies the complexity and diversity of antidemocratic predispositions on the left, the right, and beyond, and their causal impact on antidemocratic attitudes and actions, drawing on insights from multiple traditions and fields of research.
Uncovering the hidden hosts: Identifying inoculum reservoirs for Phytophthora pseudosyringae in Nothofagus forests in Chile
Authors: González Mariela P. , Mizubuti Eduardo S. G. , Gonzalez Gaston , Sanfuentes Eugenio A.
Published: January 2024

Mortality of Nothofagus trees in native forests in Chile has been observed for more than 30 years. Phytophthora pseudosyringae was identified as the causal agent of partial defoliation and bleeding cankers on Nothofagus obliqua and N. alpina. Nevertheless, to improve the conservation of natural resources it is crucial to determine potential native hosts that may act as inoculum reservoirs. Two N. obliqua stands were visited and all native plant species with symptoms resembling those caused by Phytophthora spp. were examined. Seven isolates from cortical and foliar tissues were isolated and subsequentially identified as P. pseudosyringae. Pathogenicity tests were carried out on eight species from a native forest. P. pseudosyringae caused cankers in N. obliqua, N. dombeyi and Persea lingue. Under natural conditions, no symptoms were detected on leaves of Cryptocarya alba, N. dombeyi, N. obliqua or Peumus boldus, but lesions were formed in inoculation assays under a controlled environment, suggesting that these species may act as hosts. Leaf necrosis in P. lingue was observed in both natural and controlled conditions. P. pseudosyringae can sporulate on lesions of C. alba, N. dombeyi and N. obliqua leaves. In Sophora macrocarpa, sporulation was observed both on asymptomatic tissues and on lesions. The frequent association of S. macrocarpa in the understorey of Nothofagus spp. strengthens the putative role of S. macrocarpa as an inoculum reservoir for epidemic events in Nothofagus. This is the first study carried out in the Southern Hemisphere on the life cycle of P. pseudosyringae in native Nothofagus forests.
Role of abscisic acid‐mediated stomatal closure in responses to pathogens in plants
Authors: Du Yuli , Zhang Heng , Jia Kunpeng , Chu Zongyan , Xu Shican , Tran Lam‐Son Phan , Guo Jinggong , Li Weiqiang , Li Kun
Published: January 2024

In terrestrial plants, stomata in the leaf epidermis formed by guard cells are the major pathways for gas exchange. However, opened stomata also provide a major channel for pathogen entry. At the pre‐invasive stage, plants actively close stomata to prevent pathogen attack, which is termed stomatal immunity, and plant hormones are involved in this process. Here, we summarize recent advances in the role of abscisic acid (ABA) in promoting stomatal immunity to prevent pathogen entry. Additionally, salicylic acid shares common downstream elements with ABA to promote stomatal immunity, whereas reactive oxygen species and Ca2+ act as critical signals to cross‐talk with ABA signalling to regulate stomatal movement, and they also enhance the effect of ABA in stomatal immunity. On the other hand, at the post‐invasive stage, closed stomata create a water‐soaked environment that allows pathogen multiplication, and ABA signalling is hijacked by pathogens to reduce stomatal aperture. Here, we propose a model of dual roles of ABA‐mediated stomatal closure during plant‐pathogen interaction and offer emerging consequences and questions for ABA‐mediated stomatal immunity.
Association of HLA class I and II genes with cervical cancer susceptibility in a Han Chinese population
Authors: Yao Yueting , Yan Zhiling , Li Chuanyin , Zhang Shao , Liu Shuyuan , Zhang Xinwen , Shi Lei , Liu Weipeng , Shi Li , Yao Yufeng
Published: January 2024

