bluuebunny/crossref_metadata_2025 huggingface dataset:
Cytokeratin 17 expression is commonly observed in keratinocytic skin tumours and controls tissue homeostasis impacting human papillomavirus protein expression
Authors: Hasche Daniel , Hufbauer Martin , Braspenning-Wesch Ilona , Stephan Sonja , Silling Steffi , Schmidt Gabriele , Krieg Stephan , Kreuter Alexander , Akgül Baki
Published: June 2024

Background

The structured expression of several keratins in the skin is associated with differentiation status of the epidermal layers, whereas other keratins are upregulated only during wound healing, in skin disorders and in cancers. One of these stress keratins, K17, is correlated with poor prognosis in various cancer types and its loss has been shown to decelerate tumour growth. K17 expression can also be detected in cutaneous squamous cell carcinomas, where ultraviolet irradiation and infection with cutaneous human papillomaviruses are important cofactors. It was previously reported that K17 is upregulated in papillomavirus (PV)-induced benign skin lesions in mice and induces an immunological status that is beneficial for tumour growth.

Objectives

In order to investigate whether K17 upregulation is induced by PVs, we analysed K17 levels in skin tumour specimens of different animal models and humans.

Methods

Various immunofluorescence stainings were performed to identify K17 expression as well as levels of E-cadherin, vimentin and CD271. Tissues were further analysed by polymerase chain reaction (PCR), quantitative (q)PCR and enzyme-linked immunosorbent assay to control for PV activity. K17 knockdown cells were generated and effects on viral life cycle were investigated by infection assays, qPCR and Western blotting.

Results

We showed that K17 is commonly expressed in skin tumours and that its presence is not directly linked to viral oncoprotein expression. Rather, K17 expression seems to be a marker of epithelial differentiation and its absence in tumour tissue is associated with an epithelial-to-mesenchymal transition. We further demonstrated that the absence of K17 in skin tumours increases markers of cancer stem-like cells and negatively affects viral protein synthesis.

Conclusions

Collectively, our data indicate that K17 expression is a common feature in skin tumorigenesis. While K17 is not primarily targeted by PV oncoproteins, our in vivo and in vitro data suggest that it is an important regulator of epithelial differentiation and thus may play a role in controlling viral protein synthesis.
Intrarenal pressure with hand-pump or pressurized-bag irrigation: randomized clinical trial at retrograde intrarenal surgery
Authors: Croghan Stefanie M , O’Meara Sorcha , Cunnane Eoghan M , Purtill Helen , Walsh Michael T , O’Brien Fergal J , Manecksha Rustom P , McGuire Barry B , Breen Kieran J , Davis Niall F
Published: June 2024

Background

The aim was to ascertain the impact of irrigation technique on human intrarenal pressure during retrograde intrarenal surgery.

Methods

A parallel randomized trial recruited patients across three hospital sites. Patients undergoing retrograde intrarenal surgery for renal stone treatment with an 11/13-Fr ureteral access sheath were allocated randomly to 100 mmHg pressurized-bag (PB) or manual hand-pump (HP) irrigation. The primary outcome was mean procedural intrarenal pressure. Secondary outcomes included maximum intrarenal pressure, variance, visualization, HP force of usage, procedure duration, stone clearance, and clinical outcomes. Live intrarenal pressure monitoring was performed using a COMETTMII pressure guidewire, deployed cystoscopically to the renal pelvis. The operating team was blinded to the intrarenal pressure.

Results

Thirty-eight patients were randomized between July and November 2023 (trial closure). The final analysis included 34 patients (PB 16; HP 18). Compared with PB irrigation, HP irrigation resulted in significantly higher mean intrarenal pressure (mean(s.d.) 62.29(27.45) versus 38.16(16.84) mmHg; 95% c.i. for difference in means (MD) 7.97 to 40.29 mmHg; P = 0.005) and maximum intrarenal pressure (192.71(106.23) versus 68.04(24.16) mmHg; 95% c.i. for MD 70.76 to 178.59 mmHg; P < 0.001), along with greater variance in intrarenal pressure (log transformed) (6.23(1.59) versus 4.60(1.30); 95% c.i. for MD 0.62 to 2.66; P = 0.001). Surgeon satisfaction with procedural vision reported on a scale of 10 was higher with PB compared with HP irrigation (mean(s.d.) 8.75(0.58) versus 6.28(1.27); 95% c.i. for MD 1.79 to 3.16; P < 0.001). Subjective HP usage force did not correlate significantly with transmitted intrarenal pressure (Pearson R = −0.15, P = 0.57). One patient (HP arm) developed urosepsis.

Conclusion

Manual HP irrigation resulted in higher and more fluctuant intrarenal pressure trace (with inferior visual clarity) than 100-mmHg PB irrigation.

