bluuebunny/crossref_metadata_2025 huggingface dataset:
On the multiplicativity of the Euler characteristic
Authors: Klein John , Malkiewich Cary , Ramzi Maxime
Published: July 2023

We give two proofs that the Euler characteristic is multiplicative, for fiber sequences of finitely dominated spaces. This is equivalent to proving that the Becker-Gottlieb transfer is functorial on

π
0

\pi _0

.
N acetylcysteine in the treatment of alcohol use disorder: a randomized, double-blind, placebo-controlled trial
Authors: Morley Kirsten C , Peruch Siena , Adams Claire , Towers Ellen , Tremonti Chris , Watt Joshua , Jamshidi1 Nazila , Haber Paul S
Published: July 2023

N-acetyl cysteine (NAC) is a potent antioxidant that modulates glutamatergic signalling which is thought to play a role in alcohol use disorder (AUD). There have been no clinical trials investigating NAC for AUD. We aimed to conduct a 28 day double-blind, placebo-controlled (PL) randomized trial of NAC in the treatment of AUD (NCT03879759). A total of 42 participants with AUD (56% alcohol-related liver disease) were randomized to receive placebo or NAC 2400 mg/day. Feasibility outcomes included treatment retention and adverse events. Primary clinical outcomes included alcohol consumption (heavy drinking days, standard drinks per drinking day). Secondary clinical outcome measures included craving, liver tests, and psychological outcomes. There were no significant differences in overall retention between treatment groups (χ2(1) = 0.14, P = 0.71: 86% vs 76% for placebo and NAC, respectively). The most commonly reported adverse event in NAC-treated individuals included headache (14%). For standard drinks per drinking day, there was a significant overall effect of time (F = 9.18, P < 0.001), no significant effect of treatment (F = 0.75, P = 0.79), and a significant time x treatment (NAC vs PL) effect (F = 2.73, P < 0.05). For number of heavy drinks per day, there was a significant overall effect of time (F = 3.16, P < 0.05) but no significant effect of treatment or time x treatment (P = 0.17). There were no significant NAC vs PL effects on secondary clinical outcome measures. In the first trial of NAC for the management of AUD, NAC appears to be feasible and safe. Although there was a significant effect of NAC vs placebo on some alcohol measures such as drinks per drinking day, there does appear to be a variable pattern of effect across time suggesting that a larger trial incorporating a longer treatment duration is now required to determine efficacy.
Distinctive lower incidence rates of cutaneous melanoma on the hips and lower extremities of men
Authors: Collier Victoria , Patel Jay , Chiu Chi-Yang , Fowke Jay H , Patel Tejesh Surendr , Liu-Smith Feng
Published: July 2023

Background

Cutaneous melanomas (CMs) are more frequently found on the trunk in men, and on the hip and lower extremities (legs) in women. This discrepancy has been attributed to greater exposure to ultraviolet (UV) radiation of women’s legs due to their dressing habits.

Objectives

To understand the sex difference in the bodily distribution of CMs, especially those on the legs.

Methods

This was a cancer registry-based cohort study. CM incidences, relative tumour density and tumour mutational burdens (TMBs) were compared among different body sites in different sex and racial groups using the SEER (Surveillance, Epidemiology, and End Results) and TCGA SKCM (The Cancer Genome Atlas skin cutaneous melanoma) databases.

Results

White men had lower rates and lower relative tumour density (RTD) of CMs on their legs compared with the rest of their body sites, or compared with White women. Men classified by SEER into racial groups other than White did not show such a trend. White women had comparable RTDs among different body sites. The ratios between the ‘White’ and the ‘other’ groups were used to evaluate the approximate effect of sun exposure at different body sites, which further validated a distinct protective effect of men’s legs in melanoma. TMB on leg melanomas was lower than on other sites in both sexes.

Conclusions

The legs of both sexes in White patients show lower RTDs and lower levels of TMB, suggesting a weaker association with UV exposure. Furthermore, White men are especially protected against CM on their legs, suggesting an unknown intrinsic protective factor as compared with women.
The impact of thoracic duct resection on the long-term body composition of patients who underwent esophagectomy for esophageal cancer and survived without recurrence
Authors: Nishimura Erica , Matsuda Satoru , Kawakubo Hirofumi , Okui Jun , Takemura Ryo , Takeuchi Masashi , Fukuda Kazumasa , Nakamura Rieko , Takeuchi Hiroya , Kitagawa Yuko
Published: July 2023

Background: We have reported the possible benefits of radical esophagectomy with thoracic duct (TD) resection in elective esophageal cancer surgery. However, the effect of TD resection on the long-term nutrition status remains unclear. Methods: Patients who underwent esophagectomy at Keio University between January 2006 and December 2018 were included, and those who had no recurrence for more than three years were evaluated. Changes in each body composition (muscle mass and body fat) were comparatively assessed between those who underwent TD resection or not, before and at, one, three and five years after surgery. Computed tomography images were analyzed on postoperative year 1, 3 and 5. Results: This study included 217 patients categorized in the TD-resected (TD-R) (156 patients) and TD-preserved (TD-P) (61 patients) groups. The loss of muscle mass was comparable between the groups. On the other hand, the loss of adipose tissues was significantly greater in the TD-R group than in the TD-P group at one and three years after surgery, while there was no statistical difference five years after surgery. Additionally, among patients with cT1N0M0 disease in whom survival advantage of TD resection has been reported previously, the loss of muscle mass did not differ between each group. Conclusions: The change of muscle mass between the two groups was comparable. Although body fat mass was reduced by TD resection, it eventually recovered in the long term. In patients with esophageal cancer, TD resection may be acceptable without significant impact on body composition in the long term.
The Wolff–Parkinson–White pattern in neonates: results from a large population-based cohort study
Authors: Pærregaard Maria Munk , Hartmann Joachim , Sillesen Anne-Sophie , Pihl Christian , Dannesbo Sofie , Kock Thilde Olivia , Pietersen Adrian , Raja Anna Axelsson , Iversen Kasper Karmark , Bundgaard Henning , Christensen Alex Hørby
Published: July 2023

