bluuebunny/crossref_metadata_2025 huggingface dataset:
Extreme-value analysis in nano-biological systems: applications and implications
Authors: Hayashi Kumiko , Takamatsu Nobumichi , Takaramoto Shunki
Published: October 2024

Extreme value analysis (EVA) is a statistical method that studies the properties of extreme values of datasets, crucial for fields like engineering, meteorology, finance, insurance, and environmental science. EVA models extreme events using distributions such as Fréchet, Weibull, or Gumbel, aiding in risk prediction and management. This review explores EVA’s application to nanoscale biological systems. Traditionally, biological research focuses on average values from repeated experiments. However, EVA offers insights into molecular mechanisms by examining extreme data points. We introduce EVA’s concepts with simulations and review its use in studying motor protein movements within cells, highlighting the importance of in vivo analysis due to the complex intracellular environment. We suggest EVA as a tool for extracting motor proteins’ physical properties in vivo and discuss its potential in other biological systems. While there have been only a few applications of EVA to biological systems, it holds promise for uncovering hidden properties in extreme data, promoting its broader application in life sciences.
Simultaneous treatment of large hiatal hernias during Roux-en-Y gastric bypass: technical considerations and outcome
Authors: Kollmann Lars , Thurner Annette , Miras Alexander Dimitri , Seyfried Florian
Published: October 2024

Roux-en-Y gastric bypass (RYGB) is the preferred surgical option for patients with proven gastroesophageal reflux disease and obesity grade ≥ II (BMI ≥ 35 kg/m2). Data on simultaneous treatment of larger hiatal hernias during RYGB are scarce. From 2012 until 2022, data from all consecutive patients undergoing gastric bypass procedures were collected and retrospectively analyzed. The characteristics and surgical outcomes of patients undergoing RYGB alone (RYGBa) versus RYGB with simultaneous treatment of a large hiatal hernia (RYGB-HH) were compared. Out of 573 patients who received RYGB, we identified 12 simultaneously treated for large hiatal hernia. The characteristics of RYGB-HH versus RYGBa patients were higher age (55 vs. 44 years; p = 0.004) and lower BMI (39.2 vs. 46.9 kg/m2; p = 0.001). Duration of surgery in the RYGB-HH group was longer (144 min vs. 98 min; p < 0.001), while complications > Clavien–Dindo II were similar compared to the RYGBa group (8.3 vs. 9.4%, p = 0.56). Length of stay did not differ among the groups (4 vs. 5.5 days, p = 0.051). At a median follow-up of 12 months, there was no clinical recurrence of hiatal hernia in the RYGB-HH group. Simultaneous treatment of large hiatal hernias during Roux-en-Y gastric bypass surgery prolongs operation time but seems feasible and safe in the hands of experienced surgeons.
Association of sleep quality, smartphone addiction, and depressive symptoms among undergraduate medical students in Nepal
Authors: Paudel Kiran , Shah Sangam , Khanal Pratik , Bhattarai Madhur , Gautam Kamal , Bhusal Sandesh , Bhandari Prashamsa , Pandey Anjila , Niroula Sandhya , Adhikari Tara Ballav , Shrestha Roman
Published: October 2024

Introduction

While research has examined the connections between sleep quality, smartphone addiction, and depressive symptoms in general, no studies focused on undergraduate medical students in Nepal have specifically tested the complex relationship between these factors. Therefore, this study aimed to investigate the interaction between smartphone addiction, sleep quality, and depressive symptoms among undergraduate medical students of Maharajgunj Medical Campus, Tribhuvan University Teaching Hospital, Kathmandu, Nepal.

Methods

A cross-sectional study was conducted among 212 undergraduate medical students at Maharajgunj Medical Campus, Tribhuvan University, Nepal. Sleep quality, smartphone addiction, and depressive symptoms were assessed using the Pittsburgh Sleep Quality Index, Smartphone Addiction Scale Short Version, and Patient Health Questionnaire-9. Data were analyzed using IBM SPSS version 26 via the bootstrap model approach.

Results

Out of the total participants, 67.9% were male. Males showed higher scores in smartphone addiction and depressive symptoms than females (b = 5.3, Bca 95% CI:1.2, 9.1, p < 0.05). The unadjusted model indicated that the presence of smartphone addiction explained 36.5% of the indirect impact of sleep quality on depressive symptoms. However, in the adjusted model, after introducing socio-demographic, behavioral, and educational variables as covariates, this percentage decreased to 33.02%.

Conclusion

This study highlights the significant role of both smartphone addiction and sleep quality in mediating the indirect effect on depressive symptoms among undergraduate medical students. Smartphone addiction emerged as a key mediator of depressive symptoms, indicating a potentially important factor in mental health. Investigating this relationship further through longitudinal studies will be crucial for developing effective preventative and therapeutic approaches.
Back to Kahneman
Authors: Read Daniel
Published: October 2024

