bluuebunny/crossref_metadata_2025 huggingface dataset:
Strong activation of p53 by actinomycin D and nutlin-3a overcomes the resistance of cancer cells to the pro-apoptotic activity of the FAS ligand
Authors: Łasut-Szyszka Barbara , Gdowicz-Kłosok Agnieszka , Krześniak Małgorzata , Głowala-Kosińska Magdalena , Będzińska Agnieszka , Rusin Marek
Published: July 2024

The FAS ligand (FASLG) is expressed on lymphocytes, which employ it to activate death receptors on target cells. Cancer cells are generally resistant to apoptosis triggered by FASLG. In this work, we found a way to circumvent this resistance by treatment with actinomycin D (ActD) and nutlin-3a (Nut3a). We selected this drug combination based on our transcriptomic data showing strong activation of proapoptotic genes, including those for receptor-mediated apoptosis, in cells exposed to actinomycin D and nutlin-3a. To test our hypothesis, we pre-exposed cancer cell lines to this drug combination for 45 h and then treated them with recombinant FASLG. This almost instantaneously killed most cells. Actinomycin D and nutlin-3a strongly cooperated in the sensitization because the effect of the drugs acting solo was not as spectacular as the drug combination, which together with FASLG killed more than 99% of cells. Based on the caspase activation pattern (caspase-8, caspase-9, caspase-10), we conclude that both extrinsic and intrinsic pro-apoptotic pathways were engaged. In engineered p53-deficient cells, this pro-apoptotic effect was completely abrogated. Therefore, the combination of ActD + Nut3a activates p53 in an extraordinary way, which overcomes the resistance of cancer cells to apoptosis triggered by FASLG. Interestingly, other combinations of drugs, e.g., etoposide + nutlin-3a, actinomycin D + RG7112, and actinomycin D + idasanutlin had a similar effect. Moreover, normal human fibroblasts are less sensitive to death induced by ActD + Nut3a + FASLG. Our findings create the opportunity to revive the abandoned attempts of cancer immunotherapy employing the recombinant FAS ligand.

Graphical Abstract
Screening of heat stress-tolerant weedy rice and SNP identification of heat-tolerance-related genes
Authors: Sarker Mainul Hasan , Hussain Md Hamed , Neik Ting Xiang , Hasan Md Zobaer , Wee Wei Yee , Tan Hock Siew , Ko Swee-suak , Song Beng-Kah
Published: July 2024

Rice, a staple crop that feeds more than one-third of the world’s population, encounters a wide range of biotic and abiotic stresses due to climate change. Rising temperature is one of the significant abiotic stresses affecting rice productivity worldwide. The development of heat-tolerant rice cultivars is critical in this regard. Weedy rice could potentially serve as a natural resource for genes conferring agronomically important traits beneficial to cultivated rice. However, heat tolerance in both cultivated and weedy rice is still understudied. This study screened a set of 180 weedy rice accessions for heat stress tolerance and further characterised them using genome-wide single-nucleotide polymorphisms (SNPs) analysis. Five heat-tolerant (HT) accessions (MU244, MU235, MU249, MU260 and MU237), along with five heat-susceptible (HS) accessions (MU100, MU114, MU264, MU251 and MU005), were subjected to relative electrical conductivity (REC) test and reactive oxidative species assay (ROS). These tests verified that the five HT accessions performed better under heat stress than their HS counterparts. In addition, whole-genome sequences of three HT (MU235, MU237 and MU066) and four HS (MU100, MU114, MU022 and MU005) accessions were selected for the genome-wide SNPs comparison, revealing substantial amino acid variation in the heat-tolerance-related genes between the HT and HS rice groups. The proposed genes and genome-wide SNP markers may help rice breeders better understand how different rice cultivars respond to heat stress.
Lifestyle Intervention in Reducing Insulin Resistance and Preventing type 2 Diabetes in Asia Pacific Region: A Systematic Review and Meta-Analysis
Authors: Cao Yingting , Shrestha Abha , Janiczak Amy , Li Xia , Lu Yang , Haregu Tilahun
Published: July 2024

Purpose of Review

To update the evidence of lifestyle interventions for the prevention of type 2 diabetes mellites (T2DM) in adults, particularly in the Asia Pacific region. The key questions to ask are: 1) How effective are lifestyle interventions in preventing T2DM among at-risk adults in the Asia Pacific Region? 2)What are the key characteristics of the implementation of lifestyle interventions for diabetes prevention?

Recent Findings

Lifestyle interventions for the prevention of T2DM have been suggested to be effective. There is evidence of ethnic differences in some glycaemic and anthropometric outcomes.

The meta-analysis suggested a significant result in reducing waist circumference (standardised mean difference − 019, 95%CI ( -0.31, -0.06)), and no significant effects in other outcomes. However, the implementation outcomes suggested lifestyle intervention might be a cost-effective and sustainable approach in T2DM particularly in countries in the Asia Pacific Region. The focus of lifestyle intervention in the Asia Pacific Region should not only lie in the effectiveness of the trial but a thorough evaluation of the implementation outcomes, as well as cultural adaptations, with the support of all stakeholders through all stages of the implementation.
The Roles of Asylum Seeker–Led Organisations in Settlement Processes and Determinants: Evidence from Hong Kong
Authors: Lam Ka Wang Kelvin
Published: July 2024

