bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lysosomal degradation of PD-L1 is associated with immune-related adverse events during anti-PD-L1 immunotherapy in NSCLC patients
Authors: Kashiwada Takeru , Takano Ryotaro , Ando Fumihiko , Kuroda Shoko , Miyabe Yoshishige , Asatsuma-Okumura Tomoko , Hashiguchi Masaaki , Kanazawa Yoshikazu , Yoshida Hiroshi , Seike Masahiro , Gemma Akihiko , Iwai Yoshiko 
Published: January 2024

AbstractBACKGROUNDImmune checkpoint inhibitors (ICIs) can induce immune-related adverse events (irAEs). However, the biological mechanisms underlying irAEs are not well understood. We previously developed an ELISA system to specifically detect soluble PD-L1 (sPD-L1) with PD-1-binding capacity (bsPD-L1). Here, we investigated the relationship between sPD-L1 and bsPD-L1 in gastric cancer (GC) and non-small cell lung cancer (NSCLC) patients treated with PD-1/PD-L1 blockade and their association with irAEs.METHODSWe examined sPD-L1, bsPD-L1, matrix metalloproteinases (MMPs), and proinflammatory cytokine levels by ELISA in plasma samples from 117 GC patients prior to surgery and 72 NSCLC patients prior to and at 2 months after ICI treatment (anti-PD-1, n = 48; anti-PD-L1, n = 24). In mice treated with anti-PD-1/PD-L1 antibodies (Abs), sPD-L1 levels and localization of Abs were examined by ELISA and immunohistochemistry, respectively.RESULTSsPD-L1 was detected with higher frequency in GC patients (76.9%) than in NSCLC patients (8.3%), whereas bsPD-L1 was detected with similar frequencies in GC and NSCLC patients (14.5% and 22.2%, respectively). sPD-L1 levels were correlated with IL-1α, IL-1β, TNF-α, and IL-6 levels, while bsPD-L1 levels were correlated with MMP13, MMP3, and IFN-γ levels. In NSCLC patients, anti-PD-L1, but not anti-PD-1, treatment increased sPD-L1, which was associated with irAE development, but not with clinical outcomes. In mice, trafficking of anti-PD-L1 Abs to lysosomes in F4/80+macrophages resulted in sPD-L1 production, which was suppressed by treatment with lysosomal degradation inhibitor chloroquine and macrophage depletion.CONCLUSIONSAnti-PD-L1-mediated lysosomal degradation induces sPD-L1 production, which can serve as an indicator to predict irAE development during anti-PD-L1 treatment.
Pandemic-Related Post-traumatic Stress Symptomatology in COVID-19 Patients with and without Post-COVID Conditions
Authors: Guinee Emily P. , Raza Haniya , Ballard Elizabeth D. , Shaw Jacob S. , Liang C. Jason , Sneller Michael C. , Chung Joyce Y. 
Published: January 2024

AbstractTrauma and stressor-related symptoms have been frequently reported during the COVID-19 pandemic. Few studies compare post-traumatic stress symptoms (PTSS) between patients and non-infected controls. Using data from an ongoing natural history study of COVID-19, this study compared PTSS between patients infected with SARS-CoV-2 during the first year of the pandemic and controls. Within the COVID-19 patient cohort, we also compared PTSS between patients with and without post-COVID conditions, also known as post-acute sequelae of SARS-CoV-2 infection (PASC). This study also examined the association of PTSS with trait resilience and prior trauma exposure. PTSS were assessed using the Impact of Event Scaled-Revised (IES-R), which has a validated probable PTSD cutoff (score ≥33). The results showed that patients (n=131) reported significantly higher IES-R scores than controls (n=82) and had significantly higher odds of having scores indicative of PTSD [AOR: 4.17p:0.029]. IES-R scores among PASC patients (n=68) were significantly elevated compared to patients without PASC (n=63) and PASC patients did not have higher odds for probable PTSD [AOR: 2.60;p:0.14]. Trait resilience was associated with lower PTSS. These findings help characterize the mental health impact of the COVID-19 illness experience and highlight elevated PTSS in patients with persistent post-COVID conditions.
Cytoarchitecture of SARS-CoV-2 infected hamster lungs by X-ray phase contrast tomography: imaging workflow and classification for drug testing
Authors: Reichmann Jakob , Sarrazin Clement , Schmale Sebastian , Blaurock Claudia , Balkema-Buschmann Anne , Schmitzer Bernhard , Salditt Tim 
Published: January 2024

