bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibitory Plasticity Facilitates Recovery of Stimulus Velocity Tuning in the Superior Colliculus after Chronic NMDA Receptor Blockade
Authors: Razak Khaleel A. , Pallas Sarah L.
Published: July 2007

The developing nervous system is shaped in important ways by spontaneous and stimulus-driven neural activity. Perturbation of normal activity patterns can profoundly affect the development of some neural response properties, whereas others are preserved through mechanisms that either compensate for or are unaffected by the perturbation. Most studies have examined the role of excitation in activity-dependent plasticity of response properties. Here, we examine the role of inhibition within the context of response selectivity for moving stimuli. The spatial extent of retinal input to the developing hamster superior colliculus (SC) can be experimentally increased by chronic NMDA receptor (NMDAR) blockade. Remarkably, stimulus velocity tuning is intact despite the increase in excitatory inputs. The goal of this study was to investigate whether plasticity in surround inhibition might provide the mechanism underlying this preservation of velocity tuning. Surround inhibition shapes velocity tuning in the majority of superficial layer SC neurons in normal hamsters. We show that despite the NMDAR blockade-induced increase in feedforward excitatory convergence from the retina, stimulus velocity tuning in the SC is maintained via compensatory plasticity in surround inhibition. The inhibitory surround increased in strength and spatial extent, and surround inhibition made a larger contribution to velocity tuning in the SC after chronic NMDAR blockade. These results show that inhibitory plasticity can preserve the balance between excitation and inhibition that is necessary to preserve response properties after developmental manipulations of neural activity. Understanding these compensatory mechanisms may permit their use to facilitate recovery from trauma or sensory deprivation.
Acute Stress Facilitates Hippocampal CA1 Metabotropic Glutamate Receptor-Dependent Long-Term Depression
Authors: Chaouloff Francis , Hémar Agnès , Manzoni Olivier
Published: July 2007

Acute stress affects NMDA receptor (NMDAR)-dependent synaptic plasticity in the CA1 region of the hippocampus, with long-term potentiation and long-term depression (LTD) being, respectively, diminished and facilitated by acute exposure to stress. Here, we examined whether this facilitatory effect of stress on NMDAR-dependent LTD extends to metabotropic glutamate receptor (mGluR)-dependent LTD at Schaffer collateral–CA1 synapses. Application of a low dose (50 μm) of the selective group 1 mGluR agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) promoted LTD in slices from stressed, but not from control, rats. Pretreatment of stressed rats with the glucocorticoid receptor (GR) antagonist RU38486 prevented the facilitation of DHPG-induced LTD (DHPG-LTD), indicating the involvement of corticosterone secretion and, in turn, stimulation of GRs. Finally, pretreatment of slices with an mGluR1, but not an mGluR5, antagonist blunted the sensitizing effect of stress on DHPG-LTD. These results indicate that acute stress, through corticosterone stimulation of GRs, facilitates the expression of mGluR1-dependent DHPG-LTD in the hippocampal CA1 region.
FGF/Heparin Differentially Regulates Schwann Cell and Olfactory Ensheathing Cell Interactions with Astrocytes: A Role in Astrocytosis
Authors: Santos-Silva Alessandra , Fairless Richard , Frame Margaret C. , Montague Paul , Smith George M. , Toft Andrew , Riddell John S. , Barnett Susan C.
Published: July 2007

After injury, the CNS undergoes an astrocyte stress response characterized by reactive astrocytosis/proliferation, boundary formation, and increased glial fibrillary acidic protein (GFAP) and chondroitin sulfate proteoglycan (CSPG) expression. Previously, we showed thatin vitroastrocytes exhibit this stress response when in contact with Schwann cells but not olfactory ensheathing cells (OECs). In this study, we confirm this findingin vivoby demonstrating that astrocytes mingle with OECs but not Schwann cells after injection into normal spinal cord. We show that Schwann cell-conditioned media (SCM) induces proliferation in monocultures of astrocytes and increases CSPG expression in a fibroblast growth factor receptor 1 (FGFR1)-independent manner. However, SCM added to OEC/astrocyte cocultures induces reactive astrocytosis and boundary formation, which, although sensitive to FGFR1 inhibition, was not induced by FGF2 alone. Addition of heparin to OEC/astrocyte cultures induces boundary formation, whereas heparinase or chlorate treatment of Schwann cell/astrocyte cultures reduces it, suggesting that heparan sulfate proteoglycans (HSPGs) are modulating this activity.In vivo, FGF2 and FGFR1 immunoreactivity was increased over grafted OECs and Schwann cells compared with the surrounding tissue, and HSPG immunoreactivity is increased over reactive astrocytes bordering the Schwann cell graft. These data suggest that components of the astrocyte stress response, including boundary formation, astrocyte hypertrophy, and GFAP expression, are mediated by an FGF family member, whereas proliferation and CSPG expression are not. Furthermore, after cell transplantation, HSPGs may be important for mediating the stress response in astrocytes via FGF2. Identification of factors secreted by Schwann cells that induce this negative response in astrocytes would further our ability to manipulate the inhibitory environment induced after injury to promote regeneration.
The Glial or Neuronal Fate Choice of Oligodendrocyte Progenitors Is Modulated by Their Ability to Acquire an Epigenetic Memory
Authors: Liu Aixiao , Han Yu R. , Li Jiadong , Sun Dongming , Ouyang Ming , Plummer Mark R. , Casaccia-Bonnefil Patrizia
Published: July 2007

