bluuebunny/crossref_metadata_2025 huggingface dataset:
Associations of category fluency clustering performance with in vivo brain pathology in autosomal dominant Alzheimer’s disease
Authors: Yucebas Defne , Fox-Fuller Joshua T. , Badillo Cabrera Alex , Baena Ana , Pluim McDowell Celina , Aduen Paula , Vila-Castelar Clara , Bocanegra Yamile , Tirado Victoria , Sanchez Justin S. , Cronin-Golomb Alice , Lopera Francisco , Quiroz Yakeel T.
Published: April 2023

Objectives:

Alzheimer’s disease (AD) is known to impact semantic access, which is frequently evaluated using the Category Fluency (Animals) test. Recent studies have suggested that in addition to overall category fluency scores (total number of words produced over time), poor clustering could signal AD-related cognitive difficulties. In this study, we examined the association between category fluency clustering performance (i.e., stating words sequentially that are all contained within a subcategory, such as domestic animals) and brain pathology in individuals with autosomal dominant Alzheimer’s disease (ADAD).

Methods:

A total of 29 non-demented carriers of the Presenilin1 E280A ADAD mutation and 32 noncarrier family members completed the category fluency test (Animals) and the Mini-Mental State Examination (MMSE). The participants also underwent positron emission tomography (PET) scans to evaluate in vivo amyloid-beta in the neocortex and tau in medial temporal lobe regions. Differences between carriers and noncarriers on cognitive tests were assessed with Mann-Whitney tests; associations between cognitive test performance and brain pathology were assessed with Spearman correlations.

Results:

Animal fluency scores did not differ between carriers and noncarriers. Carriers, however, showed a stronger association between animal fluency clustering and in vivo AD brain pathology (neocortical amyloid and entorhinal tau) relative to noncarriers.

Conclusion:

This study indicates that using category fluency clustering, but not total score, is related to AD pathophysiology in the preclinical and early stages of the disease.
The legal limits to the destruction of natural resources in non-international armed conflicts: Applying international humanitarian law
Authors: Bagheri Saeed
Published: April 2023

This article analyzes whether and to what extent energy resources fulfil the definition of military objective within the meaning of international humanitarian law (IHL) and customary IHL. In order to bring conceptual clarity to the duty to protect the natural environment in armed conflict, the article explores the legal limits to the destruction of energy resources (that are part of the natural environment) controlled by armed non-State actors during non-international armed conflicts (NIACs). It examines the practice of the United States, which characterizes the destruction of the natural environment during hostilities as being related to targets that contribute to the “war-sustaining capability” of enemies. Conceptual light is shed on the legality of attacks on oil refineries and installations during NIACs as a matter for IHL.
Climate Concern and Engagement: Large Face-to-Face and Online Polls by the Dutch non-profit Milieudefensie
Authors: Bosshard Anna , Chatrou Anne , Brick Cameron
Published: April 2023

Climate change mitigation depends on tracking public opinion across populations. Social scientists can collaborate with environmental organizations that conduct surveys among their audiences. We teamed up with the non-profit Milieudefensie, who surveyed Dutch attitudes towards climate change in 2019–2020. The large dataset had face-to-face (n = 3,102) and online interviews (n = 30,311) of urbanity, climate concern, policy preferences, interviewer-rated engagement with climate change, and behavior (whether the interviewee provided their email and phone number to the organization). To reveal the representativeness of these kinds of convenience samples, we tested whether attitudes and their associations with behaviors were similar to previous studies. Climate concern, preference for climate policy, and interviewer-rated engagement were high. In the online survey, 47% of respondents signed up for an email newsletter, and 7% provided their phone number. Higher climate concern and preference for climate policy predicted interviewer-rated engagement and behavior (weak to strong associations). Urbanity was not related to concern, policy preferences, or interviewer-rated engagement. Policy preferences did not differ between the face-to-face and online samples. The results provide convergent evidence to conventional online surveys. These Dutch residents appear slightly more engaged with systemic change to mitigate climate change than the general public.
Wann soll der Rückenpatient manipuliert werden?
Authors: Gorbach Christoph
Published: April 2023

Zusammenfassung. Die Wurzeln der manuellen Behandlung reichen bis weit vor Christi Geburt zurück. Heute beschäftigen sich verschiedene Berufsgruppen mit der manuellen Therapie, welche eine etablierte, akzeptierte und evidenzbasierte Form der Behandlung verschiedener Beschwerden des Bewegungsapparates darstellt. Die Hauptmechanismen, welche dem Erfolg der manuellen Behandlung zugrunde liegen, sind mechanische, neuro-reflektorische und psychologische Effekte. Die Indikation für eine manuelle Behandlung kann man auf verschiedenen Ebenen stellen. Diese beinhalten unter anderem die Organ-/Strukturebene, die Funktionsebene (Hypo- vs. Hypermobilität) und die Schmerzebene (akut vs. chronisch).
Inland Water Greenhouse Gas Budgets for RECCAP2: 1. State‐Of‐The‐Art of Global Scale Assessments
Authors: Lauerwald Ronny , Allen George H. , Deemer Bridget R. , Liu Shaoda , Maavara Taylor , Raymond Peter , Alcott Lewis , Bastviken David , Hastie Adam , Holgerson Meredith A. , Johnson Matthew S. , Lehner Bernhard , Lin Peirong , Marzadri Alessandra , Ran Lishan , Tian Hanqin , Yang Xiao , Yao Yuanzhi , Regnier Pierre
Published: April 2023