This paper examines Daniel Kahneman's concept of experienced utility and its roots in Bentham's hedonic utilitarianism. It focuses on Kahneman's call for a ‘separate value judgement’ to determine when experienced utility can be used to evaluate temporally extended outcomes (TEOs). Two potential judgements are proposed: comprehensiveness and personal independence. Comprehensiveness means that the measurement of utility captures all relevant aspects of instant utility. Personal independence means that the TEO is fully independent of other TEOs with which it might be combined (or ‘concatenated’). I argue that identifying TEOs meeting these criteria may be challenging, possibly restricting the applicability of experienced utility. I conclude by considering the implications for behavioural science's quest for an unambiguous, measurable operationalisation of utility.
New horizons in community engagement: Virtual community engagement studios amplifying community voices about health research in New Mexico
Authors: Killough Cynthia M. , Martinez Julia , Mata Holly , Sedillo Donna , Sanjuan Pilar , Roesch Alexandra , Hudson Christopher , Bishop Brenda , Gonzalez Jose , Rishel Brakey Heidi , Pandhi Nancy
Published: October 2024

There is increasing recognition of the crucial need for robust community engagement in health research and clinical trials. Despite this awareness, challenges persist in bridging the gap between researchers and communities. Much of the current discourse focuses on addressing issues such as cultural humility and equitable partnerships. To expand this conversation, we conducted community engagement studios, following the model by Joosten et al. We wanted to gather perspectives on research involvement across New Mexico. This process and resultant findings offer valuable insights into effective community engagement practices and advance clinical and translational science by amplifying community voices and needs.
Obstacles to Empathetic Listening After Sexual Violence
Authors: McKiernan Amy , Campbell Elspeth
Published: October 2024

Building on Linda Martín Alcoff's analysis of subversive speech in Rape and resistance, Lori Gruen's account of entangled empathy, and what Susan Brison calls the remaking of self in Aftermath: Violence and the remaking of a self, we introduce subversive listening as a way to resist obstacles to empathetic listening after sexual violence. Specifically, we identify and aim to interrupt five overextended frameworks (legal, medical, academic, fixing, and identifying) that commonly obstruct empathetic listening. To demonstrate the practical value of our work, we conclude by showing how a reader might avoid these overextensions when engaging with V's (formerly Eve Ensler) The apology.
Enhanced bubble growth near an advancing solidification front
Authors: Meijer Jochem G. , Rocha Duarte , Linnenbank Annemarie M. , Diddens Christian , Lohse Detlef
Published: October 2024

Frozen water might appear opaque since gas bubbles can get trapped in the ice during the freezing process. They nucleate and then grow near the advancing solidification front, due to the formation of a gas supersaturation region in its vicinity. A delicate interplay between the rate of mass transfer and the rate of freezing dictates the final shapes and sizes of the entrapped gas bubbles. In this work, we experimentally and numerically investigate the initial growth of such gas bubbles that nucleate and grow near the advancing ice front. We show that the initial growth of these bubbles is governed by diffusion and is enhanced due to a combination of the presence of the background gas concentration gradient and the motion of the approaching front. Additionally, we recast the problem into that of mass transfer to a moving spherical object in a homogeneous concentration field, finding good agreement between our experimental data and the existing scaling relations for that latter problem. Lastly, we address how fluid flow around the bubble might further affect this growth and qualitatively explore this through numerical simulations.
Effects of Rayleigh and Weber numbers on two-layer turbulent Rayleigh–Bénard convection
Authors: Demou Andreas D. , Scapin Nicolò , Crialesi-Esposito Marco , Costa Pedro , Spiga Filippo , Brandt Luca
Published: October 2024

This study presents direct numerical simulation results of two-layer Rayleigh–Bénard convection, investigating the previously unexplored Rayleigh–Weber parameter space

$10^6\leq Ra\leq 10^8$

and

$10^2\leq We\leq 10^3$

. Global properties, such as the Nusselt and Reynolds numbers, are compared against the extended Grossmann–Lohse theory for two fluid layers, confirming a weak Weber number dependence for all global quantities and considerably larger Reynolds numbers in the lighter fluid. Statistics of the flow reveal that the interface fluctuates more intensely for larger Weber and smaller Rayleigh numbers, something also reflected in the increased temperature root mean square values next to the interface. The dynamics of the deformed two-fluid interface is further investigated using spectral analysis. Temporal and spatial spectrum distributions reveal a capillary wave range at small Weber and large Rayleigh numbers, and a secondary energy peak at smaller Rayleigh numbers. Furthermore, the maxima of the space–time spectra lie in an intermediate dispersion regime, between the theoretical predictions for capillary and gravity-capillary waves, showing that the gravitational energy of the interfacial waves is strongly altered by temperature gradients.
Attention improvement to transcranial alternating current stimulation at gamma frequency over the right frontoparietal network: a preliminary report
Authors: Lee Tien-Wen , Almeida Sergio , Tramontano Gerald
Published: October 2024

Applying transcranial alternating current stimulation (tACS) at 40 Hz to the frontal and parietal regions, either unilaterally (left or right) or bilaterally, can improve cognitive dysfunctions. This study aimed to explore the influence of tACS at gamma frequency over right fronto-parietal (FP) region on attention. The analysis is based on retrospective data from a clinical intervention. We administered test of variables of attention (TOVA; visual mode) to 44 participants with various neuropsychiatric diagnoses before and after 12 sessions of tACS treatment. Alternating currents at 2.0 mA were delivered to the electrode positions F4 and P4, following the 10–20 EEG convention, for 20 mins in each session. We observed significant improvement across 3 indices of the TOVA, including reduction of variability in reaction time (p = 0.0002), increase in d-Prime (separability of targets and non-targets; p = 0.0157), and decrease in commission error rate (p = 0.0116). The mean RT and omission error rate largely remained unchanged. Artificial injection of tACS at 40 Hz over right FP network may improve attention function, especially in the domains of consistency in performance, target/non-target discrimination, and inhibitory control.
The Inarticulate Few: Agrarian voices during the modernisation of agriculture in Leicestershire 1935–1955
Authors: Fletcher Oliver , Martin John
Published: October 2024