Organisations led by refugees or migrants play an important role in their settlement, providing platforms for establishing connections and reaching the wider community. However, our knowledge of how they utilise these platforms for establishing connections and the factors affecting the formation of these connections remains limited. This paper, drawing on evidence from Hong Kong, examines the use of organisations led by asylum seekers as platforms for establishing connections, the roles of these connections in their settlement process, and the factors affecting the formation of these connections. Data were collected from an asylum seeker–led organisation in Hong Kong. The author conducted participant observation and 30 semi-structured interviews with adult asylum seekers while volunteering with this organisation between 2018 and 2021. The findings reinforce the importance of organisations led by refugees or migrants in their settlement process, particularly when official humanitarian aid is insufficient. They utilise these platforms to reach the wider community for support, thereby filling assistance gaps through establishing connections with the local community (bridging) and participating in policy advocacy activities (linking). Proficiency in the local language and institutional responsiveness were found to determine their ability to bridge with the local community and link with policymakers respectively. Overall, the findings suggest that, aside from the engagement of refugees or migrants, the support of host communities and institutional responsiveness are equally important in creating favourable conditions for them to adjust to and establish their lives in a new context.
Transcendence of certain sequences of algebraic numbers
Authors: Laursen Mathias L.
Published: July 2024

Using Schmidt’s Subspace Theorem, this paper improves and extends an existing transcendence result for sequences of algebraic numbers. The theorems thus produced correspond to a central theorem on the irrationality of sequences due to Erdős.
Robustness in binary-action supermodular games revisited
Authors: Oyama Daisuke , Takahashi Satoru
Published: July 2024

We show that in all (whether generic or nongeneric) binary-action supermodular games, an extreme action profile is robust to incomplete information if and only if it is a monotone potential maximizer. The equivalence does not hold for nonextreme action profiles.
Teacher Stereotypes and Teacher Expectations at the Intersection of Student Gender and Socioeconomic Status
Authors: Gentrup Sarah , Olczyk Melanie , Lorenz Georg
Published: July 2024

Abstract: Gender and family socioeconomic status (SES) are central dimensions of educational inequality and may interact in shaping inequality. This study addresses teacher expectations and stereotypes that possibly contribute to intersectional inequality. The study relies on two samples of teachers and students in German primary schools (sample 1: NTeachers=69, 94 % female, NStudents= 1,049 (German language)/1,027 (mathematics), 48 % female; sample 2: NTeachers= 698 (German language)/614 (mathematics), 94 % female; NStudents= 4,732 (German language)/4,117 (mathematics), 51 % female). Two-level regression analyses revealed additive gender and socioeconomic bias in teacher expectations in German language and mathematics but no intersectional bias (i. e., constant gender bias along family SES and similar socioeconomic bias for girls and boys). Further, teachers with more traditional gender stereotypes showed stronger gender bias, while SES-related stereotypes were unrelated to teacher expectations. We discuss how additive teacher expectation biases relate to the broader concept of intersectionality, potentially shaping unique educational experiences at the intersection of gender and SES.
Slip‐Dependence of Fault Frictional Stability Under Hydrothermal Conditions
Authors: Feng Wei , Yao Lu , Gomila Rodrigo , Ma Shengli , Pennacchioni Giorgio , Di Toro Giulio
Published: July 2024

In the rate‐state friction law framework, the transition from velocity weakening (V‐W) to velocity strengthening (V‐S) behavior marks the base of the seismogenic crust. Here we investigate the role of fault slip displacement under hydrothermal conditions in controlling the V‐W to V‐S transition. We shear simulated gabbro gouges at slip velocities ranging from 16 nm/s (∼50 cm/year) to 10 μm/s (∼8 cm/day) under hydrothermal conditions (300–400°C temperature; 30 MPa pore fluid pressure). We observe that cumulative fault slip increases the critical velocity for the V‐W to V‐S transition. The transition is accompanied by localized to distributed deformation mode, the formation of smectite‐type clays and occurrence of intergranular mass transfer. Our results provide insights into understanding the deepening and shallowing of V‐W/V‐S boundary (lower limit of the seismogenic zone) following a mainshock. Besides strain rate effects, slip‐enhanced chemical alteration and grain size‐sensitive deformation may temporarily contribute to the shallowing process.
Lipopolysaccharide induced systemic inflammation and heart rate variability in a term newborn piglet model
Authors: Pedersen Mette Vestergård , Renberg Ann Frida Videbæk , Christensen Julie Kehlet , Andersen Hannah Brogaard , Andelius Ted Carl Kejlberg , Kyng Kasper Jacobsen , Andersen Mads , Henriksen Tine Brink
Published: July 2024

Background

Early biomarkers are needed to improve diagnosis and support antibiotic stewardship in neonatal sepsis. Heart rate variability (HRV) is proposed as such a biomarker. However, there is a lack of studies in term newborns. Infusion of lipopolysaccharide (LPS) from Escherichia coli induces systemic inflammation comparable to sepsis in newborns. We aimed to study the effect of systemic LPS induced inflammation on HRV in term newborn piglets.

Methods

Baseline HRV was recorded for 1 h. This control period was compared to the hourly HRV for each piglet (n = 9) during 4 h of LPS infusion. For comparison, we used a mixed-effects regression model.

Results

Systemic inflammation induced by LPS was found to reduce HRV. Compared to baseline, most measures of HRV decreased to lower values compared to baseline at 2 h, 3 h, and 4 h after initiation of LPS infusion. Heart rate (HR) was increased at 2 h, 3 h, and 4 h. When adjusting for HR in the mixed-effects regression model all reductions in HRV were explained by the increase in HR.