Inland waters are important emitters of the greenhouse gasses (GHGs) carbon dioxide (CO2), methane (CH4), and nitrous oxide (N2O) to the atmosphere. In the framework of the 2nd phase of the REgional Carbon Cycle Assessment and Processes (RECCAP‐2) initiative, we review the state of the art in estimating inland water GHG budgets at global scale, which has substantially advanced since the first phase of RECCAP nearly 10 years ago. The development of increasingly sophisticated upscaling techniques, including statistical prediction and process‐based models, allows for spatially explicit estimates that are needed for regionalized assessments of continental GHG budgets such as those established for RECCAP. A few recent estimates also resolve the seasonal and/or interannual variability in inland water GHG emissions. Nonetheless, the global‐scale assessment of inland water emissions remains challenging because of limited spatial and temporal coverage of observations and persisting uncertainties in the abundance and distribution of inland water surface areas. To decrease these uncertainties, more empirical work on the contributions of hot‐spots and hot‐moments to overall inland water GHG emissions is particularly needed.
Food Production Could Add 1�C of Global Warming by 2100
Authors: Rodrigues Meghie
Published: April 2023

A new study teases apart greenhouse gas emissions from agriculture, showing how the food we eat heats up the world.
Gamma knife capsulotomy for intractable OCD: Neuroimage analysis of lesion size, location, and clinical response
Authors: McLaughlin N. C. R. , Magnotti J. F. , Banks G. P. , Nanda P. , Hoexter M. Q. , Lopes A. C. , Batistuzzo M. C. , Asaad W. F. , Stewart C. , Paulo D. , Noren G. , Greenberg B. D. , Malloy P. , Salloway S. , Correia S. , Pathak Y. , Sheehan J. , Marsland R. , Gorgulho A. , De Salles A. , Miguel E. C. , Rasmussen S. A. , Sheth S. A.
Published: April 2023

Obsessive-compulsive disorder (OCD) affects 2–3% of the population. One-third of patients are poorly responsive to conventional therapies, and for a subgroup, gamma knife capsulotomy (GKC) is an option. We examined lesion characteristics in patients previously treated with GKC through well-established programs in Providence, RI (Butler Hospital/Rhode Island Hospital/Alpert Medical School of Brown University) and São Paulo, Brazil (University of São Paolo). Lesions were traced on T1 images from 26 patients who had received GKC targeting the ventral half of the anterior limb of the internal capsule (ALIC), and the masks were transformed into MNI space. Voxel-wise lesion-symptom mapping was performed to assess the influence of lesion location on Y-BOCS ratings. General linear models were built to compare the relationship between lesion size/location along different axes of the ALIC and above or below-average change in Y-BOCS ratings. Sixty-nine percent of this sample were full responders (≥35% improvement in OCD). Lesion occurrence anywhere within the targeted region was associated with clinical improvement, but modeling results demonstrated that lesions occurring posteriorly (closer to the anterior commissure) and dorsally (closer to the mid-ALIC) were associated with the greatest Y-BOCS reduction. No association was found between Y-BOCS reduction and overall lesion volume. GKC remains an effective treatment for refractory OCD. Our data suggest that continuing to target the bottom half of the ALIC in the coronal plane is likely to provide the dorsal–ventral height required to achieve optimal outcomes, as it will cover the white matter pathways relevant to change. Further analysis of individual variability will be essential for improving targeting and clinical outcomes, and potentially further reducing the lesion size necessary for beneficial outcomes.
Thymidine phosphorylase facilitates retinoic acid inducible gene-I induced endothelial dysfunction
Authors: Baris Adrian , Fraile-Bethencourt Eugenia , Eubanks Jaiden , Khou Sokchea , Anand Sudarshan
Published: April 2023

Activation of nucleic acid sensors in endothelial cells (ECs) has been shown to drive inflammation across pathologies including cancer, atherosclerosis and obesity. We previously showed that enhancing cytosolic DNA sensing by inhibiting three prime exonuclease 1 (TREX1) in ECs led to EC dysfunction and impaired angiogenesis. Here we show that activation of a cytosolic RNA sensor, Retinoic acid Induced Gene 1 (RIG-I) diminishes EC survival, angiogenesis and triggers tissue specific gene expression programs. We discovered a RIG-I dependent 7 gene signature that affects angiogenesis, inflammation and coagulation. Among these, we identified the thymidine phosphorylase TYMP as a key mediator of RIG-I induced EC dysfunction via its regulation of a subset of interferon stimulated genes. Our RIG-I induced gene signature was also conserved in the context of human diseases – in lung cancer vasculature and herpesvirus infection of lung endothelial cells. Pharmacological or genetic inhibition of TYMP rescues RIG-I induced EC death, migration arrest and restores sprouting angiogenesis. Interestingly, using RNAseq we identified a gene expression program that was RIG-I induced but TYMP dependent. Analysis of this dataset indicated that IRF1 and IRF8 dependent transcription is diminished in RIG-I activated cells when TYMP is inhibited. Functional RNAi screen of our TYMP dependent EC genes, we found that a group of 5 genes - Flot1, Ccl5, Vars2, Samd9l and Ube2l6 are critical for endothelial cell death mediated by RIG-I activation. Our observations identify mechanisms by which RIG-I drives EC dysfunction and define pathways that can be pharmacologically targeted to ameliorate RIG-I induced vascular inflammation.
River thorium concentrations can record bedrock fracture processes including some triggered by distant seismic events
Authors: Gilbert Benjamin , Carrero Sergio , Dong Wenming , Joe-Wong Claresta , Arora Bhavna , Fox Patricia , Nico Peter , Williams Kenneth H.
Published: April 2023

