bluuebunny/crossref_metadata_2025_split huggingface dataset:
Traditional Chinese Medicine Research Activity in Switzerland. A Systematic Review and Bibliometric Analysis
Authors: Chen Bingjun , Lyu Xiaoying , Lottenbach Koryna , Zeier Chantal , Jaminet Dominic , Solongo Sarangoo , Timo Hummel , Talia Wicker , Sevik Ahmet , Wang Xiaying , Hammes Michael , Li Yiming , Pradhan Saroj K. , Furian Michael 
Published: July 2024

AbstractImportanceTraditional Chinese Medicine (TCM) becomes popular in Switzerland, however, Swiss TCM research activity and scientific output have not been investigated.ObjectiveTo describe the Swiss TCM research activities and main health conditions studied.Data SourceA systematic literature search of PubMed and Embase was performed from database inception to December 31st, 2023.Study SelectionArticles describing a TCM-related therapy modality in humans with at least one author affiliated with a Swiss institution.Data ExtractionPrimary and secondary outcomes, as well as study and author characteristics were extracted from included articles.Main Outcomes and MeasuresThe main outcome was the main health condition studied. Secondary outcomes are the total number of articles published over time, the TCM therapies used, and the Swiss institutions involved.ResultsOf the 223 articles included, 68.2% of published articles originated from the top 3 of 73 (4.1%) Swiss institutions, namely the University of Zurich (32.3%), University of Bern (30.0%) and University of Basel (7.6%). Overall, 116 (52.0%) articles described original studies including 36 (31.0%) articles reporting findings from randomized clinical trials, 29 (25.0%) from cross-sectional studies, 20 (17.2%) from prospective cohort studies, 19 (16.4%) from case reports and 12 (10.3%) from retrospective studies. The top health categories studied were Pain Management (16.4%), Psychology and Behaviour (8.6%), Neurology (6.9%), and Oncology (6.9%). The most used TCM therapies were acupuncture or moxibustion (61.2%), combination of several treatments (15.5%), herbal medicine (10.3%), and Qi Gong or martial arts (9.5%).Conclusion and RelevanceUntil 2023, the total number of scientific TCM output by Swiss authors is steadily increasing but remains small. More effort to conducted TCM research and to elucidate the TCM therapy effects in Switzerland is warranted.RegistrationPROSPERO No. CRD42023432693.
Inhibitor-induced supercharging of kinase turnover via endogenous proteolytic circuits
Authors: Scholes Natalie S. , Bertoni Martino , Comajuncosa-Creus Arnau , Kladnik Katharina , Frommelt Fabian , Hinterndorfer Matthias , Razumkov Hlib , Prokofeva Polina , Schwalm Martin P. , Imrichova Hana , Barone Eleonora , Schätz Caroline , Rukavina Andrea , Koren Anna , Kubicek Stefan , Knapp Stefan , Gray Nathanael S. , Superti-Furga Giulio , Kuster Bernhard , Aloy Patrick , Winter Georg E. 
Published: July 2024

AbstractTargeted protein degradation has emerged as a promising new pharmacological strategy. Traditionally, it relies on small molecules that induce proximity between a target protein and an E3 ubiquitin ligase to prompt target ubiquitination and degradation by the proteasome. Sporadic reports indicated that ligands designed to inhibit a target can also induce its destabilization. Among others, this has repeatedly been observed for kinase inhibitors. However, we lack an understanding of the frequency, generalizability, and mechanistic underpinnings of these phenomena. To address this knowledge gap, we generated dynamic abundance profiles of 98 kinases after cellular perturbations with 1570 kinase inhibitors, revealing 160 selective instances of inhibitor-induced kinase destabilization. Kinases prone to degradation are frequently annotated as HSP90 clients, thus affirming chaperone deprivation as an important route of destabilization. However, detailed investigation of inhibitor-induced degradation of LYN, BLK and RIPK2 revealed a differentiated, common mechanistic logic where inhibitors function by inducing a kinase state that is more efficiently cleared by endogenous degradation mechanisms. Mechanistically, effects can manifest by ligand-induced changes in cellular activity, localization, or multimerization which may be triggered by direct target engagement or network effects. Collectively, our data suggest that inhibitor-induced kinase degradation is a common event and positions supercharging of endogenous degradation circuits as an alternative to classical proximity-inducing degraders.
Functional ultrasound imaging and neuronal activity: how accurate is the spatiotemporal match?
Authors: Lambert Théo , Niknejad Hamid Reza , Kil Dries , Brunner Clément , Nuttin Bart , Montaldo Gabriel , Urban Alan 
Published: July 2024