ABSTRACTX-ray Phase Contrast Tomography (XPCT) based on wavefield propagation has been established as a high resolution three-dimensional (3D) imaging modality, suitable to reconstruct the intricate structure of soft tissues, and the corresponding pathological alterations. However, for biomedical research, more is needed than 3D visualisation and rendering of the cytoarchitecture in a few selected cases. First, the throughput needs to be increased to cover a statistically relevant number of samples. Second, the cytoarchitecture has to be quantified in terms of morphometric parameters, independent of visual impression. Third, dimensionality reduction and classification are required for identification of effects and interpretation of results. In this work, we present a workflow implemented at a laboratoryμCT setup, using semi-automated data acquisition, reconstruction and statistical quantification of lung tissue in an early screen of Covid-19 drug candidates. Different drugs were tested in a hamster model after SARS-CoV-2 infection. To make full use of the recorded high-throughput XPCT data, we then used morphometric parameter determination followed by a dimensionality reduction and classification based on optimal transport. This approach allows efficient discrimination between physiological and pathological lung structure, thereby providing invaluable insights into the pathological progression and partial recovery due to drug treatment.
Dynamic Modulation of Representational Trajectories Through Selective Attention
Authors: Zhou Yu , Zhang Liang , Axmacher Nikolai , Pacheco Estefan Daniel , Wang DaHui , Dai Yujian , Peng Xiaojing , Xue Gui 
Published: January 2024

AbstractMounting evidence indicates that information processing in the visual hierarchy follows a sequential progression from low-level perceptual to high-level conceptual features during visual perception, with the reverse order during memory retrieval. However, the nature of this hierarchical processing and its modulation by selective attention remains unclear. By integrating a deep neural network with the drift-diffusion model on reaction time data, we identified parallel processing of perceptual and conceptual features during perception, rather than sequential processing. The slower reaction times observed in conceptual tasks compared to perceptual tasks were primarily driven by the larger decision boundary and longer non-decision time associated with conceptual features, which could not be compensated by their faster evidence accumulation rates. Using single-trial multivariate decoding of MEG (magnetoencephalography) data to examine the timing of neural representations of different features, we found that selective attention reversed the onset times of perceptual and conceptual features in the occipital and parietal lobes during perception. This led to earlier detection of conceptual features compared to perceptual features in the animacy and size tasks. During retrieval, the colour task exhibited earlier peak times for perceptual features compared to conceptual features in the frontal lobe, indicating that perceptual features were reconstructed with the highest fidelity before conceptual features. These findings provide novel insights into the hierarchical nature of information processing during perception and retrieval, emphasizing the crucial role of selective attention in modulating the speed of feature information accumulation.
Discovery of the 1-naphthylamine biodegradation pathway reveals an enzyme that catalyzes 1-naphthylamine glutamylation
Authors: Zhang Shu-Ting , Deng Shi-Kai , Li Tao , Maloney Megan E. , Li De-Feng , Spain Jim C. , Zhou Ning-Yi 
Published: January 2024

Abstract1-Naphthylamine (1NA), which is harmful to human and aquatic animals, has been used widely in the manufacturing of dyes, pesticides, and rubber antioxidants. Nevertheless, little is known about its environmental behavior and no bacteria have been reported to use it as the growth substrate. Herein, we describe a pathway for 1NA degradation in isolatePseudomonassp. strain JS3066, determine the structure and mechanism of the enzyme NpaA1 that catalyzes the initial reaction, and reveal how the pathway evolved. From genetic and enzymatic analysis, a cluster of 5 genes encoding a dioxygenase system was determined to be responsible for the initial steps in 1NA degradation through glutamylation of 1NA. The γ-glutamylated 1NA was subsequently oxidized to 1,2-dihydroxynaphthalene which was further degraded by the well-established pathway of naphthalene degradation via catechol. Enzymatic analysis showed that NpaA1 catalyzed conversion of various anilines and naphthylamine derivatives. Structural and biochemical studies of NpaA1 revealed that the broad substrate specificity of NpaA1 is due to a large hydrophobic pocket, which is different from type I glutamine synthetase (GSI). The findings enhance understanding of degrading polycyclic aromatic amines, and will also enable the application of bioremediation at naphthylamine contaminated sites.
Obesity differentially effects the somatosensory cortex and striatum of TgF344-AD rats
Authors: Ahmed Minhal , Lai Aaron Y. , Hill Mary E. , Ribeiro Jessica A. , Amiraslani Ashley , McLaurin JoAnne 
Published: January 2024