Fractures are integral to the hydrology and geochemistry of watersheds, but our understanding of fracture dynamics is very limited because of the challenge of monitoring the subsurface. Here we provide evidence that long-term, high-frequency measurements of the river concentration of the ultra-trace element thorium (Th) can provide a signature of bedrock fracture processes spanning neighboring watersheds in Colorado. River Th concentrations show abrupt (subdaily) excursions and biexponential decay with approximately 1-day and 1-week time constants, concentration patterns that are distinct from all other solutes except beryllium and arsenic. The patterns are uncorrelated with daily precipitation records or seasonal trends in atmospheric deposition. Groundwater Th analyses are consistent with bedrock release and dilution upon mixing with river water. Most Th excursions have no seismic signatures that are detectable 50 km from the site, suggesting the Th concentrations can reveal aseismic fracture or fault events. We find, however, a weak statistical correlation between Th and seismic motion caused by distant earthquakes, possibly the first chemical signature of dynamic earthquake triggering, a phenomenon previously identified only through geophysical methods.
Large-scale phage-based screening reveals extensive pan-viral mimicry of host short linear motifs
Authors: Mihalič Filip , Simonetti Leandro , Giudice Girolamo , Sander Marie Rubin , Lindqvist Richard , Peters Marie Berit Akpiroro , Benz Caroline , Kassa Eszter , Badgujar Dilip , Inturi Raviteja , Ali Muhammad , Krystkowiak Izabella , Sayadi Ahmed , Andersson Eva , Aronsson Hanna , Söderberg Ola , Dobritzsch Doreen , Petsalaki Evangelia , Överby Anna K. , Jemth Per , Davey Norman E. , Ivarsson Ylva
Published: April 2023

Viruses mimic host short linear motifs (SLiMs) to hijack and deregulate cellular functions. Studies of motif-mediated interactions therefore provide insight into virus-host dependencies, and reveal targets for therapeutic intervention. Here, we describe the pan-viral discovery of 1712 SLiM-based virus-host interactions using a phage peptidome tiling the intrinsically disordered protein regions of 229 RNA viruses. We find mimicry of host SLiMs to be a ubiquitous viral strategy, reveal novel host proteins hijacked by viruses, and identify cellular pathways frequently deregulated by viral motif mimicry. Using structural and biophysical analyses, we show that viral mimicry-based interactions have similar binding strength and bound conformations as endogenous interactions. Finally, we establish polyadenylate-binding protein 1 as a potential target for broad-spectrum antiviral agent development. Our platform enables rapid discovery of mechanisms of viral interference and the identification of potential therapeutic targets which can aid in combating future epidemics and pandemics.
Revealing concealed cardioprotection by platelet Mfsd2b-released S1P in human and murine myocardial infarction
Authors: Polzin Amin , Dannenberg Lisa , Benkhoff Marcel , Barcik Maike , Helten Carolin , Mourikis Philipp , Ahlbrecht Samantha , Wildeis Laura , Ziese Justus , Zikeli Dorothee , Metzen Daniel , Hu Hao , Baensch Leonard , Schröder Nathalie H. , Keul Petra , Weske Sarah , Wollnitzke Philipp , Duse Dragos , Saffak Süreyya , Cramer Mareike , Bönner Florian , Müller Tina , Gräler Markus H. , Zeus Tobias , Kelm Malte , Levkau Bodo
Published: April 2023

Antiplatelet medication is standard of care in acute myocardial infarction (AMI). However, it may have obscured beneficial properties of the activated platelet secretome. We identify platelets as major source of a sphingosine-1-phosphate (S1P) burst during AMI, and find its magnitude to favorably associate with cardiovascular mortality and infarct size in STEMI patients over 12 months. Experimentally, administration of supernatant from activated platelets reduces infarct size in murine AMI, which is blunted in platelets deficient for S1P export (Mfsd2b) or production (Sphk1) and in mice deficient for cardiomyocyte S1P receptor 1 (S1P1). Our study reveals an exploitable therapeutic window in antiplatelet therapy in AMI as the GPIIb/IIIa antagonist tirofiban preserves S1P release and cardioprotection, whereas the P2Y12 antagonist cangrelor does not. Here, we report that platelet-mediated intrinsic cardioprotection is an exciting therapeutic paradigm reaching beyond AMI, the benefits of which may need to be considered in all antiplatelet therapies.
High-efficiency and stable short-delayed fluorescence emitters with hybrid long- and short-range charge-transfer excitations
Authors: Meng Guoyun , Dai Hengyi , Wang Qi , Zhou Jianping , Fan Tianjiao , Zeng Xuan , Wang Xiang , Zhang Yuewei , Yang Dezhi , Ma Dongge , Zhang Dongdong , Duan Lian
Published: April 2023