Aims

Wolff–Parkinson–White (WPW) syndrome is a conduction disorder characterized by an accessory electrical pathway between the atria and ventricles, which may predispose to supraventricular tachycardia (SVT) and sudden cardiac death. It can be seen as an isolated finding or associated with structural heart disease. Our aims were to determine the prevalence of a WPW pattern in a large and unselected cohort of neonates and to describe the electro- and echocardiographic characteristics as well as the natural history during early childhood.

Methods and results

Electrocardiograms and echocardiograms of neonates (aged 0–30 days) from a large, prospective, population-based cohort study were included. Neonates with a WPW pattern were identified and matched 1:4 to controls. Localization of the accessory pathway was assessed by different algorithms. Among 17 489 neonates, we identified 17 (76% boys) with a WPW pattern consistent with a prevalence of 0.1%. One neonate had moderate mitral regurgitation while other echocardiographic parameters were similar between cases and controls (all P > 0.05). The accessory pathways were primarily predicted to be left-sided. At follow-up (available in 14/17 children; mean age 3.2 years) the pre-excitation pattern persisted in only four of the children and none of the children had experienced any episodes of SVT.

Conclusion

The prevalence of a WPW pattern in our cohort of unselected neonates was 0.1%. The WPW pattern was more frequent in boys and generally not associated with structural heart disease, and the accessory pathways were primarily left-sided. At follow-up, the WPW pattern had disappeared in most of the children suggesting either an intermittent nature or that normalization occurs.

Clinical Trial Registration

Copenhagen Baby Heart, NCT02753348.
Arrhythmogenic mechanism of a novel ryanodine receptor mutation underlying sudden cardiac death
Authors: Qian Yunyun , Zuo Dongchuan , Xiong Jing , Yin Yihen , Qi Ruxi , Ma Xiaomin , Yan An , Yang Yawen , Liu Ping , Zhang Jingying , Tang Kai , Peng Wenhui , Xu Yawei , Liu Zheng
Published: July 2023

Aims

The ryanodine receptor 2 (RyR2) is essential for cardiac muscle excitation–contraction coupling; dysfunctional RyR2 participates in the development of inherited arrhythmogenic cardiac disease. In this study, a novel RyR2 mutation A690E is identified from a patient with family inheritance of sudden cardiac death, and we aimed to investigate the pathogenic basis of the mutation.

Methods and results

We generated a mouse model that carried the A690E mutation. Mice were characterized by adrenergic-induced ventricular arrhythmias similar to clinical manifestation of the patient. Optical mapping studies revealed that isolated A690E hearts were prone to arrhythmogenesis and displayed frequency-dependence calcium transient alternans. Upon β-adrenoceptor challenge, the concordant alternans was shifted towards discordant alternans that favour triggering ectopic beats and Ca2+ re-entry; similar phenomenon was also found in the A690E cardiomyocytes. In addition, we found that A690E cardiomyocytes manifested abnormal Ca2+ release and electrophysiological disorders, including an increased sensitivity to cytosolic Ca2+, an elevated diastolic RyR2-mediated Ca2+ leak, and an imbalance between Ca2+ leak and reuptake. Structural analyses reveal that the mutation directly impacts RyR2–FK506 binding protein interaction.

Conclusion

In this study, we have identified a novel mutation in RyR2 that is associated with sudden cardiac death. By characterizing the function defects of mutant RyR2 in animal, whole heat, and cardiomyocytes, we demonstrated the pathogenic basis of the disease-causing mutation and provided a deeper mechanistic understanding of a life-threatening cardiac arrhythmia.
Effect of 2-week postpartum check-ups on screening positive for postpartum depression: a population-based cohort study using instrumental variable estimation in Japan
Authors: Nakamura Naoko , Mitsuhashi Toshiharu , Nakashima Yasuko , Matsumoto Naomi , Yorifuji Takashi
Published: July 2023

Background

Postpartum depression is experienced by approximately 10% of women and affects the health and development of their children. Although it is recommended that all mothers have the opportunity for early detection and intervention for postpartum depression, it is unclear whether early postpartum check-ups help to reduce postpartum depression.

Objective

The aim of this study was to assess the effect of 2-week postpartum check-ups on screening positive for postpartum depression in Japan.

Methods

This was a population-based cohort study that used the administrative database of Tsuyama, Japan. Participants were women who received postpartum home visits from a public health nurse in Tsuyama during the fiscal years 2017–2019. Data were obtained on participant’s attendance at a 2-week postpartum check-up and their responses on the Edinburgh Postpartum Depression Scale. Owing to the initiation of a publicly funded postpartum check-up programme, participants were pseudo-randomly assigned to receive/not receive a 2-week postpartum check-up. We conducted instrumental variable estimation to assess the causal effects of the check-up on screening positive for postpartum depression.