The identity of any cell type is determined by the specific pattern of gene expression. We show here that the ability of oligodendrocyte progenitors to acquire the identity of myelin-expressing cells or choose alternative fates is dependent on the activity of histone deacetylases. Using gene expression profiling, electrophysiological recordings, transplantation studies, and pharmacological inhibition, we demonstrate that specified NG2+oligodendrocyte progenitors are plastic cells, whose decision to initiate an oligodendrocytic rather than astrocytic or neuronal program of gene expression requires the establishment of an epigenetic identity that is initiated by histone deacetylation.
FMRFamide-Like Neuropeptides and Mechanosensory Touch Receptor Neurons Regulate Male Sexual Turning Behavior inCaenorhabditis elegans
Authors: Liu Tiewen , Kim Kyuhyung , Li Chris , Barr Maureen M.
Published: July 2007

Caenorhabditis elegansmale mating provides a powerful model to study the relationship between the nervous system, genes, and innate sexual behaviors. Male mating is the most complex behavior exhibited by the nematodeC. elegansand involves the steps of response, backing, turning, vulva location, spicule insertion, and sperm transfer. Because neuropeptides are important neural regulators of many complex animal behaviors, we explored the function of the FMRFamide-like neuropeptide (flp) gene family in regulating male copulation. We found that peptidergic signaling mediated by FMRF-amide like neuropeptides (FLPs) FLP-8, FLP-10, FLP-12, and FLP-20 is required for the sensory transduction involved in male turning behavior.flp-8,flp-10,flp-12, andflp-20mutant males significantly increase repetition of substep(s) of turning behavior compared with wild-type males. Genes controlling neuropeptide processing and secretion in general, includingegl-3,egl-21,ida-1, andunc-31, are also required for inhibiting repetitive turning behavior. Neuropeptidergic signaling adjusts the repetitiveness of turning independently of serotonergic modulation of the timing of turning. Surprisingly, the mechanosensitive touch receptor neurons are found to be part of the neural circuitry regulating male turning behavior, indicating the existence of functional dimorphisms in the nervous system with regard to sex-specific behaviors.
The Rural Wings Project: Bridging the Digital Divide with Satellite-Provided Internet. Phase I: Identifying and Analysing the Learning Needs of 31 Communities in 10 Countries
Authors: Hansson Henrik , Mihailidis Paul , Larsson Ken , Sotiriou Menelaos , Sotiriou Sofoklis , Uzunoglu Nikolaos , Gargalakos Michail
Published: July 2007

The digitally marginalised communities are in focus in the EU-funded Rural Wings project 2006–2008. The aim is to identify and analyse the user learning needs in non-connected communities and to meet these needs by providing satellite Internet broadband connections, education and tools. This article reports the findings of the user needs investigation of 31 communities in 10 countries in the initial phase of the project designed and coordinated by Stockholm University, Sweden. Each national coordinator conducted a user needs study in their country using a common framework of questions and guidelines. The sites were selected according to national and regional needs and where satellite-provided Internet is believed to be the long-term solution. The 31 communities selected can be summarised as (a) mainland/lowland communities, 10 (b) mainland/highland communities, 12 (c) island/lowland communities, 5, and (d) island/highland communities, 4. The analysis reveals common threads of lack of infrastructure, accessibility and reliability concerning information and communication technology (ICT) implementation and containment in the community. There is a plethora of reasons for wanting more reliable and frequent Internet connections. Reasons range from educational opportunities, language opportunities, governmental inclusion, information/news outlets, and medical and weather initiative capabilities. This study provides in-depth macro-summaries of each participating country's user needs analysis in total. It also includes the actual analysis of each test site based on over 31 sites spanning 10 European nations. In addition, generalisations, comparisons and differences have been composed, to provide a framework for European trends in rural ICT access.
Fire Next Time: Or Revisioning Higher Education in the Context of Digital Social Creativity
Authors: Kupiainen Reijo , Suoranta Juha , Vadén Tere
Published: July 2007

This article presents an idea of ‘digital social creativity’ as part of social media and examines an approach emphasising openness and experimentation and collaborative learning in the world of information and communication technologies. Wikipedia and similar digital tools provide both challenges to and possibilities for building learning sites in higher education and other forms of education and socialisation that recognise various forms of information and knowledge creation. The dialogical nature of knowledge and the emphasis on social interaction create a tremendous opportunity for education, but at the same time form new hegemonic battlegrounds in terms of various uses of social media.
The Inequities of the Digital Divide: Is E-Learning a Solution?
Authors: Journell Wayne
Published: July 2007

This article addresses the continuing digital divide in public education, one that defines itself largely along geographic, socioeconomic, and cultural lines. The article refutes the idea that the digital divide is dwindling due to increasing access to technology within the United States, instead focusing on digital literacy and cultural barriers as perpetuating the divide, causing economic, democratic, and social ramifications for those affected. Finally, e-learning is proposed as a potential solution to narrow the divide based on the ability to receive effective instruction without geographic restraints.
Reciprocal Disconnectedness: Computer Games, Schooling and Boys at Risk
Authors: Baskin Colin , Taylor Ryan
Published: July 2007