Registration number

osf.io/jmg2h (https://osf.io/).
Effect of vitamin E δ-tocotrienol and aspirin on Wnt signaling in human colon cancer stem cells and in adenoma development in APCmin/+ mice
Authors: Husain Kazim , Coppola Domenico , Yang Chung S , Malafa Mokenge P
Published: June 2024

In this study, we evaluated the effects of vitamin E δ-tocotrienol (DT3) and aspirin on Wnt signaling in human colon cancer stem cells (CCSCs) and in the prevention of adenoma formation in APCmin/+ mice. We found that knockdown of the adenomatous polyposis coli (APC) gene led to subsequent activation of Wnt signaling in colon epithelial cells (NCM460-APCsiRNA) and induction of β-catenin and its downstream target proteins c-MYC, cyclin D1, and survivin. When aspirin and DT3 were combined, cell growth and survival were inhibited and apoptosis was induced in colon epithelial cells and CCSCs. However, DT3 and/or aspirin had little or no effect on the control of normal colon epithelial cells (NCM460-NCsiRNA). The induction of apoptosis was directly related to the activation of caspase 8 and cleavage of BH3-interacting-domain (BID) to truncated BID. In addition, DT3- and/or aspirin-induced apoptosis was associated with cleaved Poly (ADP-ribose) polymerase (PARP), elevated levels of cytosolic cytochrome c and BAX, and depletion of antiapoptotic protein BCl-2 in CCSCs. The combination of aspirin and DT3 inhibited the self-renewal capacity, Wnt/β-catenin receptor activity, and expression of β-catenin and its downstream targets c-MYC, cyclin D1, and survivin in CCSCs. We also found that treatment with DT3 alone or combined with aspirin significantly inhibited intestinal adenoma formation and Wnt/β-catenin signaling and induced apoptosis, compared with vehicle, in APCmin/+ mice. Our study demonstrated a rationale for further investigation of the combination of DT3 and aspirin for colorectal cancer prevention and therapy.
Variability of morphology–performance relationships under acute exposure to different temperatures in 3 strains of zebrafish
Authors: Miller Christina L , Dugand Robert , McGuigan Katrina
Published: June 2024

Locomotion is thermally sensitive in ectotherms and therefore it is typically expressed differently among thermally heterogenous environments. Locomotion is a complex function, and whereas physiological and behavioral traits that influence locomotor performance may respond to thermal variation throughout life, other contributing traits, like body shape, may have more restricted responses. How morphology affects locomotor performance under variable temperature conditions is unknown. Here, we investigated 3 genetically distinct strains of zebrafish, Danio rerio (AB, WIK, and Tu) with a shared multi-generational history at 28 °C. After rearing fish at 28 °C, we measured prolonged swimming speed (Ucrit) at each of 6 temperatures (between 16 °C and 34 °C). Speed was strongly positively correlated among temperatures, resulting in most among individual variation being temperature-independent (i.e., fish were relatively fast or slow across all temperatures). However, we also detected significant variation along 2 axes reflecting temperature-dependent variation. Although strains differed in mean swimming performance, within strain (among-individual) patterns of speed variation were markedly consistent. Body shape and size explained significant variation among individuals in both temperature-independent and temperature-dependent axes of swimming speed variation. Notably, morphological traits that were most strongly associated with temperature-independent performance variation (i.e., faster–slower) differed from those associated with temperature-dependent (i.e., hotter–colder) variation. Further, there were significant differences among strains in both the direction and strength of association for specific morphological traits. Our results suggest that thermally heterogenous environments could have complex effects on the evolution of traits that contribute to whole organism performance traits.
Disentangling the value equation: a step forward in value-based healthcare
Authors: García-Lorenzo Borja , Alayo Itxaso , Arrospide Arantzazu , Gorostiza Ania , Fullaondo Ane ,   VOICE Study Group, Zas Susana Castelo , Baena Patricia Cobos , Camiña Inés Gallego , Narbaiza Begoña Izaguirre , Mallabiabarrena Gaizka , Ustarroz-Aguirre Iker , Rigabert Alina , Balzi William , Maltoni Roberta , Massa Ilaria , López Isabel Álvarez , Lobera Sara Arévalo , Esteban Mónica , Calleja Marta Fernández , Mediavilla Jenifer Gómez , Fernández Manuela , del Oro Hitar Manuel , del Carmen Ortega Torres María , Ferrandez María Consuelo Sanz , Sánchez Luís Manso , Balazote Pablo Serrano , Rodríguez Carolina Varela , Campone Mario , Lann Sophie Le , Vercauter Piet , Tournoy Kurt , Borges Marina , Oliveira Ana Sofía , Soares Marta , Lerma Iratxe Vázquez , Irazabal Izaskun Artola , de Larrinoa Santamaría Aitor Fernandez , Capanaga Andere Frias , Elorduy Eduardo Vicario , Acaiturri-Ayesta Teresa , Gómez-Inhiesto Elisa , Danesi Valentina , Gentili Nicola , Roncadori Andrea , Alarz Fátima Hermoso , Iraola Karmele Imaz , Adam Valerie , De Rijck Helene , Everaert Ellen , Barreira Esmeralda , Medeiros Pedro , Barros Emanuel
Published: June 2024

Background

The value equation of value-based healthcare (VBHC) as a single figure remains ambiguous, closer to a theoretical framework than a useful tool for decision making. The challenge lies in the way patient-centred outcomes (PCOs) might be combined to produce a single value of the numerator. This paper aims to estimate the weights of PCOs to provide a single figure in the numerator, which ultimately will allow a VBHC figure to be reached.

Methods

A cohort of patients diagnosed with breast cancer (n = 690) with a 6-month follow-up recruited in 2019–20 across six European hospitals was used. Patient-reported outcomes (PROs), clinical-related outcomes (CROs), and clinical and socio-demographic variables were collected. The numerator was defined as a composite indicator of the PCOs (CI-PCO), and regression analysis was applied to estimate their weights and consequently arrive at a single figure.