1AbstractLifestyle choices leading to obesity, hypertension and diabetes in mid-life contribute directly to the risk of late-life Alzheimer’s disease (AD). However, in late-life or in late-stage AD conditions, obesity reduces the risk of AD and disease progression. To examine the mechanisms underlying this paradox, TgF344-AD rats were fed a varied high-carbohydrate, high-fat (HCHF) diet to induce obesity from nine months of age representing early stages of AD to twelve months of age in which rats exhibit the full spectrum of AD symptomology. We hypothesized regions primarily composed of gray matter, such as the somatosensory cortex (SSC), would be differentially affected compared to regions primarily composed of white matter, such as the striatum. We found increased myelin and oligodendrocytes in the somatosensory cortex of rats fed the HCHF diet with an absence of neuronal loss. We observed decreased inflammation in the somatosensory cortex despite increased AD pathology. Compared to the somatosensory cortex, the striatum had fewer changes. Overall, our results suggest that the interaction between diet and AD progression affects myelination in a brain region specific manner such that regions with a lower density of white matter are preferentially effected. Our results offer a possible mechanistic explanation for the obesity paradox.
Structure of hepatitis B/D antiviral drug Bulevirtide bound to its receptor protein NTCP
Authors: Liu Hongtao , Zakrzewicz Dariusz , Nosol Kamil , Irobalieva Rossitza N. , Mukherjee Somnath , Bang-Sørensen Rose , Goldmann Nora , Kunz Sebastian , Rossi Lorenzo , Kossiakoff Anthony A. , Urban Stephan , Glebe Dieter , Geyer Joachim , Locher Kaspar P. 
Published: January 2024

AbstractCellular entry of the hepatitis B and D viruses (HBV/HDV) require binding of the viral surface polypeptide preS1 to the hepatobiliary transporter NTCP. This interaction can be blocked by bulevirtide (BLV, formerly Myrcludex B), a preS1 derivative and approved drug for treating HDV infection. To elucidate the basis of this inhibitory function, we determined a cryo-EM structure of BLV-bound human NTCP. BLV forms two domains, a plug lodged in the bile salt transport tunnel of NTCP and a string that covers the receptor’s extracellular surface. The N-terminally attached myristoyl group of BLV interacts with the lipid-exposed surface of NTCP. Our structure reveals how BLV inhibits bile salt transport, rationalizes NTCP mutations that decrease the risk of HBV/HDV infection, and provides a basis for understanding the host specificity of HBV/HDV. Our results provide opportunities for structure-guided development of inhibitors that target HBV/HDV docking to NTCP.
Mechanism of chaperone coordination during cotranslational protein folding in bacteria
Authors: Roeselová Alžběta , Maslen Sarah L. , Shivakumaraswamy Santosh , Pellowe Grant A. , Howell Steven , Joshi Dhira , Redmond Joanna , Kjaer Svend , Skehel J. Mark , Balchin David 
Published: January 2024