Cervical cancer (CC) is one of the leading causes of cancer‐related death in females worldwide. Genome‐wide association studies (GWASs) have identified CC‐related susceptibility loci in HLA regions. To investigate the associations between HLA genes and cervical intraepithelial neoplasia (CIN) or cervical cancer (CC), six loci of HLA class I (HLA‐A, ‐B, and ‐C) and II (HLA‐DRB1, ‐DPB1, and ‐DQB1) were selected for genotyping, and the associations between these alleles or their haplotypes with CIN or CC risk or protection from disease were evaluated. In total, 2193 participants, including 909 healthy individuals in the control group, 769 patients with CC, and 515 patients with CIN2+ (CIN II and III), were enrolled in the current study. HLA genes were genotyped using the NGSgo Illumina MiSeq workflow, and the associations between these loci and CIN2+ or CC at the allele and haplotype levels were analyzed. The allele frequencies of HLA‐A*33:03, B*58:01, C*03:02, DPB1*05:01, and DRB1*12:01 were lower in both the CC and CIN2+ groups than in the control group, whereas those of B*55:02, C*04:03, and DPB1*03:01 were higher in the CC group than in the control group. In the histologic CC type analysis, the differences in the frequencies of these alleles in squamous cell carcinoma (SCC) of the cervix and stage I CC showed a consistent trend. In the haplotype analysis, the frequency of A*33:03‐C*03:02‐B*58:01 was lower in the CC and CIN2+ groups than in the control group, and that of A*24:02‐C*04:03‐B*15:25 was higher in the CC group than in both the control and CIN2+ groups. These three different haplotype frequencies were also identified in the FIGO CC stage analysis. In addition, in human papilloma virus (HPV) genotype analyses, the frequencies of HLA‐C*03:02 and DPB1*05:01 were significantly lower in the CC and CIN2+ groups than in the control group, and in SCC subgroup, the frequencies of HLA‐DQB1*04:01 and DRB1*04:05 were higher in the HPV other genotype infection group than in the HPV16 infection group. In both HPV16 single infection and coinfection with other HPVs, the frequency of haplotype A*33:03‐C*03:02‐B*58:01 was lower in both CC and CIN2+ than in the control group, while the frequencies of A*11:01‐C*14:02‐B*51:01 and A*24:02‐C*03:04‐B*13:01 were higher in the CIN2+ than in CC and the control group. In the HPV16 and other HPV infection comparisons, the frequencies of DRB1*04:05‐DQB1*04:01‐DPB1*02:01 and DRB1*11:01‐DQB1*03:01‐DPB1*05:01 were lower in the HPV16 infection group than in the other HPV infection group. Our results suggest that the HLA class I and II genes may affect the risk of CIN and CC as well as the histologic CC types and FIGO stages of CC in the Han Chinese population. In addition, HLA genes were associated with HPV16 infection at both the allelic and haplotype levels.
A practical guide to real‐world implementation of pre‐emptive therapy for Cytomegalovirus disease prevention in high‐risk seronegative liver transplant recipients with seropositive donors
Authors: Heldman Madeleine R. , Dunn Bailey , Clemens Evan , Henderson Megan , Fisher Cynthia E. , Rakita Robert M. , Kling Catherine E. , Limaye Ajit P.
Published: January 2024

The Comparison of Antiviral Preventative Strategies In Liver Transplant (CAPSIL) study showed pre‐emptive therapy (PET) to be superior to antiviral prophylaxis for Cytomegalovirus (CMV) disease prevention in high‐risk CMV seronegative liver transplant recipients (LTRs) with seropositive donors (D+R−). Despite the statistical superiority of PET over prophylaxis in research settings, PET is perceived as a logistically more complex strategy that requires careful coordination of weekly CMV PCR testing, prompt initiation of CMV antivirals upon viremia detection, and timely cessation of antivirals following viremia resolution. Transplant centers may be hesitant to use PET for CMV disease prevention in D+R− LTRs out of concern that PET coordination is not feasible in clinical practice. We recently described our experience using PET in CMV D+R− LTRs in a real‐world setting, and found it to be as effective for CMV disease prevention as PET performed as part of a clinical trial. Here, we describe a systematic approach for PET implementation in real‐world settings and provide practical tools to address anticipated challenges. This framework can support transplant programs in overcoming logistical barriers to PET and incorporating an evidence‐based and cost‐effective CMV prevention strategy into routine care for high‐risk CMV D+R− LTRs.