Results

Pain showed as the highest weight followed by physical functioning, emotional functioning, and ability to work, and then by a symptom, either arm or breast. PCOs weights were robust to sensitivity analysis. The CI-PCO value was found to be more informative than the health-related quality of life (HRQoL) value.

Conclusions

To the best of our knowledge, this is the first research to combine the PCOs proposed by ICHOM to provide a single figure in the numerator of the value equation. This figure shows a step forward in VBHC to reach a holistic benchmarking across healthcare centres and a value-based payment. This research might also be applied in other medical conditions as a methodological pathway.
Prevalence of Cefixime-Resistant Neisseria gonorrhoeae in Melbourne, Australia, 2021–2022
Authors: Chow Eric P F , Stevens Kerrie , De Petra Vesna , Chen Marcus Y , Bradshaw Catriona S , Sherry Norelle L , Barbee Lindley A , Vodstrcil Lenka A , Aguirre Ivette , Seib Kate L , Maddaford Kate , Williamson Deborah A , Howden Benjamin P , Fairley Christopher K
Published: June 2024

While ceftriaxone remains the first-line treatment for gonorrhea, the US Centers for Disease Control and Prevention recommended cefixime as a second-line treatment in 2021. We tested 1176 Neisseria gonorrhoeae isolates among clients attending the Melbourne Sexual Health Centre in 2021 and 2022. The prevalence of cefixime resistance was 6.3% (74/1176), azithromycin resistance was 4.9% (58/1176), and ceftriaxone resistance was 0% (0/1176). Cefixime resistance was highest among women (16.4%, 10/61), followed by men who have sex with women (6.4%, 7/109) and men who have sex with men (5.8%, 57/982). The prevalence of cefixime-resistant N gonorrhoeae exceeds the threshold of the 5% resistance level recommended by the World Health Organization; thus, cefixime treatment would have limited benefits in Australia.
Four-bar Geometry is Shared among Ecologically DivergentFish Species
Authors: Camarillo H , Burress E D , Muñoz M M
Published: June 2024

Synopsis

Understanding the factors that influence morphological evolution is a major goal in biology. One such factor is the ability to acquire and process prey. Prey hardness and evasiveness are important properties that can impact evolution of the jaws. Similar diets and biomechanical systems have repeatedly evolved among fish lineages, providing an opportunity to test for shared patterns of evolution across distantly related organisms. Four-bar linkages are structures often used by animals to transmit force and motion during feeding and that provide an excellent system to understand the impact of diet on morphological and biomechanical evolution. Here, we tested how diet influences the evolutionary dynamics of the oral four-bar linkage system in wrasses (Family: Labridae) and cichlids (Family: Cichlidae). We found that shifts in prey hardness/evasiveness are associated with limited modifications in four-bar geometry across these two distantly related fish lineages. Wrasse and cichlid four-bar systems largely exhibit many-to-one mapping in response to dietary shifts. Across two iconic adaptive radiations of fish, an optimal four-bar geometry has largely been co-opted for different dietary functions during their extensive ecological diversification. Given the exceptional jaw diversity of both lineages, many-to-one mapping of morphology to mechanical properties may be a core feature of fish adaptive radiation.
Digital Therapy for Negative Consumption Experiences: The Impact of Emotional and Rational Reviews on Review Writers
Authors: Wu Alisa Yinghao , Morwitz Vicki G
Published: June 2024

This research tests a solution for consumers to recover faster from negative experiences. We identify this solution by examining how the manner in which review writers express their emotions and rational thoughts in their reviews causally influences review writers. The results of five studies (field data and experiments) show that, similar to writing about traumatic life events, when review writers express both emotional and rational aspects in reviews about negative consumption experiences, they feel better afterwards (i.e., they recover affectively), and are more likely to purchase again (i.e., they recover cognitively). We further examine why writing integrated reviews has positive effects on review writers by collecting biophysiological response data, which provide support for an account related to affective recovery, and by analyzing thought listing data, which provide support for an account related to cognitive recovery. This research shows that writing online reviews can serve as a digital therapy tool that helps consumers recover from negative experiences.
The role of grit in thinking styles and academic major satisfaction
Authors: Cheng Sanyin , Deng Li , Li Jiaqi
Published: June 2024

Satisfaction with one’s academic major is critical to a university student’s development. This study explores the interrelationships among thinking styles, grit, and academic major satisfaction in both deaf or hard-of-hearing (DHH) and hearing students, employing independent samples t-tests to compare the two groups, Pearson’s correlation analysis to explore relationships among the variables, and mediation analysis to understand the mediating effect of grit on the relationship between thinking styles and academic major satisfaction. The results indicated significantly higher levels of grit and consistency of interest in DHH students than hearing students, with no significant differences in perseverance of effort. A strong correlation was found between thinking styles and both grit and academic major satisfaction, particularly in DHH students. Mediation analysis revealed that grit significantly mediated the relationship between thinking styles and academic major satisfaction, underscoring its role in enhancing students’ academic experience. These findings contribute to the limited literature on DHH students’ psychological attributes and the complex interplay of psychological constructs in academic major satisfaction, offering valuable insights for tailored educational strategies.
Higher prevalence of sacbrood virus in Apis mellifera (Hymenoptera: Apidae) colonies after pollinating highbush blueberries
Authors: McAfee Alison , French Sarah K , Wizenberg Sydney B , Newburn Laura R , Tsvetkov Nadejda , Higo Heather , Common Julia , Pernal Stephen F , Giovenazzo Pierre , Hoover Shelley E , Guzman-Novoa Ernesto , Currie Robert W , Veiga Patricia Wolf , Conflitti Ida M , Pepinelli Mateus , Tran Lan , Zayed Amro , Guarna M Marta , Foster Leonard J
Published: June 2024