Conclusions

Reduced HRV may be an early biomarker of neonatal sepsis. However, an increase in HR alone could be an already available, more accessible, and interpretable biomarker of sepsis in term neonates.

Impact

In a term newborn piglet model, systemic inflammation induced by lipopolysaccharide from Escherichia coli reduced heart rate variability measures and increased heart rate.

All reductions in heart rate variability were mediated by heart rate.

While heart rate variability may be a biomarker of sepsis in term newborns, changes in heart rate alone could be a more readily available biomarker.
Developing a phenotype risk score for tic disorders in a large, clinical biobank
Authors: Miller-Fleming Tyne W. , Allos Annmarie , Gantz Emily , Yu Dongmei , Isaacs David A. , Mathews Carol A. , Scharf Jeremiah M. , Davis Lea K.
Published: July 2024

Tics are a common feature of early-onset neurodevelopmental disorders, characterized by involuntary and repetitive movements or sounds. Despite affecting up to 2% of children and having a genetic contribution, the underlying causes remain poorly understood. In this study, we leverage dense phenotype information to identify features (i.e., symptoms and comorbid diagnoses) of tic disorders within the context of a clinical biobank. Using de-identified electronic health records (EHRs), we identified individuals with tic disorder diagnosis codes. We performed a phenome-wide association study (PheWAS) to identify the EHR features enriched in tic cases versus controls (n = 1406 and 7030; respectively) and found highly comorbid neuropsychiatric phenotypes, including: obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorder, and anxiety (p < 7.396 × 10−5). These features (among others) were then used to generate a phenotype risk score (PheRS) for tic disorder, which was applied across an independent set of 90,051 individuals. A gold standard set of tic disorder cases identified by an EHR algorithm and confirmed by clinician chart review was then used to validate the tic disorder PheRS; the tic disorder PheRS was significantly higher among clinician-validated tic cases versus non-cases (p = 4.787 × 10−151; β = 1.68; SE = 0.06). Our findings provide support for the use of large-scale medical databases to better understand phenotypically complex and underdiagnosed conditions, such as tic disorders.
ZDHHC1 downregulates LIPG and inhibits colorectal cancer growth via IGF2BP1 Palmitoylation
Authors: Zhang Qun , Du Zhouyuan , Zhou Wei , Li Wei , Yang Qinglin , Yu Haixin , Liu Tao
Published: July 2024

Alteration in lipid metabolism is recognized as a hallmark feature of colorectal cancer (CRC). Protein S-palmitoylation plays a critical role in many different cellular processes including protein-lipid interaction. Zinc Finger DHHC-Type Containing 1 (ZDHHC1, also known as ZNF377) belongs to the palmitoyl-transferase ZDHHC family, and is a potential tumor suppressor. However, our knowledge of the functional roles of ZDHHC1 in CRC is limited. We discovered that ZDHHC1 expression was downregulated in CRC tissues and that low levels of ZDHHC1 were associated with unfavorable prognosis. Functional studies showed that ZDHHC1 inhibited CRC cell proliferation and invasion in vitro and in vivo. We also found that lipase G (LIPG) is negatively regulated by ZDHHC1 and plays a key role in CRC cell growth through lipid storage. Additionally, we demonstrated that ZDHHC1 functions as a IGF2BP1-palmitoylating enzyme that induces S-palmitoylation at IGF2BP1-C337, which results in downregulated LIPG expression via m6A modification. Mechanistic investigations revealed that the ZDHHC1/IGF2BP1/LIPG signaling axis is associated with inhibition of CRC cell growth. Our study uncovers the potential role of ZDHHC1 in CRC, including inhibition of CRC growth by reducing the stability of LIPG mRNA in an m6A dependent-manner by palmitoylation of IGF2BP1.
Glucocorticoid receptor controls atopic dermatitis inflammation via functional interactions with P63 and autocrine signaling in epidermal keratinocytes
Authors: Sevilla Lisa M. , Pons-Alonso Omar , Gallego Andrea , Azkargorta Mikel , Elortza Félix , Pérez Paloma
Published: July 2024

Atopic dermatitis (AD), a prevalent chronic inflammatory disease with multifactorial etiology, features epidermal barrier defects and immune overactivation. Synthetic glucocorticoids (GCs) are widely prescribed for treating AD due to their anti-inflammatory actions; however, mechanisms are incompletely understood. Defective local GC signaling due to decreased production of endogenous ligand and/or GC receptor (GR) levels was reported in prevalent inflammatory skin disorders; whether this is a consequence or contributing factor to AD pathology is unclear. To identify the chromatin-bound cell-type-specific GR protein interactome in keratinocytes, we used rapid immunoprecipitation of endogenous proteins and mass spectrometry identifying 145 interactors that increased upon dexamethasone treatment. GR-interacting proteins were enriched in p53/p63 signaling, including epidermal transcription factors with critical roles in AD pathology. Previous analyses indicating mirrored AD-like phenotypes between P63 overexpression and GR loss in epidermis, and our data show an intricate relationship between these transcription factors in human keratinocytes, identifying TP63 as a direct GR target. Dexamethasone treatment counteracted transcriptional up-regulation of inflammatory markers by IL4/IL13, known to mimic AD, causing opposite shifts in GR and P63 genomic binding. Indeed, IL4/IL13 decreased GR and increased P63 levels in cultured keratinocytes and human epidermal equivalents (HEE), consistent with GR down-regulation and increased P63 expression in AD lesions vs normal skin. Moreover, GR knockdown (GRKD) resulted in constitutive increases in P63, phospho-P38 and S100A9, IL6, and IL33. Also, GRKD culture supernatants showed increased autocrine production of TH2-/TH1-/TH17-TH22-associated factors including IL4, CXCL10, CXCL11, and CXCL8. GRKD HEEs showed AD-like features including hyperplasia and abnormal differentiation, resembling phenotypes observed with GR antagonist or IL4/IL13 treatment. The simultaneous GR/P63 knockdown partially reversed constitutive up-regulation of inflammatory genes in GRKD. In summary, our data support a causative role for GR loss in AD pathogenesis via functional interactions with P63 and autocrine signaling in epidermal keratinocytes.
Dairy consumption and vitamin D concentration in adolescents with challenge-confirmed cow’s milk allergy during infancy
Authors: Piippo Sonja , Hauta-alus Helena , Viljanen Mirva , Savilahti Erkki , Kuitunen Mikael
Published: July 2024

