bluuebunny/crossref_metadata_2025 huggingface dataset:
Outcomes in PEERS® for Adolescents Across Neurodevelopmental Disorders: ADHD, Autism, and Their Co-occurrence
Authors: Geannopoulos Zoe F. , Moody Christine T. , McGregor Hadley A. , Baertschi Daliah , Bates Shannon , Laugeson Elizabeth A.
Published: January 2024

Objectives

Autistic individuals and those diagnosed with ADHD are at greater risk for social difficulties, with evidence suggesting that the co-occurrence of these neurodevelopmental disorders may further exacerbate social challenges. Though social skill interventions have strong empirical support in autistic populations, fewer evidence-based social skill interventions for adolescents with ADHD exist. Further, the impact of co-occurring autism and ADHD diagnoses on social skill treatment response is unknown. This study aimed to investigate the comparative efficacy of the evidence-based PEERS® for Adolescents social skills intervention in adolescents with ADHD, autistic adolescents, and adolescents with co-occurring ADHD and autism.

Methods

Adolescents (N = 144; ADHD, n = 43; Autism, n = 60; ADHD + Autism, n = 41) and their parents participated in PEERS® for Adolescents and completed questionnaires on social functioning at pre- and post-intervention. PEERS® for Adolescents is a 16-week, parent-assisted social skills intervention that teaches ecologically valid skills related to making and keeping friends as well as handling conflict and rejection in peer relationships.

Results

At baseline, a MANCOVA revealed significant differences in social behavior by diagnostic group (ADHD, Autism, ADHD + Autism), F(10,218) = 3.60, p < .001. However, in a repeated measures MANCOVA, no significant differences in treatment response following PEERS® for Adolescents across diagnostic groups emerged, F(10,214) = 1.34, p = .209. As a whole, participants significantly improved across all assessed outcomes.

Conclusion

Results suggest that adolescents with ADHD, with or without a co-occurring autism diagnosis, benefit from the novel extension of PEERS® for Adolescents, showing improved social skill proficiency and decreased problem behaviors.
Laparoscopic Tumorectomy for an Unusual Pelvic Retroperitoneal Leiomyoma: A Case Report
Authors: Pace Marco , Moretti Marco , Tierno Simone Maria , Mazzotta Alessandro Dario , Ferroni Andrea Felice , Di Giovan Paolo Marco , Gianfreda Valeria , Bianca Salvatore , Barbarosos Apostolos , Vitelli Carlo Eugenio , Boninfante Michelangelo , Stipa Francesco
Published: January 2024

Leiomyomas are benign tumors, mostly located in the uterus. The pelvic localization is quite rare, and it is associated with unusual growth patterns. It is important to make an adequate differential diagnosis between malignant and benign retroperitoneal neoplasm because treatment is different. When it is not possible to have a precise preoperative diagnosis, a laparoscopic or laparotomy surgical tumorectomy is often required. To obtain a certain diagnosis, the goal of surgery is ensuring the complete excision of neoplasms and preservation of urination, defecation, and sexual function. We report a rare case of a 58-year-old woman who underwent a laparoscopic tumorectomy for a pelvic retroperitoneal leiomyoma. The patient reported occasional episodes of dull pain in the pelvic region. Pelvic contrast CT scan and magnetic resonance imaging (MRI) showed a retroperitoneal solid mass in contiguity with the posterior wall of the uterine body-isthmus, to be referred to as a pedunculated uterine fibroma strictly posteriorly adherent to the sigma. She first underwent to explorative laparoscopy by a gynecologist who did not find any uterine mass. The patient was subsequently admitted to the department of general surgery and has done a second operative laparoscopy which highlighted the presence of an extra-peritoneal para-rectal mass which was completely excised. The histological examination of tumor indicated that it was a leiomyoma. The postoperative course was uneventful, and the patient was discharged in III post-operative day (POD).
An Enhanced Location-Aided Ant Colony Routing for Secure Communication in Vehicular Ad Hoc Networks
Authors: Ramamoorthy Raghu
Published: January 2024

The dynamic characteristics of vehicular ad hoc networks (VANETs) demand reliable and secure communication over wireless media. However, there are significant contradictions in autonomous vehicular systems related to security and privacy. Furthermore, VANETs require seamless data transmission to exchange time-critical data about accidents and traffic. Therefore, VANETs require secure seamless data transmission mechanisms to provide secure reliable communication without communication interruption to exchange time-critical data between vehicles. This paper proposes an Enhanced Location-Aided Ant colony Routing (ELAACR) for VANETs to achieve seamless secure data transmission. The proposed ELAACR is a two-fold scheme in which Phase 1 implements Location-Aided Key Management (LAKM) and Phase 2 implements Ant Colony Routing (ACR). An ACR combined with an LAKM pattern for offering secure and reliable communication. The LAKM scheme works based on the group signature concept to construct a secure network, and an ACR is used to find an efficient secure shortest path for seamless data transmission. The proposed work is simulated in Network Simulator (NS 2.35). By using an efficient and secure shortest path with secure seamless data transmission, the proposed ELAACR achieves an average throughput (T) of 640 Kbps, packet loss rate (PLR) of 0.018%, packet delivery ratio (PDR) of 98.5%, overhead (OH) of 0.157%, and 0.16 s end-to-end delay (EED) compared to Enhanced Hybrid Ant Colony Optimization Routing Protocol (EHACORP) and Fuzzy Based Ant Colony Optimization (F-ANT). The simulation results show that the proposed ELAACR registers better performance in all aspects compared to the existing EHACORP and F-ANT.
A Cultural History of the Medieval Sword
Authors: Jones Robert W.
Published: January 2024