AbstractOver the last decade, functional ultrasound (fUS) has risen as a critical tool in functional neuroimaging, leveraging hemodynamic changes to infer neural activity indirectly. Recent studies have established a strong correlation between neural spike rates (SR) and functional ultrasound signals. However, understanding their spatial distribution and variability across different brain areas is required to thoroughly interpret fUS signals. In this regard, we conducted simultaneous fUS imaging and Neuropixels recordings during stimulus-evoked activity in awake mice within three regions the visual pathway. Our findings indicate that the temporal dynamics of fUS and SR signals are linearly correlated, though the correlation coefficients vary among visual regions. Conversely, the spatial correlation between the two signals remains consistent across all regions with a spread of approximately 300 micrometers. Finally, we introduce a model that integrates the spatial and temporal components of the fUS signal, allowing for a more accurate interpretation of fUS images.
In vivotests of theE. coliTonB system working model—interaction of ExbB with unknown proteins, identification of TonB-ExbD transmembrane heterodimers and PMF-dependent ExbD structures
Authors: Postle Kathleen , Kopp Dale , Jana Bimal 
Published: July 2024

ABSTRACTThe TonB system ofEscherichia coliresolves the dilemma posed by its outer membrane that protects it from a variety of external threats, but also constitutes a diffusion barrier to nutrient uptake. Our working model involves interactions among a set of cytoplasmic membrane-bound proteins: tetrameric ExbB that serves as a scaffold for a dimeric TonB complex (ExbB4-TonB2), and also engages dimeric ExbD (ExbB4-ExbD2). Through a set of synchronized conformational changes and movements these complexes are proposed to cyclically transduce cytoplasmic membrane protonmotive force to energize active transport of nutrients through TonB-dependent transporters in the outer membrane (described in Gresock etal., J. Bacteriol. 197:3433). In this work, we provide experimental validation of three important aspects of the model. The majority of ExbB is exposed to the cytoplasm, with an ∼90-residue cytoplasmic loop and an ∼50 residue carboxy terminal tail. Here we found for the first time, that the cytoplasmic regions of ExbB served asin vivocontacts for three heretofore undiscovered proteins, candidates to move ExbB complexes within the membrane. Support for the model also came from visualization ofin vivoPMF-dependent conformational transitions in ExbD. Finally, we also show that TonB forms homodimers and heterodimers with ExbD through its transmembrane domainin vivo. This trio ofin vivoobservations suggest how and why solvedin vitrostructures of ExbB and ExbD differ significantly from thein vivoresults and submit that future inclusion of the unknown ExbB-binding proteins may bring solved structures into congruence with proposedin vivoenergy transduction cycle intermediates.
Prevalence of the Cefazolin Inoculum Effect (CzIE) in Nasal Colonizing Methicillin-SusceptibleStaphylococcus aureusin Patients from Intensive Care Units in Colombia and Use of a Modified Rapid Nitrocefin Test for Detection
Authors: Carvajal Lina P. , Rincon Sandra , Gomez-Villegas Sara I. , Matiz-González Juan M. , Ordoñez Karen , Santamaria Alejandra , Ospina-Navarro Leonardo , Beltran Jaime , Guevara Fredy , Mendez Yardany R. , Salcedo Soraya , Porras Alexandra , Valencia-Moreno Albert , Grennia Haley , Deyanov Alexander , Baptista Rodrigo , Tam Vincent H. , Panesso Diana , Tran Truc T. , Miller William R. , Arias Cesar A. , Reyes Jinnethe 
Published: July 2024