Results

The characteristics of the 1,382 participants did not differ by fiscal year of childbirth. We found a 6.7% (95% confidence interval 2.2–11.2) reduction in the prevalence of screening positive for postpartum depression as an effect of 2-week postpartum check-ups among women received 1-month postpartum home visits.

Conclusion

The results suggest that 2-week postpartum check-ups are effective in reducing the prevalence of screening positive for postpartum depression among 1-month postpartum women. Despite some limitations, early postpartum care could reduce postpartum depression.
Viral Resistance Analyses From the Remdesivir Phase 3 Adaptive COVID-19 Treatment Trial-1 (ACTT-1)
Authors: Hedskog Charlotte , Rodriguez Lauren , Roychoudhury Pavitra , Huang Meei-Li , Jerome Keith R , Hao Linhui , Ireton Renee C , Li Jiani , Perry Jason K , Han Dong , Camus Gregory , Greninger Alexander L , Gale Michael , Porter Danielle P
Published: July 2023

Background

Remdesivir is approved for treatment of coronavirus disease 2019 (COVID-19) in nonhospitalized and hospitalized adult and pediatric patients. Here we present severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) resistance analyses from the phase 3 ACTT-1 randomized placebo-controlled trial conducted in adult participants hospitalized with COVID-19.

Methods

Swab samples were collected at baseline and longitudinally through day 29. SARS-CoV-2 genomes were sequenced using next-generation sequencing. Phenotypic analysis was conducted directly on participant virus isolates and/or using SARS-CoV-2 subgenomic replicons expressing mutations identified in the Nsp12 target gene.

Results

Among participants with both baseline and postbaseline sequencing data, emergent Nsp12 substitutions were observed in 12 of 31 (38.7%) and 12 of 30 (40.0%) participants in the remdesivir and placebo arms, respectively. No emergent Nsp12 substitutions in the remdesivir arm were observed in more than 1 participant. Phenotyping showed low to no change in susceptibility to remdesivir relative to wild-type Nsp12 reference for the substitutions tested: A16V (0.8-fold change in EC50), P323L + V792I (2.2-fold), C799F (2.5-fold), K59N (1.0-fold), and K59N + V792I (3.4-fold).

Conclusions

The similar rate of emerging Nsp12 substitutions in the remdesivir and placebo arms and the minimal change in remdesivir susceptibility among tested substitutions support a high barrier to remdesivir resistance development in COVID-19 patients.

Clinical Trials Registration. NCT04280705.
Curbing the decline of local news by building relationships with the audience
Authors: Stroud Natalie Jomini , Van Duyn Emily
Published: July 2023

In the struggle to find sustainable business models, many local news sites have turned to engaged journalism, which draws from social exchange theory and aims to build relationships with audiences. The causal impact of these initiatives is unclear, but important given that local news sites are critical information sources and face dire economic situations. In this study, 20 news sites were randomly assigned to launch a six-month engaged journalism initiative where journalists reported on audience questions or to continue their current practices. Although not a panacea, over time traffic and subscription data and a two-wave survey of audience members across the sites (n = 3,998) show that the initiative resulted in more subscriptions and more positive audience evaluations. The results highlight the applicability of social exchange theory to questions of local news viability and illustrate that engaged journalism can improve relationships between newsrooms and the communities they serve.
Gut mycobiota changes in liver diseases: A systematic review
Authors: Perlin Cássio Marques , Longo Larisse , Keingeski Melina Belén , Picon Rafael V , Álvares-da-Silva Mário Reis
Published: July 2023

Intestinal fungi play an important role in the health-disease process. We observed that in liver diseases, fungal infections lead to high mortality. In this review, we were able to gather and evaluate the available scientific evidence on intestinal mycobiota and liver diseases. We searched PubMed and Embase, using a combination of several entry terms. Only studies in adults ≥ 18 years old with liver disease and published after 2010 were included. We observed that individuals with liver disease have an altered intestinal mycobioma, which accompanies the progression of these diseases. In cirrhotic patients, there are a high number of Candida sp. strains, especially Candida albicans. In early chronic liver disease, there is an increase in alpha diversity at the expense of Candida sp. and conversely, in advanced liver disease, there is a negative correlation between alpha diversity and model for end-stage liver disease score. On the other hand, patients with non-alcoholic fatty liver disease demonstrate greater diversity compared to controls. Our study concluded that the evidence on the subject is sparse, with few studies and a lack of standardization of outcome measures and reporting, and it was not possible to perform a meta-analysis capable of synthesizing relevant parameters of the human mycobiotic profile. However, certain fungal genera such as Candida play an important role in the context of liver disease and that adults with liver disease have a distinct gut mycobiotic profile from healthy controls.
Correlated short time-scale hard-soft X-ray variability of the blazars Mrk 421 and 1ES 1959+650 using AstroSat
Authors: Das Susmita , Chatterjee Ritaban
Published: July 2023