Leicestershire experienced a uniquely pronounced shift from pastoral to mixed arable agriculture during the Second World War, with changes to farming practice being overseen and enforced by the County War Agricultural Executive Committee. The invasive powers of such Committees have led them to be criticised in recent historiography as an affront to individual freedoms. Opposition and resentment towards these policies would surely be most pronounced where they caused the greatest change – in Leicestershire. This article studies oral testimonies, alongside corresponding farm surveys from the period to provide a more objective basis for comparison, to reveal contemporary farmers did not share the negative historiographical characterisation of wartime policy. By the mid-1950s, agriculture in Leicestershire had embraced the ‘modern’ scientific methods demanded by the committees, but farmers’ recollections of the committee appear to span from favourable to, at worst, ambivalent. They considered the committee’s demands and methods necessary and for the most part, entirely reasonable.
Gender, Issue Stereotypes, and the Electoral Returns to Distributive Politics in the United States
Authors: Hamel Brian T. , Bauer Nichole M.
Published: October 2024

Elected officials can often successfully increase voter support in their district by “bringing home the bacon,” yet theory suggests that the electoral effects of such efforts may depend on the legislator’s gender and whether the legislator delivered benefits in a stereotypically feminine (e.g., healthcare) or masculine (e.g., agriculture) issue area. Using both observational and experimental data in the United States, we find weak, limited evidence that issue area conditions the electoral impact of credit claiming for legislators of either gender. In addition, we show that men and women are rewarded comparably when they secure benefits for their district, regardless of issue area. Our findings suggest that women legislators — typically more effective than men at securing these benefits — can use distributive politics and credit claiming as an effective electoral strategy without concern that issue-based gender biases in the electorate will get in the way.
Breastfeeding Practices in the Twin Town of India — A Cross-Sectional Study
Authors: Bhardwaj Geeta , Smitha Moonjelly V.
Published: October 2024

The global rise in twinning rates poses health challenges due to increased risks for infants and mothers. Despite the benefits, breastfeeding rates among multiples are low, with exclusive breastfeeding (EBF) particularly scarce compared to singletons. Our study focuses on the mothers of twins in a unique population in Kodinhi village, Kerala, India, known for its high twinning rates, which aims to contribute to existing knowledge of breastfeeding practices and perspectives in a high twinning environment and offer valuable insights to promote optimal breastfeeding among mothers of twins. A retrospective cross-sectional survey was adopted. Seventy-five mothers with twins under 3 years of age from Kodinhi and neighboring areas were interviewed face to face using structured validated tools. Data collection focused on quantitative data supplemented by narrative descriptions. Most women delivered preterm (57.3%), operative delivery (58.7%), and had a late initiation of breastfeeding (32.9% within 24 hours). Colostrum feed was common (86.7%). The EBF rate was 4%, with 47.9% initiating nonexclusive breastfeeding before 3 months, and most of the twins (46.6%) were breastfed for 1−2 years. Fatigue (69.9%) and low milk supply (38.7%) were chief concerns. While 16.4% of mothers opted for a tandem breastfeeding technique, many preferred consecutive feeding as tandem was challenging. Mothers in Kodinhi demonstrated commendable efforts in breastfeeding twins; despite the low rate of EBF, breastfeeding extended to 1−2 years. Evidence-based interventions and personalized support, primarily focusing on maternal perspectives of milk insufficiency, fatigue and breastfeeding techniques, are crucial for sustaining optimal breastfeeding practices among mothers of twins.
Unwrap Intractable C‐Band Coseismic Interferograms: An Improved SNAPHU Method With Range Offset Gradients as Prior Information
Authors: Jiang Kun , Xu Wenbin , Xie Lei
Published: October 2024

C‐band Interferometric Synthetic Aperture Radar (InSAR) data are widely used to map coseismic deformation. However, phase unwrapping errors are commonly distributed near faults owing to decorrelation and steep phase gradients from short radar wavelengths. Here, we propose an improved SNAPHU phase‐unwrapping algorithm that considers the prior information of the range offset gradients (P‐SNAPHU) to overcome the constraints imposed by the phase continuity assumption. P‐SNAPHU exploits median filtering of homogeneous pixels for initial denoising of range offset and then refines range offset gradients divisionally through saliency extraction. The derived gradients are used to estimate the expected values of the cost functions for the low‐coherence fringes. The synthetic experiments show significant improvements in the phase‐unwrapping accuracy of the P‐SNAPHU method compared with classical unwrapping methods. We apply the P‐SNAPHU method to unwrap Sentinel‐1 coseismic interferograms of three large (Mw > 6.5) strike‐slip earthquake events that the existing classical methods could not successfully unwrap. In the comparison of the unwrapped interferograms with the external global navigation satellite system (GNSS) displacements and those from the classical methods, we find that P‐SNAPHU significantly reduces the phase unwrapping errors with the mean absolute error of 7.2, 2.3, and 1.8 cm for the 2023 Kahramanmaraş earthquake doublet, the 2016 Kumamoto earthquake, and the 2019 Ridgecrest earthquakes, respectively. Based on the unwrapped results derived from P‐SNAPHU, an estimate is made regarding the shallow slip deficit of the 2023 Kahramanmaraş earthquake doublet, which is approximately 7%. Therefore, P‐SNAPHU is useful for developing and applying C‐band InSAR data for large earthquakes and volcanic activity.
A Quantitative Comparison and Validation of Finite‐Fault Models: The 2011 Tohoku‐Oki Earthquake
Authors: Wong Jeremy Wing Ching , Fan Wenyuan , Gabriel Alice‐Agnes
Published: October 2024