ABSTRACTThe cefazolin inoculum effect (CzIE) has been associated with poor clinical outcomes in patients with MSSA infections. We aimed to investigate the point prevalence of the CzIE among nasal colonizing MSSA isolates from ICU patients in a multicenter study in Colombia (2019-2023). Patients underwent nasal swabs to assess forS. aureuscolonization on admission to the ICU and some individuals had follow-up swabs. We performed cefazolin MIC by broth-microdilution using standard and high-inoculum and developed a modified nitrocefin-based rapid test to detect the CzIE. Whole genome sequencing was carried out to characterize BlaZ types and allotypes, phylogenomics and Agr-typing. All swabs were subjected to 16S-rRNA metabarcoding sequencing to evaluate microbiome characteristics associated with the CzIE. A total of 352 patients were included; 46/352 (13%) patients were colonized withS. aureus; 22% (10/46) and 78% (36/46) with MRSA and MSSA, respectively. Among 36 patients that contributed with 43 MSSA colonizing isolates, 21/36 (58%) had MSSA exhibiting the CzIE. BlaZ type A and BlaZ-2 were the predominant type and allotype in 56% and 52%, respectively. MSSA belonging to CC30 were highly associated with the CzIE and SNP analyses supported transmission of MSSA exhibiting the CzIE among some patients of the same unit. The modified nitrocefin rapid test had 100%, 94.4% and 97.7% sensitivity, specificity and accuracy, respectively. We found a high prevalence point prevalence of the CzIE in MSSA colonizing the nares of critically-ill patients in Colombia. A modified rapid test was highly accurate in detecting the CzIE in this patient population.
Harnessing confounding and genetic pleiotropy to identify causes of disease through proteomics and Mendelian randomisation – ‘MR Fish’
Authors: Warwick Alasdair N , Hingorani Aroon D , Khawaja Anthony P , Gordillo-Marañón María , Olvera-Barrios Abraham , Stuart Kelsey V , Egan Catherine , Tufail Adnan , Sofat Reecha , Kuan Po Ai Valerie , Finan Chris , Schmidt Amand F 
Published: July 2024

AbstractWe propose an extension of the Mendelian randomisation (MR) paradigm (‘MR-Fish’) in which the confounded disease association of an index protein (‘the bait’) is harnessed to identify the causal role of different proteins (‘the catch’) for the same disease. Using C-reactive protein (CRP) as the bait,cis-MR analyses refuted a causal relationship of CRP with a wide range of diseases that associate with CRP in observational studies, including type 2 diabetes (T2DM) and coronary heart disease (CHD), suggesting these associations are confounded. Using ‘MR-Fish’, and leveraging large-scale proteomics data, we find evidence of a causal relationship with multiple diseases for several proteins encoded by genes that aretranshits in genome wide association analysis of CRP. These include causal associations of IL6R and FTO with CHD and T2DM; as well as ZDHHC18 with several circulating blood lipid fractions. Among the proteins encoded by genes that aretrans-for-CRP we identified 28 that are druggable. Our findings point to a general approach using MR analysis with proteomics data to identify causal pathways and therapeutic targets from non-causal observational associations of an index protein with a disease.
Instrumental variable analysis: choice of control variables is critical and can lead to biased results
Authors: Hamilton Fergus , Lee Todd C , Butler-Laporte Guillaume 
Published: July 2024

AbstractInstrumental variable (IV) analysis is a widely used technique in econometrics to estimate causal effects in the presence of confounding. A recent application of this technique was used in a high-profile analysis inJAMA Internal Medicineto estimate the effect of cefepime, a broad-spectrum antibiotic, on mortality in severe infection. There has been ongoing concern that piperacillin-tazobactam, another broad-spectrum antibiotic with greater anaerobic activity might be inferior to cefepime, however this has not been shown in randomized controlled trials. The authors used an international shortage of piperacillin-tazobactam as an instrument, as during this shortage period, cefepime was used as an alternative. The authors report a strong mortality effect (5% absolute increase) with piperacillin-tazobactam. In this paper, we closely examine this estimate and find it is likely conditional on inclusion of a control variable (metronidazole usage). Inclusion of this variable is highly likely to lead to collider bias, which we show via simulation. We then generate estimates unadjusted for metronidazole which are much closer to the null and may represent residual confounding or confounding by indication. We highlight the ongoing challenge of collider bias in empirical IV analyses and the potential for large biases to occur. We finally suggest the authors consider including these unadjusted estimates in their manuscript, as the large increase in mortality reported with piperacillin-tazobactam is unlikely to be true.
A Cost-utility Analysis of Ferric Derisomaltose versus Ferric Carboxymaltose in Patients with Iron Deficiency Anemia in China
Authors: Zhang F , Shen A , Ahmed Waqas , Pollock Richard F. 
Published: July 2024