Background/Objectives

Milk is an important source of dietary calcium and, if fortified, vitamin D. Cow’s milk allergy (CMA) is treated with a milk elimination diet. Although most children become tolerant by age 3 years, some continue dairy avoidance. It remains unclear whether adolescents with a history of CMA adopt similar milk consumption as their peers. We assessed dairy consumption and concentration of serum 25-hydroxyvitamin D (25(OH)D) in adolescents with either confirmed CMA or a negative CMA challenge in infancy (CMA-refuted group) and age-matched controls.

Subjects/Methods

This study is based on a previously reported randomized controlled trial from 1999 to 2002 on the treatment effect of probiotics on atopic eczema in participants aged <12 months (n = 230) with data on CMA status. We followed up these participants, aged 15–18 years, in 2017 (n = 104). A 20-item food frequency questionnaire assessed dairy consumption. An automated immunoassay measured 25(OH)D concentration.

Results

Median dairy product consumption did not differ between adolescents with CMA (449 g/d, n = 40), the CMA-refuted group (566 g/d, n = 36), and controls (235 g/d, n = 51) (P = 0.117). Median 25(OH)D concentrations were 76.0, 79.3, and 80.8 nmol/l, respectively (P = 0.844). Among participants, 93% were vitamin D sufficient (25(OH)D ≥ 50 nmol/l), with no differences between groups (P = 0.914).

Conclusion

Among adolescents with a history of CMA during infancy, our study found no reintroduction failure of milk and no difference in vitamin D insufficiency rate compared with peers. Current management of CMA seems to adequately minimize later nutritional disadvantages associated with a cow’s milk elimination diet.
Interplay of valley, layer and band topology towards interacting quantum phases in moiré bilayer graphene
Authors: Jeong Yungi , Park Hangyeol , Kim Taeho , Watanabe Kenji , Taniguchi Takashi , Jung Jeil , Jang Joonho
Published: July 2024

In Bernal-stacked bilayer graphene (BBG), the Landau levels give rise to an intimate connection between valley and layer degrees of freedom. Adding a moiré superlattice potential enriches the BBG physics with the formation of topological minibands — potentially leading to tunable exotic quantum transport. Here, we present magnetotransport measurements of a high-quality bilayer graphene–hexagonal boron nitride (hBN) heterostructure. The zero-degree alignment generates a strong moiré superlattice potential for the electrons in BBG and the resulting Landau fan diagram of longitudinal and Hall resistance displays a Hofstadter butterfly pattern with a high level of detail. We demonstrate that the intricate relationship between valley and layer degrees of freedom controls the topology of moiré-induced bands, significantly influencing the energetics of interacting quantum phases in the BBG superlattice. We further observe signatures of field-induced correlated insulators, helical edge states and clear quantizations of interaction-driven topological quantum phases, such as symmetry broken Chern insulators.
Pt nanoshells with a high NIR-II photothermal conversion efficiency mediates multimodal neuromodulation against ventricular arrhythmias
Authors: Wang Chenlu , Zhou Liping , Liu Chengzhe , Qiao Jiaming , Han Xinrui , Wang Luyang , Liu Yaxi , Xu Bi , Qiu Qinfang , Zhang Zizhuo , Wang Jiale , Zhou Xiaoya , Zeng Mengqi , Yu Lilei , Fu Lei
Published: July 2024

Autonomic nervous system disorders play a pivotal role in the pathophysiology of cardiovascular diseases. Regulating it is essential for preventing and treating acute ventricular arrhythmias (VAs). Photothermal neuromodulation is a nonimplanted technique, but the response temperature ranges of transient receptor potential vanilloid 1 (TRPV1) and TWIK-related K+ Channel 1 (TREK1) exhibit differences while being closely aligned, and the acute nature of VAs require that it must be rapid and precise. However, the low photothermal conversion efficiency (PCE) still poses limitations in achieving rapid and precise treatment. Here, we achieve a nearly perfect blackbody absorption and a high PCE in the second near infrared (NIR-II) window (73.7% at 1064 nm) via a Pt nanoparticle shell (PtNP-shell). By precisely manipulating the photothermal effect, we successfully achieve rapid and precise multimodal neuromodulation encompassing neural activation (41.0–42.9 °C) and inhibition (45.0–46.9 °C) in a male canine model. The NIR-II photothermal modulation additionally achieves multimodal reversible autonomic modulation and confers protection against acute VAs associated with myocardial ischemia and reperfusion injury in interventional therapy.
Gene body DNA hydroxymethylation restricts the magnitude of transcriptional changes during aging
Authors: Occean James R. , Yang Na , Sun Yan , Dawkins Marshall S. , Munk Rachel , Belair Cedric , Dar Showkat , Anerillas Carlos , Wang Lin , Shi Changyou , Dunn Christopher , Bernier Michel , Price Nathan L. , Kim Julie S. , Cui Chang-Yi , Fan Jinshui , Bhattacharyya Moitrayee , De Supriyo , Maragkakis Manolis , de Cabo Rafael , Sidoli Simone , Sen Payel
Published: July 2024

