bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and application of an integrated system of dewatering and recharge for the deep foundation pit
Authors: Zhang Zhenjie , Zeng Chunpin , Zhang Enzhong , Su Qingwei , Li Min , Gong Liang , Geng Fuqiang , Zhang Zhigang
Published: December 2023

A large amount of pumping in the deep foundation pit will reduce the groundwater level and lead to surface cracking, building settlement, ground collapse and spring water cut-off. And the groundwater recharge is a good control measure. An integrated system of dewatering and recharge for the deep foundation pit is developed, and it is mainly composed of a pumping system, an assembled water tank, a variable frequency pressure system, a cleaning and filtering system, a recharge pressure tank, a recharge well system and a central control system. This system can realize intelligent automatic control according to the monitoring data. It does not require staff to operate on site and can be remotely adjusted by computer or mobile phone. Taking a subway station under construction in Jinan as the background, the single well recharge test and the multiple wells recharge test were carried out. It can be found that with the increase of recharge pressure, the recharge volume gradually increases, but the increasing trend is smaller and smaller. The relationship between the groundwater level and the recharge volume is a logarithmic function. Blindly increasing recharge wells may not improve the overall reinjection volume, and the relationship between the number of recharge wells, the diameter of reinjection pipes and the maximum recharge capacity of the variable frequency pressure system needs to be comprehensively considered.
Mentalizing and Binge Eating Disorder
Authors: Myhre Julianne Solvik , Ødegård Magnar
Published: December 2023

Binge eating disorder (BED) is presumed to be the most common kind of eating disorder. However, the knowledge of BED in general society is low, and treatment options have been lacking or not been of sufficient quality. This article applies mentalizing as a theoretical framework to analyze descriptions of BED. The study suggests that descriptions of social, emotional, and cognitive characteristics of BED can be interpreted as impaired mentalizing. However, several of these impaired mentalizing traits can also be seen as a result of cultural and social tendencies, more so than a pathological component solely linked to BED. This article aims to gain deeper insights into the social, emotional, and cognitive aspects of BED. We refer to interviews with three adult females who earlier struggled with BED. Our theoretical and empirical exploration indicates that BED touches upon a wide array of areas related to mentalizing, such as inner confusion, psychological reality, and (social) self-concept.
Model Risk Management
Authors: Rüschendorf Ludger , Vanduffel Steven , Bernard Carole
Published: December 2023

This book provides the first systematic treatment of model risk, outlining the tools needed to quantify model uncertainty, to study its effects, and, in particular, to determine the best upper and lower risk bounds for various risk aggregation functionals of interest. Drawing on both numerical and analytical examples, this is a thorough reference work for actuaries, risk managers, and regulators. Supervisory authorities can use the methods discussed to challenge the models used by banks and insurers, and banks and insurers can use them to prioritize the activities on model development, identifying which ones require more attention than others. In sum, it is essential reading for all those working in portfolio theory and the theory of financial and engineering risk, as well as for practitioners in these areas. It can also be used as a textbook for graduate courses on risk bounds and model uncertainty.
Christians, Muslims, and Jews: Turkey and the management of refugees from Greece during World War II
Authors: Lamprou Alexandros
Published: December 2023

Approximately 70,000 people were displaced from Greece to Turkey and the Middle East during World War II. Following a presentation of the geography, statistics, and timeframe of the displacement, and Turkey’s interwar demographic policies, the article studies Turkey’s management of this refugee movement. Based on Greek, Turkish, and British archival material, the article argues that Turkish wartime refugee policy took shape in the intersection of two occasionally contradictory attributes. On the one hand, there were the state’s demographic desiderata and policies that differentiated incoming refugees on account of their ethnic and religious identities. On the other, Turkey’s reaction was necessarily conditioned by the military, political, and diplomatic conjuncture of the war. It was this conditionality that explains the inconsistences and shifts in refugee management and its rationale during the war, for instance, the differentiation in the treatment of Jewish and Christian refugees, but also in the management of Greek Muslims in 1941–1942 and in 1944–1945.
Housing and Patrimonial (Property) Violence against Women: The Reproduction of Gender Asset Inequalities in Brazil
Authors: Ludermir Raquel
Published: December 2023

Accessing and retaining adequate housing can be a major challenge for low-income city residents, particularly women trying to escape domestic abuse. Focusing on housing struggles amidst urban poverty, this article explores a specific kind of gender-based violence – violation of women's property rights – recognised by Latin American legal systems as ‘patrimonial violence against women’. Drawing on qualitative research in Brazil, this article shows how women are likely to experience gendered evictions and dispossession, and why patrimonial violence against women remains largely misunderstood and underreported, despite legal progress. The discussion expands current understandings of the interplay between gender, violence (explicit or otherwise) and the reproduction of asset inequalities.
A buffer-gas trap for the NEPOMUC positron beam: optimization studies with electrons
Authors: Deller A. , Rogge C.W. , Desopo S. , Stenson E.V. , Danielson J.R. , Stoneking M.R. , Hugenschmidt C. , Sunn Pedersen T. , Surko C.M.
Published: December 2023

Buffer-gas traps (BGTs) use inelastic interactions with nitrogen molecules to capture positrons from a continuous beam. These devices are invaluable for high-resolution studies of matter–antimatter interactions, antihydrogen research and positronium laser spectroscopy. We present a new project with the goal of producing a non-neutral plasma containing