AimsIntravenous (IV) iron is the recommended treatment for patients with iron deficiency anemia (IDA) who are unresponsive to oral iron treatment or require rapid iron replenishment. Ferric derisomaltose (FDI) and ferric carboxymaltose (FCM) are high-dose, rapid infusion, IV iron formulations that have recently been compared in three head-to-head randomized controlled trials (RCTs), which showed significantly higher incidence of hypophosphatemia after administration of FCM than FDI. The present study objective was to evaluate the cost-utility of FDI versus FCM in a population of Chinese patients with IDA.Materials and methodsA previously-published patient-level simulation model was used to model the cost-utility of FDI versus FCM in China. The number of infusions of FDI and FCM was modeled based on the approved posology of the respective formulations using simplified tables of iron need in a population of patients with bodyweight and hemoglobin levels informed by a Chinese RCT of FCM. Data on the incidence of hypophosphatemia was obtained from the PHOSPHARE-IDA RCT, while data on disease-related quality of life was obtained from SF-36v2 data from the PHOSPHARE-IBD RCT.ResultsOver the five-year time horizon, patients received 3.98 courses of iron treatment on average, requiring 0.90 fewer infusions of FDI than FCM (7.69 versus 6.79). This resulted in iron procurement and administration cost savings of RMB 206 with FDI (RMB 3,519 versus RMB 3,312). Reduced incidence of hypophosphatemia resulted in an increase of 0.07 quality-adjusted life years and further cost savings of RMB 782 over five years, driven by reduced need for phosphate testing and replenishment. FDI was therefore the dominant intervention.ConclusionsResults showed that FDI would improve patient quality of life and reduce direct healthcare expenditure versus FCM in patients with IDA in China.
Modulating delirium through stimulation (MoDeSt): study protocol for a randomized, double-blind, sham-controlled trial assessing the effect of postoperative transcranial electrical stimulation on delirium incidence
Authors: Leroy Sophie , Bublitz Viktor , Grittner Ulrike , Fleischmann Robert , von Dincklage Falk , Antonenko Daria 
Published: July 2024

AbstractBackground:Postoperative delirium (POD) is the most common neurological adverse event among elderly patients undergoing surgery. POD is associated with an increased risk for postoperative complications, long-term cognitive decline, an increase in morbidity and mortality as well as extended hospital stays. Delirium prevention and treatment options are currently limited. This study will evaluate the effect of transcranial electrical stimulation (tES) on the incidence of POD.Methods:We will perform a randomized, double-blind, sham-controlled trial using single-session postoperative application of tES in the recovery room in 225 patients (>65 years) undergoing elective major surgery. Patients will be randomly allocated (ratio 1:1:1) to one of three study groups: (1) alpha-tACS over posterior parietal cortex [2 mA, 20 min], (2) anodal tDCS over left dorsolateral prefrontal cortex [2 mA, 20 min], (3) sham [2 mA, 30 s]. Delirium will be screened twice daily with the 3-minute diagnostic interview Confusion Assessment Method (3D-CAM) in the five days following surgery. The primary outcome is the incidence of POD defined as at least one positive screening during the five first postoperative days compared between tACS and sham groups. Secondary outcomes include delirium severity, duration, phenotype, postoperative pain, postoperative nausea and vomiting, electroencephalographic (EEG) markers, and fluid biomarkers.Discussion: If effective, tES is a novel, easily applicable, non-invasive method to prevent the occurrence of POD. The comprehensive neurophysiological and biofluid assessments for markers of (neuro-)inflammation and neurodegeneration will shed light on the pathomechanisms behind POD and further elucidate the (after-)effects of tES. The potential implications for the postoperative recovery comprise enhanced patient safety, neurocognitive outcome, perioperative manageability but also reduced healthcare costs.Trial registration: German Clinical Trial Registry, DRKS00033703, registered on 23 February 2024.
Towards the elimination of cervical cancer in Tanzania, transdisciplinary science for smarter implementation strategies (TRACCTION): a mixed methods study protocol
Authors: Mhalu Grace , Dumbaugh Mari , Kipo Daniel , Somba Magreat , Mnzava Dorcas , Bohlius Julia , Mtenga Sally , Merten Sonja 
Published: July 2024