The pursuit of ideal short-delayed thermally activated delayed fluorescence (TADF) emitters is hampered by the mutual exclusion of a small singlet-triplet energy gap (ΔEST) and a large oscillator strength (f). Here, by attaching an multiresonance-acceptor onto a sterically-uncrowded donor, we report TADF emitters bearing hybrid electronic excitations with a main donor-to-acceptor long-range (LR) and an auxiliary bridge-phenyl short-range (SR) charge-transfer characters, balancing a small ΔEST and a large f. Moreover, the incorporation of dual equivalent multiresonance-acceptors is found to double the f value without affecting the ΔEST. A large radiative decay rate over an order of magnitude higher than the intersystem crossing (ISC) rate, and a decent reverse ISC rate of >106 s−1 are simultaneously obtained in one emitter, leading to a short delayed-lifetime of ~0.88 μs. The corresponding organic light-emitting diode exhibits a record-high maximum external quantum efficiency of 40.4% with alleviated efficiency roll-off and extended lifetime.
Physical and virtual nutrient flows in global telecoupled agricultural trade networks
Authors: Chen Xiuzhi , Hou Yue , Kastner Thomas , Liu Liu , Zhang Yuqian , Yin Tuo , Li Mo , Malik Arunima , Li Mengyu , Thorp Kelly R. , Han Siqi , Liu Yaoze , Muhammad Tahir , Liu Jianguo , Li Yunkai
Published: April 2023

Global agricultural trade creates multiple telecoupled flows of nitrogen (N) and phosphorus (P). The flows of physical and virtual nutrients along with trade have discrepant effects on natural resources in different countries. However, existing literature has not quantified or analyzed such effects yet. Here we quantified the physical and virtual N and P flows embedded in the global agricultural trade networks from 1997 to 2016 and elaborated components of the telecoupling framework. The N and P flows both increased continuously and more than 25% of global consumption of nutrients in agricultural products were related to physical nutrient flows, while virtual nutrient flows were equivalent to one-third of the nutrients inputs into global agricultural system. These flows have positive telecoupling effects on saving N and P resources at the global scale. Reducing inefficient trade flows will enhance resource conservation, environmental sustainability in the hyper-globalized world.
Allylic hydroxylation of enones useful for the functionalization of relevant drugs and natural products
Authors: Zheng Cheng-Yu , Yue Jian-Min
Published: April 2023

Enones are privileged structural motifs in bioactive natural products and pharmaceuticals, but the γ-hydroxylation of enones is challenging. Here we show a mild and efficient method for the direct C(sp3)–H hydroxylation of enones via visible-light-induced hydrogen-atom transfer (HAT), which facilitates γ-hydroxylation of primary, secondary, and tertiary C–H bonds of different enones without involving metal and peroxide. The mechanism study shows that Na2-eosin Y serves as both the photocatalyst and the source of catalytic bromine radical species in the HAT-based catalytic cycle, and finally sacrifices itself completely by oxidative degradation to produce bromine radical and a major product phthalic anhydride in an environmentally friendly way. This scalable method was demonstrated by plenty of substrates (41 examples) including 10 clinical drugs and 15 natural products to be useful for the late-stage functionalization of enone-containing compounds, and, in particular, has potential application in industry for large-scale production.
Periaqueductal grey and spinal cord pathology contribute to pain in Parkinson’s disease
Authors: Buhidma Yazead , Hobbs Carl , Malcangio Marzia , Duty Susan
Published: April 2023

Pain is a key non-motor feature of Parkinson’s disease (PD) that significantly impacts on life quality. The mechanisms underlying chronic pain in PD are poorly understood, hence the lack of effective treatments. Using the 6-hydroxydopamine (6-OHDA) lesioned rat model of PD, we identified reductions in dopaminergic neurons in the periaqueductal grey (PAG) and Met-enkephalin in the dorsal horn of the spinal cord that were validated in human PD tissue samples. Pharmacological activation of D1-like receptors in the PAG, identified as the DRD5+ phenotype located on glutamatergic neurons, alleviated the mechanical hypersensitivity seen in the Parkinsonian model. Downstream activity in serotonergic neurons in the Raphé magnus (RMg) was also reduced in 6-OHDA lesioned rats, as detected by diminished c-FOS positivity. Furthermore, we identified increased pre-aggregate α-synuclein, coupled with elevated activated microglia in the dorsal horn of the spinal cord in those people that experienced PD-related pain in life. Our findings have outlined pathological pathways involved in the manifestation of pain in PD that may present targets for improved analgesia in people with PD.
Low-energy gap emerging from confined nematic states in extremely underdoped cuprate superconductors
Authors: Li Huazhou , Li Han , Wang Zhaohui , Wan Siyuan , Yang Huan , Wen Hai-Hu
Published: April 2023

The pairing mechanism of high-temperature superconductivity in cuprates is regarded as one of the most challenging issues in condensed matter physics. The core issue concerns how the Cooper pairs are formed. Here we report spin-resolved tunneling measurements on extremely underdoped Bi2Sr2−xLaxCuO6+δ. Our data reveal that, when holes are doped into the system, the antiferromagnetic order is destroyed, while at the same time an increasing density of states (DOS) peaked at around 200 meV appears within the charge transfer gap. Meanwhile, an electronic structure with 4a0 × 4a0 basic plaquettes emerges inhomogeneously, with an area fraction that grows with hole doping. In each plaquette, there are some unidirectional bars (along the Cu-O bond) which are most pronounced at energies near peaks in the DOS around at 25 meV, with an intensity that is especially pronounced at oxygen sites. We argue that the atomically resolved low-energy DOS and related gap are closely associated with some kinds of density waves, possibly reflecting modulations of the electron density, or a pair-density wave, i.e. a modulation of the local pairing. Our work sheds new light on the doping induced electronic evolution from the “parent” insulator of the cuprate superconductors.
Development of an ultrahigh resolution real time alpha particle imaging system for observing the trajectories of alpha particles in a scintillator
Authors: Yamamoto Seiichi , Yoshino Masao , Kamada Kei , Yajima Ryuga , Yoshikawa Akira , Nakanishi Kohei , Kataoka Jun
Published: April 2023