Large earthquakes rupture faults over hundreds of kilometers within minutes. Finite‐fault models image these processes and provide observational constraints for understanding earthquake physics. However, finite‐fault inversions are subject to non‐uniqueness and uncertainties. The diverse range of published models for the well‐recorded 2011 9.0 Tohoku‐Oki earthquake illustrates this challenge, and its rupture process remains under debate. Here, we comprehensively compare 32 published finite‐fault models of the Tohoku‐Oki earthquake. We aim to identify the most coherent slip features of the Tohoku‐Oki earthquake from these slip models and develop a new method for quantitatively analyzing their variations. We find that the models correlate poorly at 1‐km subfault size, irrespective of the data type. In contrast, model agreement improves significantly with increasing subfault sizes, consistently showing that the largest slip occurs up‐dip of the hypocenter near the trench. We use the set of models to test the sensitivity of available teleseismic, regional seismic, and geodetic observations. For the large Tohoku‐Oki earthquake, we find that the analyzed finite‐fault models are less sensitive to slip features smaller than 64 km. When we use the models to compute synthetic seafloor deformation, we observe strong variations in the synthetics, suggesting their sensitivity to small‐scale slip features. Our newly developed approach offers a quantitative framework to identify common features in distinct finite‐fault slip models and to analyze their robustness using regional and global geophysical observations for megathrust earthquakes. Our results indicate that dense offshore instrumentation is critical for resolving the rupture complexities of megathrust earthquakes.
Elevated plasma bile acids coincide with cardiac stress and inflammation in young Cyp2c70−/− mice
Authors: de Vries Hilde D. , Eijgenraam Tim R. , Bloks Vincent W. , Mulder Niels L. , van Zutphen Tim , Silljé Herman H. W. , Kuipers Folkert , de Boer Jan Freark
Published: October 2024

Background

High plasma bile acids (BAs), for instance due to intrahepatic cholestasis of pregnancy or neonatal cholestasis, are associated with cardiac abnormalities. Here, we exploited the variability in plasma BA levels in Cyp2c70−/− mice with a human-like BA composition to investigate the acute effects of elevated circulating BAs on the heart.

Methods

RNA sequencing was performed on hearts of 3-week-old Cyp2c70−/− mice lacking mouse-specific BA species that show features of neonatal cholestasis. Cardiac transcriptomes were compared between wild-type pups, Cyp2c70−/− pups with low or high plasma BAs, and Cyp2c70−/− pups from dams that were perinatally treated with ursodeoxycholic acid (UDCA).

Results

We identified 1355 genes that were differentially expressed in hearts of Cyp2c70−/− mice with high versus low plasma BAs with enrichment of inflammatory processes. Strikingly, expression of 1053 (78%) of those genes was normalized in hearts of pups of UDCA-treated dams. Moreover, 645 cardiac genes strongly correlated to plasma BAs, of which 172 genes were associated with cardiovascular disease.

Conclusions

Elevated plasma BAs alter gene expression profiles of hearts of mice with a human-like BA profile, revealing cardiac stress and inflammation. Our findings support the notion that high plasma BAs induce cardiac complications in early life.

Impact

Cyp2c70−/− mice with a human-like bile acid composition show features of neonatal cholestasis but the extrahepatic consequences hereof have so far hardly been addressed

Elevated plasma bile acids in Cyp2c70−/− pups coincide with cardiac stress and inflammation

Perinatal treatment with UDCA prevents dysregulated cardiac gene expression patterns in Cyp2c70−/− pups
Loss of EMI1 compromises chromosome stability and is associated with cellular transformation in colonic epithelial cell contexts
Authors: Campos Gudiño Rubi , Neudorf Nicole M. , Andromidas Demi , Lichtensztejn Zelda , McManus Kirk J.
Published: October 2024

Background

Colorectal cancer (CRC) is still a leading cause of cancer deaths worldwide. Thus, identifying the aberrant genes and proteins underlying disease pathogenesis is critical to improve early detection methods and develop novel therapeutic strategies. Chromosome instability (CIN), or ongoing changes in chromosome complements, is a predominant form of genome instability. It is a driver of genetic heterogeneity found in ~85% of CRCs. Although CIN contributes to CRC pathogenesis, the molecular determinants underlying CIN remain poorly understood. Recently, EMI1, an F-box protein, was identified as a candidate CIN gene. In this study, we sought to determine the impact reduced EMI1 expression has on CIN and cellular transformation.

Methods

Coupling siRNA-based silencing and CRISPR/Cas9 knockout clones with quantitative imaging microscopy we evaluated the impact reduced EMI1 expression has on CIN and cellular transformation in four colonic epithelial cell contexts.

Results

Quantitative imaging microscopy data revealed that reduced EMI1 expression induces increases in CIN phenotypes in both transient (siRNA) and constitutive (CRISPR/Cas9) cell models that are associated with increases in DNA damage and cellular transformation phenotypes in long-term studies.

