bluuebunny/crossref_metadata_2025_split huggingface dataset:
Scale‐invariant changes in corticospinal excitability reflect multiplexed oscillations in the motor output
Authors: Emanuele Marco , D'Ausilio Alessandro , Koch Giacomo , Fadiga Luciano , Tomassini Alice 
Published: December 2023

AbstractIn the absence of disease, humans produce smooth and accurate movement trajectories. Despite such ‘macroscopic’ aspect, the ‘microscopic’ structure of movements reveals recurrent (quasi‐rhythmic) discontinuities. To date, it is unclear how the sensorimotor system contributes to the macroscopic and microscopic architecture of movement. Here, we investigated how corticospinal excitability changes in relation to microscopic fluctuations that are naturally embedded within larger macroscopic variations in motor output. Participants performed a visuomotor tracking task. In addition to the 0.25 Hz modulation that is required for task fulfilment (macroscopic scale), the motor output shows tiny but systematic fluctuations at ∼2 and 8 Hz (microscopic scales). We show that motor‐evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) during task performance are consistently modulated at all (time) scales. Surprisingly, MEP modulation covers a similar range at both micro‐ and macroscopic scales, even though the motor output differs by several orders of magnitude. Thus, corticospinal excitability finely maps the multiscale temporal patterning of the motor output, but it does so according to a principle of scale invariance. These results suggest that corticospinal excitability indexes a relatively abstract level of movement encoding that may reflect the hierarchical organisation of sensorimotor processes.
imageKey points
Motor behaviour is organised on multiple (time)scales.
Small but systematic (‘microscopic’) fluctuations are engrained in larger and slower (‘macroscopic’) variations in motor output, which are instrumental in deploying the desired motor plan.
Corticospinal excitability is modulated in relation to motor fluctuations on both macroscopic and microscopic (time)scales.
Corticospinal excitability obeys a principle of scale invariance, that is, it is modulated similarly at all (time)scales, possibly reflecting hierarchical mechanisms that optimise motor encoding.
Ultrasensitive quantification of HIV-1 cell-to-cell transmission in primary human CD4
+
T cells measures viral sensitivity to broadly neutralizing antibodies
Authors: Mazurov Dmitriy , Herschhorn Alon 
Published: December 2023

ABSTRACT

HIV-1 can efficiently replicate by direct transmission from infected to uninfected CD4
+
T cells at confined local sites designated virological synapses (VSs). VSs are formed by cell junctions between HIV-1 envelope glycoproteins (Envs) on an infected cell and CD4 on an uninfected cell. These sites facilitate highly efficient viral transmission and contribute to HIV-1 evasion from neutralizing antibodies, but accurate quantification of the efficiency of cell-cell transmission is still challenging. Here, we developed an ultrasensitive HIV-1 cell-to-cell transmission assay that triggers the expression of the
nanoluciferase (nluc
) gene in target cells upon transmission and after reverse transcription of the HIV-1 RNA genome. The assay is based on the insertion of the
nluc
gene in an antisense orientation into the HIV-1 provirus. Nluc expression is blocked in virus-producing cells because the
nluc
gene contains an intron that can be efficiently spliced out only when mRNA is transcribed from the opposite (sense) strand. Thus, only sense mRNA that is spliced and subsequently reverse transcribed during transmission to target cells will support Nluc expression. Assay optimization resulted in a very low background, >99% splicing efficiency, high sensitivity, and wide dynamic range for the detection of cell-cell transmission in T cell lines and primary CD4
+
T cells. The optimized reporter vector detects cell-cell transmission using single-round viral vectors and HIV-1 molecular clones, which provide viral proteins of different HIV-1 strains, and reproducibly measures the sensitivity of HIV-1 transmission to antibody neutralization
in vitro
. This assay will contribute to understanding the fundamental mechanisms of HIV-1 cell-to-cell transmission, allow evaluation of pre-existing or acquired HIV-1 resistance in clinical trials, and can be adapted to study other retroviruses.