${\sim }10^8$

low-energy positrons by installing a BGT on the NEPOMUC (NEutron induced POsitron source MUniCh) high-intensity positron beam. Details of the BGT are outlined and results are presented from experiments in which an electron beam, with a similar intensity and energy spread to the remoderated NEPOMUC beam, was used to create pulses of non-neutral electron plasma. The device is a vital component of the APEX (A Positron Electron eXperiment) project, which aims to create a low-temperature electron–positron pair plasma.
Reciprocity, Inequality, and Unsuccessful Rescues
Authors: Eskens Romy
Published: December 2023

Forced choices between rescuing imperilled persons are subject to a presumption of equality. Unless we can point to a morally relevant difference between these persons' imperilments, each should get an equal chance of rescue. Sometimes, this presumption is overturned. For example, when one imperilled person has wrongfully caused the forced choice, most think that this person (rather than an innocent person) should bear the harm. The converse scenario, in which a forced choice resulted from the supererogatory action of one of the imperilled people, has received little attention in distributive ethics. I argue that, sometimes, we need not offer equal chances in these cases either. When the supererogatory act places the initially imperilled person under a reciprocal duty to bear risks for the supererogatory agent's sake in the forced choice, we may fulfil this duty for them if they are unable to do it themselves, by favouring the supererogatory agent.
The risk of highly pathogenic avian influenza in the Southern Ocean: a practical guide for operators and scientists interacting with wildlife
Authors: Dewar Meagan , Wille Michelle , Gamble Amandine , Vanstreels Ralph E.T. , Bouliner Thierry , Smith Adrian , Varsani Arvind , Ratcliffe Norman , Black Jennifer , Lynnes Amanda , Barbosa Andrés , Hart Tom
Published: December 2023

Advice from avian influenza experts suggests that there is a high risk that highly pathogenic avian influenza will arrive in the Southern Ocean during the austral summers.
Subcutaneous administration of drugs and hydration in acute palliative care units: Physician attitudes and beliefs in the United States and Canada
Authors: Tang Michael , Khan Rida , Ruiz Buenrostro Alejandra , Andersen Clark R. , Lau Jenny , Hui David , Zimmermann Camilla , Bruera Eduardo
Published: December 2023

Objectives

The objective of this study was to compare the attitudes and beliefs of PCU physicians leaders in the United States versus Canada regarding the subcutaneous method in the administration of medications and hydration in order to gain a better understanding as to why variations in practice exist.

Methods

This survey trial took place from November 2022 to May 2023. The MD Anderson Cancer Center institutional review board in Houston, Texas, approved this study. The participants were the physician leaders of the acute palliative care units (PCUs) in the United States and Canada. The survey comprised questions formulated by the study investigators regarding the perceived comfort, efficiency, and preference of using the subcutaneous versus the intravenous method. The consent form and survey links were emailed to the participants.

Results

Sixteen PCUs were identified in the United States and 15 PCUs in Canada. Nine US and 8 Canadian physicians completed the survey. Physicians in Canada were more likely to use the subcutaneous route for administering opioids, antiemetics, neuroleptics, and hydration. They preferred subcutaneous over intravenous or intramuscular routes (p= 0.017). Canadian physicians felt their nursing staff was more comfortable with subcutaneous administration (p= 0.022) and that it was easier to administer (p= 0.02). US physicians felt the intravenous route was more efficient (p= 0.013).

Significance of results

The study results suggest that exposure to the subcutaneous route influences a physician’s perception. Further research is needed to explore ways to incorporate its use to a greater degree in the US healthcare system.
BEYOND LINGUISTIC INTERPRETATION IN THEORY COMPARISON
Authors: MEADOWS TOBY
Published: December 2023

This paper assembles a unifying framework encompassing a wide variety of mathematical instruments used to compare different theories. The main theme will be the idea that theory comparison techniques are most easily grasped and organized through the lens of category theory. The paper develops a table of different equivalence relations between theories and then answers many of the questions about how those equivalence relations are themselves related to each other. We show that Morita equivalence fits into this framework and provide answers to questions left open in Barrett and Halvorson [4]. We conclude by setting up a diagram of known relationships and leave open some questions for future work.
No benefit of soluble fiber on liver function
Authors: Ghavami Abed , Talebi Sepide , Barghchi Hanieh , Nattagh‐Eshtivani Elyas , Mohammadi Hamed , Ziaei Rahele
Published: December 2023

Abstract: Background: To conduct a systematic review and dose-response meta-analysis of current findings from randomized controlled trials (RCTs) on the effect of soluble fiber supplementation on liver function in both healthy individuals and people with specific health conditions, PubMed, Scopus, and ISI Web of Science were systematically searched for relevant RCTs published prior to April 2022. Methods: We estimated the change in liver function parameters for each 5 g/d increment in soluble fiber in each trial and then calculated the mean difference (MD) and 95%CI. A total of 25 RCTs with 27 treatment arms (1744 subjects; 884 cases, 860 controls) were included. Results: A total of 25 RCTs with 27 treatment arms were included. The intervention duration of the included studies ranged from 3 to 52 weeks and the dose of soluble fiber supplementation varied from 0.0025 to 40 g/d. Soluble fiber supplementation could not significantly affect serum alanine transaminase (MD: −0.02 U/L, 95% CI: −1.06 to 1.01), aspartate transaminase (MD: −0.34 U/L, 95% CI: −0.84 to 0.15), alkaline phosphatase (MD: 0.29 U/L, −0.14 to 0.71), gamma-glutamyl transferase (MD: 0.12 U/L; 95% CI: −0.81 to 1.05), serum bilirubin (MD: 0.42μmol/L, 95% CI: −0.08 to 0.93) and albumin (MD: 0.64 g/dl, 95% CI: −0.42 to 1.70) levels. Conclusions: Findings from this study did not support the beneficial effects of soluble fiber supplementation on liver function biomarkers. There is a need for long-term high-quality interventions to examine the effects of different types and doses of soluble fibers on liver function as primary outcome.
Web-Based Positive Psychology Intervention for Adolescents With Current or Remitted Major Depressive Disorder
Authors: Kaubisch Sara , Kloek Maria , Primbs Regine , Iglhaut Lucia , Piechaczek Charlotte E. , Keim Pia-Marie , Feldmann Lisa , Schulte-Körne Gerd , Greimel Ellen
Published: December 2023