This study takes the sword beyond its functional role as a tool for killing, considering it as a cultural artifact , and the broader meaning and significance it had to its bearer.
The effect of timers and precommitments on handwashing: a randomised controlled trial in a kitchen laboratory
Authors: Thom James , Bowen Sarah , Yang Yuchen , Devarajan Sanjeev , Doran Helen , Zampetis Marios , Papakonstantinou Trisevgeni , McDonagh Maria , McPhedran Robert , Toombs Ben , Ibrahimi Jarchlo Ayla , Rayner Alice , Jones Philip , Gold Natalie
Published: January 2024

Many foodborne illness outbreaks originate in food service establishments. We tested two behavioural interventions designed to improve the duration and quality of handwashing. We ran a three-armed parallel trial in a laboratory kitchen, from 7 March to 27 May 2022. Participants were n = 195 workers who handle food. We randomly allocated participants to three groups: Timer – tap-mounted timer that counted seconds while participants washed their hands; Precommitment – agreed to five statements on good hand hygiene before attending the kitchen; and Control. Participants completed a food preparation task under time pressure. Cameras focused on the sink captured handwashing. Outcome measures were number of times participants washed their hands; number of times they washed their hands using soap; number of times they washed using soap and washed the backs of their hands; and mean duration of handwashing attempts using soap. Participants in Timer washed their hands for 1.9 s longer on average than Control (β = 2.20, 95% CI = 0.34-4.06, p = 0.021). Participants in Precommitment washed their hands for 2.5 s longer on average than Control (β = 2.30, 95% CI = 0.33-4.27, p = 0.022). We found no statistically significant differences on any other outcome measure.
Assertions: Deterrent or Handicap? A Reply to Graham (2020)
Authors: Bruner Justin P.
Published: January 2024

According to one influential tradition, to assert that p is to express a belief that p. Yet how do assertions provide strong evidence for belief? Philosophers have recently drawn on evolutionary biology to help explain the stability of assertive communication. Mitchell Green suggests that assertions are akin to biological handicaps. Peter Graham argues against the handicap view and instead claims that the norms of assertion are deterrents. Contra Graham, I argue that both mechanisms may play a role in assertive communication, although assertions as deterrents will often fail to provide strong evidence for belief.
A World by Themselves: Protectionism and the Political Economy of Trade in the Ohio Valley, 1816–1828
Authors: Harris Keith
Published: January 2024

This paper explores American tariff politics and the embrace of protectionism within the Ohio Valley in the two decades following the War of 1812. During these years, residents of the western states navigated the emergence of steam transportation, a growing number of state-chartered banks, and intense population growth. This fueled an economic boom that went bust during the Panic of 1819. Western farmers, merchants, and manufacturers blamed harmful patterns of trade for this economic crisis, which bolstered a distinct regional identity that embraced a properly constructed restrictive tariff as a “western” measure. Consequently, the decade of the 1820s featured the most sustained period of conflict over the tariff issue in the antebellum era. This article examines western participation in conflicts over commerce and roots the political economy of trade policy in changing economic conditions that inspired distinct northern, southern, and western perspectives on trade and economic development. I conclude that both protectionist claims to economic nationalism and free trade embrace of international exchange overlook the individual assessments of local and regional markets that set the terms on which participants in the tariff debates of the early republic imagined future development.
Analytical results for pitching kinematics and propulsion performance of flexible foil
Authors: Du Feng , Wu Jianghao
Published: January 2024

Natural flyers and swimmers employ flexible wings or fins to propel. While the complex interaction between the foil with deformation and the surrounding non-steady fluid environment defines the propulsion performance of the propellers, elucidating the interaction mechanism through theoretical models earns much challenge. Based on elastokinetics and linear potential flow theory, this study proposes a simplified analytical model to clarify the kinematics and the propulsion performance of a flexible thin foil pitching in flow. The dynamical forces, including the inertial force of the foil and the non-steady fluid pressure, are used to determine the averaged deformation angle of the foil. Combining the averaged deformation angle and the prescribed driving pitching motion, the kinematics of the foil is resolved analytically. Based on the analytical expressions for the corresponding pitching motion, analytical relations among the physical parameters of the stiffness and the mass of the foil and the driving frequency are given to these critical conditions, including resonance of the flow–structure system, equal pitching amplitude between the flexible foil and the rigid counterpart, phase angle transition from

${\rm \pi}/2$

to

$- {\rm \pi}/2$

. Subsequently, the performance of the foil, including the thrust, the power and the propulsive efficiency, as a function of the flexibility of the foil are derived, together with the introduction of a bluff body type offset drag to the thrust. The formulated analytical theory, which matches nicely with previous reports, will help to interpret the effect of the flexibility and regulate the propulsive performance of the flexible foil when pitching in fluid.
Meso-level planning for mine closure and transition: How do we optimise closure benefits and minimise risk at the regional scale?
Authors: Jacquet Jeffrey B. , Measham Thomas , Haggerty Julia H.
Published: January 2024