High-resolution imaging of alpha particles is required in the detection of alpha radionuclides in cells or small organs for the development of radio-compounds for targeted alpha-particle therapy or other purposes. We developed an ultrahigh resolution, real time alpha-particle imaging system for observing the trajectories of alpha particles in a scintillator. The developed system is based on a magnifying unit and a cooled electron multiplying charge-coupled device (EM-CCD) camera, combined with a 100-µm-thick Ce-doped Gd3Al2Ga3O12 (GAGG) scintillator plate. Alpha particles from an Am-241 source were irradiated to the GAGG scintillator and imaged with the system. Using our system, we measured the trajectories of the alpha particles having different shapes in real time. In some of these measured trajectories, the line shapes of the alpha particles that flew in the GAGG scintillator were clearly observed. The lateral profiles of the alpha-particle trajectories were imaged with widths of ~ 2 µm. We conclude that the developed imaging system is promising for research on targeted alpha-particle therapy or other alpha particle detections that require high spatial resolution.
Single-cell transcriptomes reveal heterogeneity of chlorine-induced mice acute lung injury and the inhibitory effect of pentoxifylline on ferroptosis
Authors: Zhao Chen-qian , Wang Chong , Liu Meng-meng , Cao Meng , Peng Jie , Kong De-qin , Ren Xiao-ting , Liu Rui , Hai Chun-xu , Zhang Xiao-di
Published: April 2023

To investigate the effect of pentoxifylline (PTX) on Chlorine (Cl2)-induced acute lung injury (ALI) by single-cell RNA sequencing (scRNA-seq). Female BALB/c mice were exposed to Cl2 at 400 ppm for 15 min. H&E staining was used to observe the degree of lung injury. scRNA-seq was conducted to analysis of normal and Cl2-exposed mice lung tissues. Immunofluorescence was used to observe genes of interest. Thirty-two mice were randomly divided into four groups: Control, Cl2, Cl2+Fer-1, Cl2+PTX. TEM, WB and ELISA were used to detect ferroptosis-related indicators. The 5, 8, 10, 12, 16, 20 clusters were epithelial cells and 4, 15, 18, 19, 21 clusters were endothelial cells. Pseudo-time analysis revealed the differentiation trajectory of epithelial cells and key regulatory genes (Gclc, Bpifa1, Dnah5 and Dnah9) during the process of injury. Cell–cell communication analysis identified several important receptor–ligand complexes (Nrp1-Vegfa, Nrp2-Vegfa, Flt1-Vegfa and Flt4-Vegfa). Ferroptosis were found up-regulated in epithelial and endothelial cells by GSVA analysis. Highly expressed genes to which closely related ferroptosis were found by SCENIC analysis. PTX could significantly decrease the levels of MDA and abnormal high expression of solute carrier family 7 member 11 (SLC7A11, the key transporter of cystine) as well as increase the expression of GSH/GSSG and glutathione peroxidase 4 (GPX4) (p < 0.05). This study revealed novel molecular features of Cl2-induced ALI. PTX may be a potential specific drug by inhibiting the process of ferroptosis in epithelial and endothelial cells.
A prospective study on linking diarrheagenic E. coli with stunted childhood growth in relation to gut microbiome
Authors: Aziz Israr , Noreen Zobia , Ijaz Umer Zeeshan , Gundogdu Ozan , Hamid Muhammad Haroon , Muhammad Nazir , Khan Abdullah , Bokhari Habib
Published: April 2023

Stunted growth is an emerging global challenge affecting children under the age of 5 years in low- and middle-income countries. Despite such a high global prevalence of stunting, the mechanism of pathogenesis and the role of associated gut microbiota is poorly understood. The present study was designed to investigate the association of pathogenic strains of E. coli with the residential gut microbiota of stunted growth children. A total of 64 stool sample were collected from children aged ≤ 5 years, and were processed for isolation and molecular characterization of diarrheagenic E. coli. Selected stool samples (n = 39 including three normal controls) were then analysed for microbial community profiling using 16S ribosomal RNA (rRNA) gene sequencing. Furthermore, associations between changes in the microbiota in the presence of different E. coli strains was explored. Pathotyping of the isolated E. coli (n = 64) has shown that 39.68% belonged to one of the five pathotypes of E. coli whilst the remaining ones were non-typeable. Amongst the different pathotypes, EPEC was found to be the most prevalent (52%; n = 13), followed by EAEC (20%; n = 5), EIEC (12%; n = 3), EHEC (8%; n = 2) and ETEC 2 (8%; n = 2). Phylogrouping analysis has shown that majority of the strains belonged to B2 (28.12%). Microbial diversity is shown to be significant and varied when the samples are organized under the recovered phylogroups. Moreover, based on predictive metabolism, the colonization of these strains were found to be significantly associated with energy utilization pathways such as Denovoprine-2 and glyoxylate-by. Differential analysis has shown that Escherichia-Shigella and Enterococcus were altered for the children with stunted growth.
Uncovering the fast, directional signal flow through the human temporal pole during semantic processing
Authors: Tiesinga P. , Platonov A. , Pelliccia V. , LoRusso G. , Sartori I. , Orban G. A.
Published: April 2023