Ethnomethodology is the analytical frame used here to recover embedded cultural discursive phenomena in the language of ‘at risk’ middle-school boys as they talk about ‘computer games’ and ‘schooling’. What emerges is a rich picture of myths and heroes, identities of participation where member values and a discernible moral order are part of the ‘gaming’ culture. A second picture emerges of ‘boys in school’. Here ‘sleepers, avoiders and disconnected teachers’ are disclosed through conversational structures as identities of non-participation in the classroom. Through student talk we learn that identities of non-participation are a reciprocal phenomena, wherein these students and their teachers co-construct a reciprocal disconnectedness, each to the other. To the individual learner, the computer game is ‘serious fun’ to the classroom it is a ‘peripheral distraction’; to the school community it is a marker for identifying boys ‘at risk’ of disengaging. Each of these individual accounts stands only as a ‘partial’ explanation of the role of computer games in schooling. The article argues that our ability to nourish learners' inner capacities is not dependent on the level or nature of technology, but on the creative learning applications it invokes.
E-Learning as a Tool for Knowledge Transfer through Traditional and Independent Study at Two United Kingdom Higher Educational Institutions: A Case Study
Authors: Owens Jonathan D. , Floyd David
Published: July 2007

Much has been made of the advances in computer-aided learning activities. Websites, virtual campus, the increased use of WebCT (an online proprietary virtual learning environment system) and chat rooms and further advances in the use of WebCT are becoming more commonplace in United Kingdom universities. However, the effectiveness of these learning methods from the student point of view needs to be questioned. This article looks for ways of changing higher education students' perception of the usefulness of recommended Internet websites for learning purposes, with the intention of increasing the usage rate of recommended module websites. The change could represent an adaptation of the existing, well-known technology to change students' perception regarding its potentially formative role. Subsequently, the outcomes from this preliminary research could be used in order to enhance the quality of Internet use for teaching and learning purposes. The article further draws on secondary sources, including the 2005 Oxford Internet survey that gives constructive perspectives into future policy direction. The article examines some of the learning technologies and introduces the discussion on the evaluation of web-based learning. The research problem that emerges from the discussion is defined and followed by the illustration of the investigative method deployed. The analysis of findings and recommendations conclude the article.
PESTE Factors in Developing a Framework for E-Learning
Authors: Graham Deryn
Published: July 2007

This article describes the development of a framework for e-learning and presents the findings of a study investigating whether the use of blended learning can fulfil or at least accommodate some of the human requirements presently neglected by current e-learning systems. The study evaluated the in-house system, Teachmat, and discussed how the use of blended learning has become increasingly prevalent as a result of its enhancement and expansion, its relationship to the human and pedagogical issues, and both the positive and negative implications of this reality. PESTE (Political, Economic, Social, Technical, and Environmental) factors from sociology are then applied to appraise the employment of e-learning, leading to the proposal of PESTE factors for educational software and e-learning in particular.
Home-Based Physical Therapy Intervention With Adherence-Enhancing Strategies Versus Clinic-Based Management for Patients With Ankle Sprains
Authors: Bassett Sandra F , Prapavessis Harry
Published: July 2007

Background and Purpose: To some extent, favorable treatment outcomes for physical therapy intervention programs depend on patients attending their clinic appointments and adhering to the program requirements. Previous studies have found less-than-optimal levels of clinic attendance, and a viable option might be physical therapy intervention programs with a large component of home treatment. This study investigated the effects of a standard physical therapy intervention program—delivered primarily at either the clinic or home—on ankle function, rehabilitation adherence, and motivation in patients with ankle sprains.

Subjects: Forty-seven people with acute ankle sprains who were about to start a course of physical therapy intervention participated in the study.

Methods: Using a prospective design, subjects were randomly assigned to either a clinic intervention group or a home intervention group. Ankle function and motivation were measured before and after rehabilitation, and adherence to the clinic- and home-based programs was measured throughout the study.

Results: The groups had similar scores for post-treatment ankle function, adherence, and motivation. The home intervention group had a significantly higher percentage of attendance at clinic appointments and better physical therapy intervention program completion rate.

Discussion and Conclusion: Home-based physical therapy intervention appears to be a viable option for patients with sprained ankles.
Fatal Traffic Risks With a Total Solar Eclipse in the US
Authors: Redelmeier Donald A. , Staples John A.
Published: March 2024

This case-control study describes the incidence of fatal traffic crashes in the US during the 2017 total solar eclipse.
Effectiveness of an Artificial Intelligence–Enabled Intervention for Detecting Clinical Deterioration
Authors: Gallo Robert J. , Shieh Lisa , Smith Margaret , Marafino Ben J. , Geldsetzer Pascal , Asch Steven M. , Shum Kenny , Lin Steven , Westphal Jerri , Hong Grace , Li Ron Chen
Published: March 2024

Importance

Inpatient clinical deterioration is associated with substantial morbidity and mortality but may be easily missed by clinicians. Early warning scores have been developed to alert clinicians to patients at high risk of clinical deterioration, but there is limited evidence for their effectiveness.

Objective

To evaluate the effectiveness of an artificial intelligence deterioration model–enabled intervention to reduce the risk of escalations in care among hospitalized patients using a study design that facilitates stronger causal inference.

Design, Setting, and Participants

This cohort study used a regression discontinuity design that controlled for confounding and was based on Epic Deterioration Index (EDI; Epic Systems Corporation) prediction model scores. Compared with other observational research, the regression discontinuity design facilitates causal analysis. Hospitalized adults were included from 4 general internal medicine units in 1 academic hospital from January 17, 2021, through November 16, 2022.