IMPORTANCE
HIV-1 can efficiently transmit from one cell to another but accurate quantification of this mode of transmission is still challenging. Here, we developed an ultrasensitive assay to measure HIV-1 transmission between cells and to evaluate HIV-1 escape from broadly neutralizing antibodies in primary human T cells. This assay will contribute to understanding the fundamental mechanisms of HIV-1 cell-to-cell transmission, allow evaluation of pre-existing or acquired HIV-1 resistance in clinical trials, and can be adapted to study the biology of other retroviruses.
Nitroxoline resistance is associated with significant fitness loss and diminishes
in vivo
virulence of
Escherichia coli
Authors: Deschner Felix , Risch Timo , Baier Claas , Schlüter Dirk , Herrmann Jennifer , Müller Rolf 
Published: December 2023

ABSTRACT

Nitroxoline (NTX) is an antibiotic approved for the treatment of uncomplicated urinary tract infections (UTIs) caused by Enterobacteriaceae like
Escherichia coli
, and it has been on the market for more than 50 years. Despite being in use longer than several other clinically relevant antibiotics, the resistance of clinical isolates against NTX has not evolved significantly. To better understand this observation, we performed a standardized
in vitro
evaluation of NTX in comparison to other UTI drugs with a focus on resistance development and especially their consequences. We have managed to generate low-level resistant mutants in
E. coli
and
Klebsiella pneumoniae
using a long-term exposure setup, and identified mutations in different efflux-related genes and in other pleiotropic regulators as well as the sensor histidine kinase
envZ
. Subsequently, mutants were characterized by metabolic and proteomic analyses confirming major effects of NTX resistance on both metabolism and differential protein expression of
E. coli
, which ultimately also translates into reduced
in vitro
motility and
in vivo
virulence of mutant strains as shown in a zebrafish larvae infection model.

IMPORTANCE

Antimicrobial resistance (AMR) poses a global threat and requires the exploration of underestimated treatment options. Nitroxoline, an effective broad-spectrum antibiotic, does not suffer from high resistance rates in the clinics but surprisingly, it is not heavily used yet. Our findings provide compelling evidence that Nitroxoline resistance renders bacteria unable to cause an infection
in vivo
, thereby reinvigorating the potential of Nitroxoline in combating AMR.
Morfofunctional and Molecular Changes in Placenta and Peripheral Blood in Preeclampsia and Gestational Diabetes Mellitus
Authors: Artemieva K. A. , Stepanova Yu. V. , Stepanova I. I. , Shamarakova M. V. , Tikhonova N. B. , Nizyaeva N. V. , Tsakhilova S. G. , Mikhaleva L. M. 
Published: December 2023

Abstract
Gestational diabetes mellitus (GDM) and preeclampsia (PE) are common pregnancy complications with similar risk factors. Although GDM is associated with PE, the exact mechanism underlying the association is unclear. The objective of this work was to study the morphofunctional and molecular changes in the placenta and peripheral blood in PE and GDM. Local and systemic changes in the production of several placental proteins were assessed along with markers of inflammation and metabolic disorders. Expression of placental lactogen, trophoblastic β1-glycoprotein, placental alpha-1-microglobulin, and proteinase 3 in villi was found to change in complicated pregnancy groups. Similarity of underlying pathogenic mechanisms was demonstrated for PE and GDM.
Trauma in the elderly: a bilateral rectus sheath haematoma
Authors: McArdle Michael 
Published: December 2023

Life expectancy has more than doubled in the last century, and a new cohort of elderly and increasingly frail patients is presenting to emergency departments with new clinical challenges. When this patient cohort presents after injury, all aspects of clinical practice have to be recalibrated to provide safe and appropriate care. The prevalence of chronic disease, levels of organ failure, multiple comorbidities, greater use of anticoagulation and incidence of recurrent low- and high-impact trauma may delay and obscure diagnosis and, ultimately, increase mortality.Older age is a risk factor for rectus sheath haematoma (RSH), which is haemorrhage into the potential space surrounding the rectus abdominis muscle/s. It is a rare presentation following trauma but can provide diagnostic challenges and be fatal. Even more rare is bilateral RSH with only 12 reported in the literature since 1981.This case report describes bilateral RSH presenting in an elderly woman following a fall and the consequences of seemingly minor trauma in the elderly.
Methamphetamine-associated pulmonary arterial hypertension: data from the national biological sample and data repository for pulmonary arterial hypertension (PAH Biobank)
Authors: Charoenpong Prangthip , Dhillon Navneet , Murnane Kevin , Goeders Nicholas , Hall Nicole , Keller Courtney , Bhuiyan Mohammad Alfrad Nobel , Walter Robert 
Published: December 2023