SUMMARYProtein folding is assisted by molecular chaperones that bind nascent polypeptides during mRNA translation. Several structurally-distinct classes of chaperone promotede novofolding, suggesting that their activities are coordinated at the ribosome. We used biochemical reconstitution and structural proteomics to explore the molecular basis for cotranslational chaperone action in bacteria. We found that chaperone binding is disfavoured close to the ribosome, allowing folding to precede chaperone recruitment. Trigger factor subsequently recognises compact folding intermediates exposing extensive non-native surface and dictates DnaJ access to nascent chains. DnaJ uses a large surface to bind structurally diverse intermediates, and recruits DnaK to sequence-diverse solvent-accessible sites. Neither Trigger factor, DnaJ nor DnaK destabilize cotranslational folding intermediates. Instead, the chaperones collaborate to create a protected space for protein maturation that extends well beyond the ribosome exit tunnel. Our findings show how the chaperone network selects and modulates cotranslational folding intermediates.
Culture-free whole genome sequencing ofMycobacterium tuberculosisusing ligand-mediated bead enrichment method
Authors: Vasanthaiah Shruthi , Verma Renu , Kumar Ajay , Bandari Aravind , George John , Rastogi Mona , Manjunath Gowrang Kasaba , Sharma Jyoti , Kumar Abhishek , Subramani Janavi , Chawla Kiran , Pandey Akhilesh 
Published: January 2024

ABSTRACTBackgroundDirect whole genome sequencing (WGS) ofMycobacterium tuberculosis(Mtb) can be used as a tool to study drug resistance, mixed infections, and within host diversity. However, WGS is challenging from clinical samples due to low number of bacilli against a high background.MethodsWe prospectively collected 34 samples (sputum, n=17; bronchoalveolar lavage, BAL, n=13 and pus, n=4) from patients with active tuberculosis (TB). Prior to DNA extraction, we used a ligand-mediated magnetic bead method to enrichMtbfrom clinical samples and performed WGS on Illumina platform.ResultsMtbwas definitively identified based on WGS from 88.2% (30/34) of the samples of which 35.3% (12/34) were smear negative. The overall median genome coverage was 15.2% (IQR = 7.9-39.3). There was a positive correlation between load of bacilli on smears and genome coverage (p-value < 0.001). We detected 58 genes listed in the WHO mutation catalogue in each positive sample (median coverage = 85%, IQR = 61%-94%), enabling the identification of mutations missed by routine diagnostics. Mutations causing resistance to rifampicin, isoniazid, streptomycin, and ethambutol were detected in 5/34 (14.7%) samples, including therpoBS441A mutation that confers resistance to rifampicin which is not covered by Xpert MTB/RIF. This approach also allowed us to identify mixed infections in eight samples (BAL=4/8, pus=2/3 and sputum= 2/10) including samples that were infected with three or more different strains ofMtb.ConclusionsWe demonstrate the feasibility of magnetic bead-based enrichment for culture-free WGS ofMtbfrom clinical specimens, including smear-negative samples. This approach can also be integrated with low-cost sequencing workflows such as targeted sequencing for rapid detection ofMtband drug resistance.
Hidden charmonium decays of spin-2 partner of
X(3872)
Authors: Zheng Yuanxin , Cai Zuxin , Li Gang , Liu Shidong , Wu Jiajun , Wu Qi 
Published: January 2024

The Belle Collaboration recently reported a promising candidate for the spin-2 D*D¯* partner of the X(3872), called the X2 for short, having a mass of (4014.3±4.0±1.5)  MeV and a width of (4±11±6)  MeV. Assuming the X2 as a pure molecule of the D*D¯*, we calculated in detail the hidden charmonium decays of the X2→J/ψV and X2→ηcP via the intermediate meson loops, where V=ρ0,ω and P=π0,η,η′. The results indicate that the decay widths are strongly dependent on the X2 mass. At present center value of the mass 4014.3 MeV, the width for the X2→J/ψρ0 is predicted to be a few tens of keV, while it is on the order of 102−3  keV for the X2→J/ψω; the predicted width for the X2→ηcπ0 is about a few keV, while the widths for X2→ηcη and ηcη′ are around a few tens and tenths of keV, respectively. We also investigated the dependence of the ratios between these widths on the X2 mass and on the η−η′ mixing angle, which may be good quantities for experiments. We hope that the present calculations will be checked experimentally in the future.