Mining activity can have small geographic footprints compared to the significant economic, employment, and environmental impacts that are experienced at a much larger scale. Likewise, the closure of these mines can lead to regional-scale transformations in economic and sociodemographic structure that exhibit cumulative or interactive effects with regional trends (Haggerty et al., 2018; Syahrir et al., 2021). Yet regional- or meso-level planning and regulation of mining activity and mine closure is often overlooked as extractive industries are typically regulated at state, provincial or national levels, with local oversight typically limited to where the mine is located (Lobao et al., 2009). Regional-level analysis also must include a diversity of rightsholders and stakeholders that may be impacted differently and with varying levels of influence or agency over how economic futures are defined (Monosky and Keeling 2021; Roemer and Haggerty, 2021).
BOUNDING ZETA ON THE 1-LINE UNDER THE PARTIAL RIEMANN HYPOTHESIS
Authors: CHIRRE ANDRÉS
Published: January 2024

We provide explicit bounds for the Riemann zeta-function on the line
$\mathrm {Re}\,{s}=1$
, assuming that the Riemann hypothesis holds up to height T. In particular, we improve some bounds in finite regions for the logarithmic derivative and the reciprocal of the Riemann zeta-function.
Tectonic evolution of the Middle-Late Permian orogenic belt in the eastern part of the CAOB: Implications from the magmatism in the Changchun-Kaiyuan area
Authors: Zhang Nuo , Liu Zhenghong , Xu Zhongyuan , Li Gang , Dong Xiaojie , Liu Jin , Li Wenqing
Published: January 2024

Various magmatisms during the subduction-collision process are crucial to reveal the long-term tectonic evolution of the eastern Central Asian Orogenic Belt. In this paper, we present major and trace elements of whole-rock, zircon U-Pb dating and Hf isotope of the Shanmen pluton. Results imply that the Shanmen pluton consists of quartz diorite and mylonitic granite, with zircon U-Pb ages of 263.7–259.6 Ma. The studied quartz diorite contains high Sr/Y (51.19–90.87) and (La/Yb)N (7.82–13.62) ratios, and belongs to adakitic rocks. Coupled with the positive εHf(t) values of +5.71 to +12.8 with no obvious Eu anomaly, we propose that quartz diorite is the product of the interaction between different degrees of slab melt and the overlying mantle wedge. In contrast, the mylonitic granite has lower MgO (0.28 wt% – 0.47 wt%) contents and positive εHf(t) values of +7.79 to +10.15, indicating an affinity with I-type granite originated by partial melting of the intermediate-basic lower crust. The geochemical characteristics and lithological assemblages, along with the Permian magmatic rocks in the Changchun-Kaiyuan area displaying arc rocks affinity, propose their formation is related to the southward subduction of the Paleo-Asian Ocean (PAO). Based on this study and previous evidence, we lean towards adopting a middle-late Permian slab break-off model, wherein the PAO did not close until the late Permian.
Safeguarding South African Consumers’ Socio-Economic Rights During COVID-19: Competition Commission v Babelegi Workwear and Industrial Supplies
Authors: Tavuyanago Simbarashe , Mpofu Kudzai
Published: January 2024

This article explores the responses of the South African competition authorities to the impact of the COVID-19 pandemic on the socio-economic rights of consumers in relation to the price gouging of essential and medical supplies. After discussing the constitutional and legislative context of socio-economic rights and excessive pricing, it examines the first case in which the competition authorities were called upon to decide on the excessive pricing of medical supplies during COVID-19. The article finds that, while the competition authorities were swift to interpret the Competition Act widely and act against suppliers charging excessive prices, there remains a gap in South Africa's legislative framework as there is no specific legislation regulating price gouging during states of pandemic or disaster. The article identifies the need for legislative development and concludes by offering recommendations for addressing future incidents of price gouging.
Power and ritual in the city: Mourning and political juncture at Bangkok's Sanam Luang
Authors: Renwick Trude , Isaacs Bronwyn
Published: January 2024

This article argues that ritual remains a potent instrument for the generation of national identity and citizenship in Southeast Asia. We focus our analysis on the ritualisation of public space in Bangkok, Thailand, under the military-led government of General Prayut Chan-o-cha. The authors provide an ethnographic analysis of Sanam Luang, arguing that between 2016 and 2017 funeral rites held in this public space would reanimate it as a catalyst of national unification. As in other cases of ritual in public space, however, the intensified securitisation and control over national mourning for King Bhumibol by the military government, gave way to a range of reactions, including increased protests and criticism of the ruling government and Thailand's lesé-majesté laws by a predominantly youth-led movement in 2020.
In defence of qua-Christology
Authors: Rubio Daniel
Published: January 2024

Recent analytic theology has seen a wave of excellent work on the fundamental problem of Christology, the question of how one and the same person can be human full stop and divine full stop. Along the way, new objections have been raised for a venerable family of Christological views, whose distinctive is the employment of qua-devices to dissolve the difficulties stemming from the dual nature doctrine of Chalcedon and its successors. My objective in this article is twofold. First, I propose to lay out a hierarchy of principles that should guide the search for a Christological theory. I then use these principles to illuminate the best qua-theoretic approach to Christology. Finally, I argue that the best qua-theory is at worst on a par with major recent views.
Religion and Trust in Hong Kong
Authors: Cai Yongshun , Hung Sin Yu
Published: January 2024