Abstract: Theoretical Background: Youth with major depressive disorder often do not receive appropriate treatment. Furthermore, evidence-based, highly acceptable, and easily accessible information about depression and its treatment along with services as a complementary strategy to professional treatment is needed for young people seeking help for depression. In autumn 2021, we launched the website www.ich-bin-alles.de. Besides evidence-based information about depression, the website provides self-help exercises based on principles of positive psychology, which might attract young people and can be easily implemented in daily life as a hands-on support. Objective: This randomized controlled trial (preregistered at ClinicalTrials.gov: NCT04994470) examined the efficacy of this positive psychology intervention (PPI) to improve affect- and stress-related outcomes in adolescents with a history of major depressive disorder and assessed its acceptability and adherence aspects. Methods: Data from 77 youth with current or remitted major depressive disorder (who were undergoing or had undergone psychiatric and/or psychotherapeutic treatment) aged 12 – 18 years were analyzed. Participants were randomized to receive either 14 daily web-based self-help exercises based on positive psychology in the experimental group or a web-based sham intervention in the control group. Self-report inventories were applied to assess changes in affect- and stress-related outcome measures as well as the acceptability of and adherence to the intervention. Results: No differential effects of the experimental intervention on affect- and stress-related outcomes were revealed. More than 78 % of the participants in the experimental group reported that they would recommend the self-help exercises of the PPI to other youth and the overall acceptance of the PPI exercises was good. Moreover, 75 % of the participants in the experimental group reported that they carried out the PPI self-help exercises. Discussion and Conclusion: The results have important implications for future approaches that aim to implement web-based self-help exercises based on positive psychology for adolescents with depression, for which we found good adherence and acceptance. In future studies, it would be important to investigate whether a more intensive PPI might also specifically improve affect- and stress-related outcomes and be a promising way to augment the efficacy of traditional therapy approaches in adolescents affected by major depressive disorder.
Evaluating the Psychometric Properties of the Romanian Version of	Thriving at Work Scale
Authors: Okros Norberth , Vîrgă Delia
Published: December 2023

Abstract: The present research aims to evaluate the psychometric properties of the Romanian version of the thriving at work scale (TWS). Three studies were conducted to test the reliability and validity of the TWS. The first study ( N = 451) aimed to adapt and validate the Romanian version of TWS. The confirmatory factor analysis results indicated that the second-order model with 10-items has a good value of the fit indices. The second study ( N = 435) tested measurement invariances, demonstrating that the Romanian version of this scale has varying levels of thriving at work across job tenure and a differential functioning of items 2 and 9 across age. The third study ( N = 312) cross-validated the second-order model. It tested the construct-related validity of TWS with other relevant constructs (job and career satisfaction, burnout, mental health complaints, performance). The results indicated that the TWS is a reliable and valid instrument demonstrating the crucial implications for Romanian working people’s well-being and career development.
Development and Validation of the Work Orientation Questionnaire Short-Form (WOQ-SF)
Authors: Liu Doudou , Wang Yiming , Li Chaoping
Published: December 2023

Abstract: This research aims to develop a 15-item short form of the WOQ (WOQ-SF) and provide evidence for its reliability and validity. In Study 1 ( N = 305), we simplified the WOQ into a short version in line with the scale reduction procedure and recommendations ( Kruyen et al., 2013 ; Stanton et al., 2002 ). The exploratory factor analysis (EFA) reveals that the five factors of the WOQ-SF are conceptually distinct and correlated with each other. In Study 2 ( N = 442), the psychometric properties of the WOQ-SF were investigated. The findings of the confirmatory factor analysis (CFA) confirm a good factor structure. In addition, the measurement invariance of this shortened scale was examined across gender, age, education level, and job tenure. Regarding validity, significant correlations between the WOQ-SF and the original WOQ were found. Furthermore, the WOQ-SF demonstrates relationships with career satisfaction, work engagement, job satisfaction, and career planning, providing evidence for its validity. In sum, the WOQ-SF shows good psychometric properties comparable to the WOQ, suggesting it is a suitable alternative.
Civic-Mindedness Is More Than Personality
Authors: Van Matre Joseph C. , Bekkers René , Huizinga Mariëtte , de Wit Arjen
Published: December 2023