The temporal pole (TP) plays a central role in semantic memory, yet its neural machinery is unknown. Intracerebral recordings in patients discriminating visually the gender or actions of an actor, yielded gender discrimination responses in the ventrolateral (VL) and tip (T) regions of right TP. Granger causality revealed task-specific signals travelling first forward from VL to T, under control of orbitofrontal cortex (OFC) and neighboring prefrontal cortex, and then, strongly, backwards from T to VL. Many other cortical regions provided inputs to or received outputs from both TP regions, often with longer delays, with ventral temporal afferents to VL signaling the actor’s physical appearance. The TP response timing reflected more that of the connections to VL, controlled by OFC, than that of the input leads themselves. Thus, visual evidence for gender categories, collected by VL, activates category labels in T, and consequently, category features in VL, indicating a two-stage representation of semantic categories in TP.
Psychometric evaluation and Rasch analyses of the German Overall Anxiety Severity and Impairment Scale (OASIS-D)
Authors: Hiller Thomas S. , Hoffmann Sabine , Teismann Tobias , Lukaschek Karoline , Gensichen Jochen
Published: April 2023

The Overall Anxiety Severity and Impairment Scale (OASIS) is a 5-item self-report measure that captures symptoms of anxiety and associated functional impairments. This study evaluates a German version (OASIS-D) that was administered to a convenience sample of 1398 primary care patients of whom 419 were diagnosed with panic disorder with/without agoraphobia. Psychometric properties were analyzed using classical test theory as well as probabilistic test theory. Factor analyses suggested a unitary (latent) factor structure. The internal consistency was good to excellent. Convergent as well as discriminant validity with other self-report measures was found. A sum score (range 0–20) of ≥ 8 emerged as optimal cut-score for screening purposes. A difference score of ≥ 5 was indicative of reliable individual change. A Rasch analysis of local item independence suggested response dependency between the first two items. Rasch analyses of measurement invariance detected noninvariant subgroups associated with age and gender. Analyses of validity and optimal cut-off score were solely based on self-report measures, which may have introduced method effects. In sum, the findings support the transcultural validity of the OASIS and indicate its applicability to naturalistic primary care settings. Caution is warranted when using the scale to compare groups that differ in age or gender.
Revealing the stimulus-driven component of attention through modulations of auditory salience by timbre attributes
Authors: Bouvier Baptiste , Susini Patrick , Marquis-Favre Catherine , Misdariis Nicolas
Published: April 2023

Attention allows the listener to select relevant information from their environment, and disregard what is irrelevant. However, irrelevant stimuli sometimes manage to capture it and stand out from a scene because of bottom-up processes driven by salient stimuli. This attentional capture effect was observed using an implicit approach based on the additional singleton paradigm. In the auditory domain, it was shown that sound attributes such as intensity and frequency tend to capture attention during auditory search (cost to performance) for targets defined on a different dimension such as duration. In the present study, the authors examined whether a similar phenomenon occurs for attributes of timbre such as brightness (related to the spectral centroid) and roughness (related the amplitude modulation depth). More specifically, we revealed the relationship between the variations of these attributes and the magnitude of the attentional capture effect. In experiment 1, the occurrence of a brighter sound (higher spectral centroid) embedded in sequences of successive tones produced significant search costs. In experiments 2 and 3, different values of brightness and roughness confirmed that attention capture is monotonically driven by the sound features. In experiment 4, the effect was found to be symmetrical: positive or negative, the same difference in brightness had the same negative effect on performance. Experiment 5 suggested that the effect produced by the variations of the two attributes is additive. This work provides a methodology for quantifying the bottom-up component of attention and brings new insights on attention capture and auditory salience.
Hematic auto-management and extraction for arterial line (HAMEL), a blood-preserving arterial line system: an animal study
Authors: Lee Hanyoung , Lee Jae-myeong
Published: April 2023

Invasive arterial line insertion is a common procedure in the intensive care unit ICU; however, it can cause unnecessary blood loss while procuring blood for laboratory tests. To reduce blood loss resulting from flushing out the arterial line dead space, we developed a new blood-preserving arterial line system: Hematic Auto-Management & Extraction for arterial Line (HAMEL, MUNE Corp.). Five male three-way crossbred pigs were used to evaluate the necessary amount of blood to be withdrawn before sampling to produce accurate results. We then tested whether the traditional sampling method and the HAMEL system showed non-inferior results for blood tests. Blood gas (CG4 + cartridge) and chemistry (CHEM8 + cartridge) analyses were used for comparison. The total unnecessary blood loss in the traditional sampling group was 5 mL/sample. For HAMEL, withdrawing 3 mL of blood before sampling yielded hematocrit and hemoglobin results within 90% confidence interval of traditional sampling group. Most intra-class correlation coefficients between the traditional sampling and HAMEL system groups were > 0.90. When compared to the traditional sampling method, withdrawal of 3 mL with HAMEL was sufficient before blood sampling. Utilization of the HAMEL system was not inferior to the traditional hand-sampling method. In addition, no unnecessary blood loss occurred in the HAMEL system.
Natural history of changes in knee skin temperature following total knee arthroplasty: a systematic review and meta-analysis
Authors: Gavish Lilach , Kandel Leonid , Rivkin Gurion , Gertz S. David , Hoffer Oshrit
Published: April 2023