ObjectiveThis study compares the clinical and haemodynamic severity of methamphetamine-associated pulmonary arterial hypertension (MA-PAH) with idiopathic pulmonary arterial hypertension (IPAH) and connective tissue-associated pulmonary arterial hypertension (CTD-PAH). It also examines sex differences in clinical and physiological parameters among those with MA-PAH.DesignThis is a cross-sectional study using clinically derived data from the National Biological Sample and Data Repository for Pulmonary Arterial Hypertension (PAH biobank), a US-based registry, to compare clinical and physiological characteristics between males and females with MA-PAH.PopulationThe analysis included 1830 patients enrolled in the PAH biobank, with a diagnosis of MA-PAH (n=42), IPAH (n=1073), or CTD-PAH (n=715).Main outcome measuresThe study assessed and compared the clinical and haemodynamic parameters of patients with MA-PAH, IPAH and CTD-PAH.ResultsAmong the patients analysed, 42 had MA-PAH, with 69.1% being female. There were no statistically significant differences in functional class among patients with MA-PAH, IPAH and CTD-PAH. The per cent predicted 6-min walk distance (6MWD) was comparable between the three groups. Patients with MA-PAH had similar mean pulmonary artery pressure and pulmonary vascular resistance to patients with IPAH but higher compared with patients with CTD-PAH. Male patients with MA-PAH exhibited a worse functional class and lower per cent predicted 6MWD, but no significant differences in haemodynamic findings were observed between the sexes.ConclusionThere were no differences in haemodynamic between MA-PAH and IPAH but we found that MA-PAH differed from CTD-PAH. The study did not find evidence of sex differences in MA-PAH. Further research is necessary to identify risk factors and underlying mechanisms of MA-PAH, particularly considering the increasing prevalence of methamphetamine use. Such investigations will contribute to the development of effective prevention and treatment strategies for this condition.
Assault-related anoxia and neck injuries in US emergency departments
Authors: Khurana Bharti , Prakash Jaya , Lewis-O'Connor Annie , Green William , Rexrode Kathryn M. , Loder Randall T. 
Published: December 2023

BackgroundEarly identification of non-fatal strangulation in the context of intimate partner violence (IPV) is crucial due to its severe physical and psychological consequences for the individual experiencing it. This study investigates the under-reported and underestimated burden of IPV-related non-fatal strangulation by analysing assault-related injuries leading to anoxia and neck injuries.MethodsAn IRB-exempt, retrospective review of prospectively collected data were performed using the National Electronic Injury Surveillance System All Injury Programme data from 2005 to 2019 for all assaults resulting in anoxia and neck injuries. The type and mechanism of assault injuries resulting in anoxia (excluding drowning, poisoning and aspiration), anatomical location of assault-related neck injuries and neck injury diagnosis by morphology, were analysed using statistical methods accounting for the weighted stratified nature of the data.ResultsOut of a total of 24 493 518 assault-related injuries, 11.6% (N=2 842 862) resulted from IPV (defined as perpetrators being spouses/partners). Among 22 764 cases of assault-related anoxia, IPV accounted for 40.4%. Inhalation and suffocation were the dominant mechanisms (60.8%) of anoxia, with IPV contributing to 41.9% of such cases. Neck injuries represented only 3.0% of all assault-related injuries, with IPV accounting for 21% of all neck injuries and 31.9% of neck contusions.ConclusionsThe study reveals a significant burden of IPV-related anoxia and neck injuries, highlighting the importance of recognising IPV-related strangulation. Comprehensive screening for IPV should be conducted in patients with unexplained neck injuries, and all IPV patients should be screened for strangulation events.
4′-Ethynyl-2′-Deoxycytidine (EdC) Preferentially Targets Lymphoma and Leukemia Subtypes by Inducing Replicative Stress
Authors: Calbert Marissa L. , Chandramouly Gurushankar , Adams Clare M. , Saez-Ayala Magali , Kent Tatiana , Tyagi Mrityunjay , Ayyadevara V.S.S. Abhinav , Wang Yifan , Krais John J. , Gordon John , Atkins Jessica , Toma Monika M. , Betzi Stéphane , Boghossian Andrew S. , Rees Matthew G. , Ronan Melissa M. , Roth Jennifer A. , Goldman Aaron R. , Gorman Nicole , Mitra Ramkrishna , Childers Wayne E. , Graña Xavier , Skorski Tomasz , Johnson Neil , Hurtz Christian , Morelli Xavier , Eischen Christine M. , Pomerantz Richard T. 
Published: December 2023