Affiliation with different religions can have different effects on practitioners’ trust in state institutions and in social actors. Based on a survey of 3,740 residents in Hong Kong in 2021, we examine the relationship between religious affiliation and believers’ trust in the political authorities in Beijing and Hong Kong and in civil actors in the city. We find that affiliation with traditional Chinese religions and Eastern religions has a positive and significant effect on believers’ trust in the political authorities, whereas belief in Western religions does not have such an effect. Affiliation with Western religions, however, has a stronger positive and significant effect on interpersonal trust and on tolerance for unconventional behaviour. These findings shed light on the interaction between the government and religious groups in Hong Kong after 1997.
Rabies vaccination adherence and associated factors among rabies-exposed patients in Shenzhen, China: a hospital-based cross-sectional study
Authors: Lu Ruiqi , Lin Jinsheng , Zhou Yang , Chen Qian , Fan Zaiying , Wu Shuning , Qin Pei , Li Liping
Published: January 2024

Adherence to post-exposure prophylaxis and post-exposure vaccination (PEV) is an important measure to prevent rabies. The purpose of this study was to explore the adherence to the vaccination protocol and its influencing factors among rabies-exposed patients in Shenzhen, China. A cross-sectional survey was conducted in a tertiary hospital in Shenzhen, China, to obtain epidemiological characteristics of patients; knowledge, attitude, and practice scores of rabies prevention; and medical records. A total of 326 patients requiring full rabies PEV were included in this study, and only 62% (202) completed the full course of vaccination according to the norms of the vaccination guidelines. After multifactor logistic regression, the factors influencing adherence to vaccination were as follows: age 31 to 40 years, time spent to reach the nearest rabies prevention clinic was >60 min, the time of injury was at night to early morning, the place of injury was a school/laboratory, the animal causing injury was a cat, the health status of the animal causing injury could not be determined, and patients with higher practice scores (all p<0.05). Understanding the factors influencing rabies vaccination adherence among rabies-exposed patients in urban areas of China and promote changes in patients’ practice toward rabies prevention is essential for rabies elimination by 2030.
Shifting Electorates and Preferences in Chile’s Constitutional Process
Authors: Keefer Philip , Negretto Gabriel L.
Published: January 2024

Normatively, democratic constitutions should express how citizens want to govern themselves collectively. Little is known, however, about how citizens’ constitutional preferences can be elicited and aggregated in practice. An intuitively appealing approach is to allow various forms of popular participation during a constitution-making process, including a popular vote to accept or reject the draft constitution (Fishkin 2011). Based on the Chilean experience with democratic constitution making, this article identifies unanticipated and previously unexplored distortions that can lead to incongruence between the preferences of voters and representatives regarding the extent and direction of constitutional change.
Shape-shifting and Strategic In/visibility: Comparing Sex Work Activism in Singapore and the Philippines
Authors: Parmanand Sharmila
Published: January 2024

Research on public health, crime, and policing regularly discusses sex workers in Southeast Asia but rarely recognises them as agents of social and political activism. This paper shows that sex workers and their allies in Singapore and the Philippines have long and rich histories of challenging their criminalisation and stigmatisation through cultural activism, political advocacy, consciousness-raising, and the provision of direct services to fellow sex workers. Using feminist ethnography, including interviews and participant observation with Project X in Singapore and the Philippine Sex Workers Collective, this paper explores how sex work activists have strategically adapted to their political environments. In Singapore, they maintain resistance through ‘shape-shifting,’ working within state-sanctioned mechanisms, positioning themselves as public health service providers, and creating spaces for radical political advocacy. In the Philippines, where an anti-sex work position is more deeply entrenched within dominant social blocs, sex work activists aggressively criticise state policies on social media and in carefully vetted forums but remain strategically invisible to avoid exposure, harassment, misrepresentation, and prosecution. This paper looks at how sex work activists engage in claims-making — underscoring the differences in the political resonance of human rights in both countries — and interrogates how sex work activism challenges social hierarchies, especially concerning migrants and trans individuals. Overall, it contributes to a richer understanding of non-traditional forms of political activism in Southeast Asia and makes visible sex workers’ contributions to feminism and labour movements in the global south and non-Western contexts.
On the Sensitivity of Coastal Hypoxia to Its External Physical Forcings
Authors: St‐Laurent P. , Friedrichs M. A. M.
Published: January 2024

The development of low‐oxygen zones threatening marine life (hypoxia) occurs annually in multiple coastal regions of the world. The largest estuary of the continental United States, the Chesapeake Bay, typically has ≈10 km3 of water with dioxygen concentrations <3 mg L−1 in July. As numerical methods for refining model resolutions in targeted areas are becoming common, there is interest in assessing the feasibility of simulating coastal hazards such as hypoxia in Earth System Models (ESMs). These coupled models are typically not constrained by observations and thus likely to feature systematic biases in their land, atmosphere, or ocean components. This study relies on four numerical experiments to evaluate the sensitivity of Chesapeake Bay hypoxia to changes or biases in its external physical forcings. Hypoxia exhibits only a minor decrease (−1.6%) after reducing the Bay's terrestrial freshwater discharge by 9.5% (but keeping terrestrial nutrient loadings the same). Changes in freshwater discharges have their largest impact on hypoxia during one extreme event (−37% during 2011 tropical storm Lee). Similarly, changing oceanic conditions on the shelf or their temporal frequency impact hypoxia by only 5%–6%, indicating that the latter is predominantly dictated by local conditions. Although these results are promising from the perspective of ESMs, additional components of ESMs will need to be evaluated before general conclusions can be reached. We notably speculate that the Bay's hypoxia would exhibit higher sensitivity to other forcings not examined here, notably air temperatures and nutrient loadings.
Socio-economic differences in body mass index: the contribution of genetic factors
Authors: Silventoinen Karri , Lahtinen Hannu , Kilpi Fanny , Morris Tim T. , Davey Smith George , Martikainen Pekka
Published: January 2024

Background

Higher mean body mass index (BMI) among lower socioeconomic position (SEP) groups is well established in Western societies, but the influence of genetic factors on these differences is not well characterized.