ABSTRACTIntroductionCervical cancer is the leading cause of cancer-related mortality for Tanzanian women. Multi-level, intersecting factors prevent access to care along the cervical cancer care cascade. However, there is a paucity of data, especially in non-urban areas, exploring the specificity and nuances of these factors locally, such as perceptions and embodied experiences of cervical cancer, use of traditional medicine, stigma, information generation and circulation and loss to follow up care. TRACCTION is an exploratory, mixed-methods study running from 2023-2025 to expand understanding of barriers to and facilitators of uptake of cervical pre-cancer screening and treatment and cervical cancer care in southeastern Tanzania.Methods and analysisResearch activities include a two-stage randomised cross sectional survey of women 18 years of age and older, qualitative data collection using diverse, community-based methods and a longitudinal public health facility record linkage of patients accessing cervical pre-cancer screening and treatment. By employing a transdisciplinary approach, TRACCTION will inform a participatory process to formulate cervical cancer education and policy recommendations.Ethics and DisseminationThis study received ethical approval in Tanzania and Switzerland. Informed written consent will be obtained from each study participant and a waiver of informed consent was obtained to retrospectively analyse public health facility records related to study objectives. A Policy and Technical Advisory Group, comprised of a diverse group of stakeholders including community members, will co-design a policy and service delivery analysis, followed by recommendations and dissemination plans. Study results for each work package will be published in peer reviewed journals and shared at relevant conferences globally.
Fermionic signal of vacuum polarization in strong laser fields
Authors: Dai Ya-Nan , Hatsagortsyan Karen Z. , Keitel Christoph H. , Chen Yue-Yue 
Published: July 2024

Vacuum polarization (VP) is investigated for the interaction of a polarized γ-ray beam of GeV photons with a counterpropagating ultraintense laser pulse. In a conventional setup of a vacuum birefringence measurement, a VP signal is the emerging small circular (linear) polarization of the initially linearly (circularly) polarized probe photons. The pair production via the nonlinear Breit-Wheeler process in such a high-energy environment eliminates part of the γ photons in the outgoing γ beam, increasing the statistical error and decreasing the accuracy of this VP signal. In contrast, we investigate the conversion of the emerging circular polarization of γ photons into longitudinal polarization of the created positrons, considering the latter as the main VP signal. To study the VP effects in the highly nonlinear regime, where the Euler-Heisenberg effective Lagrangian method breaks down, we have developed a Monte Carlo simulation method, incorporating vacuum birefringence and dichroism via the one-loop QED probabilities in the locally constant field approximation. Our Monte Carlo method will enable the study of VP effects in strong fields of arbitrary configuration. With 10 PW laser systems, we demonstrate the feasibility of detecting the fermionic signal of the VP effect at the 5σ confidence level with a few hours of measurement time.

Published by the American Physical Society
2024
Measurement of the Isolated Nuclear Two-Photon Decay in
Ge72
Authors: Freire-Fernández D. , Korten W. , Chen R. J. , Litvinov S. , Litvinov Yu. A. , Sanjari M. S. , Weick H. , Akinci F. C. , Albers H. M. , Armstrong M. , Banerjee A. , Blaum K. , Brandau C. , Brown B. A. , Bruno C. G. , Carroll J. J. , Chen X. , Chiara C. J. , Cortes M. L. , Dellmann S. F. , Dillmann I. , Dmytriiev D. , Forstner O. , Geissel H. , Glorius J. , Görgen A. , Górska M. , Griffin C. J. , Gumberidze A. , Harayama S. , Hess R. , Hubbard N. , Ide K. E. , John Ph. R. , Joseph R. , Jurado B. , Kalaydjieva D. , Kanika  , Kondev F. G. , Koseoglou P. , Kosir G. , Kozhuharov Ch. , Kulikov I. , Leckenby G. , Lorenz B. , Marsh J. , Mistry A. , Ozawa A. , Pietralla N. , Podolyák Zs. , Polettini M. , Sguazzin M. , Sidhu R. S. , Steck M. , Stöhlker Th. , Swartz J. A. , Vesic J. , Walker P. M. , Yamaguchi T. , Zidarova R. 
Published: July 2024

The nuclear two-photon or double-gamma (2γ) decay is a second-order electromagnetic process whereby a nucleus in an excited state emits two gamma rays simultaneously. To be able to directly measure the 2γ decay rate in the low-energy regime below the electron-positron pair-creation threshold, we combined the isochronous mode of a storage ring with Schottky resonant cavities. The newly developed technique can be applied to isomers with excitation energies down to ∼100  keV and half-lives as short as ∼10  ms. The half-life for the 2γ decay of the first-excited 0+ state in bare Ge72 ions was determined to be 23.9(6) ms, which strongly deviates from expectations.

Published by the American Physical Society
2024