We study simultaneous soft (0.7–7 keV) and hard (7–20 keV) X-ray light curves at a total of eight epochs during 2016–2019 of two TeV blazars Mrk 421 and 1ES 1959+650 observed by the SXT and LAXPC instruments on-board AstroSat. The light curves are 45–450 ks long and may be sampled with time bins as short as 600–800 s with high signal-to-noise ratio. The blazars show a harder when brighter trend at all epochs. Discrete cross-correlation functions indicate that the hard and soft X-ray variability are strongly correlated. The time lag is consistent with zero in some epochs, and indicates hard or soft lag of a few hours in the rest. In the leptonic model of blazar emission, soft lag may be due to slower radiative cooling of lower energy electrons while hard lag may be caused by gradual acceleration of the high energy electrons emitting at the hard X-ray band. Assuming the above scenario and the value of the Doppler factor (δ) to be 10–20, the hard and soft lags may be used to estimate the magnetic field to be ∼0.1 Gauss and the acceleration parameter to be ∼104 in the emission region. Due to the availability of the high time resolution (∼ minutes to hours) light curves from AstroSat, the value of the illusive acceleration parameter could be estimated, which provides a stringent constraint on the theories of particle acceleration in blazar jets.
Gaia21bty: An EXor light curve exhibiting a FUor spectrum
Authors: Siwak Michał , Hillenbrand Lynne A , Kóspál Ágnes , Ábrahám Péter , Giannini Teresa , De Kishalay , Moór Attila , Szilágyi Máté , Janík Jan , Koen Chris , Park Sunkyung , Nagy Zsófia , Cruz-Sáenz de Miera Fernando , Fiorellino Eleonora , Marton Gábor , Kun Mária , Lucas Philip W , Udalski Andrzej , Szabó Zsófia Marianna
Published: July 2023

Gaia21bty, a pre-main-sequence star that previously had shown aperiodic dips in its light curve, underwent a considerable ΔG ≈ 2.9 mag brightening that occurred over a few months between 2020 October and 2021 February. The Gaia light curve shows that the star remained near maximum brightness for about 4–6 months, and then started slowly fading over the next 2 yr, with at least three superimposed ∼1 mag sudden rebrightening events. Whereas the amplitude and duration of the maximum is typical for EX Lupi-type stars, optical and near-infrared spectra obtained at the maximum are dominated by features which are typical for FU Ori-type stars (FUors). Modelling of the accretion disc at the maximum indicates that the disc bolometric luminosity is 43 L⊙ and the mass accretion rate is 2.5 × 10−5 M⊙ yr−1, which are typical values for FUors even considering the large uncertainty in the distance ($1.7_{-0.4}^{+0.8}$ kpc). Further monitoring is necessary to understand the cause of the quick brightness decline, the rebrightening, and the other post-outburst light changes, as our multicolour photometric data suggest that they could be caused by a long and discontinuous obscuration event. We speculate that the outburst might have induced large-scale inhomogeneous dust condensations in the line of sight leading to such phenomena, whilst the FUor outburst continues behind the opaque screen.
A Sun-like star orbiting a boson star
Authors: Pombo Alexandre M , Saltas Ippocratis
Published: July 2023

The high-precision astrometric mission GAIA recently reported the remarkable discovery of a Sun-like star closely orbiting a dark object with a semimajor axis and period of 1.4 au and 187.8 d, respectively. While the plausible expectation for the central dark object is a black hole, the evolutionary mechanism leading to the formation of such a two-body system is highly challenging. Here, we challenge the scenario of a central black hole and show that the observed orbital dynamics can be explained under fairly general assumptions if the central dark object is a stable clump of bosonic particles of spin-0 or spin-1, known as a boson star. Aside from possible formation mechanisms leading to a star orbiting a boson star, we show that the theory space of boson stars allows for a fairly natural mimicker of binary observations such as the recent one by GAIA. We further explain how future astrometric measurements of similar systems will provide an exciting opportunity to probe the fundamental nature of compact objects and test compact alternatives to black holes.
Landscape of semi-extractable RNAs across five human cell lines
Authors: Zeng Chao , Chujo Takeshi , Hirose Tetsuro , Hamada Michiaki
Published: July 2023

Phase-separated membraneless organelles often contain RNAs that exhibit unusual semi-extractability using the conventional RNA extraction method, and can be efficiently retrieved by needle shearing or heating during RNA extraction. Semi-extractable RNAs are promising resources for understanding RNA-centric phase separation. However, limited assessments have been performed to systematically identify and characterize semi-extractable RNAs. In this study, 1074 semi-extractable RNAs, including ASAP1, DANT2, EXT1, FTX, IGF1R, LIMS1, NEAT1, PHF21A, PVT1, SCMH1, STRG.3024.1, TBL1X, TCF7L2, TVP23C-CDRT4, UBE2E2, ZCCHC7, ZFAND3 and ZSWIM6, which exhibited consistent semi-extractability were identified across five human cell lines. By integrating publicly available datasets, we found that semi-extractable RNAs tend to be distributed in the nuclear compartments but are dissociated from the chromatin. Long and repeat-containing semi-extractable RNAs act as hubs to provide global RNA–RNA interactions. Semi-extractable RNAs were divided into four groups based on their k-mer content. The NEAT1 group preferred to interact with paraspeckle proteins, such as FUS and NONO, implying that RNAs in this group are potential candidates of architectural RNAs that constitute nuclear bodies.
Smokeless Tobacco Cessation Support in Dental Hospitals in Pakistan: Dentists and Dental Patients’ Perspectives on Current Practices, Support Needed, and Opportunities Available
Authors: Rasool Shaista , Dobbie Fiona , Ahmad Fayaz , Khan Zohaib , Holliday Richard , Bauld Linda
Published: July 2023

Introduction

Despite evidence on the effectiveness of tobacco cessation interventions in dental settings, the implementation remains low, especially for smokeless tobacco (ST). The purpose of this study was to develop an understanding of the influences governing the implementation of ST cessation support in dental hospitals.

Aims and Methods

A multicenter qualitative study was conducted at two tertiary-care dental hospitals, in Pakistan. Semi-structured interview guide, guided by the Capability-Opportunity-Motivation-Behavior (COM-B) model, were used to capture the views of dentists (n = 12) and dental patients (n = 12), regarding ST cessation support in dental hospitals. Framework approach was used to thematically analyze the data.