Abstract: Many colleges and universities have embraced the goal of increasing students’ civic-mindedness. The research associated with theorizing and measuring civic-mindedness, however, has thus far progressed in a silo away from the established literature of personality psychology. This paper bridges this gap – adopting civic efficacy and service motivation as two measures of civic-mindedness – and examines how well they are explained by the five-factor model of personality (FFM). Using survey data from undergraduate students at a large, public research university, we estimated a structural equation model to measure personality traits from the FFM, service motivation, and civic efficacy. Results showed that variation in personality accounts for approximately 40% of the variation in Service Motivation and 53% of the variation in Civic Efficacy, which does not support a clear assertion that either construct can neatly be categorized as a facet of the FFM. Our findings provide an additional theoretical basis for community service learning courses and other educational opportunities that blend traditional pedagogical strategies with experiential and reflective opportunities aiming to produce change across state-like and trait-like attributes.
Resilience in Times of a Pandemic
Authors: Bellesia Francesca
Published: December 2023

Abstract: This study uncovers how workers of the gig economy adjusted to the COVID-19 pandemic and exhibited capacity for resilience. Following the grounded theory approach, it analyzes more than 400 Upwork and Uber workers' conversations that were posted on Reddit during the first year of the pandemic. Findings reveal that, to face the pandemic risks, gig workers shared news and strategic knowledge with the community, temporarily transformed their work and designed new working practices, and sought emotional support from peers. These findings underscore the processes of resilience among gig workers, allow for comparisons between Upwork and Uber workers, and reveal how gig workers support each other in online communities, which functioned as relational resources.
The SNP rs460089 in the gene promoter of the drug transporter OCTN1 has prognostic value for treatment-free remission in chronic myeloid leukemia patients treated with imatinib
Authors: Machova Polakova Katerina , Albeer Ali , Polivkova Vaclava , Krutska Monika , Vlcanova Katerina , Curik Nikola , Fabarius Alice , Klamova Hana , Spiess Birgit , Waller Cornelius F. , Brümmendorf Tim H. , Dengler Jolanta , Kunzmann Volker , Burchert Andreas , Belohlavkova Petra , Mustjoki Satu , Faber Edgar , Mayer Jiri , Zackova Daniela , Panayiotidis Panayiotis , Richter Johan , Hjorth-Hansen Henrik , Kamińska Magdalena , Płonka Magdalena , Szczepanek Elżbieta , Szarejko Monika , Bober Grażyna , Hus Iwona , Grzybowska-Izydorczyk Olga , Wasilewska Ewa , Paczkowska Edyta , Niesiobędzka-Krężel Joanna , Giannopoulos Krzysztof , Mahon Francois X. , Sacha Tomasz , Saußele Susanne , Pfirrmann Markus
Published: December 2023

Membrane transporters are important determinants of drug bioavailability. Their expression and activity affect the intracellular drug concentration in leukemic cells impacting response to therapy. Pharmacogenomics represents genetic markers that reflect allele arrangement of genes encoding drug transporters associated with treatment response. In previous work, we identified SNP rs460089 located in the promotor of SLC22A4 gene encoding imatinib transporter OCTN1 as influential on response of patients with chronic myeloid leukemia treated with imatinib. Patients with rs460089-GC pharmacogenotype had significantly superior response to first-line imatinib treatment compared to patients with rs460089-GG. This study investigated whether pharmacogenotypes of rs460089 are associated with sustainability of treatment-free remission (TFR) in patients from the EUROpean Stop Kinase Inhibitor (EURO-SKI) trial. In the learning sample, 176 patients showed a significantly higher 6-month probability of molecular relapse free survival (MRFS) in patients with GC genotype (73%, 95% CI: 60–82%) compared to patients with GG (51%, 95% CI: 41–61%). Also over time, patients with GC genotype had significantly higher MRFS probabilities compared with patients with GG (HR: 0.474, 95% CI: 0.280-0.802, p = 0.0054). Both results were validated with data on 93 patients from the Polish STOP imatinib study. In multiple regression models, in addition to the investigated genotype, duration of TKI therapy (EURO-SKI trial) and duration of deep molecular response (Polish study) were identified as independent prognostic factors. The SNP rs460089 was found as an independent predictor of TFR.
Management of mild degenerative cervical myelopathy and asymptomatic spinal cord compression: an international survey
Authors: Brannigan Jamie F. M. , Davies Benjamin M. , Mowforth Oliver D. , Yurac Ratko , Kumar Vishal , Dejaegher Joost , Zamorano Juan J. , Murphy Rory K. J. , Tripathi Manjul , Anderson David B. , Harrop James , Molliqaj Granit , Wynne-Jones Guy , Arbatin Jose Joefrey F. , Kato So , Ito Manabu , Wilson Jefferson , Romelean Ronie , Dea Nicolas , Graves Daniel , Tessitore Enrico , Martin Allan R. , Nouri Aria
Published: December 2023

Study design

Cross-sectional survey.

Objective

Currently there is limited evidence and guidance on the management of mild degenerative cervical myelopathy (DCM) and asymptomatic spinal cord compression (ASCC).

Anecdotal evidence suggest variance in clinical practice. The objectives of this study were to assess current practice and to quantify the variability in clinical practice.

Methods

Spinal surgeons and some additional health professionals completed a web-based survey distributed by email to members of AO Spine and the Cervical Spine Research Society (CSRS) North American Society. Questions captured experience with DCM, frequency of DCM patient encounters, and standard of practice in the assessment of DCM. Further questions assessed the definition and management of mild DCM, and the management of ASCC.