Conclusions

This study determined that reduced EMI1 expression induces CIN and promotes cellular transformation, which is consistent with a role in early CRC development.
Inhibition of poly(ADP-Ribosyl)ation reduced vascular smooth muscle cells loss and improves aortic disease in a mouse model of human accelerated aging syndrome
Authors: Cardoso Déborah , Guilbert Solenn , Guigue Philippe , Carabalona Aurélie , Harhouri Karim , Peccate Cécile , Tournois Johana , Guesmia Zoheir , Ferreira Lino , Bartoli Catherine , Levy Nicolas , Colleaux Laurence , Nissan Xavier , Muchir Antoine
Published: October 2024

Hutchinson-Gilford progeria syndrome (HGPS) is an extremely rare genetic disorder associated with features of accelerated aging. HGPS is an autosomal dominant disease caused by a de novo mutation of LMNA gene, encoding A-type lamins, resulting in the truncated form of pre-lamin A called progerin. While asymptomatic at birth, patients develop symptoms within the first year of life when they begin to display accelerated aging and suffer from growth retardation, and severe cardiovascular complications including loss of vascular smooth muscle cells (VSMCs). Recent works reported the loss of VSMCs as a major factor triggering atherosclerosis in HGPS. Here, we investigated the mechanisms by which progerin expression leads to massive VSMCs loss. Using aorta tissue and primary cultures of murine VSMCs from a mouse model of HGPS, we showed increased VSMCs death associated with increased poly(ADP-Ribosyl)ation. Poly(ADP-Ribosyl)ation is recognized as a post-translational protein modification that coordinates the repair at DNA damage sites. Poly-ADP-ribose polymerase (PARP) catalyzes protein poly(ADP-Ribosyl)ation by utilizing nicotinamide adenine dinucleotide (NAD+). Our results provided the first demonstration linking progerin accumulation, augmented poly(ADP-Ribosyl)ation and decreased nicotinamide adenine dinucleotide (NAD+) level in VSMCs. Using high-throughput screening on VSMCs differentiated from iPSCs from HGPS patients, we identified a new compound, trifluridine able to increase NAD+ levels through decrease of PARP-1 activity. Lastly, we demonstrate that trifluridine treatment in vivo was able to alleviate aortic VSMCs loss and clinical sign of progeria, suggesting a novel therapeutic approach of cardiovascular disease in progeria.
A Drosophila computational brain model reveals sensorimotor processing
Authors: Shiu Philip K. , Sterne Gabriella R. , Spiller Nico , Franconville Romain , Sandoval Andrea , Zhou Joie , Simha Neha , Kang Chan Hyuk , Yu Seongbong , Kim Jinseop S. , Dorkenwald Sven , Matsliah Arie , Schlegel Philipp , Yu Szi-chieh , McKellar Claire E. , Sterling Amy , Costa Marta , Eichler Katharina , Bates Alexander Shakeel , Eckstein Nils , Funke Jan , Jefferis Gregory S. X. E. , Murthy Mala , Bidaye Salil S. , Hampel Stefanie , Seeds Andrew M. , Scott Kristin
Published: October 2024

The recent assembly of the adult Drosophila melanogaster central brain connectome, containing more than 125,000 neurons and 50 million synaptic connections, provides a template for examining sensory processing throughout the brain1,2. Here we create a leaky integrate-and-fire computational model of the entire Drosophila brain, on the basis of neural connectivity and neurotransmitter identity3, to study circuit properties of feeding and grooming behaviours. We show that activation of sugar-sensing or water-sensing gustatory neurons in the computational model accurately predicts neurons that respond to tastes and are required for feeding initiation4. In addition, using the model to activate neurons in the feeding region of the Drosophila brain predicts those that elicit motor neuron firing5—a testable hypothesis that we validate by optogenetic activation and behavioural studies. Activating different classes of gustatory neurons in the model makes accurate predictions of how several taste modalities interact, providing circuit-level insight into aversive and appetitive taste processing. Additionally, we applied this model to mechanosensory circuits and found that computational activation of mechanosensory neurons predicts activation of a small set of neurons comprising the antennal grooming circuit, and accurately describes the circuit response upon activation of different mechanosensory subtypes6–10. Our results demonstrate that modelling brain circuits using only synapse-level connectivity and predicted neurotransmitter identity generates experimentally testable hypotheses and can describe complete sensorimotor transformations.
RNA m5C oxidation by TET2 regulates chromatin state and leukaemogenesis
Authors: Zou Zhongyu , Dou Xiaoyang , Li Ying , Zhang Zijie , Wang Juan , Gao Boyang , Xiao Yu , Wang Yiding , Zhao Lijie , Sun Chenxi , Liu Qinzhe , Yu Xianbin , Wang Hao , Hong Juyeong , Dai Qing , Yang Feng-Chun , Xu Mingjiang , He Chuan
Published: October 2024