Results

Screening of ST users in routine dental practice was seldom practiced and the cessation support offered was brief advice. Barriers identified by dentists included: Fear of offending and stereotyping patients; lack of knowledge and skills; lack of privacy; lack of belief in the effectiveness of behavioral support; lack of time and workload pressure; ST use amongst dentists; lack of referral systems and; the absence of a mandatory requirement of offering ST cessation support. Facilitators included: Delivering support through junior dentists and the length of interaction between the dentist and the patient. Naswar was the most common ST product used by dental patients. Patients reported receiving negligible cessation support from any healthcare provider.

Conclusions

A range of influences governing the implementation of ST cessation support in dental hospitals were identified. These findings can inform the implementation of behavioral interventions for ST cessation in dental and other clinical settings, in low and middle-income countries.

Implications

Smokeless tobacco control considerably lags, in comparison to the control of combustible tobacco. This is the first study that qualitatively explores the implementation of ST cessation support in dental settings in Pakistan. Utilizing the “Capability-Opportunity-Motivation-Behavior” model, it provides an in-depth understanding of the inability of dentists in implementing effective behavioral interventions for ST cessation support in routine dental practice. Highlighting the striking discrepancy between the patient’s need for and receptivity towards cessation support and the dentists’ concerns over their patients’ receptivity towards cessation support, it calls for the need for effective implementation strategies to optimize dentist-led tobacco cessation interventions in low-resource settings.
A double-blind, placebo-controlled, randomized withdrawal trial of sarilumab for the treatment of glucocorticoid-dependent sarcoidosis
Authors: Baker Matthew C , Horomanski Audra , Wang Yiwen , Liu Yuhan , Parsafar Shima , Fairchild Robert , Mooney Joshua J , Raj Rishi , Witteles Ronald , Genovese Mark C
Published: July 2023

Objectives

Effective steroid-sparing therapies for the treatment of sarcoidosis are lacking; IL-6 antagonists may reduce sarcoidosis disease activity. This study assessed the safety and efficacy of the IL-6 receptor antagonist, sarilumab, in subjects with glucocorticoid-dependent sarcoidosis.

Methods

This phase II, double-blind, placebo-controlled, randomized withdrawal trial enrolled 15 subjects with biopsy-proven sarcoidosis at Stanford University from November 2019 to September 2022. In period 1, subjects were treated with open-label s.c. sarilumab 200 mg every 2 weeks for 16 weeks, with predefined tapering of prednisone. Subjects who completed period 1 without a sarcoidosis flare entered period 2 and were randomized to continue sarilumab or to receive matching placebo for 12 weeks. The end points included flare-free survival, as well as changes in pulmonary function tests, chest imaging, patient-reported outcomes, and laboratory values.

Results

Fifteen subjects were enrolled in the study (median age 57 years, 80% male, 73.3% White), and 10 subjects successfully completed period 1. During period 1, 4 of the 15 subjects (26.7%) discontinued due to worsening of their sarcoidosis, and CT chest imaging worsened in 5 of the 15 subjects (35.7%). During period 2, 0 of 2 subjects in the sarilumab group and 1 of 8 subjects (12.5%) in the placebo group had a flare. Treatment with sarilumab 200 mg was generally well tolerated in subjects with sarcoidosis.

Conclusion

In this double-blind, placebo-controlled, randomized withdrawal trial, a meaningful signal of improvement in subjects with sarcoidosis treated with sarilumab was not observed. Given the small numbers in this study, no definitive conclusions can be drawn.

Trial Registration

ClinicalTrials.gov, http://clinicaltrials.gov, NCT04008069.
What is PFAPA syndrome? Genetic clues about the pathogenesis
Authors: Manthiram Kalpana
Published: July 2023

Purpose of review

Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is the most common periodic fever syndrome in childhood. Recent studies report genetic susceptibility variants for PFAPA syndrome and the efficacy of tonsillectomy in a broader cohort of patients with recurrent stereotypical fever. In this review, we highlight the findings of these studies and what they may reveal about the pathogenesis of PFAPA.

Recent findings

Newly identified genetic susceptibility loci for PFAPA suggest that it is a complex genetic disorder linked to Behçet's disease and recurrent aphthous ulcers. Patients who have PFAPA with some features of Behçet's disease have been reported. Moreover, the efficacy of tonsillectomy has now been described in patients who do not meet the full diagnostic criteria for PFAPA, although the immunologic profile in the tonsils is different from those with PFAPA. Factors that predict response to tonsillectomy are also reported.

These findings highlight the heterogeneous phenotypes that may be related to PFAPA due to common genetic susceptibility or response to therapy. These relationships raise questions about how to define PFAPA and highlight the importance of understanding of the genetic architecture of PFAPA and related diseases.
Symbolic and substantive legitimation: examining corporate commitments to sustainable development goal 12
Authors: Eng Nicholas , Troy Cassandra L.C. , Bortree Denise S.
Published: July 2023

Purpose

The purpose of this paper is to assess online corporate communication around commitments to sustainable development goal (SDG) 12, sustainable production and consumption.

Design/methodology/approach

Guided by legitimacy theory, a qualitative directed content analysis was conducted on 13 companies' webpages (81 webpages, 78,947 words).

Findings

Companies broadly failed to communicate about all 11 SDG 12 targets, neglected to consistently address multiple stakeholder groups, missed opportunities to provide concrete evidence of progress and relied on a mix of substantive and symbolic legitimation strategies.