Exposure

An artificial intelligence deterioration model–enabled intervention, consisting of alerts based on an EDI score threshold with an associated collaborative workflow among nurses and physicians.

Main Outcomes and Measures

The primary outcome was escalations in care, including rapid response team activation, transfer to the intensive care unit, or cardiopulmonary arrest during hospitalization.

Results

During the study, 9938 patients were admitted to 1 of the 4 units, with 963 patients (median [IQR] age, 76.1 [64.2-86.2] years; 498 males [52.3%]) included within the primary regression discontinuity analysis. The median (IQR) Elixhauser Comorbidity Index score in the primary analysis cohort was 10 (0-24). The intervention was associated with a −10.4–percentage point (95% CI, −20.1 to −0.8 percentage points; P = .03) absolute risk reduction in the primary outcome for patients at the EDI score threshold. There was no evidence of a discontinuity in measured confounders at the EDI score threshold.

Conclusions and Relevance

Using a regression discontinuity design, this cohort study found that the implementation of an artificial intelligence deterioration model–enabled intervention was associated with a significantly decreased risk of escalations in care among inpatients. These results provide evidence for the effectiveness of this intervention and support its further expansion and testing in other care settings.
High‐Tech Industry
Authors: Yu Zhou
Published: March 2024

High‐tech industry encompasses technology‐driven manufacturing and services, playing a critical role in global/regional economic restructuring and producing distinct geographical patterns. Over time, these industries have acted as catalysts for job creation and regional growth in the era of globalization. They have, however, also been associated with labor market polarization, inequality, and insecurity of low‐wage jobs within neoliberal economic systems. Initially concentrated in the United States, Europe, and Japan from World War II to the 1990s, high‐tech development has now expanded to newly industrialized countries, particularly in Asia. This shift has intensified global competition and, in some cases, created geographical tensions related to technology supremacy. The high‐tech industry's geographical distribution is influenced by uneven human resources and regional institutional environments, and by varying public investment and policies.
Incident Use of Hydroxychloroquine for the Treatment of Rheumatoid Arthritis and Systemic Lupus Erythematosus During the COVID‐19 Pandemic
Authors: Mercadé‐Besora Núria , Guo Yuchen , Du Mike , Li Xintong , Ramírez‐Anguita Juan Manuel , Moreno Alberto , Valente António , Villalobos Felipe , Cheng Iek Leng , Carrasco‐Ribelles Lucía A. , van Swieten Maaike M. H. , Merkelbach Manon , Magoya Mary , Lasalvia Paolo , Pericàs‐Pulido Pau , Berg Paul , Bosco‐Lévy Pauline , Lillini Roberto , Ribeiro Rogerio , Bagga Trinamjot Kaur , Ramella Vittoria , Khalid Sara , Mayer Miguel Angel , Leis Angela , Jödicke Annika M. , Burn Edward , Prieto‐Alhambra Daniel , Català Martí , Prats‐Uribe Albert
Published: March 2024

Objective

We studied whether the use of hydroxychloroquine (HCQ) for COVID‐19 resulted in supply shortages for patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE).

Methods

We used US claims data (IQVIA PHARMETRICS® Plus for Academics [PHARMETRICS]) and hospital electronic records from Spain (Institut Municipal d'Assistència Sanitària Information System [IMASIS]) to estimate monthly rates of HCQ use between January 2019 and March 2022, in the general population and in patients with RA and SLE. Methotrexate (MTX) use was estimated as a control.

Results

More than 13.5 million individuals (13,311,811 PHARMETRICS, 207,646 IMASIS) were included in the general population cohort. RA and SLE cohorts enrolled 135,259 and 39,295 patients, respectively, in PHARMETRICS. Incidence of MTX and HCQ were stable before March 2020. On March 2020, the incidence of HCQ increased by 9‐ and 67‐fold in PHARMETRICS and IMASIS, respectively, and decreased in May 2020. Usage rates of HCQ went back to prepandemic trends in Spain but remained high in the United States, mimicking waves of COVID‐19. No significant changes in HCQ use were noted among patients with RA and SLE. MTX use rates decreased during HCQ approval period for COVID‐19 treatment.

Conclusion

Use of HCQ increased dramatically in the general population in both Spain and the United States during March and April 2020. Whereas Spain returned to prepandemic rates after the first wave, use of HCQ remained high and followed waves of COVID‐19 in the United States. However, we found no evidence of general shortages in the use of HCQ for both RA and SLE in the United States.
Design of distributed event‐triggered states and unknown disturbances observers for time‐varying delay interconnected systems
Authors: Cong Huong Dinh
Published: March 2024

This article considers the problem of designing distributed event‐triggered states and unknown disturbances observers for a class of nonlinear interconnected systems where the local state vectors are affected by unknown delays and the nonlinear function satisfying the Lipschitz condition. Distributed observers are designed based on the local input vector and both the local and remote output vectors. Different from previously distributed observers for interconnected systems where the local and remote output vectors are updated continuously, the one in this article uses only information on the local and remote output vectors updating at triggering instants of proposed event‐triggered mechanisms. This indicates that the proposed method in this article is better than the existing ones in saving communication resources while still keeping an acceptable estimation performance. Sufficient conditions for the existence of the proposed distributed observers are established and are formed in a convex optimization problem which can be easily solved by using the MATLAB LMI Control Toolbox. Finally, a numerical example is given to confirm the effectiveness and advantages of the proposed method.
Enhancing Triplet–Triplet Annihilation Upconversion Performance Through Anthracene–Carbazole Interactions for Organic Optoelectronic Applications
Authors: Hsieh Kai‐Hong , Zhuang Yuan‐Zhen , Huang Jing‐Xiang , Wei Zheng‐Yu , Zhang Yong‐Yun , Lee Jiun‐Haw , Chiu Tien‐Lung , Leung Man‐kit
Published: March 2024