Patients undergoing total-knee arthroplasty (TKA) have transient increases in anterior knee skin temperature (ST) that subside as recovery progresses–except in cases of systemic or local prosthetic joint infections (PJI). This meta-analysis was designed to quantify the changes in knee ST following TKA in patients with uncomplicated recovery as a prerequisite for assessing the usefulness of thermal imaging for diagnosis of PJI. This meta-analysis (PROSPERO-CRD42021269864) was performed according to PRISMA guidelines. PUBMED and EMBASE were searched for studies reporting knee ST of patients that underwent unilateral TKA with uncomplicated recovery. The primary outcome was the weighted means of the differences in ST between the operated and the non-operated knees (ΔST) for each time point (before TKA, and 1 day; 1,2, and 6 weeks; and 3,6, and 12-months post-TKA). For this analysis, 318 patients were included from 10 studies. The elevation in ST was greatest during the first 2-weeks (ΔST = 2.8 °C) and remained higher than pre-surgery levels at 4–6 weeks. At 3-months, ΔST was 1.4 °C. It decreased to 0.9 °C and 0.6 °C at 6 and 12-months respectively. Establishing the baseline profile of knee ST following TKA provides the necessary first step for evaluating the usefulness of thermography for the diagnosis of post-procedural PJI.
Sex differences in patients with heart failure and mildly reduced left ventricular ejection fraction
Authors: Liu Zhican , Zhu Yunlong , Chen Sihao , Wu Mingxin , Huang Haobo , Peng Ke , Zhang Lingling , Zhao Wenjiao , Peng Xin , Li Na , Zhang Hui , Zhou Yuying , Peng Yiqun , Fan Jie , Zeng Jianping
Published: April 2023

Clinical studies on heart failure with mildly reduced left ventricular ejection fraction (HFmrEF) have gradually increased. However, studies on the prognostic differences between men and women among patients with HFmrEF are few, and no evidence on sex differences in such patients exists. Therefore, we retrospectively assessed the data of patients with HFmrEF using propensity score-matched analysis (PSMA). A total of 1691 patients with HFmrEF were enrolled in the Outcome of Discharged HFmrEF Patients study (OUDI-HF study), which included 1095 men and 596 women. After propensity score matching, we compared the difference in cardiovascular (CV) events (cardiovascular death or heart failure readmission) and all-cause mortality at 90 days and 1 year after discharge between men and women using Kaplan–Meier analysis and Cox regression. After PSMA, men with HFmrEF were 2.2 times more likely to die at 90 days than women with HFmrEF [hazard ratio (HR) 1.88; 95% confidence interval (95% CI) 1.03–3.46; P = 0.041]. However, there was no difference in the 90-day CV events (HR 0.96; 95% CI 0.75–1.22; P = 0.718). Similarly, there was no difference in all-cause mortality (HR 1.16; 95% CI 0.81–1.65; P = 0.417) and CV events (HR 0.98; 95% CI 0.83–1.16; P = 0.817) between men and women after 1 year. Among the patients with HFmrEF, men had a higher 90-day risk of all-cause mortality than women after hospital discharge, and this risk disappeared after 1 year.

Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT05240118 (ESC Heart Failure. (2022). doi: https://doi.org/10.1002/ehf2.14044).
Loss of fungal symbionts and changes in pollinator availability caused by climate change will affect the distribution and survival chances of myco-heterotrophic orchid species
Authors: Kolanowska Marta
Published: April 2023

The first comprehensive species distribution models for orchid, its fungal symbionts and pollinator are presented. To evaluate impact of global warming on these organisms three different projections and four various climate change scenarios were analysed. The niche modelling was based on presence-only records of Limodorum abortivum, two species of Russula and three insects pollinating orchid (Anthophora affinis, Bombus terrestris, Rhodanthidium septemdentatum). Two sets of orchid predictions were examined—the first one included only climatic data and the second one was based on climate data and data on future distribution of orchid fungal symbionts. Overall, a poleward range shift is predicted to occur as a result of climate change and apparently global warming will be favorable for L. abortivum and its potential geographical range will expand. However, due to the negative effect of global warming on fungal symbionts of L. abortivum, the actual extension of the suitable niches of the orchid will be much limited. Considering future possibility of cross-pollination, the availability of A. affinis for L. abortivum will decrease and this bee will be available in the worst case scenarios only for 21% of orchid populations. On the other hand, the overlap of orchid and the buff-tailed bumblebee will increase and as much as 86.5% of plant populations will be located within B. terrestris potential range. Also the availability of R. septemdentatum will be higher than currently observed in almost all analysed climate change projections. This study showed the importance of inclusion of ecological factors in species distribution models as the climate data itself are not enough to estimate the future distribution of plant species. Moreover, the availability of pollen vectors which is crucial for long-term survival of orchid populations should be analysed in context of climate changes.
High spontaneous integration rates of end-modified linear DNAs upon mammalian cell transfection
Authors: Lim Samuel , Yocum R. Rogers , Silver Pamela A. , Way Jeffrey C.
Published: April 2023