Originality/value

SDG 12 has been under-researched and this paper is one of the first to offer an in-depth analysis of corporate communication regarding SDG 12.
Implantoplasty and the risk of fracture of narrow implants with advanced bone loss: A laboratory study
Authors: Stavropoulos Andreas , Bertl Kristina , Isidor Flemming , Vult von Steyern Per
Published: July 2023

Objectives

To assess the impact of implantoplasty (IP) on maximum implant failure strength of narrow diameter implants of different type/design and material, with simulated advanced bone loss.

Materials and Methods

Narrow, parallel‐walled implants (3.3 mm in diameter × 10 mm long) with an internal connection of different type/design [bone level (BL), tissue level (TL)] and material [Titanium grade IV (Ti), Titanium‐Zirconium alloy (TiZr)] from one specific manufacturer were used. Half of the implants were subjected to IP in their coronal 5 mm; the remaining were used as controls (seven implants per group). Dynamic loading prior to maximum load strength testing was included.

Results

During dynamic loading, the fracture rate of BL implants was low and independent of IP, while that of TL implants increased significantly with IP compared with controls (p = .001). Maximum implant failure strength reduction (in %) due to IP, was 1.3%–25.4%; TiZr BL implants were least affected. Implants subjected to IP compared to those without IP as well as TL implants compared to BL implants showed a significantly lower maximum implant failure strength (p < .002); implant material was not significant (p = .845).

Conclusions

Based on data from implants of one specific manufacturer, IP has a significant negative impact on the fracture strength of narrow implants suffering from advanced peri‐implantitis. TL implants have been more severely affected compared to BL implants and presented an increased risk for failure during normal chewing forces. In addition, this negative impact of IP on TL implants was independent of the implant material (i.e., Ti or TiZr).

Clinical Relevance

Narrow single TL implants with advanced horizontal bone loss (e.g., 5 mm), when subjected to IP, appear to have an increased fracture risk during normal function.
Sustainable Development Frontiers: Is ‘Sustainable’ Cocoa Delivering Development and Reducing Deforestation?
Authors: Lock Will , Alexander Anthony
Published: July 2023

Forest frontiers are important areas for sustainable development as they combine the need to halt deforestation with the challenges of rural poverty. In the region of San Martín, Peru, the ‘Production, Protection and Inclusion’ model combines narratives of conservation, economic development and social inclusion in what can be defined as a ‘sustainable development frontier’. This article asks how such sustainable development frontiers change social, economic and ecological outcomes in the localities where they are found. The authors examine the reality of sustainable cocoa production linked to conservation and development goals, as promoted by government bodies, international agencies, cooperatives and chocolate brands in Peru, and show how, paradoxically, sustainability goals intensify production and attract smallholders into forest frontier areas. In doing so, the boom in demand for sustainable commodities has inadvertently created conditions encouraging further colonization of forested areas leading to a continuing rise in deforestation, ecological degradation and economic instability. Narratives of sustainable development can thus reinforce commodity intensification, as they obscure alternative approaches and reproduce traditional frontier dynamics.
Triploid Pacific oysters exhibit stress response dysregulation and elevated mortality following heatwaves
Authors: George Matthew N. , Cattau Olivia , Middleton Mollie A. , Lawson Delaney , Vadopalas Brent , Gavery Mackenzie , Roberts Steven B.
Published: July 2023

Polyploidy has been suggested to negatively impact environmental stress tolerance, resulting in increased susceptibility to extreme climate events. In this study, we compared the genomic and physiological response of diploid (2n) and triploid (3n) Pacific oysters (Crassostrea gigas) to conditions present during an atmospheric heatwave that impacted the Pacific Northwestern region of the United States in the summer of 2021. Climate stressors were applied either singly (single stressor; elevated seawater temperature, 30°C) or in succession (multiple stressor; elevated seawater temperature followed by aerial emersion at 44°C), replicating conditions present within the intertidal over a tidal cycle during the event. Oyster mortality rate was elevated within stress treatments with respect to the control and was significantly higher in triploids than diploids following multiple stress exposure (36.4% vs. 14.8%). Triploids within the multiple stressor treatment exhibited signs of energetic limitation, including metabolic depression, a significant reduction in ctenidium Na+/K+ ATPase activity, and the dysregulated expression of genes associated with stress response, innate immunity, glucose metabolism, and mitochondrial function. Functional enrichment analysis of ploidy‐specific gene sets identified that biological processes associated with metabolism, stress tolerance, and immune function were overrepresented within triploids across stress treatments. Our results suggest that triploidy impacts the transcriptional regulation of key processes that underly the stress response of Pacific oysters, resulting in downstream shifts in physiological tolerance limits that may increase susceptibility to extreme climate events that present multiple environmental stressors. The impact of chromosome set manipulation on the climate resilience of marine organisms has important implications for domestic food security within future climate scenarios, especially as triploidy induction becomes an increasingly popular tool to elicit reproductive control across a wide range of species used within marine aquaculture.
Supranational Entrepreneurship Through the Administrative Backdoor: The Commission, the Green Deal and the CAP 2023–2027
Authors: Becker Stefan
Published: July 2023

The Green Deal, the European Commission's current economic and environmental flagship initiative, demands policy change in many fields. One of them is the Common Agricultural Policy (CAP), which has a history of complex and controversial reforms. This raises a classic question of EU studies: To what extent and under what conditions can the Commission act as a policy entrepreneur? Analysing its efforts to align the latest CAP reform with the Green Deal, this article shows that, whilst struggling to make an impact in the legislative arena, the Commission used its implementation powers to pressure member states to engage with the Green Deal in their national CAP plans. In doing so, it effectively blended hard and soft law to strengthen its position. The case offers evidence how Commission entrepreneurship can materialize even under adverse conditions.
Evaluating the risk of infections under interleukin 23 and interleukin 17 inhibitors relative to tumour necrosis factor inhibitors – A population‐based study
Authors: Kridin Khalaf , Zirpel Henner , Mruwat Noor , Ludwig Ralf J. , Thaci Diamant
Published: July 2023

Background

The risk of infections among patients with psoriasis undergoing interleukin (IL)‐23 inhibitors (IL‐23i) and IL‐17 inhibitors (IL‐17i) is yet to be exhaustively determined.