Methods

We analyzed these associations using Finnish health surveys conducted between 1992 and 2017 (N = 33 523; 53% women) with information on measured weight and height, polygenic risk scores of BMI (PGS-BMI) and linked data from administrative registers to measure educational attainment, occupation-based social class and personal income.

Results

In linear regressions, largest adjusted BMI differences were found between basic and tertiary educated men (1.4 kg/m2, 95% confidence interval [CI] 1.2; 1.6) and women (2.5 kg/m2, 95% CI 2.3; 2.8), and inverse BMI gradients were also found for social class and income. These SEP differences arose partly because mean PGS-BMI was higher and partly because PGS-BMI predicted BMI more strongly in lower SEP groups. The inverse SEP gradients of BMI were steeper in women than in men, but sex differences were not found in the genetic contributions to these differences.

Conclusions

Better understanding of the interplay between genes and environment provides insight into the mechanisms explaining SEP differences in BMI.
Effects of swimming training in hot and cold temperatures combined with cinnamon supplementation on HbA1C levels, TBC1D1, and TBC1D4 in diabetic rats
Authors: Tayebi Seyed Morteza , Nouri Amir Hossein , Tartibian Bakhtyar , Ahmadabadi Somayeh , Basereh Aref , Jamhiri Iman
Published: January 2024

Aims

Diabetes is one of the main causes of mortality in developing countries. Performing physical activity in various ways and different environments using herbal supplements can be used as a non-pharmacological solution to prevent and improve diabetes. Hence, this study aimed to investigate the effects of eight weeks of cold water swimming exercise training combined with cinnamon supplementation on HbA1C (Hemoglobin A1c) levels, TBC1D1 (TBC1 domain family member 1), and TBC1D4 (TBC1 Domain Family Member 4) in diabetic rats.

Materials and methods

Ninety-one rats (n = 78 diabetic, n = 13 healthy) were divided into seven groups (n = 13 per group): (1) healthy control (HC), (2) diabetic control (DC), (3) swimming training in cold water (5 °C) (S5), (4) swimming training in cold water (5 °C) with a cinnamon supplementation (200 mg/kg body weight) (S5+Ci), (5) swimming training in warm water (36-35 °C) (S35), (6) swimming training in warm water (35–36 °C) with a cinnamon supplementation (S35+Ci), and (7) a cinnamon supplementation only (Ci). To evaluate the hypothesis, a one-way ANOVA and Tukey’s post hoc test were used.

Results

Findings showed that the TBC1D1 and TBC1D4 levels in the DC and S35 groups were higher than in the HC group (p < 0.001). Also, swimming training in cold water (5 °C) with cinnamon supplementation (S5+Ci) decreased the level of TBC1D1, TBC1D4, HbA1c, and glucose compared to other groups (p < 0.05).

Conclusions

The study revealed that the combination of swimming training in cold water and cinnamon consumption led to a significant reduction in TBC1D1, TBC1D4, and HbA1c. Therefore, this non-traditional exercise approach coupled with cinnamon supplementation can be considered an effective method for improving insulin sensitivity, fasting blood glucose, and HbA1c levels and is proposed as an optimal method to improve glucose indices.
A therapeutic antibody targeting annexin-A1 inhibits cancer cell growth in vitro and in vivo
Authors: Al-Ali Hussein N. , Crichton Scott J. , Fabian Charlene , Pepper Chris , Butcher David R. , Dempsey Fiona C. , Parris Christopher N.
Published: January 2024

In this study we conducted the first investigation to assess the efficacy of a novel therapeutic antibody developed to target annexin-A1 (ANXA1). ANXA1 is an immunomodulatory protein which has been shown to be overexpressed in, and promote the development and progression of, several cancer types. In particular, high ANXA1 expression levels correlate with poorer overall survival in pancreatic and triple-negative breast cancers, two cancers with considerable unmet clinical need. MDX-124 is a humanised IgG1 monoclonal antibody which specifically binds to ANXA1 disrupting its interaction with formyl peptide receptors 1 and 2 (FPR1/2). Here we show that MDX-124 significantly reduced proliferation (p < 0.013) in a dose-dependent manner across a panel of human cancer cell lines expressing ANXA1. The anti-proliferative effect of MDX-124 is instigated by arresting cell cycle progression with cancer cells accumulating in the G1 phase of the cell cycle. Furthermore, MDX-124 significantly inhibited tumour growth in both the 4T1-luc triple-negative breast and Pan02 pancreatic cancer syngeneic mouse models (p < 0.0001). These findings suggest ANXA1-targeted therapy is a viable and innovative approach to treat tumours which overexpress ANXA1.
Intratumoural microbiota: a new frontier in cancer development and therapy
Authors: Cao Yaqi , Xia Hui , Tan Xueyun , Shi Chunwei , Ma Yanling , Meng Daquan , Zhou Mengmeng , Lv Zhilei , Wang Sufei , Jin Yang
Published: January 2024