Published by the American Physical Society
2024
Numerical calculation of shock wave overpressure produced by multiple cloud detonation
Authors: Fu Zeye , Zou Jiahao , Han Luxin , Zhang Qi 
Published: January 2024

PurposeA model for calculating the global overpressure time history of a single cloud detonation from overpressure time history of discrete positions in the range of single cloud detonation is to be proposed and verified. The overpressure distribution produced by multiple cloud detonation and the influence of cloud spacing and fuel mass of every cloud on the overpressure distribution are to be studied.Design/methodology/approachA calculation method is used to obtain the global overpressure field distribution after single cloud detonation from the overpressure time history of discrete distance to detonation center after single cloud detonation. On this basis, the overpressure distribution produced by multi-cloud under different cloud spacing and different fuel mass conditions is obtained.FindingsThe results show that for 150 kg fuel, when the spacing of three clouds is 40 m, 50 m, respectively, the overpressure range of larger than 0.1 MPa is 5496.48 mˆ2 and 6235.2 mˆ2, which is 2.89 times and 3.28 times of that of single cloud detonation. The superposition effect can be ignored when the spacing between the three clouds is greater than 60 m. In the case of fixed cloud spacing, once the overpressure forms continuous effective superposition, the marginal utility of fuel decreases.Originality/valueA model for calculating the global overpressure time history of a single cloud detonation from overpressure time history of discrete positions in the range of single cloud detonation is proposed and verified. Based on this method, the global overpressure field of single cloud detonation is reconstructed, and the superimposed overpressure distribution characteristics of three cloud detonation are calculated and analyzed.
Abusive supervisor triggers counterproductive work behaviors in nursing staff: role of psychological contract breach and Islamic work ethics
Authors: Maqbool Mehak , Lyu Bei , Ullah Sami , Khan Muhammad Tasnim , Abeden Ali Zain ul , Kukreti Mohit 
Published: January 2024

PurposeAbusive supervision (AS) provides insights into the darker aspects of leadership behavior and its effects on employees. Understanding and addressing AS can contribute to creating healthier work environments and promoting employee well-being. The effect of abusive leadership (AS) on counterproductive work behaviors (CWB) in nursing staff is examined through the theoretical lens of the social exchange theory.Design/methodology/approachData were collected from 302 nursing staff working at public and private hospitals through a self-administered questionnaire. Measurement scales were adapted from the literature and the data were tested for validity and reliability before performing hypotheses testing through structural equation modeling in SmartPLS 4.0.FindingsAS positively affects CWB, and psychological contract breach mediates this relationship. However, employees with high Islamic work ethics (IWE) are less concerned with supervisors' dysfunctional behaviors and pay less attention to them; thus, IWE buffers the effect of AS on CWBs.Originality/valueA positive and supportive organizational climate is crucial for attracting and retaining skilled healthcare professionals. When healthcare professionals are subjected to abusive behaviors, their ability to share knowledge, adopt safety protocols and provide the best patient care may be hampered. Therefore, addressing AS in hospitals is vital to promoting a positive work environment, enhancing employee well-being and improving patient care.
Impact of individual-focused transformational leadership on individual work performance: mediating role of work engagement and moderating role of regulatory focus
Authors: Fernando Panawannage Bhagya Dewmini , Jayawardana Ananda K.L. 
Published: January 2024

PurposeThis study aims to investigate how the individual-focused transformational leadership effect of transformational leadership impacts the team member’s individual work performance through the intermediary mechanisms of work engagement and regulatory focus.Design/methodology/approachA moderated mediation model was analyzed through PLS-SEM by using a sample of 462 team members across diverse work teams in Sri Lankan organizations.FindingsResults revealed that individual-focused transformational leadership positively impacts the team member’s individual work performance through the mediation of the team member’s work engagement. The direct relationship between individual-focused transformational leadership and the team member’s work engagement was found to be positively moderated by the team member’s promotion regulatory focus.Practical implicationsThis paper demonstrates implications for team designing and leadership development and highlights the importance of team leaders utilizing individual-focused transformational leadership to gain improved work performance from each team member.Originality/valueThis study provides empirical evidence for the mediating role of work engagement and the moderating role of promotion regulatory focus in deriving the team member’s work performance, which contributes to constructing a more refined profile of individual-focused transformational leadership.