Objective

To assess the risk of infectious complications in patients with psoriasis managed by IL‐23i and IL‐17i with tumour necrosis factor inhibitors (TNFi) as a comparator.

Methods

A global cohort study comprised two distinct analyses comparing patients with psoriasis under different therapeutic modalities; (i) new users of IL‐23i (n = 5272) versus TNFi (n = 5272) and (ii) new users of IL‐17i (n = 15,160) versus TNFi (n = 15,160). Study groups were compared regarding the risk of 26 different infections. Propensity score matching was conducted to optimize between‐group comparability.

Results

Patients under IL‐23i had a lower risk of otitis media (HR, 0.66; 95% CI, 0.44–0.97), encephalitis (HR, 0.18; 95% CI, 0.04–0.78), herpes zoster (HZ; HR, 0.58; 95% CI, 0.41–0.82), hepatitis B virus (HBV) reactivation (HR, 0.24; 95% CI, 0.12–0.47), cytomegalovirus (HR, 0.25; 95% CI, 0.07–0.86), influenza (HR, 0.52; 95% CI, 0.38–0.71) and parasitic diseases (HR, 0.78; 95% CI, 0.64–0.95). IL‐17i was associated with a decreased risk of pneumonia (HR, 0.76; 95% CI, 0.68–0.85), septicaemia (HR, 0.84; 95% CI, 0.72–0.97), upper respiratory tract infection (HR, 0.84; 95% CI, 0.77–0.92), HZ (HR, 0.79; 95% CI, 0.67–0.92), HBV (HR, 0.59; 95% CI, 0.46–0.76) and hepatitis C virus (HR, 0.71; 95% CI, 0.57–0.88) reactivation, cytomegalovirus (HR, 0.58; 95% CI, 0.36–0.93), Epstein–Barr virus (HR, 0.38; 95% CI, 0.19–0.75), influenza (HR, 0.70; 95% CI, 0.61–0.81) and parasitic diseases (HR, 0.80; 95% CI, 0.72–0.88).

Conclusion

Compared with TNFi, IL‐23i and IL‐17i are associated with decreased risk of several infectious diseases. These agents might be preferred in patients with susceptibility to infections.
Pledgeability and Asset Prices: Evidence from the Chinese Corporate Bond Markets
Authors: CHEN HUI , CHEN ZHUO , HE ZHIGUO , LIU JINYU , XIE RENGMING
Published: July 2023

We provide causal evidence on the value of asset pledgeability by exploiting a unique feature of Chinese corporate bond markets: bonds with identical fundamentals are traded on two segmented markets with different rules for repo transactions. Using a policy shock that rendered AA+ and AA bonds ineligible for repo on one market only, we compare how bond prices changed across markets and rating classes around this event. When the haircut increases from 0% to 100%, bond yields increase by 39 bps to 85 bps. These estimates help us infer the magnitude of the shadow cost of capital in China.
Investment case for the prevention and reduction of childhood and adolescent overweight and obesity in Mexico
Authors: Brero Mauro , Meyer Christina L. , Jackson‐Morris Angela , Spencer Garrison , Ludwig‐Borycz Elizabeth , Wu Daphne , Espinosa De Candido Anabel Fiorella , Ferre Eguiluz Maria Isabel , Bonvecchio Arenas Anabelle , Jewell Jo , Nugent Rachel
Published: July 2023

Despite efforts to curb the rise in Mexico's child and adolescent overweight and obesity rates, prevalence in Mexico has grown by 120% since 1990 to 43.3% in 2022. This investment case identifies policies that will produce the largest returns for Mexico. The investment case model builds beyond a cost‐of‐illness analysis by predicting the health and societal economic impact of implementing child and adolescent overweight and obesity interventions in a cohort aged 0–19 from 2025 to 2090. The Markov model's impacts include healthcare expenditures, years of life lost, and reduced wages and productivity. We projected and compared costs in a status quo scenario to an intervention scenario to estimate cost savings and calculate return‐on‐investment (ROI). Total lifetime health and economic costs amount to USD 1.8 trillion—USD 30 billion on average per year. Implementing five interventions can reduce lifetime costs by approximately 7%. Each intervention has a low cost per disability‐adjusted life year averted over 30‐year, 50‐year, and lifetime horizons. The findings demonstrate that a package of interventions mitigating child and adolescent overweight and obesity offers a strong ROI. The novel investment case methods should be applied to other countries, particularly low‐ and middle‐income countries.
Early-set POMC methylation variability is accompanied by increased risk for obesity and is addressable by MC4R agonist treatment
Authors: Lechner Lara , Opitz Robert , Silver Matt J. , Krabusch Philipp M. , Prentice Andrew M. , Field Martha S. , Stachelscheid Harald , Leitão Elsa , Schröder Christopher , Fernandez Vallone Valeria , Horsthemke Bernhard , Jöckel Karl-Heinz , Schmidt Börge , Nöthen Markus M. , Hoffmann Per , Herms Stefan , Kleyn Patrick W. , Megges Matthias , Blume-Peytavi Ulrike , Weiss Katja , Mai Knut , Blankenstein Oliver , Obermayer Benedikt , Wiegand Susanna , Kühnen Peter
Published: July 2023