Highbush blueberry pollination depends on managed honey bees (Apis mellifera L.) for adequate fruit sets; however, beekeepers have raised concerns about the poor health of colonies after pollinating this crop. Postulated causes include agrochemical exposure, nutritional deficits, and interactions with parasites and pathogens, particularly Melisococcus plutonius [(ex. White) Bailey and Collins, Lactobacillales: Enterococcaceae], the causal agent of European foulbrood disease, but other pathogens could be involved. To broadly investigate common honey bee pathogens in relation to blueberry pollination, we sampled adult honey bees from colonies at time points corresponding to before (t1), during (t2), at the end (t3), and after (t4) highbush blueberry pollination in British Columbia, Canada, across 2 years (2020 and 2021). Nine viruses, as well as M. plutonius, Vairimorpha ceranae, and V. apis [Tokarev et al., Microsporidia: Nosematidae; formerly Nosema ceranae (Fries et al.) and N. apis (Zander)], were detected by PCR and compared among colonies located near and far from blueberry fields. We found a significant interactive effect of time and blueberry proximity on the multivariate pathogen community, mainly due to differences at t4 (corresponding to ~6 wk after the beginning of the pollination period). Post hoc comparisons of pathogens in near and far groups at t4 showed that detections of sacbrood virus (SBV), which was significantly higher in the near group, not M. plutonius, was the primary driver. Further research is needed to determine if the association of SBV with highbush blueberry pollination is contributing to the health decline that beekeepers observe after pollinating this crop.
The devil is in the divisional: an analysis of divisional patents, deadlines, declarations and suggestions for future practice
Authors: Filler Mieke
Published: June 2024

This article argues that divisional patent applications and litigation are strategically employed in the pharmaceutical sector to delay generic and biosimilar market entry. These practices are given a legitimate basis in the European Patent Convention and the Patents Act 1977, but recent UK case law shows that their misuse results in deliberate obfuscation of existing safeguards. Nonetheless, patent law should not be passive. The reintroduction of the divisional filing time limit coupled with shorter compliance periods would offer practical administrative steps for shortening the time frame within which divisionals can be filed. Moreover, further clarity surrounding the implementation of the double patenting prohibition would reduce the number of substantially similar divisional patents that are successfully obtained. This article also discusses Arrow declarations at length, before concluding with a brief analysis of the suitability of the abuse of process doctrine for dealing with divisional misuse.
Separated, united or a bit of both? Infringement and validity at the Unified Patent Court
Authors: Kessler Nora , Palzer Christoph
Published: June 2024

The so-called separation principle, according to which claims for infringement and the validity of a patent are assigned to different specialized courts, is a peculiarity of the German patent system, albeit not unique to it. Much more widespread across Europe is the so-called principle of unity, which provides infringement and validity to be decided jointly at the same court. The drafters of the Agreement on a Unified Patent Court (UPCA), however, did not favour one principle over the other, and thus did not opt for a bifurcated or a non-bifurcated system; rather they decided in favour of a hybrid system. Against this background, at the Unified Patent Court (UPC), the interplay of infringement and validity is rather complex. What this looks like exactly is the focus of this article, which also keeps an eye on the legal situation in Germany.
Intellectual property norms in the polycrisis—(still) omnipresent, distracting, irrelevant?
Authors: Ncube Caroline B
Published: June 2024

Twenty years since Professor Cornish asked whether IP is ‘omnipresent, distracting, irrelevant?’, this article revisits that question following recent times of instability, which have compounded the polycrisis the world is facing, whilst the 2030 deadline to achieve the UN Sustainable Development Goals looms closer and closer. This contribution argues that IP plays a critical role as one of multiple regulatory systems seeking solutions in the highly dynamic and insecure contexts of the climate emergency, uneven global development and pandemics, requiring timely and comprehensive normative development. However, over the last two decades there has been a glacial pace towards setting appropriate IP norms and states, policymakers and legislatures have to move beyond merely settling for a ‘more of the same’ approach. The ongoing World Health Organization’s Pandemic Accord negotiations present an opportunity to confirm IP’s relevance to combatting the polycrisis by setting effective norms and a technology transfer mechanism. It is concluded that missing this opportunity would render debates about IP no more than a deadly distraction.
Correlation adjusted debiased Lasso: debiasing the Lasso with inaccurate covariate model
Authors: Celentano Michael , Montanari Andrea
Published: June 2024