Human microorganisms, including bacteria, fungi, and viruses, play key roles in several physiological and pathological processes. Some studies discovered that tumour tissues once considered sterile actually host a variety of microorganisms, which have been confirmed to be closely related to oncogenesis. The concept of intratumoural microbiota was subsequently proposed. Microbiota could colonise tumour tissues through mucosal destruction, adjacent tissue migration, and hematogenic invasion and affect the biological behaviour of tumours as an important part of the tumour microenvironment. Mechanistic studies have demonstrated that intratumoural microbiota potentially promote the initiation and progression of tumours by inducing genomic instability and mutations, affecting epigenetic modifications, promoting inflammation response, avoiding immune destruction, regulating metabolism, and activating invasion and metastasis. Since more comprehensive and profound insights about intratumoral microbiota are continuously emerging, new methods for the early diagnosis and prognostic assessment of cancer patients have been under examination. In addition, interventions based on intratumoural microbiota show great potential to open a new chapter in antitumour therapy, especially immunotherapy, although there are some inevitable challenges. Here, we aim to provide an extensive review of the concept, development history, potential sources, heterogeneity, and carcinogenic mechanisms of intratumoural microorganisms, explore the potential role of microorganisms in tumour prognosis, and discuss current antitumour treatment regimens that target intratumoural microorganisms and the research prospects and limitations in this field.
Phase 1 study of high-dose DFMO, celecoxib, cyclophosphamide and topotecan for patients with relapsed neuroblastoma: a New Approaches to Neuroblastoma Therapy trial
Authors: Hogarty Michael D. , Ziegler David S. , Franson Andrea , Chi Yueh-Yun , Tsao-Wei Denice , Liu Kangning , Vemu Rohan , Gerner Eugene W. , Bruckheimer Elizabeth , Shamirian Anasheh , Hasenauer Beth , Balis Frank M. , Groshen Susan , Norris Murray D. , Haber Michelle , Park Julie R. , Matthay Katherine K. , Marachelian Araz
Published: January 2024

Background

MYC genes regulate ornithine decarboxylase (Odc) to increase intratumoral polyamines. We conducted a Phase I trial [NCT02030964] to determine the maximum tolerated dose (MTD) of DFMO, an Odc inhibitor, with celecoxib, cyclophosphamide and topotecan.

Methods

Patients 2–30 years of age with relapsed/refractory high-risk neuroblastoma received oral DFMO at doses up to 9000 mg/m2/day, with celecoxib (500 mg/m2 daily), cyclophosphamide (250 mg/m2/day) and topotecan (0.75 mg/m2/day) IV for 5 days, for up to one year with G-CSF support.

Results

Twenty-four patients (median age, 6.8 years) received 136 courses. Slow platelet recovery with 21-day courses (dose-levels 1 and 2) led to subsequent dose-levels using 28-day courses (dose-levels 2a-4a). There were three course-1 dose-limiting toxicities (DLTs; hematologic; anorexia; transaminases), and 23 serious adverse events (78% fever-related). Five patients (21%) completed 1-year of therapy. Nine stopped for PD, 2 for DLT, 8 by choice. Best overall response included two PR and four MR. Median time-to-progression was 19.8 months, and 3 patients remained progression-free at >4 years without receiving additional therapy. The MTD of DFMO with this regimen was 6750 mg/m2/day.

Conclusion

High-dose DFMO is tolerable when added to chemotherapy in heavily pre-treated patients. A randomized Phase 2 trial of DFMO added to chemoimmunotherapy is ongoing [NCT03794349].
Neutrophil extracellular traps and neutrophilic dermatosis: an update review
Authors: Li Sheng , Ying Shuni , Wang Yuqian , Lv Yelu , Qiao Jianjun , Fang Hong
Published: January 2024

Neutrophils have both antimicrobial ability and pathogenic effect in the immune system, neutrophil extracellular traps (NETs) formation is one of the representative behaviors of their dual role. NETs formation was triggered by pathogen-related components and pathogen non-related proteins as cytokines to exert its effector functions. Recent studies indicate that the pathogenicity of NETs contributed to several skin diseases such as psoriasis, Stevens-Johnson syndrome, toxic epidermal necrolysis, and neutrophilic dermatosis. Especially in neutrophilic dermatosis, a heterogeneous group of inflammatory skin disorders characterized with sterile neutrophilic infiltrate on dermis, NETs formation was reported as the way of participation of neutrophils in the pathogenesis of these diseases. In this review, we describe the different processes of NETs formation, then summarized the most recent updates about the pathogenesis of neutrophilic dermatosis and the participation of NETs, including pyoderma gangrenosum and PAPA syndrome, Behçet syndrome, hidradenitis suppurativa, Sweet Syndrome, pustular dermatosis and other neutrophilic dermatosis. Furthermore, we discuss the link between NETs formation and the development of neutrophilic dermatosis.
Accelerated prime-and-trap vaccine regimen in mice using repRNA-based CSP malaria vaccine
Authors: MacMillen Zachary , Hatzakis Kiara , Simpson Adrian , Shears Melanie J. , Watson Felicia , Erasmus Jesse H. , Khandhar Amit P. , Wilder Brandon , Murphy Sean C. , Reed Steven G. , Davie James W. , Avril Marion
Published: January 2024