Increasing evidence points toward epigenetic variants as a risk factor for developing obesity. We analyzed DNA methylation of the
POMC
(pro-opiomelanocortin) gene, which is pivotal for satiety regulation. We identified sex-specific and nongenetically determined
POMC
hypermethylation associated with a 1.4-fold (confidence interval, 1.03 to 2.04) increased individual risk of developing obesity. To investigate the early embryonic establishment of
POMC
methylation states, we established a human embryonic stem cell (hESC) model. Here, hESCs (WA01) were transferred into a naïve state, which was associated with a reduction of DNA methylation. Naïve hESCs were differentiated via a formative state into POMC-expressing hypothalamic neurons, which was accompanied by re-establishment of DNA methylation patterning. We observed that reduced
POMC
gene expression was associated with increased
POMC
methylation in
POMC
-expressing neurons. On the basis of these findings, we treated
POMC
-hypermethylated obese individuals (
n
= 5) with an MC4R agonist and observed a body weight reduction of 4.66 ± 2.16% (means ± SD) over a mean treatment duration of 38.4 ± 26.0 weeks. In summary, we identified an epigenetic obesity risk variant at the
POMC
gene fulfilling the criteria for a metastable epiallele established in early embryonic development that may be addressable by MC4R agonist treatment to reduce body weight.
The Strong Menger Connectivity of the Directed k-Ary n-Cube
Authors: Xie Guoqiang , Meng Jixiang
Published: July 2023

A strong digraph [Formula: see text] is strongly Menger (arc) connected if, for [Formula: see text], [Formula: see text] can reach [Formula: see text] by min[Formula: see text] internally (arc) disjoint-directed paths. A digraph [Formula: see text] is [Formula: see text](-arc)-fault-tolerant strongly Menger([Formula: see text]-(A)FTSM, for short) (arc) connected if [Formula: see text] is strongly Menger (arc) connected for every [Formula: see text](respectively, [Formula: see text]) with [Formula: see text]. A digraph [Formula: see text] is [Formula: see text]-conditional (arc)-fault-tolerant strongly Menger ([Formula: see text]-C(A)FTSM, for short) (arc) connected if [Formula: see text] is strongly Menger (arc) connected for every [Formula: see text](respectively, [Formula: see text]) with [Formula: see text] and [Formula: see text]. The directed [Formula: see text]-ary [Formula: see text]-cube [Formula: see text] [Formula: see text] and [Formula: see text] is a digraph with vertex set [Formula: see text]. For two vertices [Formula: see text] and [Formula: see text], [Formula: see text] dominates [Formula: see text] if there exists an integer [Formula: see text], [Formula: see text], satisfying [Formula: see text]mod [Formula: see text] and [Formula: see text], when [Formula: see text]. In this paper, we show that [Formula: see text] is [Formula: see text]-arc-fault-tolerant strongly Menger arc connected for [Formula: see text], [Formula: see text]-fault-tolerant strongly Menger connected for [Formula: see text], [Formula: see text]-conditional arc-fault-tolerant strongly Menger arc connected for [Formula: see text], and [Formula: see text]-conditional fault-tolerant strongly Menger connected for [Formula: see text]. we show that [Formula: see text] [Formula: see text] is [Formula: see text]-AFTSM arc connected when [Formula: see text], [Formula: see text]-FTSM connected when [Formula: see text], [Formula: see text]-CAFTSM arc connected when [Formula: see text], and [Formula: see text]-CFTSM connected when [Formula: see text].
Review—Nanofibers: Empowering Electrochemical Sensors for Reliable Detection of Food and Environmental Toxins
Authors: Kogularasu Sakthivel , Lee Yen-Yi , Chang-Chien Guo-Ping , Govindasamy Mani , Sheu Jinn-Kong
Published: July 2023

Electrochemical sensors have become indispensable tools for the detection and monitoring of food and environmental toxins. In recent years, nanofiber-based materials have emerged as promising candidates for constructing electrochemical sensors, offering a plethora of unique advantages, such as a large surface area, enhanced electron transfer kinetics, and the ability to immobilize diverse recognition elements. This comprehensive review sheds light on the pivotal role of nanofibers in advancing electrochemical sensors for the detection of food and environmental toxins. Various fabrication methods for nanofibers, including electrospinning, template-assisted synthesis, and self-assembly techniques, are elucidated in detail. It highlights the integration of nanofibers as electrode materials, nanocomposites, and immobilization platforms for recognition elements like enzymes, antibodies, and aptamers. The influence of nanofiber properties, encompassing morphology, composition, and surface modification, on the sensing performance is meticulously discussed. Moreover, a comprehensive overview of the latest advancements in nanofiber-based electrochemical sensors for detecting pesticide residues, heavy metals, mycotoxins, and other environmental contaminants is presented. We address challenges and future perspectives in the field, including scalability, cost-effectiveness, and seamless integration with wearable devices. This review illuminates new horizons for the development of sensitive, selective, and portable analytical devices, thereby significantly contributing to improved food safety and environmental monitoring.