We consider the problem of estimating a low-dimensional parameter in high-dimensional linear regression. Constructing an approximately unbiased estimate of the parameter of interest is a crucial step towards performing statistical inference. Several authors suggest to orthogonalize both the variable of interest and the outcome with respect to the nuisance variables, and then regress the residual outcome with respect to the residual variable. This is possible if the covariance structure of the regressors is perfectly known, or is sufficiently structured that it can be estimated accurately from data (e.g. the precision matrix is sufficiently sparse). Here we consider a regime in which the covariate model can only be estimated inaccurately, and hence existing debiasing approaches are not guaranteed to work. We propose the correlation adjusted debiased Lasso, which nearly eliminates this bias in some cases, including cases in which the estimation errors are neither negligible nor orthogonal.
Lessons Learned From a Large-Scale Military Mass Casualty Incident: Reevaluation of the Response to the Khobar Towers Bombing
Authors: Obiajulu Joseph , DeSoucy Erik , Robb Douglas , Atkins Michael , Rush Stephen
Published: June 2024

The 1996 Khobar Towers bombing, a large-scale mass casualty incident (MASCAL) at a coalition forces housing complex, resulted in 519 casualties. Key lessons learned include the importance of MASCAL exercises, self-aid and buddy care, and casualty triage, all critical to preparation for future terrorist attacks or near-peer combat operations MASCALs.
Effects of feedback-free starburst galaxies on the 21-cm signal and reionization history
Authors: Libanore Sarah , Flitter Jordan , Kovetz Ely D , Li Zhaozhou , Dekel Avishai
Published: June 2024

Different star formation models at Cosmic Dawn produce detectable signatures in the observables of upcoming 21-cm experiments. In this work, we consider the physical scenario of feedback-free starbursts (FFB), according to which the star formation efficiency (SFE) is enhanced in sufficiently massive haloes at early enough times, thus explaining the indication from the JWST for an excess of bright galaxies at $z \ge 10$. We model the contribution of FFBs to popII SFE and compute the impact these have on the 21-cm global signal and power spectrum. We show that FFBs affect the evolution of the brightness temperature and the 21-cm power spectrum, but they only have a limited effect on the neutral hydrogen fraction. We investigate how the observables are affected by changes in the underlying star formation model and by contribution from popIII stars. Finally, we forecast the capability of next-generation Hydrogen Epoch of Reionization Array (HERA) to detect the existence of FFB galaxies via power spectrum measurements. Our results show the possibility of a significant detection, provided that popII stars are the main drivers of lowering the spin temperature. Efficient popIII star formation will make the detection more challenging.
Companion-launched jets at varying companion masses
Authors: Shiber Sagiv , Iaconi Roberto
Published: June 2024

We conduct three-dimensional hydrodynamic simulations, and show that when a secondary star launches jets while interacting with a primary $0.88~\mathrm{ M}_{\rm \odot }$ giant star in a close orbit, the system can avoid entering the common envelope evolution (CEE). Instead of a fast in-spiral, the companion slowly enters the envelope as the jets facilitate the unbinding of the giant star envelope outside the companion orbit, in what is termed the grazing envelope evolution (GEE). The assumptions are that the secondary main-sequence star accretes mass via an accretion disc, and that the accretion disc launches the jets. We perform two sets of simulations with and without jets for different companion masses at the range of 0.1–0.9 M$_{\odot }$, maintaining a constant jet power in the former case of $1.5\times 10^{38}~{\rm ergs~s^{-1}}$. We examine which of the simulated systems undergo a GEE rather than a CEE and how efficiently the jets unbind the envelope. The results indicate that systems with companion masses at the range of 0.1–0.3 M$_{\odot }$ are more likely to result in a phase of GEE lasting 1–3 yr. With the smallest companion, a 0.1 solar mass star, the jets unbind 65 per cent of the envelope mass, while almost none of the envelope is unbound if jets are not present. The results of the simulations show that the GEE can serve as an alternative to the CEE, in forming short-period binaries that have compact objects and an ejected envelope.
Psychedelics and disorders of consciousness: the current landscape and the path forward
Authors: Cardone Paolo , Alnagger Naji , Annen Jitka , Bicego Aminata , Gosseries Olivia , Martial Charlotte
Published: June 2024

Modern medicine has been shaken by the surge of psychedelic science that proposes a new approach to mitigate mental disorders, such as depression and post-traumatic stress disorder. Clinical trials to investigate whether psychedelic substances can treat psychiatric conditions are now underway, yet less discussion gravitates around their use in neurological disorders due to brain injury. One suggested implementation of brain-complexity enhancing psychedelics is to treat people with post-comatose disorders of consciousness (DoC). In this article, we discuss the rationale of this endeavour, examining possible outcomes of such experiments by postulating the existence of an optimal level of complexity. We consider the possible counterintuitive effects of both psychedelics and DoC on the functional connectivity of the default mode network and its possible impact on selfhood. We also elaborate on the role of computational modelling in providing complementary information to experimental studies, both contributing to our understanding of the treatment mechanisms and providing a path towards personalized medicine. Finally, we update the discourse surrounding the ethical considerations, encompassing clinical and scientific values.
Discovery of natural few-layer graphene on the Moon
Authors: Zhang Wei , Liang Qing , Li Xiujuan , Ma Lai-Peng , Li Xinyang , Zhao Zhenzhen , Zhang Rui , Cao Hongtao , Wang Zizhun , Li Wenwen , Wang Yanni , Liu Meiqi , Yue Nailin , Liu Hongyan , Hu Zhenyu , Liu Li , Zhou Qiang , Li Fangfei , Zheng Weitao , Ren Wencai , Zou Meng
Published: June 2024

Natural few-layer graphene is unambiguously identified from the Chang'e-5 lunar soil samples, which serves as a new platform for investigating extraterrestrial bodies.
Risks of occupational mental disorders in Korean civil servants (2009–18)
Authors: Choi B-Y , Min K-B , Ryoo S-W , Min J-Y
Published: June 2024

Background

Previous studies have suggested that firefighters, police officers and civil servants in the education sector, particularly in Western countries, are vulnerable to mental stress and disorders; however, evidence for this association in South Korea is lacking.