DNA hydroxymethylation (5hmC), the most abundant oxidative derivative of DNA methylation, is typically enriched at enhancers and gene bodies of transcriptionally active and tissue-specific genes. Although aberrant genomic 5hmC has been implicated in age-related diseases, its functional role in aging remains unknown. Here, using mouse liver and cerebellum as model organs, we show that 5hmC accumulates in gene bodies associated with tissue-specific function and restricts the magnitude of gene expression changes with age. Mechanistically, 5hmC decreases the binding of splicing associated factors and correlates with age-related alternative splicing events. We found that various age-related contexts, such as prolonged quiescence and senescence, drive the accumulation of 5hmC with age. We provide evidence that this age-related transcriptionally restrictive function is conserved in mouse and human tissues. Our findings reveal that 5hmC regulates tissue-specific function and may play a role in longevity.
Bayesian blacksmithing: discovering thermomechanical properties and deformation mechanisms in high-entropy refractory alloys
Authors: Startt Jacob , McCarthy Megan J. , Wood Mitchell A. , Donegan Sean , Dingreville Rémi
Published: July 2024

Finding alloys with specific design properties is challenging due to the large number of possible compositions and the complex interactions between elements. This study introduces a multi-objective Bayesian optimization approach guiding molecular dynamics simulations for discovering high-performance refractory alloys with both targeted intrinsic static thermomechanical properties and also deformation mechanisms occurring during dynamic loading. The objective functions are aiming for excellent thermomechanical stability via a high bulk modulus, a low thermal expansion, a high heat capacity, and for a resilient deformation mechanism maximizing the retention of the BCC phase after shock loading. Contrasting two optimization procedures, we show that the Pareto-optimal solutions are confined to a small performance space when the property objectives display a cooperative relationship. Conversely, the Pareto front is much broader in the performance space when these properties have antagonistic relationships. Density functional theory simulations validate these findings and unveil underlying atomic-bond changes driving property improvements.
Tailored molecular for ultra-stability and biocompatible pseudohalide metal-free perovskite towards X-ray detectors with record sensitivity
Authors: Lei Yutian , Yin Mengying , Shi Chang , Wu Lingxi , Peng Guoqiang , Xu Youkui , Wang Haoxu , Tang Rongbing , Li ZhenHua , Jin Zhiwen
Published: July 2024

The emerging pseudohalide metal-free perovskite (pseudohalide–MFPs) X-ray detector caters to the demands of timely mobile diagnosis owing to its lightweight, flexibility, and cost-effectiveness. However, the performance of these devices is severely limited by poor X-ray absorption, ultra-wide band gap, relative instability, and their unknown biotoxicity. Herein, we construct heavy atom covalent bonds (C–Br/Cl) on the A-site organic cation to reinforce component coordination to modulate X-ray absorption and band gap in pseudohalide–MFPs and further enhance its stability. Molecular dynamics simulations demonstrate that the introduction of halogen atoms can strengthen hydrogen bonding interactions, thereby improving the coordination between different components. The resultant (MDABCOBr)–NH4(BF4)3 (MDABCO = N-methyl-N’-diazabicyclo[2.2.2]octonium) single crystal significantly increases X-ray absorption cross-section and crystalline density (from 1.728 to 1.950 g cm−3), and synergistically realizes the band nature modulation (from 7.4 to 5.5 eV) and enhanced ionic migration inhibition (628 meV) with optimized stability. As such, our X-ray detectors realized a sensitivity of 2377 μC Gyair−1 cm−2, an ultralow detection limit of 50.1 nGyair s−1, and impressive operation stability. Moreover, cytotoxicity assay confirmed the compatibility of pseudohalide metal-free perovskite. Finally, within this framework, we successfully fabricate the (MDABCOBr)–NH4(BF4)3-based flexible device to create an ideal in vitro wearable X-ray detection.
Human tripartite cortical network model for temporal assessment of alpha-synuclein aggregation and propagation in Parkinson’s Disease
Authors: Kapucu Fikret Emre , Tujula Iisa , Kulta Oskari , Sukki Lassi , Ryynänen Tomi , Gram Hjalte , Vuolanto Valtteri , Vinogradov Andrey , Kreutzer Joose , Jensen Poul Henning , Kallio Pasi , Narkilahti Susanna
Published: July 2024