Results

A total of 699 respondents, mostly surgeons, completed the survey. Every world region was represented in the responses. Half (50.1%, n = 359) had greater than 10 years of professional experience with DCM. For mild DCM, standardised follow-up for non-operative patients was reported by 488 respondents (69.5%). Follow-up included a heterogeneous mix of investigations, most often at 6-month intervals (32.9%, n = 158). There was some inconsistency regarding which clinical features would cause a surgeon to counsel a patient towards surgery. Practice for ASCC aligned closely with mild DCM. Finally, there were some contradictory definitions of mild DCM provided in the form of free text.

Conclusions

Professionals typically offer outpatient follow up for patients with mild DCM and/or asymptomatic ASCC. However, what this constitutes varies widely. Further research is needed to define best practice and support patient care.
CHARIOT: a phase I study of berzosertib with chemoradiotherapy in oesophageal and other solid cancers using time to event continual reassessment method
Authors: Javed S. R. , Lord S. , El Badri S. , Harman R. , Holmes J. , Kamzi F. , Maughan T. , McIntosh D. , Mukherjee S. , Ooms A. , Radhakrishna G. , Shaw P. , Hawkins M. A.
Published: December 2023

Background

Berzosertib (M6620) is a highly potent (IC50  =  19 nM) and selective, first-in-class ataxia telangiectasia-mutated and Rad3-related protein kinase (ATR) inhibitor. This trial assessed the safety, preliminary efficacy, and tolerance of berzosertib in oesophageal cancer (A1 cohort) with RT and advanced solid tumours (A2 cohort) with cisplatin and capecitabine.

Methods

Single-arm, open-label dose-escalation (Time-to-Event Continual Reassessment Method) trial with 16 patients in A1 and 18 in A2. A1 tested six dose levels of berzosertib with RT (35 Gy over 15 fractions in 3 weeks).

Results

No dose-limiting toxicities (DLTs) in A1. Eight grade 3 treatment-related AEs occurred in five patients, with rash being the most common. The highest dose (240 mg/m2) was determined as the recommended phase II dose (RP2D) for A1. Seven DLTs in two patients in A2. The RP2D of berzosertib was 140 mg/m2 once weekly. The most common grade ≥3 treatment-related AEs were neutropenia and thrombocytopenia. No treatment-related deaths were reported.

Conclusions

Berzosertib combined with RT is feasible and well tolerated in oesophageal cancer patients at high palliative doses. Berzosertib with cisplatin and capecitabine was well tolerated in advanced cancer. Further investigation is warranted in a phase 2 setting.

Clinical trials identifier

EU Clinical Trials Register (EudraCT) - 2015-003965-27 ClinicalTrials.gov - NCT03641547.
UBE2O reduces the effectiveness of interferon-α via degradation of IFIT3 in hepatocellular carcinoma
Authors: Li Heng , Liu Yao , Cheng Can , Wu Yang , Liang Shu-Hang , Wu Liang , Wang Hong , Tu Cong-yin , Yao Han-Hui , Meng Fan-Zheng , Zhang Bo , Wang Wei , Wang Jia-Bei , Liu Lian-Xin
Published: December 2023

Interferon (IFN) exerts its effects through interferon-stimulated genes (ISGs), but its efficacy is limited by interferon resistance, which can be caused by the ubiquitination of key proteins. UBE2O was initially identified as a promising therapeutic target based on data from the TCGA and iUUCD 2.0 databases. Through the inhibition of UBE2O, interferon α/β signaling and overall interferon signaling were activated. Integrating data from proteomic, mass spectrometry, and survival analyses led to the identification of IFIT3, a mediator of interferon signaling, as a ubiquitination substrate of UBE2O. The results of in vitro and in vivo experiments demonstrated that the knockdown of UBE2O can enhance the efficacy of interferon-α by upregulating IFIT3 expression. K236 was identified as a ubiquitination site in IFIT3, and the results of rescue experiments confirmed that the effect of UBE2O on interferon-α sensitivity is dependent on IFIT3 activity. ATO treatment inhibited UBE2O and increased IFIT3 expression, thereby increasing the effectiveness of interferon-α. In conclusion, these findings suggest that UBE2O worsens the therapeutic effect of interferon-α by targeting IFIT3 for ubiquitination and degradation.
Structural insights into the regulation, ligand recognition, and oligomerization of bacterial STING
Authors: Hou Mei-Hui , Wang Yu-Chuan , Yang Chia-Shin , Liao Kuei-Fen , Chang Je-Wei , Shih Orion , Yeh Yi-Qi , Sriramoju Manoj Kumar , Weng Tzu-Wen , Jeng U-Ser , Hsu Shang-Te Danny , Chen Yeh
Published: December 2023

The cyclic GMP-AMP synthase (cGAS)/stimulator of interferon gene (STING) signaling pathway plays a critical protective role against viral infections. Metazoan STING undergoes multilayers of regulation to ensure specific signal transduction. However, the mechanisms underlying the regulation of bacterial STING remain unclear. In this study, we determined the crystal structure of anti-parallel dimeric form of bacterial STING, which keeps itself in an inactive state by preventing cyclic dinucleotides access. Conformational transition between inactive and active states of bacterial STINGs provides an on-off switch for downstream signaling. Some bacterial STINGs living in extreme environment contain an insertion sequence, which we show codes for an additional long lid that covers the ligand-binding pocket. This lid helps regulate anti-phage activities. Furthermore, bacterial STING can bind cyclic di-AMP in a triangle-shaped conformation via a more compact ligand-binding pocket, forming spiral-shaped protofibrils and higher-order fibril filaments. Based on the differences between cyclic-dinucleotide recognition, oligomerization, and downstream activation of different bacterial STINGs, we proposed a model to explain structure-function evolution of bacterial STINGs.
Janus particles with tunable patch symmetry and their assembly into chiral colloidal clusters
Authors: Zhang Tianran , Lyu Dengping , Xu Wei , Feng Xuan , Ni Ran , Wang Yufeng
Published: December 2023