Three carbazole‐substituted anthracene 2CbzAn, 26CbzAn, and 246CbzAn have been developed. The introduction of these carbazole substituents could generate more triplet states with energy levels close to 2× E(T1) that could successfully facilitate the triplet‐triplet annihilation upconversion (TTA‐UC) process to achieve high upconversion quantum yield (UCQY). This observation aligns with the Adachi theory about TTA‐UC mechanisms. In organic light‐emitting diode (OLED) device investigation, in a non‐doped state show an external quantum efficiency (EQEmax) of 5.82% with exceptional pure‐blue emission (CIEy of 0.101), and the DPaNIF doped DMPPP/26CbzAn bilayer structure reaches an impressive EQEmax of 11.12%.
Noninvasive Tracking of Embryonic Cardiac Dynamics and Development with Volumetric Optoacoustic Spectroscopy
Authors: Hatami Maryam , Özbek Ali , Deán‐Ben Xosé Luís , Gutierrez Jessica , Schill Alexander , Razansky Daniel , Larin Kirill V.
Published: March 2024

Noninvasive monitoring of cardiac development can potentially prevent cardiac anomalies in adulthood. Mouse models provide unique opportunities to study cardiac development and disease in mammals. However, high‐resolution noninvasive functional analyses of murine embryonic cardiac models are challenging because of the small size and fast volumetric motion of the embryonic heart, which is deeply embedded inside the uterus. In this study, a real time volumetric optoacoustic spectroscopy (VOS) platform for whole‐heart visualization with high spatial (100 µm) and temporal (10 ms) resolutions is developed. Embryonic heart development on gestational days (GDs) 14.5–17.5 and quantify cardiac dynamics using time‐lapse‐4D image data of the heart is followed. Additionally, spectroscopic recordings enable the quantification of the blood oxygenation status in heart chambers in a label‐free and noninvasive manner. This technology introduces new possibilities for high‐resolution quantification of embryonic heart function at different gestational stages in mammalian models, offering an invaluable noninvasive method for developmental biology.
Depression and associated risk factors among emergency medicine interns: Results from a national longitudinal cohort study
Authors: Folk Destiny D. , Brown Cortlyn , Bissell Carrie C. , Fowler Lauren A.
Published: March 2024

Objective

Despite depression being common in residents, there are no published studies on the prevalence and risk factors for depression in emergency medicine (EM) interns. Our objectives were to explore the prevalence of depression among EM interns and to identify risk factors for depression including sleep, work hours, rotation type, race, ethnicity, sex, and age.

Methods

The Intern Health Study is a national longitudinal cohort study on intern mental health in all specialties. Secondary analysis was performed for EM interns only in this study. Data were collected from 2007 to 2021 and study participants completed a pre–intern year baseline survey and quarterly surveys throughout intern year, which included demographics and information on depressive symptoms, work hours, sleep, and rotation specifics. Depression severity was objectified using the Patient Health Questionnaire (PHQ9) with scores of 10 and higher meeting criteria for moderate to severe depression.

Results

A total of 1123 EM interns completed all surveys. The prevalence of moderate to severe depression among EM interns before starting internship was 4.8%. At Months 3, 6, 9, and 12 of intern year, the prevalence of moderate to severe depression was 17.8%, 20.5%, 20.8%, and 18.8%, respectively. PHQ9 scores were significantly higher at Month 3 of intern year compared to pre–intern year, but there were no differences at subsequent time points during intern year (p < 0.001). Females were more likely to have PHQ9 scores of 10 or above at all time points (p < 0.001). Clinical rotation type had a significant effect on PHQ9 scores, with intensive care unit rotations having a significantly higher PHQ9 score than other rotations (p < 0.001). Pearson's correlation revealed significant weak positive correlations between work hours and PHQ9 at each time point (r = 0.195, 0.200, 0.202, 0.243) and significant weak negative correlations between sleep hours and time off with PHQ9 (−0.162, −0.223, −0.180, −0.178; all p < 0.001).

Conclusions

Many EM interns experience moderate to severe depression. Female EM interns are more likely to be depressed than male interns. Numerous factors influence depression scores for interns, many of which are modifiable.
C─H···π interaction induced H‐aggregates for wide range water content detection in organic solvents
Authors: Xu Jiajun , Huang Meifen , Pang Haijun , Weng Zhehui , Hu Guangzhi , Zhang Siman , Yang Qiuling , Wu Qiong
Published: March 2024