Previous studies have shown that aggregated alpha-synuclein (α-s) protein, a key pathological marker of Parkinson’s disease (PD), can propagate between cells, thus participating in disease progression. This prion-like propagation has been widely studied using in vivo and in vitro models, including rodent and human cell cultures. In this study, our focus was on temporal assessment of functional changes during α-s aggregation and propagation in human induced pluripotent stem cell (hiPSC)-derived neuronal cultures and in engineered networks. Here, we report an engineered circular tripartite human neuronal network model in a microfluidic chip integrated with microelectrode arrays (MEAs) as a platform to study functional markers during α-s aggregation and propagation. We observed progressive aggregation of α-s in conventional neuronal cultures and in the exposed (proximal) compartments of circular tripartite networks following exposure to preformed α-s fibrils (PFF). Furthermore, aggregated forms propagated to distal compartments of the circular tripartite networks through axonal transport. We observed impacts of α-s aggregation on both the structure and function of neuronal cells, such as in presynaptic proteins, mitochondrial motility, calcium oscillations and neuronal activity. The model enabled an assessment of the early, middle, and late phases of α-s aggregation and its propagation during a 13-day follow-up period. While our temporal analysis suggested a complex interplay of structural and functional changes during the in vitro propagation of α-s aggregates, further investigation is required to elucidate the underlying mechanisms. Taken together, this study demonstrates the technical potential of our introduced model for conducting in-depth analyses for revealing such mechanisms.
Observational threat learning influences costly avoidance behaviour in healthy humans
Authors: Mueller Madeleine , Cohen Oded , Shechner Tomer , Haaker Jan
Published: July 2024

Avoidance is an essential behaviour for ensuring safety in uncertain and dangerous environments. One way to learn what is dangerous and must be avoided is through observational threat learning. This online study explored the behavioural implications of observed threat learning, examining how participants avoided or approached a learned threat and how this affected their movement patterns. Participants (n = 89) completed an observational threat learning task, rating their fear, discomfort, and physical arousal in response to conditioned stimuli. The retrieval of learned threat was reassessed 24 h later, followed by a reminder of the observed threat associations. Participants subsequently completed a computerised avoidance task, in which they navigated from a starting point to an endpoint by selecting one of two doors, each associated with either safety or danger, relying on observed information. Opting for the safe door entailed increased effort to attain the goal. Results demonstrated that observational threat learning influenced avoidance behaviour and decision-making dependent on baseline effort level. Participants tended to exhibit thigmotaxis, staying close to walls and taking extra steps to reach their goal. This behaviour indirectly mediated the number of steps taken. This study provides valuable insights into avoidance behaviour following observational threat learning in healthy humans.
The impact of tetrodotoxin (TTX) on the gut microbiome in juvenile tiger pufferfish, Takifugu rubripes
Authors: Wassel Mai A. , Makabe-Kobayashi Yoko , Iqbal Md Mehedi , Takatani Tomohiro , Sakakura Yoshitaka , Hamasaki Koji
Published: July 2024

Tetrodotoxin (TTX) is a potent neurotoxin that accumulates in Takifugu rubripes, commonly known as pufferfish, through the ingestion of TTX-bearing organisms as part of their food chain. Although researchers believe that pufferfish use TTX to relieve stress, data are not currently available on how TTX affects the gut microbiota of pufferfish. To address this gap, our study aimed to investigate whether administering TTX to fish could alter their gut microbiota and overall health under various salinity conditions, including 30.0 ppt, 8.5 ppt, and 1.7 ppt salinity, which represent full-strength, isosmotic, and low-salinity stress, respectively. We analyzed the effect of TTX ingestion on the community structure, core microbiome, and metabolic capabilities of the gut microbiome using high-throughput sequencing technologies. The predominant bacterial taxa within the gut microbiome were Firmicutes (21–85%), Campilobacterota (2.8–67%), Spirochaetota (0.5–14%), and Proteobacteria (0.7–9.8%), with Mycoplasma, uncultured Arcobacteraceae, Brevinema, Vibrio, Rubritalea, and uncultured Pirellulaceae as core genera. Our findings indicated that the impact of TTX on high-abundance genera at 30.0 ppt and 8.5 ppt salinity levels was negligible, indicating their stability and resilience to TTX ingestion. However, at 1.7 ppt, TTX-fed fish showed a significant increase in uncultured Arcobacteraceae. Furthermore, our analysis of TTX-fed fish revealed taxonomic alterations in low-abundance taxa, which altered the predicted functions of the gut microbiota at all salinity levels. These results suggest that TTX administration could cause subtle effects on the metabolic functions of gut microbial communities. Overall, our study provides insights into the complex relationship between a TTX-accumulating animal, T. rubripes, and its gut microbiota.
Enhancing autonomous vehicle navigation using SVM-based multi-target detection with photonic radar in complex traffic scenarios
Authors: Chaudhary Sushank , Sharma Abhishek , Khichar Sunita , Meng Yahui , Malhotra Jyoteesh
Published: July 2024

Efficient transportation systems are essential for the development of smart cities. Autonomous vehicles and Intelligent Transportation Systems (ITS) are crucial components of such systems, contributing to safe, reliable, and sustainable transportation. They can reduce traffic congestion, improve traffic flow, and enhance road safety, thereby making urban transportation more efficient and environmentally friendly. We present an innovative combination of photonic radar technology and Support Vector Machine classification, aimed at improving multi-target detection in complex traffic scenarios. Central to our approach is the Frequency-Modulated Continuous-Wave photonic radar, augmented with spatial multiplexing, enabling the identification of multiple targets in various environmental conditions, including challenging weather. Notably, our system achieves an impressive range resolution of 7 cm, even under adverse weather conditions, utilizing an operating bandwidth of 4 GHz. This feature is particularly crucial for precise detection and classification in dynamic traffic environments. The radar system's low power requirement and compact design enhance its suitability for deployment in autonomous vehicles. Through comprehensive numerical simulations, our system demonstrated its capability to accurately detect targets at varying distances and movement states, achieving classification accuracies of 75% for stationary and 33% for moving targets. This research substantially contributes to ITS by offering a sophisticated solution for obstacle detection and classification, thereby improving the safety and efficiency of autonomous vehicles navigating through urban environments.
Evaluating prompt engineering on GPT-3.5’s performance in USMLE-style medical calculations and clinical scenarios generated by GPT-4
Authors: Patel Dhavalkumar , Raut Ganesh , Zimlichman Eyal , Cheetirala Satya Narayan , Nadkarni Girish N , Glicksberg Benjamin S. , Apakama Donald U. , Bell Elijah J. , Freeman Robert , Timsina Prem , Klang Eyal
Published: July 2024