Aims

This study aimed to identify whether firefighters, police officers and teachers are at a higher risk for occupational mental health disorders.

Methods

We used workers’ compensation claims from civil servants (2009–18). Our target population comprised 46 209 civil servants (9009 civil servants in administrative and technical positions, 23 107 police officers, 4417 firefighters and 8676 civil servants in the educational sector). Occupational and environmental medicine physicians and medical doctors defined and confirmed mental disorders. We conducted Cox proportional hazards regression analyses to evaluate civil servants’ risk of occupational mental health disorders.

Results

Compared with the civil servants in administrative and technical positions, civil servants in the education sector (hazard ratio [HR] = 2.16; 95% confidence interval [CI]:1.65–2.84) showed a statistically significant increased risk of mental disorders; conversely, firefighters did not (HR = 0.80; 95% CI 0.51–1.27). Police officers had a significantly decreased mental disorder risk compared with civil servants in administrative and technical positions (HR = 0.17; 95% CI 0.11–0.25).

Conclusions

The risk of occupational mental health disorders was higher in civil servants in the education sector but lower in police officers and firefighters than civil servants in administrative and technical positions. Further studies on civil servants’ mental health awareness are required to confirm our results.
Long-acting HIV Treatments: Study Design, Logistics, and Access
Authors: Murdock Nicholas A , Alajaji Nayri E , Schaefer Robin , Boone Cheriko A , Campo Rafael E , Dore Gregory J , Gandhi Monica , Gorospe J Rafael , Gulick Roy M , Hodder Sally L , Liu Jonathan , Rhee Martin S , Rooney James F , Vannappagari Vani , Wilkin Timothy , Miller Veronica
Published: June 2024

New long-acting HIV treatment products have the potential to change the HIV epidemic in the United States and globally. Phase 3 clinical trials of HIV treatments tend to underrepresent populations bearing a disproportionate burden of the HIV epidemic—including women, racial minorities, trans and gender-diverse people, older adults, the unhoused, people who inject drugs, those in rural areas, individuals with mental illness, and other marginalized groups. These populations commonly face significant challenges in adhering to daily HIV treatment regimens. Conducting clinical trials of long-acting treatment targeting specific unmet medical needs of these populations can improve understanding of optimal care approaches, broaden the indication for use of long-acting products, and inform treatment guidelines, all of which can influence reimbursement and access policies. Innovative trial designs and programmatic implementation can improve inclusivity for long-acting therapy. This article summarizes discussions of a multistakeholder workshop on study designs for long-acting HIV treatments.
The emerging role of effector functions exerted by tissue-resident memory T cells
Authors: Iijima Norifumi
Published: June 2024

The magnitude of the effector functions of memory T cells determines the consequences of the protection against invading pathogens and tumor development or the pathogenesis of autoimmune and allergic diseases. Tissue-resident memory T cells (TRM cells) are unique T-cell populations that persist in tissues for long periods awaiting re-encounter with their cognate antigen. Although TRM cell reactivation primarily requires the presentation of cognate antigens, recent evidence has shown that, in addition to the conventional concept, TRM cells can be reactivated without the presentation of cognate antigens. Non-cognate TRM cell activation is triggered by cross-reactive antigens or by several combinations of cytokines, including interleukin (IL)-2, IL-7, IL-12, IL-15 and IL-18. The activation mode of TRM cells reinforces their cytotoxic activity and promotes the secretion of effector cytokines (such as interferon-gamma and tumor necrosis factor-alpha). This review highlights the key features of TRM cell maintenance and reactivation and discusses the importance of effector functions that TRM cells exert upon being presented with cognate and/or non-cognate antigens, as well as cytokines secreted by TRM and non-TRM cells within the tissue microenvironment.
Secret Weapon of Insects: The Oral Secretion Cocktail and Its Modulation of Host Immunity
Authors: Prajapati Vinod Kumar , Vijayan Vishakh , Vadassery Jyothilakshmi
Published: June 2024

Plants and insects have co-existed for almost 400 million years and their interactions can be beneficial or harmful, thus reflecting their intricate co-evolutionary dynamics. Many herbivorous arthropods cause tremendous crop loss, impacting the agro-economy worldwide. Plants possess an arsenal of chemical defenses that comprise diverse secondary metabolites that help protect against harmful herbivorous arthropods. In response, the strategies that herbivores use to cope with plant defenses can be behavioral, or molecular and/or biochemical of which salivary secretions are a key determinant. Insect salivary secretions/oral secretions (OSs) play a crucial role in plant immunity as they contain several biologically active elicitors and effector proteins that modulate plants’ defense responses. Using this oral secretion cocktail, insects overcome plant natural defenses to allow successful feeding. However, a lack of knowledge of the nature of the signals present in oral secretion cocktails has resulted in reduced mechanistic knowledge of their cellular perception. In this review, we discuss the latest knowledge on herbivore oral secretion derived elicitors and effectors and various mechanisms involved in plant defense modulation. Identification of novel herbivore-released molecules and their plant targets should pave the way for understanding the intricate strategies employed by both herbivorous arthropods and plants in their interactions.
Characterization of the Arabidopsis Mutant oligocellula6-D Reveals the Importance of Leaf Initiation in Determining the Final Leaf Size
Authors: Takeda Risa , Sato Shoki , Ui Takumi , Tsukaya Hirokazu , Horiguchi Gorou
Published: June 2024