Janus particles, which have an attractive patch on the otherwise repulsive surface, have been commonly employed for anisotropic colloidal assembly. While current methods of particle synthesis allow for control over the patch size, they are generally limited to producing dome-shaped patches with a high symmetry (C∞). Here, we report on the synthesis of Janus particles with patches of various tunable shapes, having reduced symmetries ranging from C2v to C3v and C4v. The Janus particles are synthesized by partial encapsulation of an octahedral metal-organic framework particle (UiO-66) in a polymer matrix. The extent of encapsulation is precisely regulated by a stepwise, asymmetric dewetting process that exposes selected facets of the UiO-66 particle. With depletion interaction, the Janus particles spontaneously assemble into colloidal clusters reflecting the particles’ shapes and patch symmetries. We observe the formation of chiral structures, whereby chirality emerges from achiral building blocks. With the ability to encode symmetry and directional bonding information, our strategy could give access to more complex colloidal superstructures through assembly.
Magnetic order in 2D antiferromagnets revealed by spontaneous anisotropic magnetostriction
Authors: Houmes Maurits J. A. , Baglioni Gabriele , Šiškins Makars , Lee Martin , Esteras Dorye L. , Ruiz Alberto M. , Mañas-Valero Samuel , Boix-Constant Carla , Baldoví Jose J. , Coronado Eugenio , Blanter Yaroslav M. , Steeneken Peter G. , van der Zant Herre S. J.
Published: December 2023

The temperature dependent order parameter provides important information on the nature of magnetism. Using traditional methods to study this parameter in two-dimensional (2D) magnets remains difficult, however, particularly for insulating antiferromagnetic (AF) compounds. Here, we show that its temperature dependence in AF MPS3 (M(II) = Fe, Co, Ni) can be probed via the anisotropy in the resonance frequency of rectangular membranes, mediated by a combination of anisotropic magnetostriction and spontaneous staggered magnetization. Density functional calculations followed by a derived orbital-resolved magnetic exchange analysis confirm and unravel the microscopic origin of this magnetization-induced anisotropic strain. We further show that the temperature and thickness dependent order parameter allows to deduce the material’s critical exponents characterising magnetic order. Nanomechanical sensing of magnetic order thus provides a future platform to investigate 2D magnetism down to the single-layer limit.
Fast free energy estimates from λ-dynamics with bias-updated Gibbs sampling
Authors: Robo Michael T. , Hayes Ryan L. , Ding Xinqiang , Pulawski Brian , Vilseck Jonah Z.
Published: December 2023

Relative binding free energy calculations have become an integral computational tool for lead optimization in structure-based drug design. Classical alchemical methods, including free energy perturbation or thermodynamic integration, compute relative free energy differences by transforming one molecule into another. However, these methods have high operational costs due to the need to perform many pairwise perturbations independently. To reduce costs and accelerate molecular design workflows, we present a method called λ-dynamics with bias-updated Gibbs sampling. This method uses dynamic biases to continuously sample between multiple ligand analogues collectively within a single simulation. We show that many relative binding free energies can be determined quickly with this approach without compromising accuracy. For five benchmark systems, agreement to experiment is high, with root mean square errors near or below 1.0 kcal mol−1. Free energy results are consistent with other computational approaches and within statistical noise of both methods (0.4 kcal mol−1or less). Notably, large efficiency gains over thermodynamic integration of 18–66-fold for small perturbations and 100–200-fold for whole aromatic ring substitutions are observed. The rapid determination of relative binding free energies will enable larger chemical spaces to be more readily explored and structure-based drug design to be accelerated.
Asymmetric coding of reward prediction errors in human insula and dorsomedial prefrontal cortex
Authors: Hoy Colin W. , Quiroga-Martinez David R. , Sandoval Eduardo , King-Stephens David , Laxer Kenneth D. , Weber Peter , Lin Jack J. , Knight Robert T.
Published: December 2023

The signed value and unsigned salience of reward prediction errors (RPEs) are critical to understanding reinforcement learning (RL) and cognitive control. Dorsomedial prefrontal cortex (dMPFC) and insula (INS) are key regions for integrating reward and surprise information, but conflicting evidence for both signed and unsigned activity has led to multiple proposals for the nature of RPE representations in these brain areas. Recently developed RL models allow neurons to respond differently to positive and negative RPEs. Here, we use intracranially recorded high frequency activity (HFA) to test whether this flexible asymmetric coding strategy captures RPE coding diversity in human INS and dMPFC. At the region level, we found a bias towards positive RPEs in both areas which paralleled behavioral adaptation. At the local level, we found spatially interleaved neural populations responding to unsigned RPE salience and valence-specific positive and negative RPEs. Furthermore, directional connectivity estimates revealed a leading role of INS in communicating positive and unsigned RPEs to dMPFC. These findings support asymmetric coding across distinct but intermingled neural populations as a core principle of RPE processing and inform theories of the role of dMPFC and INS in RL and cognitive control.
Unraveling the causal genes and transcriptomic determinants of human telomere length
Authors: Chang Ying , Zhou Yao , Zhou Junrui , Li Wen , Cao Jiasong , Jing Yaqing , Zhang Shan , Shen Yongmei , Lin Qimei , Fan Xutong , Yang Hongxi , Dong Xiaobao , Zhang Shijie , Yi Xianfu , Shuai Ling , Shi Lei , Liu Zhe , Yang Jie , Ma Xin , Hao Jihui , Chen Kexin , Li Mulin Jun , Wang Feng , Huang Dandan
Published: December 2023