Abstract
Anticancer nucleosides are effective against solid tumors and hematologic malignancies, but typically are prone to nucleoside metabolism resistance mechanisms. Using a nucleoside-specific multiplexed high-throughput screening approach, we discovered 4′-ethynyl-2′-deoxycytidine (EdC) as a third-generation anticancer nucleoside prodrug with preferential activity against diffuse large B-cell lymphoma (DLBCL) and acute lymphoblastic leukemia (ALL). EdC requires deoxycytidine kinase (DCK) phosphorylation for its activity and induces replication fork arrest and accumulation of cells in S-phase, indicating it acts as a chain terminator. A 2.1Å cocrystal structure of DCK bound to EdC and UDP reveals how the rigid 4′-alkyne of EdC fits within the active site of DCK. Remarkably, EdC was resistant to cytidine deamination and SAMHD1 metabolism mechanisms and exhibited higher potency against ALL compared with FDA-approved nelarabine. Finally, EdC was highly effective against DLBCL tumors and B-ALL in vivo. These data characterize EdC as a preclinical nucleoside prodrug candidate for DLBCL and ALL.
Depression and Subclinical Coronary Atherosclerosis in Adults Without Clinical Coronary Artery Disease
Authors: Park Jangho , Lee Hyeji , Jeon Young‐Jee , Park Eun Ji , Park Sangwoo , Ann Soe Hee , Kim Yong‐Giun , Lee Yongjik , Park Gyung‐Min , Choi Seong Hoon 
Published: December 2023

Background
The relationship between depression and subclinical coronary atherosclerosis in asymptomatic individuals is not clear. We evaluated this relationship in a Korean population.

Methods and Results

We analyzed 3920 individuals (mean age 54.7±7.9 years and 2603 men [66.4%]) with no history of coronary artery disease who voluntarily underwent coronary computed tomographic angiography and screening for depression using the Beck Depression Inventory as part of a general health examination. The degree and extent of subclinical coronary atherosclerosis were evaluated by coronary computed tomographic angiography, and ≥50% diameter stenosis was defined as significant. Participants were categorized into groups of those with or without depression using the Beck Depression Inventory scores ≥16 as a cutoff value. Of the study participants, 272 (6.9%) had a Beck Depression Inventory score of 16 or higher. After adjustment for cardiovascular risk factors, depression was not significantly associated with any coronary plaque (adjusted odds ratio [OR], 1.05 [95% CI, 0.78–1.41];
P
=0.746), calcified plaque (OR, 0.95 [95% CI, 0.71–1.29];
P
=0.758), noncalcified plaque (OR, 1.31 [95% CI, 0.79–2.17];
P
=0.305), mixed plaque (OR, 1.16 [95% CI, 0.60–2.23];
P
=0.659), or significant coronary artery stenosis (OR, 1.22 [95% CI, 0.73–2.03];
P
=0.450). In the propensity score‐matched population (n=1318) as well, none of the coronary artery disease measures of subclinical coronary atherosclerosis were statistically significantly associated with depression (all
P
>0.05).

Conclusions
In this large cross‐sectional study with asymptomatic individuals undergoing coronary computed tomographic angiography and Beck Depression Inventory evaluation, depression was not associated with an increased risk of subclinical coronary atherosclerosis.
Association Between New‐Onset Type 2 Diabetes and Cardiac Conduction Diseases: A Prospective Cohort Study
Authors: Zhao Maoxiang , Gao Jingli , Chen Shuohua , Yao Siyu , Wang Miao , Wang Chi , Zhang Sijin , Feng Zekun , Tian Lu , Li Yanjie , Liu Yang , Wu Shouling , Xue Hao 
Published: December 2023

Background
Cardiac conduction diseases can lead to life‐threatening outcomes. However, the evidence on risk factors for conduction disease that is needed to underpin prevention strategies is limited. The present study aimed to determine the association between type 2 diabetes and cardiac conduction diseases.

Methods and Results
This study included 101 080 participants free of prevalent diabetes and cardiac conduction diseases at baseline from the Kailuan Study. All participants were monitored biennially until December 31, 2020. During follow‐up, 14 397 participants were diagnosed as having type 2 diabetes. For each case subject, 1 control subject was randomly selected, matched for age (±1 year) and sex. The final analysis comprised 10 744 case‐control pairs. Cox regression models with age as the underlying time scale were used. During a median follow‐up of 5.46 years, 571 incident events occurred, including 164 atrioventricular blocks, 414 bundle‐branch blocks (BBBs), 274 right BBBs, and 210 left BBBs. After adjustment for potential confounders, participants with type 2 diabetes diagnosed had greater relative risks for most outcomes relative to controls, with hazard ratios of 1.42 (95% CI, 1.18–1.67) for conduction diseases, 1.40 (95% CI, 1.00–1.96) for atrioventricular blocks, 1.43 (95% CI, 1.16–1.75) for BBBs, and 1.69 (95% CI, 1.15–2.49) for left BBBs. In contrast, no association between diabetes and right BBB was observed.