J‐aggregation and H‐aggregation are identified as two classical models of functionally oriented non‐covalent interactions, and significant attention has been drawn by researchers. However, due to the scarcity of single‐crystal examples of H‐aggregation, a comprehensive understanding of the relationship between its stacking mode and optical behaviour has been hindered. In recent studies, two polyaromatic Schiff base compounds, Cl‐Salmphen and H‐Salmphen, were successfully synthesized, and both were found to exhibit H‐aggregation. In the findings, H‐Salmphen was shown to display typical C─H···π interactions, characteristic of Aggregation‐Induced Emission (AIE) active molecules, whereas its halogenated counterpart was identified as behaving similar to Aggregation‐Caused Quenching (ACQ) active molecules. These types of results suggest that identical intermolecular interactions can produce differing optical behaviours. Light was shed, at least in part, on the formation mechanisms of H‐type aggregates and their luminescence properties from these observations. Additionally, the high optical signal‐to‐noise ratio inherent to H‐aggregates was utilized for the exploration of water content detection. As an outcome, a high‐performance fluorescent filter paper was developed, enabling easy real‐time detection using a smartphone.
Treatment of unilateral olfactory neuroblastoma: Appropriate extent of surgical resection and potential for olfactory preservation
Authors: Dharmarajan Harish , Choby Garret , Abi Hachem Ralph , Kuan Edward C. , Levine Corinna G. , Sanusi Olabisi , Schuman Theodore , Tang Dennis , Yim Michael , Geltzeiler Mathew
Published: March 2024

Historically, comprehensive surgical resection for olfactory neuroblastoma has included the bilateral olfactory epithelium, cribriform plate, overlying dura, olfactory bulbs and tracts. This results in postoperative anosmia that may significantly impact a patient's quality of life without definitive added benefit in survival. The prevalence of occult intracranial disease is low, especially for Hyams grade I and II tumors. A unilateral approach sparing the contralateral cribriform plate and olfactory system can be considered for select cases of early stage, low‐grade tumors when the disease does not cross midline to involve the contralateral olfactory cleft or septal mucosa and when midline dural margins can be cleared with frozen pathology. Approximately half of patients who undergo unilateral resection may have residual olfaction even with adjuvant unilateral radiation. Early data suggest favorable disease‐free survival and overall survival for patients who underwent the unilateral approach; however, larger sample studies are needed to confirm comparability to bilateral resections regarding oncologic outcomes.
A Tandem‐Locked Chemiluminescent Probe for Imaging of Tumor‐Associated Macrophage Polarization
Authors: Huang Jingsheng , Xu Mengke , Cheng Penghui , Yu Jie , Wu Jiayan , Pu Kanyi
Published: March 2024

Tumor‐associated macrophages (TAMs) play a role in both pro‐ and anti‐tumor functions; and the targeted polarization from M2 to M1 TAMs has become an effective therapy option. Although detection of M1 TAMs is imperative to assess cancer immunotherapeutic efficacy, existing optical probes suffer from shallow tissue penetration depth and poor specificity toward M1 TAMs. Herein, we report a tandem‐locked NIR chemiluminescent (CL) probe for specific detection of M1 TAMs. Through a combined molecular engineering approach via both atomic alternation and introduction of electron‐withdrawing groups, near‐infrared (NIR) chemiluminophores are screened out to possess record‐long emission (over 800 nm), record‐high CL quantum yield (2.7 % einstein/mol), and prolonged half‐life (7.7 h). Based on an ideal chemiluminophore, the tandem‐locked probe (DPDGN) is developed to only activate CL signal in the presence of both tumour (γ‐glutamyl transpeptidase) and M1 macrophage biomarkers (nitric oxide). Such a tandem‐lock design ensures its high specificity towards M1 macrophages in the tumor microenvironment over those in normal tissues or peripheral blood. Thus, DPDGN permits noninvasive imaging and tracking of M1 TAM in the tumor of living mice during R837 treatment, showing a good correlation with ex vivo methods. This study not only reports a new molecular approach towards highly efficient chemiluminophores but also reveals the first tandem‐locked CL probes for enhanced imaging specificity.
Multipolar Conjugated Polymer Framework Derived Ionic Sieves via Electronic Modulation for Long‐Life All‐Solid‐State Li Batteries
Authors: Yang Xue , Fang Long , Li Jing , Liu Cong , Zhong Linfeng , Yang Fan , Wang Xiaotong , Zhang Zishou , Yu Dingshan
Published: March 2024

Here, we build a tunable multipolar conjugated polymer framework platform via pore wall chemistry to probe the role of electronic structure engineering in improving the Li+ conduction by theoretical studies. Guided by theoretical prediction, we develop a new cyano‐vinylene‐linked multipolar polymer framework namely CNF‐COF, which can act as efficient ion sieves to modify solid polymer electrolytes to simultaneously tune Li+ migration and stable Li anodes for long‐lifespan all‐solid‐state (ASS) Li metal batteries at high rate. The dual‐decoration of cyano and fluorine groups in CNF‐COF favorably regulates electronic structure via multipolar donor‐acceptor electronic effects to afford proper energy band structure and abundant electron‐rich sites for enhanced oxidative stability, facilitated ion‐pair dissociation and suppressed anion movements. Thus, the CNF‐COF incorporation into poly (ethylene oxide) (PEO) electrolytes not only renders fast selective Li+ transport but also facilitates the Li dendrite suppression. Specifically, the constructed PEO composite electrolyte with an ultra‐low CNF‐COF content of only 0.5 wt % is endowed with a wide electrochemical window, a high ionic conductivity of 0.634 mS cm−1 at 60 °C and a large Li+ transference number of 0.81—remarkably outperforming CNF‐COF‐free counterparts (0.183 mS cm−1 and 0.22). As such, the Li symmetric cell delivers stable Li plating/stripping over 1400 h at 0.1 mA cm−2. Impressively, by coupling with LiFePO4 (LFP) cathodes, the assembled ASS Li battery under 60 °C allows for stable cycling over 2000 cycles at 1 C and over 1000 cycles even at 2 C with a large capacity retention of ~75 %, surpassing most reported ASS Li batteries using PEO‐based electrolytes.
Non‐halogenated Solvent‐Processed Organic Solar Cells with Approaching 20 % Efficiency and Improved Photostability
Authors: Song Jiali , Zhang Chen , Li Chao , Qiao Jiawei , Yu Jifa , Gao Jiaxin , Wang Xunchang , Hao Xiaotao , Tang Zheng , Lu Guanghao , Yang Renqiang , Yan He , Sun Yanming
Published: March 2024