Mutation of tet methylcytosine dioxygenase 2 (encoded by TET2) drives myeloid malignancy initiation and progression1–3. TET2 deficiency is known to cause a globally opened chromatin state and activation of genes contributing to aberrant haematopoietic stem cell self-renewal4,5. However, the open chromatin observed in TET2-deficient mouse embryonic stem cells, leukaemic cells and haematopoietic stem and progenitor cells5 is inconsistent with the designated role of DNA 5-methylcytosine oxidation of TET2. Here we show that chromatin-associated retrotransposon RNA 5-methylcytosine (m5C) can be recognized by the methyl-CpG-binding-domain protein MBD6, which guides deubiquitination of nearby monoubiquitinated Lys119 of histone H2A (H2AK119ub) to promote an open chromatin state. TET2 oxidizes m5C and antagonizes this MBD6-dependent H2AK119ub deubiquitination. TET2 depletion thereby leads to globally decreased H2AK119ub, more open chromatin and increased transcription in stem cells. TET2-mutant human leukaemia becomes dependent on this gene activation pathway, with MBD6 depletion selectively blocking proliferation of TET2-mutant leukaemic cells and largely reversing the haematopoiesis defects caused by Tet2 loss in mouse models. Together, our findings reveal a chromatin regulation pathway by TET2 through retrotransposon RNA m5C oxidation and identify the downstream MBD6 protein as a feasible target for developing therapies specific against TET2 mutant malignancies.
Three spectrophotometric quantitative analysis of bisoprolol fumarate and telmisartan in fixed-dose combination utilizing ratio spectra manipulation methods
Authors: Sattar Osama I. Abdel , Abuseada Hamed H. M. , Ramzy Sherif , Abuelwafa Mahmoud M.
Published: October 2024

Hypertension is a chronic condition with multiple drug regimens. Limiting these medicines is critical to patient compliance. Therefore, bisoprolol and telmisartan were recently developed in a fixed-dose combination to control blood pressure. The UV absorption spectra of bisoprolol and telmisartan overlapped significantly. Thus, three spectrophotometric methods have been developed for simultaneous determination of bisoprolol and telmisartan without prior separation. Method A is ratio difference of ratio spectra (RD), which measures the amplitude difference between (210–224) nm for bisoprolol and between (255–365) nm for telmisartan. Method B, the first derivative of ratio spectra (1DD), measures amplitude signals at 232 and 243 nm for bisoprolol and telmisartan, respectively. Method C is the mean centering of ratio spectra (MC), which measures the mean-centered ratio spectra's values at 223 nm for bisoprolol and 245 nm for telmisartan. The applied methods showed good linearity 2–20 µg/mL for bisoprolol, 4–32 µg/mL for telmisartan, with sufficient accuracy and precision. The methods were sensitive, with LOD values of 0.243 µg/mL and 0.596 µg/mL in RD method, 0.313 µg/mL and 0.914 µg/mL in 1DD method, and 0.406 and 0.707 µg/mL in MC method for bisoprolol and telmisartan, respectively, the methods were validated per ICH criteria. The novel methods are precise and accurate and can be used for routine analysis and quality control of bisoprolol and telmisartan in pure and dosage form. Furthermore, the greenness of the approaches was evaluated using Analytical Greenness assessment (AGREE), and the suggested method received a high greenness score.
The role of TiO2 and gC3N4 bimetallic catalysts in boosting antibiotic resistance gene removal through photocatalyst assisted peroxone process
Authors: Cong Xiaoyu , Mazierski Paweł , Miodyńska Magdalena , Zaleska-Medynska Adriana , Horn Harald , Schwartz Thomas , Gmurek Marta
Published: October 2024

Antibiotics are extensively used in human medicine, aquaculture, and animal husbandry, leading to the release of antimicrobial resistance into the environment. This contributes to the rapid spread of antibiotic-resistant genes (ARGs), posing a significant threat to human health and aquatic ecosystems. Conventional wastewater treatment methods often fail to eliminate ARGs, prompting the adoption of advanced oxidation processes (AOPs) to address this growing risk. The study investigates the efficacy of visible light-driven photocatalytic systems utilizing two catalyst types (TiO2-Pd/Cu and g-C3N4-Pd/Cu), with a particular emphasis on their effectiveness in eliminating blaTEM, ermB, qnrS, tetM. intl1, 16 S rDNA and 23 S rDNA through photocatalytic ozonation and peroxone processes. Incorporating O3 into photocatalytic processes significantly enhances target removal efficiency, with the photocatalyst-assisted peroxone process emerging as the most effective AOP. The reemergence of targeted contaminants following treatment highlights the pivotal importance of AOPs and the meticulous selection of catalysts in ensuring sustained treatment efficacy. Furthermore, Polymerase Chain Reaction-Denaturing Gradient Gel Electrophoresis (PCR-DGGE) analysis reveals challenges in eradicating GC-rich bacteria with TiO2 and g-C3N4 processes, while slight differences in Cu/Pd loadings suggest g-C3N4-based ozonation improved antibacterial effectiveness. Terminal Restriction Fragment Length Polymorphism analysis highlights the efficacy of the photocatalyst-assisted peroxone process in treating diverse samples.
Human bias and CNNs’ superior insights in satellite based poverty mapping
Authors: Sarmadi Hamid , Wahab Ibrahim , Hall Ola , Rögnvaldsson Thorsteinn , Ohlsson Mattias
Published: October 2024