This study was designed to assess how different prompt engineering techniques, specifically direct prompts, Chain of Thought (CoT), and a modified CoT approach, influence the ability of GPT-3.5 to answer clinical and calculation-based medical questions, particularly those styled like the USMLE Step 1 exams. To achieve this, we analyzed the responses of GPT-3.5 to two distinct sets of questions: a batch of 1000 questions generated by GPT-4, and another set comprising 95 real USMLE Step 1 questions. These questions spanned a range of medical calculations and clinical scenarios across various fields and difficulty levels. Our analysis revealed that there were no significant differences in the accuracy of GPT-3.5's responses when using direct prompts, CoT, or modified CoT methods. For instance, in the USMLE sample, the success rates were 61.7% for direct prompts, 62.8% for CoT, and 57.4% for modified CoT, with a p-value of 0.734. Similar trends were observed in the responses to GPT-4 generated questions, both clinical and calculation-based, with p-values above 0.05 indicating no significant difference between the prompt types. The conclusion drawn from this study is that the use of CoT prompt engineering does not significantly alter GPT-3.5's effectiveness in handling medical calculations or clinical scenario questions styled like those in USMLE exams. This finding is crucial as it suggests that performance of ChatGPT remains consistent regardless of whether a CoT technique is used instead of direct prompts. This consistency could be instrumental in simplifying the integration of AI tools like ChatGPT into medical education, enabling healthcare professionals to utilize these tools with ease, without the necessity for complex prompt engineering.
Prevalence and incidence of venous thromboembolism in geriatric patients admitted to long-term care hospitals
Authors: Wagner Gernot , Steiner Daniel , Ohrenberger Gerald , Smeikal Michael , Gisinger Christoph , Moertl Deddo , Nopp Stephan , Gartlehner Gerald , Pabinger Ingrid , Ay Cihan
Published: July 2024

The risk of venous thromboembolism (VTE) increases with age. However, the risk of VTE in the setting of long-term care hospitals is understudied. Our objective was to provide data on the prevalence and incidence of VTE in older adults admitted to long-term care hospitals. In this retrospective cohort study, we collected data about chronically ill and multimorbid patients aged 65 years and older from two long-term care hospitals. The primary endpoint of this study was the lifetime prevalence of VTE, and the secondary endpoint was VTE incidence during residency in long-term care hospitals. We analysed data from 1148 patients with a mean age of 84.1 ± 7.9 years, of whom 74.2% were women. The lifetime prevalence of VTE at baseline was 9.6% (95% CI 7.9–11.4). Cumulative incidence of VTE at 1, 2, and 3 years from baseline was estimated at 3.5% (95% CI 2.5–4.7), 4.2% (95% CI 3.1–5.5), and 5.4% (95% CI 4.1–7.0), respectively. Overall, the incidence rate of VTE in our study was 2.82 (95% CI 2.18–3.66) per 100 person-years. The study indicated a considerably high lifetime prevalence and incidence of VTE during residence in long-term care hospital settings, requiring further evaluation in larger prospective studies.
Identification of novel toxins associated with the extracellular contractile injection system using machine learning
Authors: Danov Aleks , Pollin Inbal , Moon Eric , Ho Mengfei , Wilson Brenda A , Papathanos Philippos A , Kaplan Tommy , Levy Asaf
Published: July 2024

Secretion systems play a crucial role in microbe-microbe or host-microbe interactions. Among these systems, the extracellular contractile injection system (eCIS) is a unique bacterial and archaeal extracellular secretion system that injects protein toxins into target organisms. However, the specific proteins that eCISs inject into target cells and their functions remain largely unknown. Here, we developed a machine learning classifier to identify eCIS-associated toxins (EATs). The classifier combines genetic and biochemical features to identify EATs. We also developed a score for the eCIS N-terminal signal peptide to predict EAT loading. Using the classifier we classified 2,194 genes from 950 genomes as putative EATs. We validated four new EATs, EAT14-17, showing toxicity in bacterial and eukaryotic cells, and identified residues of their respective active sites that are critical for toxicity. Finally, we show that EAT14 inhibits mitogenic signaling in human cells. Our study provides insights into the diversity and functions of EATs and demonstrates machine learning capability of identifying novel toxins. The toxins can be employed in various applications dependently or independently of eCIS.
A plant root cell-inspired interphase layer for practical aqueous zinc–iodine batteries with super-high areal capacity and long lifespan
Authors: Xu Yuting , Zhang Minghao , Tang Rong , Li Siyang , Sun Chenxi , Lv Zeheng , Yang Wenhao , Wen Zhipeng , Li Cheng Chao , Li Xue , Yang Yang
Published: July 2024

A plant root cell-inspired interphase layer is designed to stabilize Zn anode interphasial chemistry, enabling synergistic regulation of all interface species.
A step-scheme mechanism in a NiO/CdS heterojunction nanoarray for visible light-activated gas sensing at room temperature
Authors: Gong Wufei , Yao Shenman , Wang Dehua , Li Jiahao , Zhu Yulin , You Jianxian , Liang Yan , Yang Yanxing , Yang Yong
Published: July 2024