The development of high‐efficiency organic solar cells (OSCs) processed from non‐halogenated solvents is crucially important for their scale‐up industry production. However, owing to the difficulty of regulating molecular aggregation, there is a huge efficiency gap between non‐halogenated and halogenated solvent processed OSCs. Herein, we fabricate o‐xylene processed OSCs with approaching 20 % efficiency by incorporating a trimeric guest acceptor named Tri‐V into the PM6:L8‐BO‐X host blend. The incorporation of Tri‐V effectively restricts the excessive aggregation of L8‐BO‐X, regulates the molecular packing and optimizes the phase‐separation morphology, which leads to mitigated trap density states, reduced energy loss and suppressed charge recombination. Consequently, the PM6:L8‐BO‐X:Tri‐V‐based device achieves an efficiency of 19.82 %, representing the highest efficiency for non‐halogenated solvent‐processed OSCs reported to date. Noticeably, with the addition of Tri‐V, the ternary device shows an improved photostability than binary PM6:L8‐BO‐X‐based device, and maintains 80 % of the initial efficiency after continuous illumination for 1380 h. This work provides a feasible approach for fabricating high‐efficiency, stable, eco‐friendly OSCs, and sheds new light on the large‐scale industrial production of OSCs.
Single‐Molecule Characterization and Super‐Resolution Imaging of Alzheimer's Disease‐Relevant Tau Aggregates in Human Samples
Authors: Böken Dorothea , Cox Dezerae , Burke Melanie , Lam Jeff Y. L. , Katsinelos Taxiarchis , Danial John S. H. , Fertan Emre , McEwan William A. , Rowe James B. , Klenerman David
Published: March 2024

Hyperphosphorylation and aggregation of the protein tau play key roles in the development of Alzheimer's disease (AD). While the molecular structure of the filamentous tau aggregates has been determined to atomic resolution, there is far less information available about the smaller, soluble aggregates, which are believed to be more toxic. Traditional techniques are limited to bulk measures and struggle to identify individual aggregates in complex biological samples. To address this, we developed a novel single‐molecule pull‐down‐based assay (MAPTau) to detect and characterize individual tau aggregates in AD and control post‐mortem brain and biofluids. Using MAPTau, we report the quantity, as well as the size and circularity of tau aggregates measured using super‐resolution microscopy, revealing AD‐specific differences in tau aggregate morphology. By adapting MAPTau to detect multiple phosphorylation markers in individual aggregates using two‐color coincidence detection, we derived compositional profiles of the individual aggregates. We find an AD‐specific phosphorylation profile of tau aggregates with more than 80 % containing multiple phosphorylations, compared to 5 % in age‐matched non‐AD controls. Our results show that MAPTau is able to identify disease‐specific subpopulations of tau aggregates phosphorylated at different sites, that are invisible to other methods and enable the study of disease mechanisms and diagnosis.
Parahydrogen‐Induced Polarization of 14N Nuclei
Authors: Salnikov Oleg G. , Trofimov Ivan A. , Bender Zachary T. , Trepakova Alexandra I. , Xu Jingyan , Wibbels Garrett L. , Shchepin Roman V. , Koptyug Igor V. , Barskiy Danila A.
Published: March 2024

Hyperpolarization techniques provide a dramatic increase in sensitivity of nuclear magnetic resonance spectroscopy and imaging. In spite of the outstanding progress in solution‐state hyperpolarization of spin‐1/2 nuclei, hyperpolarization of quadrupolar nuclei remains challenging. Here, hyperpolarization of quadrupolar 14N nuclei with natural isotopic abundance of >99 % is demonstrated. This is achieved via pairwise addition of parahydrogen to tetraalkylammonium salts with vinyl or allyl unsaturated moieties followed by a subsequent polarization transfer from 1H to 14N nuclei at high magnetic field using PH‐INEPT or PH‐INEPT+ radiofrequency pulse sequence. Catalyst screening identified water‐soluble rhodium complex [Rh(P(m‐C6H4SO3Na)3)3Cl] as the most efficient catalyst for hyperpolarization of the substrates under study, providing up to 1.3 % and up to 6.6 % 1H polarization in the cases of vinyl and allyl precursors, respectively. The performance of PH‐INEPT and PH‐INEPT+ pulse sequences was optimized with respect to interpulse delays, and the resultant experimental dependences were in good agreement with simulations. As a result, 14N NMR signal enhancement of up to 760‐fold at 7.05 T (corresponding to 0.15 % 14N polarization) was obtained.
A Sensitive Technique Unravels the Kinetics of Activation and Trans‐Cleavage of CRISPR‐Cas Systems
Authors: Feng Wei , Peng Hanyong , Zhang Hongquan , Weinfeld Michael , Le X. Chris
Published: March 2024