Satellite imagery is a potent tool for estimating human wealth and poverty, especially in regions lacking reliable data. This study compares a range of poverty estimation approaches from satellite images, spanning from expert-based to fully machine learning-based methodologies. Human experts ranked clusters from the Tanzania DHS survey using high-resolution satellite images. Then expert-defined features were utilized in a machine learning algorithm to estimate poverty. An explainability method was applied to assess the importance and interaction of these features in poverty prediction. Additionally, a convolutional neural network (CNN) was employed to estimate poverty from medium-resolution satellite images of the same locations. Our analysis indicates that increased human involvement in poverty estimation diminishes accuracy compared to machine learning involvement, exemplified with the case of Tanzania. Expert defined features exhibited significant overlap and poor interaction when used together in a classifier. Conversely, the CNN-based approach outperformed human experts, demonstrating superior predictive capability with medium-resolution images. These findings highlight the importance of leveraging machine learning explainability methods to identify predictive elements that may be overlooked by human experts. This study advocates for the integration of emerging technologies with traditional methodologies to optimize data collection and analysis of poverty and welfare.
CHK1 controls zygote pronuclear envelope breakdown by regulating F-actin through interacting with MICAL3
Authors: Zhang Honghui , Cui Ying , Yang Bohan , Hou Zhenzhen , Zhang Mengge , Su Wei , Chen Tailai , Bian Yuehong , Li Mei , Chen Zi-Jiang , Zhao Han , Zhao Shigang , Wu Keliang
Published: October 2024

CHK1 mutations could cause human zygote arrest at the pronuclei stage, a phenomenon that is not well understood at the molecular level. In this study, we conducted experiments where pre-pronuclei from zygotes with CHK1 mutation were transferred into the cytoplasm of normal enucleated fertilized eggs. This approach rescued the zygote arrest caused by the mutation, resulting in the production of a high-quality blastocyst. This suggests that CHK1 dysfunction primarily disrupts crucial biological processes occurring in the cytoplasm. Further investigation reveals that CHK1 mutants have an impact on the F-actin meshwork, leading to disturbances in pronuclear envelope breakdown. Through co-immunoprecipitation and mass spectrometry analysis of around 6000 mouse zygotes, we identified an interaction between CHK1 and MICAL3, a key regulator of F-actin disassembly. The gain-of-function mutants of CHK1 enhance their interaction with MICAL3 and increase MICAL3 enzymatic activity, resulting in excessive depolymerization of F-actin. These findings shed light on the regulatory mechanism behind pronuclear envelope breakdown during the transition from meiosis to the first mitosis in mammals.
Polymer-based Organic Room-temperature Phosphorescent Materials
Authors: Wang He , Gan Nan , Han Limingke , Meng Zhengong , An Zhongfu
Published: October 2024

Room-temperature phosphorescent (RTP) materials have garnered significant attention in recent years owing to their diverse applications in optoelectronics and bioelectronics, particularly metal-free RTP polymers. The RTP polymers possess inherent benefits such as excellent flexibility, high thermal stability, easy processing and low cost in large-scale production and applications. Besides, complex polymer networks and multi-level microphase structures may provide a rigid environment for the generation of RTP, along with dynamic photophysical properties by controlling the morphology and microphase structures. This chapter outlines the recent advancements in metal-free RTP polymers, encompassing synthetic strategies via chemical bonding engineering and nonvalent bonding, photophysical properties, luminescent mechanisms and potential applications. Finally, the advancements and challenges faced in the development of metal-free RTP polymers have been comprehensively discussed, providing an outlook for future research directions in this field.
Evaluating protocols for reproducible targeted metabolomics by NMR
Authors: Cochran Darcy , Takis Panteleimon G. , Alexander James L. , Mullish Benjamin H. , Powell Nick , Marchesi Julian R. , Powers Robert
Published: October 2024

Evaluating how sample preparation methods and data analysis platforms impact measured metabolite concentrations underscores the need for a universal consensus in the followed approaches for metabolomics data analysis.
Recent advances on COF-based single-atom and dual-atom sites for oxygen catalysis
Authors: Yan Xinru , Liu Ning , Liu Wencai , Zeng Jiajun , Liu Cong , Chen Shufen , Yang Yuhua , Gui Xuchun , Yu Dingshan , Yang Guowei , Zeng Zhiping
Published: October 2024

The COF-based SACs and DACs, including their design, synthesis, applications, and electrocatalysis mechanism, are reviewed by investigating their catalytic mechanisms underlying both the oxygen reduction reaction and oxygen evolution reaction.
Harnessing benzotriazole as a sustainable ligand in metal-catalyzed coupling reactions
Authors: Sharma Manvi , Thakur Deepika , Nidhi  , Verma Akhilesh K.
Published: October 2024

This feature article highlights the recent development in metal-catalyzed C–C, C–N, C–O, and C–S coupling reactions using benzotriazole as a ligand with an emphasis on their plausible mechanism.
Metal–support interactions in metal oxide-supported atomic, cluster, and nanoparticle catalysis
Authors: Leybo Denis , Etim Ubong J. , Monai Matteo , Bare Simon R. , Zhong Ziyi , Vogt Charlotte
Published: October 2024

Metal–support interactions (MSI) impact catalyst activity, stability, and selectivity. This review critically evaluates recent findings, theoretical advances, and MSI tuning strategies, offering new perspectives for future research in the field.
A spatially integrated electrochemical–thermal tandem reaction for continuous mild synthesis of propylene oxide
Authors: Qiu Yuefeng , Jiang Peng , Ye Wenkai , Hu Jiahao , Zhang Bin , Ji Tuo , Mu Liwen , Feng Xin , Lu Xiaohua , Zhu Jiahua
Published: October 2024