A novel step-scheme NiO/CdS heterojunction nanoarray sensor was constructed in situ on a commercial alumina flat surface to detect triethylamine under visible light activation.
High efficiency of biosurfactants in stabilizing oil micro-droplets within the aging time scale of milliseconds: a microfluidic study
Authors: Yang Zhi-yuan , Yang Shi-zhong , Sun Gang-zheng , Wang Wei-dong , Fei Dan , Mu Bo-Zhong , Gang Hong-ze
Published: July 2024

Rapid adsorption of surfactants onto a freshly formed interface is vital for emulsification because emulsification is a competitive process occurring between the very short time span of interface formation and surfactant mass transport.
The construction of stance in English and Arabic newspaper editorials: a case study
Authors: Alghazo Sharif , Al-Anbar Khulood , Rabab’ah Ghaleb , Abusalim Nimer , Rayyan Mohammad
Published: July 2024

This study explores the construction of authorial stance in English and Arabic newspaper editorials. To achieve this objective, the study examines a corpus of 80 newspaper editorials retrieved from two newspapers: The first publishes in English (The Guardian, the UK), and the second publishes in Arabic (Addustour, Jordan). The study adopts Hyland’s taxonomy of stance, which includes features of hedges, boosters, attitude markers and self-mentions. To analyse the data, the study follows a mixed-methods approach to identify differences, if any, in the construction of authorial stance in the two languages in the editorial genre. A functional analysis is carried out to capture these markers within contexts. The results reveal that the most frequently used stance devices in Arabic editorials are the attitude markers, followed by boosters, hedges and self-mentions. Contrariwise, the findings showcase that the most frequently used stance device is hedging, followed by attitude markers, boosters, and self-mention. The study concludes that the two languages differ in the way they construct stance in editorials, a conclusion that provides implications for second-language professional writing teachers and students. The findings provide insights that might enhance the skills of argumentative writing in English for media courses.
Enhanced phase sensitivity in a feedback-assisted interferometer
Authors: Jiao Gao-Feng
Published: July 2024

The topology of feedback optical parametric amplifier (FOPA) renders a number of significant advantages over the topology of traditional optical parametric amplifier (TOPA) such as a higher degree of quantum correlation, all-phase entanglement enhancement, and the robustness of the losses. Here, we propose a feedback-assisted interferometer based on the topology of FOPA for quantum metrology. We theoretically study the phase sensitivity with the method of homodyne detection and product detection. By manipulating the feedback strength of the FOPA, the phase sensitivity can be further enhanced, and approach the quantum Cramér-Rao bound. Furthermore, we demonstrate that our proposal is superior to the SU(1,1) interferometer based on the topology of TOPA.
ClusterMatch aligns single-cell RNA-sequencing data at the multi-scale cluster level via stable matching
Authors: Ba Teer , Miao Hao , Zhang Lirong , Gao Caixia , Wang Yong
Published: July 2024

Motivation

Unsupervised clustering of single-cell RNA sequencing (scRNA-seq) data holds the promise of characterizing known and novel cell type in various biological and clinical contexts. However, intrinsic multi-scale clustering resolutions poses challenges to deal with multiple sources of variability in the high-dimensional and noisy data.

Results

We present ClusterMatch, a stable match optimization model to align scRNA-seq data at the cluster level. In one hand, ClusterMatch leverages the mutual correspondence by canonical correlation analysis and multi-scale Louvain clustering algorithms to identify cluster with optimized resolutions. In the other hand, it utilizes stable matching framework to align scRNA-seq data in the latent space while maintaining interpretability with overlapped marker gene set. Through extensive experiments, we demonstrate the efficacy of ClusterMatch in data integration, cell type annotation, and cross-species/timepoint alignment scenarios. Our results show ClusterMatch’s ability to utilize both global and local information of scRNA-seq data, sets the appropriate resolution of multi-scale clustering, and offers interpretability by utilizing marker genes.

Availability and implementation

The code of ClusterMatch software is freely available at https://github.com/AMSSwanglab/ClusterMatch.
Community context influences the conjugation efficiency of Escherichia coli
Authors: Bustamante Misshelle , Koopman Floor , Martens Jesper , Brons Jolanda K , DelaFuente Javier , Hackl Thomas , Kuipers Oscar P , van Doorn G Sander , de Vos Marjon G J
Published: July 2024

In urinary tract infections (UTIs), different bacteria can live in a polymicrobial community consisting of different species. It is unknown how community members affect the conjugation efficiency of uropathogenic Escherichia coli. We investigated the influence of individual species often coisolated from urinary infections (UTI) on the conjugation efficiency of E. coli isolates in artificial urine medium. Pairwise conjugation rate experiments were conducted between a donor E. coli strain containing the pOXA-48 plasmid and six uropathogenic E. coli isolates, in the presence and absence of five different species commonly coisolated in polymicrobial UTIs to elucidate their effect on the conjugation efficiency of E. coli. We found that the basal conjugation rates of pOXA-48, in the absence of other species, are dependent on the bacterial host genetic background. Additionally, we found that bacterial interactions have an overall positive effect on the conjugation rate of pOXA-48. Particularly, Gram-positive enterococcal species were found to enhance the conjugation rates towards uropathogenic E. coli isolates. We hypothesize that the nature of the coculture and physical interactions are important for these increased conjugation rates in an artificial urine medium environment.