Malaria, caused by Plasmodium parasites, remains one of the most devastating infectious diseases worldwide, despite control efforts to lower morbidity and mortality. Both advanced candidate vaccines, RTS,S and R21, are subunit (SU) vaccines that target a single Plasmodium falciparum (Pf) pre-erythrocytic (PE) sporozoite (spz) surface protein known as circumsporozoite (CS). These vaccines induce humoral immunity but fail to elicit CD8 + T-cell responses sufficient for long-term protection. In contrast, whole-organism (WO) vaccines, such as Radiation Attenuated Sporozoites (RAS), achieved sterile protection but require a series of intravenous doses administered in multiple clinic visits. Moreover, these WO vaccines must be produced in mosquitos, a burdensome process that severely limits their availability. To reduce reliance on WO while maintaining protection via both antibodies and Trm responses, we have developed an accelerated vaccination regimen that combines two distinct agents in a prime-and-trap strategy. The priming dose is a single dose of self-replicating RNA encoding the full-length P. yoelii CS protein, delivered via an advanced cationic nanocarrier (LIONTM). The trapping dose consists of one dose of WO RAS. Our vaccine induces a strong immune response when administered in an accelerated regimen, i.e., either 5-day or same-day immunization. Additionally, mice after same-day immunization showed a 2-day delay of blood patency with 90% sterile protection against a 3-week spz challenge. The same-day regimen also induced durable 70% sterile protection against a 2-month spz challenge. Our approach presents a clear path to late-stage preclinical and clinical testing of dose-sparing, same-day regimens that can confer sterilizing protection against malaria.
Encoding a magic state with beyond break-even fidelity
Authors: Gupta Riddhi S. , Sundaresan Neereja , Alexander Thomas , Wood Christopher J. , Merkel Seth T. , Healy Michael B. , Hillenbrand Marius , Jochym-O’Connor Tomas , Wootton James R. , Yoder Theodore J. , Cross Andrew W. , Takita Maika , Brown Benjamin J.
Published: January 2024

To run large-scale algorithms on a quantum computer, error-correcting codes must be able to perform a fundamental set of operations, called logic gates, while isolating the encoded information from noise1–8. We can complete a universal set of logic gates by producing special resources called magic states9–11. It is therefore important to produce high-fidelity magic states to conduct algorithms while introducing a minimal amount of noise to the computation. Here we propose and implement a scheme to prepare a magic state on a superconducting qubit array using error correction. We find that our scheme produces better magic states than those that can be prepared using the individual qubits of the device. This demonstrates a fundamental principle of fault-tolerant quantum computing12, namely, that we can use error correction to improve the quality of logic gates with noisy qubits. Moreover, we show that the yield of magic states can be increased using adaptive circuits, in which the circuit elements are changed depending on the outcome of mid-circuit measurements. This demonstrates an essential capability needed for many error-correction subroutines. We believe that our prototype will be invaluable in the future as it can reduce the number of physical qubits needed to produce high-fidelity magic states in large-scale quantum-computing architectures.
A lethal mitonuclear incompatibility in complex I of natural hybrids
Authors: Moran Benjamin M. , Payne Cheyenne Y. , Powell Daniel L. , Iverson Erik N. K. , Donny Alexandra E. , Banerjee Shreya M. , Langdon Quinn K. , Gunn Theresa R. , Rodriguez-Soto Rebecca A. , Madero Angel , Baczenas John J. , Kleczko Korbin M. , Liu Fang , Matney Rowan , Singhal Kratika , Leib Ryan D. , Hernandez-Perez Osvaldo , Corbett-Detig Russell , Frydman Judith , Gifford Casey , Schartl Manfred , Havird Justin C. , Schumer Molly
Published: January 2024

The evolution of reproductive barriers is the first step in the formation of new species and can help us understand the diversification of life on Earth. These reproductive barriers often take the form of hybrid incompatibilities, in which alleles derived from two different species no longer interact properly in hybrids1–3. Theory predicts that hybrid incompatibilities may be more likely to arise at rapidly evolving genes4–6 and that incompatibilities involving multiple genes should be common7,8, but there has been sparse empirical data to evaluate these predictions. Here we describe a mitonuclear incompatibility involving three genes whose protein products are in physical contact within respiratory complex I of naturally hybridizing swordtail fish species. Individuals homozygous for mismatched protein combinations do not complete embryonic development or die as juveniles, whereas those heterozygous for the incompatibility have reduced complex I function and unbalanced representation of parental alleles in the mitochondrial proteome. We find that the effects of different genetic interactions on survival are non-additive, highlighting subtle complexity in the genetic architecture of hybrid incompatibilities. Finally, we document the evolutionary history of the genes involved, showing signals of accelerated evolution and evidence that an incompatibility has been transferred between species via hybridization.
Nasopharyngeal lymphatic plexus is a hub for cerebrospinal fluid drainage
Authors: Yoon Jin-Hui , Jin Hokyung , Kim Hae Jin , Hong Seon Pyo , Yang Myung Jin , Ahn Ji Hoon , Kim Young-Chan , Seo Jincheol , Lee Yongjeon , McDonald Donald M. , Davis Michael J. , Koh Gou Young
Published: January 2024