Activation of the CRISPR‐Cas13a system requires the formation of a crRNA‐Cas13a ribonucleoprotein (RNP) complex and the binding of an RNA activator to the RNP. These two binding processes play a crucial role in the performance of the CRISPR‐Cas13a system. However, the binding kinetics remain poorly understood, and a main challenge is the lack of a sensitive method for real‐time measurements of the dynamically formed active CRISPR‐Cas13a enzyme. We describe here a new method to study the binding kinetics and report the rate constants (kon and koff) and dissociation constant (Kd) for the binding between Cas13a and its activator. The method is able to unravel and quantify the kinetics of binding and cleavage separately, on the basis of measuring the real‐time trans‐cleavage rates of the CRISPR‐Cas system and obtaining the real‐time concentrations of the active CRISPR‐Cas ternary complex. We further discovered that once activated, the Cas13a system operates at a wide range of temperatures (7–37 °C) with fast trans‐cleavage kinetics. The new method and findings are important for diverse applications of the Cas13a system, such as the demonstrated quantification of microRNA at ambient temperatures (e.g., 25 °C).
Human‐centered explainable artificial intelligence: An Annual Review of Information Science and Technology (ARIST) paper
Authors: Ridley Michael
Published: March 2024

Explainability is central to trust and accountability in artificial intelligence (AI) applications. The field of human‐centered explainable AI (HCXAI) arose as a response to mainstream explainable AI (XAI) which was focused on algorithmic perspectives and technical challenges, and less on the needs and contexts of the non‐expert, lay user. HCXAI is characterized by putting humans at the center of AI explainability. Taking a sociotechnical perspective, HCXAI prioritizes user and situational contexts, preferences reflection over acquiescence, and promotes the actionability of explanations. This review identifies the foundational ideas of HCXAI, how those concepts are operationalized in system design, how legislation and regulations might normalize its objectives, and the challenges that HCXAI must address as it matures as a field.
Yb‐TCPP metal–organic framework as fluorescence sensor for detecting tetracycline in milk
Authors: Zhang Ximan , Zhang Yun , Zhao Lina
Published: March 2024

Developing effective means for detecting contamination in milk during production, processing, and storage is both important and challenging. Tetracycline (TC), due to its use in treating animal infections, is among the most prevalent organic pollutants in milk, posing potential and significant threats to human health. However, efficient and in situ monitoring of TC remains lacking. Nevertheless, we have successfully developed a highly sensitive and selective fluorescence method for detecting TC in milk using a metal–organic framework material made from Yb‐TCPP (ytterbium‐tetra(4‐carboxyphenyl)porphyrin). The calculated Stern–Volmer constant (KSV) was 12,310.88 M−1, and the detection limit was 2.44 × 10−6 M, surpassing previous reports. Crucially, Yb‐TCPP fluoresces in the near‐infrared region, promising its development into a specific fluorescence detection product for practical TC detection in milk, offering potential application value.
Complete DPYD genotyping combined with dihydropyrimidine dehydrogenase phenotyping to prevent fluoropyrimidine toxicity: A retrospective study
Authors: De Metz Côme , Hennart Benjamin , Aymes Estelle , Cren Pierre‐Yves , Martignène Niels , Penel Nicolas , Barthoulot Maël , Carnot Aurélien
Published: March 2024

Introduction

In April 2019, French authorities mandated dihydropyrimidine dehydrogenase (DPD) screening, specifically testing uracilemia, to mitigate the risk of toxicity associated with fluoropyrimidine‐based chemotherapy. However, this subject is still of debate as there is no consensus on a standardized DPD deficiency screening test. We conducted a real‐life retrospective study with the aim of assessing the impact of DPD screening on the occurrence of severe toxicity and exploring the potential benefits of complete genotyping using next‐generation sequencing.

Methods

All adult patients consecutively treated with 5‐fluorouracil (5‐FU) or its oral prodrug at six cancer centers between March 2018 and February 2019 were considered for inclusion. Dihydropyrimidine dehydrogenase deficiency screening included gene encoding DPD (DPYD) genotyping using complete genome sequencing and DPD phenotyping (uracilemia or dihydrouracilemia/uracilemia ratio) or both tests. Associations between each DPD screening method and (i) severe (grade ≥3) early toxicity and (ii) fluoropyrimidine dose reduction in the second chemotherapy cycle were evaluated using multivariable logistic regression analysis. Furthermore, we assessed the concordance between DPD genotype and phenotype using Cohen's kappa.

Results

A total of 551 patients were included. Most patients were tested for DPD deficiency (86%) including DPYD genotyping only (6%), DPD phenotyping only (8%), or both (72%). Complete DPD deficiency was not detected in the study population. Severe early toxicity events were observed in 73 patients (13%), with two patients (0.30%) presenting grade 5 toxicity. Despite the numerically higher toxicity rate in untested patients, the occurrence of severe toxicity was not significantly associated with the DPD screening method (p = 0.69). Concordance between the DPD genotype and phenotype was weak (Cohen's kappa of 0.14).

Conclusion

Due to insufficient numbers, our study was not able to demonstrate any added value of DPYD genotyping using complete genome sequencing to prevent 5‐FU toxicity. The optimal strategy for DPD screening before fluoropyrimidine‐based chemotherapy requires further clinical evaluation.