A spatially integrated electrochemical–thermal tandem reaction generates propylene oxide at 1 atm using hydrogen, oxygen, and propylene as feedstock.
Regulatable selective synthesis of benzofurans and coumarins from aryl propargyl ethers via an electrochemical tandem cyclization reaction
Authors: Feng Zhaoyue , Guan Xueyi , Ma Haiyang , Fan Yingsibing , Liu Ping , Sun Peipei
Published: October 2024

A divergent protocol for the selective synthesis of benzofuran-2-carboxaldehydes and 3-organoselenyl-2H-coumarins from propargylic aryl ethers in the presence of dialkyl(aryl) diselenides under electrochemical reaction conditions was established.
Valorization of shoe sole waste into high-performance cationic dye sorbents via sulfonation
Authors: Robertson Mark , Barbour Andrew , Qiang Zhe
Published: October 2024

This work demonstrates a straightforward method to convert real-world shoe waste midsoles into water remediation sorbents for the removal of cationic organic pollutants.
Cyclocondensation of o-phenylenediamines with α-ketothioesters: a novel approach for the synthesis of 2-acylbenzimidazoles
Authors: Kavya Kumar , Honnabandar Kanaka Vijayashankar , Sridhar Bilagumba T. , Swaroop Toreshettahally R. , Shivakumar Anantharaman , Mantelingu Kempegowda
Published: October 2024

We herein present a novel and an unexpected method for the synthesis of α-ketothioesters by the reaction of pyrrolidine with α-oxodithioester followed by treatment with methyl iodide in methanol.
Self-assembly of a NiO@NiFe2O4/rGO architecture for stable and ultra-long-life lithium-ion storage
Authors: Yao Lihua , Yao Linhua
Published: October 2024

A self-assembled NiO@NiFe2O4/rGO architecture exhibits stable and ultra-long-life lithium storage performance. This provides guidelines for finding next-generation lithium-ion storage materials and pushes lithium-ion storage to its new zenith.
Metals in nanomotion: probing the role of extracellular vesicles in intercellular metal transfer
Authors: Lei Qingyu , Phan Thanh H. , Divakarla Shiva Kamini , Kalionis Bill , Chrzanowski Wojciech
Published: October 2024

Metals are essential for cellular homeostasis, and extracellular vesicles facilitate the transfer of these metals between cells.
Concise syntheses of (–)-quinocarcinol methyl ester and (–)-oxa-quinocarcinol methyl ester
Authors: Song Tianhang , Wu Yifan , Ren Jun , Wang Zhongwen
Published: October 2024

Concise total syntheses of (–)-quinocarcinol methyl ester and (–)-oxa-quinocarcinol methyl ester have been achieved. The features of the synthetic strategy include a stereoselective [3 + 2]IMCC and a stereoselective Krapcho decarboxylation.
Tuning acid extraction of magnesium and calcium from platinum group metal tailings for CO2 conversion and storage
Authors: Woodall Caleb M. , Vaz Gomes Katherine , Voigt Andreas , Sundmacher Kai , Wilcox Jennifer
Published: October 2024

Optimizing calcium and magnesium extraction from platinum group metal mine tailings for enhanced CO2 storage via a pH-swing process.
Investigating the consistency of the shape and flux of X-ray reflection spectra in the hard state with an accretion disk reaching close to the black hole
Authors: Datta Sudeb Ranjan , Dovčiak Michal , Bursa Michal , Zhang Wenda , Horák Jiří , Karas Vladimír
Published: October 2024

Context. The observed spectra from black hole (BH) X-ray binaries (XRBs) typically consist of two primary components. A multitemperature blackbody originating from the accretion disk in the soft X-ray, and a power law-like component in the hard X-ray, due to the Comptonization of soft photons by the hot corona. The illumination of the disk by the corona gives rise to another key component known as reflection. A fraction of the incident hard X-ray radiation is naturally absorbed and re-emitted as a blackbody at lower energies and referred to as the “reprocessed blackbody”.

Aims. For densities relevant to XRBs and typical ionization values, the reprocessed blackbody may become significant in the soft X-ray region (approximately 0.1–1.0 keV) and should be noticeable in the observed spectra as a consequence of reflection. The absence of any blackbody component in the low/hard state of a BH XRB may not be consistent with the reflection of highly irradiating flux, observed as a power law from an appropriately dense disk of XRB.

Methods. We focus on the low/hard state of the BH XRB MAXI J1820+070. In contrast to previous works, we simultaneously fit the shape and flux of the reflection spectra. This allowed us to estimate the correct density and ionization of the slab as well as the corresponding reprocessed blackbody.

Results. Our fitting of the representative observation of the BH XRB low/hard state suggests that the disk may, in principle, extend very close to the BH, even though the reprocessed thermal emission (due to disk illumination) remains cold (and thus low) enough to be consistent with the data in contrast to the results of a previous study. The inner reflection component is highly ionized and its fit is primarily driven by its contribution to the continuum, rather than by the shape of the relativistic iron line.

Conclusions. The reprocessed blackbody cannot help determine whether the disk extends close to the BH or not in the hard state. For this specific observation, the flux in inner reflection component turns out to be quite low with respect to the outer reflection or power law. The outflowing slab corona covering the inner region of the disk could be the plausible geometry of the source, with the underlying disk approaching near to the BH.