Conclusions
In this study, participants with type 2 diabetes are at an increased risk of cardiac conduction disease but not associated with the development of right BBB.
How Well Do Professional Reference Ratings Predict Teacher Performance?
Authors: Goldhaber Dan , Grout Cyrus , Wolff Malcolm 
Published: December 2023

Abstract
While the practice of collecting information from applicants’ professional references is widespread, there is a paucity of research linking references’ assessments of applicants to subsequent performance. In this paper, we examine the predictive validity of a specific type of reference-provided information: categorical ratings of teacher applicants collected from their professional references—a potentially low-cost means of enhancing the applicant information available during the hiring process. We find an overall significant relationship between reference ratings and teacher performance as measured by observational evaluation ratings and teacher value added in math, but that this relationship is moderated by two factors. First, while references’ ratings of applicants with prior teaching experience are predictive of performance, those of novice applicants are not. Second, the predictive validity of reference ratings varies according to rater type: Ratings from references identified as the applicants’ Principal/Other Supervisor, Instructional Coach/Department Chair, or Colleague are significantly predictive of performance whereas those from other types of raters are not. Overall, our findings show that meaningful information can be solicited from applicants’ references in the form of categorical ratings but also demonstrate some limitations in the potential for this type of information to inform hiring decisions.
Productivity Gains from Trade: Bunching Estimates from Trading Rights in China
Authors: Li Yunong , Lu Yi , Wang Jianguo 
Published: December 2023

Abstract
This paper identifies productivity gains from trade by studying the manipulation behavior of firms in response to regulatory policies on international trade in China. Bunching estimates show that participation in international trade increases firm productivity. The productivity gains increase over time, indicating dynamic learning from trading. Further exploration shows no effects on R&D investment, product rationalization and markup. Young firms and nonstate-owned firms (non-SOEs) gain more from participating in trade. Workers share productivity gains through increased wages but not from increased employment.
Relationship Stickiness, International Trade, and Economic Uncertainty
Authors: Martin Julien , Mejean Isabelle , Parenti Mathieu 
Published: December 2023

Abstract
We study how stickiness in business relationships influences the trade impact of aggregate uncertainty. To begin, we construct a product-level index of relationship stickiness using firm-to-firm relationship duration data. We then demonstrate how relationship stickiness shapes trade dynamics in response to uncertainty shocks. We find that episodes of uncertainty lead to a decline in the overall establishment of new business relationships, with the impact varying depending on the level of stickiness. In markets characterized by high stickiness, uncertainty shocks primarily impede investments in new firm-to-firm relationships. In contrast, for non-sticky products, the adjustment to uncertainty shocks mainly manifests as the disruption of existing relationships.
The Intended and Unintended Effects of Promoting Labor Market Mobility
Authors: Caliendo Marco , Künn Steffen , Mahlstedt Robert 
Published: December 2023

Abstract
We investigate the causal effects of financial incentives supporting geographical mobility among unemployed workers on their job search behavior and labor market outcomes. Exploiting regional variation in the promotion of mobility programs along administrative borders of German employment agency districts, we show that promoting mobility – as intended – causes job seekers to increase their search radius, apply for, and accept distant jobs. At the same time, local job search is reduced with adverse consequences for reemployment and earnings. A detailed analysis of the underlying mechanisms suggests spatial search frictions as the driver of the unintended adverse labor market effects.
Imperfect Private Information in Insurance Markets
Authors: Solomon Adam 
Published: December 2023

Abstract
This paper studies imperfectly-perceived private information in insurance markets when contracts endogenously respond. Equilibrium contracts, pooling and welfare depend on the joint distribution of risk and misperception. In the Health and Retirement Study (HRS), I show that misperceptions typically co-vary with (medical, long-term care, disability and mortality) risk type: high types under-perceive their risk, low types over-perceive. I develop a general model and algorithm to estimate the equilibrium contracts, pooling and welfare impact of misperceptions that is applicable in many settings. I offer suggestive evidence from US annuity markets that contracts are distorted due to misperceptions, with welfare likely increasing.