Cerebrospinal fluid (CSF) in the subarachnoid space around the brain has long been known to drain through the lymphatics to cervical lymph nodes1–17, but the connections and regulation have been challenging to identify. Here, using fluorescent CSF tracers in Prox1-GFP lymphatic reporter mice18, we found that the nasopharyngeal lymphatic plexus is a major hub for CSF outflow to deep cervical lymph nodes. This plexus had unusual valves and short lymphangions but no smooth-muscle coverage, whereas downstream deep cervical lymphatics had typical semilunar valves, long lymphangions and smooth muscle coverage that transported CSF to the deep cervical lymph nodes. α-Adrenergic and nitric oxide signalling in the smooth muscle cells regulated CSF drainage through the transport properties of deep cervical lymphatics. During ageing, the nasopharyngeal lymphatic plexus atrophied, but deep cervical lymphatics were not similarly altered, and CSF outflow could still be increased by adrenergic or nitric oxide signalling. Single-cell analysis of gene expression in lymphatic endothelial cells of the nasopharyngeal plexus of aged mice revealed increased type I interferon signalling and other inflammatory cytokines. The importance of evidence for the nasopharyngeal lymphatic plexus functioning as a CSF outflow hub is highlighted by its regression during ageing. Yet, the ageing-resistant pharmacological activation of deep cervical lymphatic transport towards lymph nodes can still increase CSF outflow, offering an approach for augmenting CSF clearance in age-related neurological conditions in which greater efflux would be beneficial.
Capturing the generation and structural transformations of molecular ions
Authors: Heo Jun , Kim Doyeong , Segalina Alekos , Ki Hosung , Ahn Doo-Sik , Lee Seonggon , Kim Jungmin , Cha Yongjun , Lee Kyung Won , Yang Jie , Nunes J. Pedro F. , Wang Xijie , Ihee Hyotcherl
Published: January 2024

Molecular ions are ubiquitous and play pivotal roles1–3 in many reactions, particularly in the context of atmospheric and interstellar chemistry4–6. However, their structures and conformational transitions7,8, particularly in the gas phase, are less explored than those of neutral molecules owing to experimental difficulties. A case in point is the halonium ions9–11, whose highly reactive nature and ring strain make them short-lived intermediates that are readily attacked even by weak nucleophiles and thus challenging to isolate or capture before they undergo further reaction. Here we show that mega-electronvolt ultrafast electron diffraction (MeV-UED)12–14, used in conjunction with resonance-enhanced multiphoton ionization, can monitor the formation of 1,3-dibromopropane (DBP) cations and their subsequent structural dynamics forming a halonium ion. We find that the DBP+ cation remains for a substantial duration of 3.6 ps in aptly named ‘dark states’ that are structurally indistinguishable from the DBP electronic ground state. The structural data, supported by surface-hopping simulations15 and ab initio calculations16, reveal that the cation subsequently decays to iso-DBP+, an unusual intermediate with a four-membered ring containing a loosely bound17,18 bromine atom, and eventually loses the bromine atom and forms a bromonium ion with a three-membered-ring structure19. We anticipate that the approach used here can also be applied to examine the structural dynamics of other molecular ions and thereby deepen our understanding of ion chemistry.
Public platform with 39,472 exome control samples enables association studies without genotype sharing
Authors: Artomov Mykyta , Loboda Alexander A. , Artyomov Maxim N. , Daly Mark J.
Published: January 2024

Acquiring a sufficiently powered cohort of control samples matched to a case sample can be time-consuming or, in some cases, impossible. Accordingly, an ability to leverage genetic data from control samples that were already collected elsewhere could dramatically improve power in genetic association studies. Sharing of control samples can pose significant challenges, since most human genetic data are subject to strict sharing regulations. Here, using the properties of singular value decomposition and subsampling algorithm, we developed a method allowing selection of the best-matching controls in an external pool of samples compliant with personal data protection and eliminating the need for genotype sharing. We provide access to a library of 39,472 exome sequencing controls at http://dnascore.net enabling association studies for case cohorts lacking control subjects. Using this approach, control sets can be selected from this online library with a prespecified matching accuracy, ensuring well-calibrated association analysis for both rare and common variants.
Curated mode-of-action data and effect concentrations for chemicals relevant for the aquatic environment
Authors: Kramer Lena , Schulze Tobias , Klüver Nils , Altenburger Rolf , Hackermüller Jörg , Krauss Martin , Busch Wibke
Published: January 2024

Chemicals in the aquatic environment can be harmful to organisms and ecosystems. Knowledge on effect concentrations as well as on mechanisms and modes of interaction with biological molecules and signaling pathways is necessary to perform chemical risk assessment and identify toxic compounds. To this end, we developed criteria and a pipeline for harvesting and summarizing effect concentrations from the US ECOTOX database for the three aquatic species groups algae, crustaceans, and fish and researched the modes of action of more than 3,300 environmentally relevant chemicals in literature and databases. We provide a curated dataset ready to be used for risk assessment based on monitoring data and the first comprehensive collection and categorization of modes of action of environmental chemicals. Authorities, regulators, and scientists can use this data for the grouping of chemicals, the establishment of meaningful assessment groups, and the development of in vitro and in silico approaches for chemical testing and assessment.