In gene therapy, potential integration of therapeutic transgene into host cell genomes is a serious risk that can lead to insertional mutagenesis and tumorigenesis. Viral vectors are often used as the gene delivery vehicle, but they are prone to undergoing integration events. More recently, non-viral delivery of linear DNAs having modified geometry such as closed-end linear duplex DNA (CELiD) have shown promise as an alternative, due to prolonged transgene expression and less cytotoxicity. However, whether modified-end linear DNAs can also provide a safe, non-integrating gene transfer remains unanswered. Herein, we compare the genomic integration frequency upon transfection of cells with expression vectors in the forms of circular plasmid, unmodified linear DNA, CELiDs with thioester loops, and Streptavidin-conjugated blocked-end linear DNA. All of the forms of linear DNA resulted in a high fraction of the cells being stably transfected—between 10 and 20% of the initially transfected cells. These results indicate that blocking the ends of linear DNA is insufficient to prevent integration.
Effects of liquid surface tension on gas capillaries and capillary forces at superamphiphobic surfaces
Authors: Eriksson Mimmi , Claesson Per M. , Järn Mikael , Wallqvist Viveca , Tuominen Mikko , Kappl Michael , Teisala Hannu , Vollmer Doris , Schoelkopf Joachim , Gane Patrick A. C. , Mäkelä Jyrki M. , Swerin Agne
Published: April 2023

The formation of a bridging gas capillary between superhydrophobic surfaces in water gives rise to strongly attractive interactions ranging up to several micrometers on separation. However, most liquids used in materials research are oil-based or contain surfactants. Superamphiphobic surfaces repel both water and low-surface-tension liquids. To control the interactions between a superamphiphobic surface and a particle, it needs to be resolved whether and how gas capillaries form in non-polar and low-surface-tension liquids. Such insight will aid advanced functional materials development. Here, we combine laser scanning confocal imaging and colloidal probe atomic force microscopy to elucidate the interaction between a superamphiphobic surface and a hydrophobic microparticle in three liquids with different surface tensions: water (73 mN m−1), ethylene glycol (48 mN m−1) and hexadecane (27 mN m−1). We show that bridging gas capillaries are formed in all three liquids. Force-distance curves between the superamphiphobic surface and the particle reveal strong attractive interactions, where the range and magnitude decrease with liquid surface tension. Comparison of free energy calculations based on the capillary menisci shapes and the force measurements suggest that under our dynamic measurements the gas pressure in the capillary is slightly below ambient.
Upregulation of alveolar fluid clearance is not sufficient for Na+,K+-ATPase β subunit-mediated gene therapy of LPS-induced acute lung injury in mice
Authors: Liu Jing , Schiralli-Lester Gillian M. , Norman Rosemary , Dean David A.
Published: April 2023

Acute Lung Injury/Acute Respiratory Distress Syndrome (ALI/ARDS) is characterized by diffuse alveolar damage and significant edema accumulation, which is associated with impaired alveolar fluid clearance (AFC) and alveolar‐capillary barrier disruption, leading to acute respiratory failure. Our previous data showed that electroporation‐mediated gene delivery of the Na+, K+-ATPase β1 subunit not only increased AFC, but also restored alveolar barrier function through upregulation of tight junction proteins, leading to treatment of LPS‐induced ALI in mice. More importantly, our recent publication showed that gene delivery of MRCKα, the downstream effector of β1 subunit-mediated signaling towards upregulation of adhesive junctions and epithelial and endothelial barrier integrity, also provided therapeutic potential for ARDS treatment in vivo but without necessarily accelerating AFC, indicating that for ARDS treatment, improving alveolar capillary barrier function may be of more benefit than improving fluid clearance. In the present study, we investigated the therapeutical potential of β2 and β3 subunits, the other two β isoforms of Na+, K+-ATPase, for LPS‐induced ALI. We found that gene transfer of either the β1, β2, or β3 subunits significantly increased AFC compared to the basal level in naïve animals and each gave similar increased AFC to each other. However, unlike that of the β1 subunit, gene transfer of the β2 or β3 subunit into pre-injured animal lungs failed to show the beneficial effects of attenuated histological damage, neutrophil infiltration, overall lung edema, or increased lung permeability, indicating that β2 or β3 gene delivery could not treat LPS induced lung injury. Further, while β1 gene transfer increased levels of key tight junction proteins in the lungs of injured mice, that of either the β2 or β3 subunit had no effect on levels of tight junction proteins. Taken together, this strongly suggests that restoration of alveolar-capillary barrier function alone may be of equal or even more benefit than improving AFC for ALI/ARDS treatment.
Position-reconfigurable pinning for magnetic domain wall motion
Authors: Lee Taekhyeon , Jeong Seyeop , Kim Sanghoon , Kim Kab-Jin
Published: April 2023

Precise control of magnetic domain wall (DW) motion is crucial for DW-based spintronic devices. To date, artificially designed DW pinning sites, such as notch structures, have been used to precisely control the DW position. However, the existing DW pinning methods are not reconfigurable because they cannot change the position of pinning site after being fabricated. Herein, a novel method for attaining reconfigurable DW pinning is proposed, which relies on the dipolar interactions between two DWs located in different magnetic layers. Repulsion between DWs in both layers was observed, indicating that one of the DWs acts as a pinning barrier for the other. Because the DW is mobile in the wire, the position of pinning can be modulated, thereby resulting in reconfigurable pinning that was experimentally demonstrated for current-driven DW motion. These findings provide additional controllability of DW motion, which may expand the functionality of DW-based devices to broader spintronic applications.