Telomere length (TL) shortening is a pivotal indicator of biological aging and is associated with many human diseases. The genetic determinates of human TL have been widely investigated, however, most existing studies were conducted based on adult tissues which are heavily influenced by lifetime exposure. Based on the analyses of terminal restriction fragment (TRF) length of telomere, individual genotypes, and gene expressions on 166 healthy placental tissues, we systematically interrogate TL-modulated genes and their potential functions. We discover that the TL in the placenta is comparatively longer than in other adult tissues, but exhibiting an intra-tissue homogeneity. Trans-ancestral TL genome-wide association studies (GWASs) on 644,553 individuals identify 20 newly discovered genetic associations and provide increased polygenic determination of human TL. Next, we integrate the powerful TL GWAS with placental expression quantitative trait locus (eQTL) mapping to prioritize 23 likely causal genes, among which 4 are functionally validated, including MMUT, RRM1, KIAA1429, and YWHAZ. Finally, modeling transcriptomic signatures and TRF-based TL improve the prediction performance of human TL. This study deepens our understanding of causal genes and transcriptomic determinants of human TL, promoting the mechanistic research on fine-grained TL regulation.
Authigenic mineralization in Surtsey basaltic tuff deposits at 50 years after eruption
Authors: Montesano Giovanna , Rispoli Concetta , Petrosino Paola , Jackson Marie D. , Weisenberger Tobias B. , Gudmundsson Magnús T. , Cappelletti Piergiulio
Published: December 2023

Alteration of basaltic glass and in situ mineral growth are fundamental processes that influence the chemical and material properties of Earth’s oceanic crust. These processes have evolved at the basaltic island of Surtsey (SW Iceland) since eruptions terminated in 1967. Here, subaerial and submarine lapilli tuff samples from a 192 m-deep borehole drilled in 2017 (SE-02b) are characterized through petrographic studies, X-ray powder diffraction analyses, and SEM–EDS imaging and chemical analyses. The integrated results reveal (i) multi-stage palagonitization processes in basaltic glass and precipitation of secondary minerals from matrix pore fluids, (ii) multi-stage crystallization of secondary phillipsite, analcime and Al-tobermorite in the vesicles of basaltic pyroclasts and (iii) variations in palagonitization processes as a function of thermal and hydrological domains. Although temperature appears to be an important factor in controlling rates of secondary mineralization, the chemistry of original basaltic components and interstitial fluids also influences reaction pathways in the young pyroclastic deposits. The integration of systematic mineralogical analyses of the 50-year-old tuff from one of the most carefully monitored volcanic sites on Earth, together with temperature monitoring in boreholes since 1980, provide a reference framework for evaluating mineralogical evolution in other Surtseyan-type volcanoes worldwide.
Mir-142-3P regulates MAPK protein family by inhibiting 14-3-3η to enhance bone marrow mesenchymal stem cells osteogenesis
Authors: Liu Ya-qian , Xu Yue-chen , Shuai Zong-wen
Published: December 2023

Clinical studies have found 14-3-3η to be associated with osteoporosis through undefined mechanisms. We aimed to investigate the role of 14-3-3η in osteoporosis and its potential associations with miRNAs. The Gene Expression Omnibus(GEO) and Human Protein Atlas 1 databases were analyzed to examine both the mRNA and protein expression of 14-3-3η in OP. Gene enrichment analyses were performed to explore the underlying mechanism of 14-3-3η based on DAVID. miRWalk was used to predict the associated miRNAs. The statistics were analysed by R software and SPSS software. 14-3-3η was overexpressed and knock down expressed in BMSCs by lentiviral vector transfecting. And BMSCs were induced by hypoxia. qRT-PCR and Western-Blot verified the expression of mRNA and protein. Scratch assay detected the migration of osteocytes. Co-immunoprecipitation and luciferase assay studied the 14-3-3η targeted protein and miRNA. overexpression and knock down of miRNA to verify the relationship of 14-3-3η and target genes. The 14-3-3η mRNA expression level was low in patients with osteoporosis, as corroborated by immunohistochemical staining images. Functional analyses revealed enrichment of the MAPK-associated cascade. 14-3-3η was correlated with MAPK family proteins and five key miRNAs, including mir-142-3p. In addition, 14-3-3η knockdown in BMSCs increased the mRNA and protein expression levels of Hif-α, VEGF, BMP-2, OPN, OST, and Runx2, and enhanced the cells migration ability. Under hypoxic conditions, Hif-α and BMP-2 protein expression levels were upregulated, whereas those of 14-3-3η and MAPK3 were downregulated. Co-immunoprecipitation experiments showed decreased binding of 14-3-3η to MAPK3. 14-3-3η knockdown produced the same results as hypoxia induction. Adding caspase3 inhibitor and knocking down 14-3-3η again prevented MAPK3 cleavage by caspase3 and inhibited BMP-2 expression. Moreover, under hypoxic conditions, miR-142-3P expression was upregulated and luciferase assays revealed 14-3-3η as its target gene. miR-142-3P overexpression decreased mRNA and protein levels of 14-3-3η and MAPK3, while increasing BMP-2 expression. miR-142-3P knockdown reversed these results. BMSC osteogenesis was suppressed by 14-3-3η, whereas miRNA-142-3p promoted it through the inhibition of 14-3-3η.
Inhibition of the Nogo-pathway in experimental spinal cord injury: a meta-analysis of 76 experimental treatments
Authors: Hirt Julian , Khanteymoori Alireza , Hohenhaus Marc , Kopp Marcel A. , Howells David W. , Schwab Jan M. , Watzlawick Ralf
Published: December 2023