The leaf is a determinate organ with a final size under genetic control. Numerous factors that regulate the final leaf size have been identified in Arabidopsis thaliana; although most of these factors play their roles during the growth of leaf primordia, much less is known about leaf initiation and its effects on the final leaf size. In this study, we characterized oligocellula6-D (oli6-D), a semidominant mutant of A. thaliana with smaller leaves than the wild type (WT) due to its reduced leaf cell numbers. A time-course analysis showed that oli6-D had approximately 50% fewer leaf cells even immediately after leaf initiation; this difference was maintained throughout leaf development. Next-generation sequencing showed that oli6-D had chromosomal duplications involving 2-kb and 3-Mb regions of chromosomes 2 and 4, respectively. Several duplicated genes examined had approximately 2-fold higher expression levels, and at least one gene acquired a new intron/exon structure due to a chromosome fusion event. oli6-D showed reduced auxin responses in leaf primordia, primary roots and embryos, as well as reduced apical dominance and partial auxin-resistant root growth. CRISPR-associated protein-9-mediated genome editing enabled the removal of a 3-Mb duplicated segment, the largest targeted deletion in plants thus far. As a result, oli6-D restored the WT leaf phenotypes, demonstrating that oli6-D is a gain-of-function mutant. Our results suggest a new regulatory point of leaf size determination that functions at a very early stage of leaf development and is negatively regulated by one or more genes located in the duplicated chromosomal segments.
Neutrino Phenomenology and keV Dark Matter in the Two-Higgs Doublet Model with A4 Symmetry
Authors: Vien V V
Published: June 2024

We propose a minimal extended seesaw scheme based on the discrete symmetry $A_4\times Z_4\times Z_2\times Z_8$, which can successfully address neutrino phenomenology and keV sterile neutrino dark matter. The lepton mass hierarchy is naturally achieved. Active neutrino mixing angles can reached the best-fit points with the predictive Dirac CP violation phase. The active–sterile mixing matrix elements are small enough to access the observed cosmological dark matter abundance constraint with keV sterile neutrino dark matter. The effective neutrino masses are predicted to be in the ranges of the recent experimental limits.
Plasma interferon-alpha protein levels during pregnancy are associated with lower birth weight in systemic lupus erythematosus
Authors: Stockfelt Marit , Torell Agnes , Gunnarsson Iva , Svenungsson Elisabet , Zickert Agneta , Sennström Maria Majcuk , Trysberg Estelle , Bengtsson Anders A , Jönsen Andreas , Strevens Helena , Sjöwall Christopher , Saleh Muna , Pihl Sofia , Leonard Dag , Rönnblom Lars , Akhter Tansim , Blennow Kaj , Zetterberg Henrik , Jacobsson Bo , Lundell Anna-Carin , Rudin Anna
Published: June 2024

Objectives

Adverse pregnancy outcomes are more common in women with SLE compared with healthy women, but we lack prognostic biomarkers. Plasma IFN-α protein levels are elevated in a subgroup of pregnant women with SLE, but whether this is associated with pregnancy outcomes is unknown. We investigated the relationship between IFN-α, adverse pregnancy outcomes and the presence of autoantibodies in SLE pregnancy.

Methods

We followed 76 women with SLE prospectively. Protein levels of IFN-α were quantified in plasma collected in the second and third trimester with single-molecule array. Positivity for ANA and aPL antibodies was assessed during late pregnancy with multiplexed bead assay. Clinical outcomes included the adverse pregnancy outcomes small for gestational age (SGA), preterm birth and preeclampsia.

Results

During SLE pregnancy, women with SGA infants compared with those without had higher levels of plasma IFN-α protein, and IFN-α positivity was associated with lower birth weight of the infant. Preterm birth was associated with autoantibodies against chromatin. IFN-α protein levels associated positively with autoantibodies against chromatin, Smith/RNP (SmRNP) and RNP, but negatively with aPL antibodies.

Conclusion

Elevated IFN-α protein in plasma of women with SLE is a potential risk factor for lower birth weight of their infants. The association between IFN-α and lower birth weight warrants further investigation regarding the pathophysiological role of IFN-α during SLE pregnancy.
Evo-devo applied to sleep research: an approach whose time has come
Authors: Brown Ritchie E
Published: June 2024

Sleep occurs in all animals but its amount, form, and timing vary considerably between species and between individuals. Currently, little is known about the basis for these differences, in part, because we lack a complete understanding of the brain circuitry controlling sleep–wake states and markers for the cell types which can identify similar circuits across phylogeny. Here, I explain the utility of an “Evo-devo” approach for comparative studies of sleep regulation and function as well as for sleep medicine. This approach focuses on the regulation of evolutionary ancient transcription factors which act as master controllers of cell-type specification. Studying these developmental transcription factor cascades can identify novel cell clusters which control sleep and wakefulness, reveal the mechanisms which control differences in sleep timing, amount, and expression, and identify the timepoint in evolution when different sleep–wake control neurons appeared. Spatial transcriptomic studies, which identify cell clusters based on transcription factor expression, will greatly aid this approach. Conserved developmental pathways regulate sleep in mice, Drosophila, and C. elegans. Members of the LIM Homeobox (Lhx) gene family control the specification of sleep and circadian neurons in the forebrain and hypothalamus. Increased Lhx9 activity may account for increased orexin/hypocretin neurons and reduced sleep in Mexican cavefish. Other transcription factor families specify sleep–wake circuits in the brainstem, hypothalamus, and basal forebrain. The expression of transcription factors allows the generation of specific cell types for transplantation approaches. Furthermore, mutations in developmental transcription factors are linked to variation in sleep duration in humans, risk for restless legs syndrome, and sleep-disordered breathing. This paper is part of the “Genetic and other molecular underpinnings of sleep, sleep disorders, and circadian rhythms including translational approaches” collection.
National Beef Quality Audit—2022: in-plant assessments of quality and yield determining carcass characteristics of fed steers and heifers
Authors: Mayer Thachary R , Borders Sydni E , Schwartz Trent E , Gehring Kerri B , Griffin Davey B , Kerth Christopher R , Belk Keith E , Scanga John A , Nair Mahesh N , Pfeiffer Morgan M , Mafi Gretchen G , Harr Keayla M , Lawrence Ty E , Tennant Travis C , Lucherk Loni W , O’Quinn Travis G , Beyer Erin S , Bass Phil D , Garcia Lyda G , Bohrer Benjamin M , Pempek Jessica A , Garmyn Andrea J , Maddock Robert J , Carr C Chad , Pringle T Dean , Scheffler Tracy L , Scheffler Jason M , Stelzleni Alexander M , Gonzalez John M , Underwood Keith R , Harsh Bailey N , Waters Crystal M , Savell Jeffrey W
Published: June 2024

The National Beef Quality Audit – 2022 serves as a benchmark of the current fed steer and heifer population of the U.S. beef industry and allows comparison to previous audits as a method of monitoring industry progress. In-plant cooler assessments and collections of beef carcass data took place from July 2021 to November 2022. During in-plant evaluations, 10% of 1-d production was surveyed for quality and yield indicating characteristics of fed beef carcasses (n = 9,746 beef carcasses). Distributions of sex classes among sampled carcasses were steer (65.0%) and heifer (35.0%), whereas distributions of breed type were native (87.7%), dairy (11.3%), and Bos indicus (0.9%). Mean values were observed for USDA Yield Grades (YG; 3.3), USDA Quality Grade (QG; Choice16), marbling score (Small98), ribeye area (91.0 cm2), adjusted fat thickness (1.49 cm), hot carcass weight (401.9 kg), and KPH (2.5%). Mean overall maturity was A66, with a mean lean maturity of A56 and mean skeletal maturity of A72. There were 28.1% of carcasses identified for use in a USDA-certified beef G-Schedule Program. Defects, such as dark cutting and blood splash, were observed at 1.8% and 0.5%, respectively. Distributions of USDA YG were YG 1 (8.2%), YG 2 (30.7%), YG 3 (40.2%), YG 4 (16.6%), and YG 5 (4.3%). USDA QGs were observed at 7.5% Prime, 69.2% Choice, 16.4% Select, and 6.8% other. The results of this study provide an updated look at the current grading trends of beef carcasses in the United States to drive progress in the fed beef industry.
To explore the protective effect of gastrodin on PC12 cells against oxidative stress induced by lead acetate based on network pharmacology
Authors: Pan Si-Wen , Zou Yu , Xu Tian-Jiao , Ma Chun-Hui , Li Xiao-Ming , Yu Chun-Lei
Published: June 2024

Objective

Screening and predicting potential targets for gastrodin antioxidant stress based on network pharmacology methods, and exploring the effect of gastrodin on lead acetate induced oxidative stress in PC12 cells through cell experiments.

Methods

Through the Pharmaper database Predict the target of action of gastrodin. Through OMIM and GeneCards to collect oxidative stress targets from database, and intersect with drug targets to obtain drug disease intersection targets; Construct a PPI network diagram using the STRING database. Perform GO enrichment analysis and KEGG pathway enrichment analysis on intersection targets through the DAVID platform. Lead acetate (PbAc) exposure was used to establish a lead poisoning cell model, and intracellular ROS levels, ALB, AKT1, and Caspase-3 levels were measured.

Results

A total of 288 targets of gastrodin action, 638 targets related to oxidative stress, and 62 drug disease intersection targets were obtained, among which core targets such as ALB, AKT1, CASP3 may be closely related to oxidative stress. KEGG pathway analysis showed that gastrodin antioxidant stress mainly involved in lipid, cancer pathway and other signaling pathways. The results of the cell experiment showed that 50 μM is the optimal effective concentration for PbAc induced ROS production in PC12 cells. Gastrodin significantly increased the ROS content of PC12 cells treated with PbAc, Upregulation of ALB expression and downregulation of AKT1 and CASP3 expression.

Conclusions

Gastrodin may alleviate PbAc-induced ROS in PC12 cells, indicating potential protective effects against oxidative stress. Further studies are needed to confirm these findings and explore the underlying mechanisms.