Recovery after spinal cord injury (SCI) may be propagated by plasticity-enhancing treatments. The myelin-associated nerve outgrowth inhibitor Nogo-A (Reticulon 4, RTN4) pathway has been shown to restrict neuroaxonal plasticity in experimental SCI models. Early randomized controlled trials are underway to investigate the effect of Nogo-A/Nogo-Receptor (NgR1) pathway blockers. This systematic review and meta-analysis of therapeutic approaches blocking the Nogo-A pathway interrogated the efficacy of functional locomotor recovery after experimental SCI according to a pre-registered study protocol. A total of 51 manuscripts reporting 76 experiments in 1572 animals were identified for meta-analysis. Overall, a neurobehavioral improvement by 18.9% (95% CI 14.5–23.2) was observed. Subgroup analysis (40 experiments, N = 890) revealed SCI-modelling factors associated with outcome variability. Lack of reported randomization and smaller group sizes were associated with larger effect sizes. Delayed treatment start was associated with lower effect sizes. Trim and Fill assessment as well as Egger regression suggested the presence of publication bias. Factoring in theoretically missing studies resulted in a reduced effect size [8.8% (95% CI 2.6–14.9)]. The available data indicates that inhibition of the Nogo-A/NgR1pathway alters functional recovery after SCI in animal studies although substantial differences appear for the applied injury mechanisms and other study details. Mirroring other SCI interventions assessed earlier we identify similar factors associated with outcome heterogeneity.
Comparison of markerless and marker-based motion capture systems using 95% functional limits of agreement in a linear mixed-effects modelling framework
Authors: Das Kishor , de Paula Oliveira Thiago , Newell John
Published: December 2023

Biomechanics analysis of human movement has been proven useful for maintenance of health, injury prevention, and rehabilitation in both sports and clinical populations. A marker-based motion capture system is considered the gold standard method of measurement for three dimensional kinematics measurements. However, the application of markers to anatomical bony points is a time consuming process and constrained by inter-, intra-tester and session reliability issues. The emergence of novel markerless motion capture systems without the use of reflective markers is a rapidly growing field in motion analysis. However an assessment of the level of agreement of a markerless system with an established gold standard marker-based system is needed to ensure the applicability of a markerless system. An extra layer of complexity is involved as the kinematics measurements are functional responses. In this paper a new approach is proposed to generate 95% functional limits of agreement (fLoA) using the linear mixed-effects modelling framework for hierarchical study designs. This approach is attractive as it will allow practitioners to extend their use of linear mixed models to assess agreement in method comparison studies in all domains where functional responses are recorded.
Identification of the length and location of the A1 pulley combining palpation technique with palm landmarks: a cadaveric study
Authors: Zhong Wei-xing , Li Jun-hua , Chen Zu-jiang , Peng Wei-jie , Gu Rui-bin , Chen Chao , Li Yi-kai
Published: December 2023

Through anatomical morphology, to accumulate the relevant parameters of the A1 pulley of each adult finger. A total of 100 fingers were selected, dissected layer by layer, and the A1 pulley and neurovascular of each finger were observed. Measure the length of the A1 pulley, the distance between the needle knife insertion point and the proximal edge of A1 pulley, and the nerves and blood vessels on both sides. (1) The length of A1 pulleys of each finger is 6.18 ± 0.33 mm, 6.58 ± 0.73 mm, 5.98 ± 0.67 mm, 5.36 ± 1.08 mm, 5.63 ± 1.09 mm. (2) The distances between the needle knife entry point of each finger and the volar proper nerve of the ulnar finger are 7.00 ± 1.55 mm, 8.29 ± 1.46 mm, 5.10 ± 0.25 mm, 5.30 ± 0.24 mm, 0 mm; the distances from the volar proper nerve of the radial finger are 9.08 ± 0.87 mm, 4.70 ± 1.10 mm, 7.03 ± 0.72 mm, 6.81 ± 0.22 mm, 7.81 ± 0.57 mm. (3) The distances between the needle knife entry point of each finger and the proper volar artery of the ulnar finger are 10.40 ± 0.75 mm, 8.89 ± 0.53 mm, 6.35 ± 0.44 mm, 7.26 ± 0.16 mm, 0 mm, respectively; The distances from the volar proper artery of the radial finger are 8.75 ± 1.07 mm, 6.10 ± 0.35 mm, 11.44 ± 0.41 mm, 8.19 ± 0.60 mm, 9.78 ± 0.68 mm, respectively. The landmarks of the needle entry points are located at the position corresponding to the highest point of the metacarpal heads, except the tail finger. From the needle knife entry point to distal, cut the proximal edge of the A1 pulley longitudinally along the midline until the patient can flex autonomously, and pay attention to the distance between the two sides of 3.60–11.85 mm neurovascular bundle.