bluuebunny/crossref_metadata_2025 huggingface dataset:
In situ seeding assay: A novel technique for direct tissue localization of bioactive tau
Authors: Perbet Romain , Mate de Gerando Anastasie , Glynn Calina , Donahue Cameron , Gaona Angelica , Taddei Raquel N , Gomez-Isla Teresa , Lathuiliere Aurelien , Hyman Bradley T
Published: June 2024

Proteins exhibiting prion-like properties are implicated in tauopathies. The prion-like traits of tau influence disease progression and correlate with severity. Techniques to measure tau bioactivity such as RT-QuIC and biosensor cells lack spatial specificity. Therefore, we developed a histological probe aimed at detecting and localizing bioactive tau in situ. We first induced the recruitment of a tagged probe by bioactive Tau in human brain tissue slices using biosensor cell lysates containing a fluorescent probe. We then enhanced sensitivity and flexibility by designing a recombinant probe with a myc tag. The probe design aimed to replicate the recruitment process seen in prion-like mechanisms based on the cryo-EM structure of tau aggregates in Alzheimer disease (AD). Using this novel probe, we observed selective staining of misfolded tau in pre- and post-synaptic structures within neurofibrillary tangles and neurites, whether or not associated with neuritic plaques. The probe specifically targeted AD-associated bioactive tau and did not recognize bioactive tau from other neurodegenerative diseases. Electron microscopy and immunolabeling further confirmed the identification of fibrillar and non-fibrillar tau. Finally, we established a correlation between quantifying bioactive tau using this technique and gold standard biosensor cells. This technique presents a robust approach for detecting bioactive tau in AD tissues and has potential applications for deciphering mechanisms of tau propagation and degradation pathways.
The Grammar of Emotion Verbs in the Qurʾān: A Case Study of the verb Xāfa
Authors: Dror Yehudit , Saied Salam , Amara Bayan
Published: June 2024

The concept of emotions has been studied from numerous perspectives in psychology, the history of emotions and religion. This study sheds light on the linguistic devices implemented to articulate emotions in the Qurʾān by taking the emotion verb xāfa ‘to fear’ or ‘to be afraid’ (and its derivatives) as a case study. In both modern and classical dictionaries of the Arabic language as well as in Quranic exegesis, the verb xāfa is often replaced by another verb that expresses fear such as xašiya ‘to be afraid’ or ‘to be in awe’. Here it is shown that the verb xāfa occurs in certain syntactic structures and has specific meanings that are not denoted by other verbs expressing fear in the Qurʾān. Specifically, when the verb xāfa is followed by a subordinate clause that starts with the particle ‘an, it can be rendered as ‘to fear’ or ‘to be afraid’ since the cause of this fear is a probable event. When the verb xāfa is followed by the preposition ‘alā it denotes ‘to fear for [the wellbeing of] someone (e.g., a family member)’ because of a situation in which they are likely to be found. When it is followed by the noun rabb ‘Lord’ or Allāh ‘God’, the verb refers to ‘fear of God’, where fear of His punishment motivates the people to worship Him. When the verbal noun xawf has no object and is used in conjunction with the verbal noun ‘amn (‘security’) it can be interpreted as ‘insecurity about something’. Because the verb xāfa is central to the religious concept of fear of God, it is used in the Qurʾān to express a general and collective attitude of fear or awe. However, xāfa is also used to express individual experiences of fright at specific times or places.
Prevention of Bullying and Other Forms of Victimization
Authors: Srabstein Jorge C.
Published: June 2024

This chapter provides a review of the increasing number of research-based bullying prevention strategies and programs developed in the last three decades. The most promising outcomes have been found with the implementation of whole-school intervention programs, but the reduction in the prevalence of bullying they have achieved is mild to moderate. The Olweus and the KiVa programs are the most globally recognized and most broadly implemented programs so far. The chapter further examines several research-based strategies implemented to avert the occurrence of victimization beyond the school milieu, including a few approaches to prevent victimization in cyberspace, in the workplace, and in dating relations, as well as to prevent childhood maltreatment. In the future, work should aim toward the development of three-tier whole-community strategies to prevent the occurrence of victimization across social settings and along the life span, as well as to reduce the morbidity and mortality associated with victimization.
Intervention and Treatment for Bullying and Other Forms of Victimization
Authors: Srabstein Jorge C.
Published: June 2024

This chapter examines the concept of intervention as a prevention strategy to stop “in progress” victimization and the notion of treatment as an approach to remedy the morbidity resulting from and/or preceding victimization as well as to reduce related mortality risk. These two strategies may be implemented consecutively and/or concurrently, or they may be construed as being intertwined or having similar meaning. The chapter reviews known methods to stop or cope with bullying, including direct sanctions, restorative practice, strengthening the victim, mediation, the support group method, and the method of shared concern. In addition, the chapter explores what is known about psychopharmacological and psychotherapeutic treatment of morbidity associated with victimization within the framework of diagnoses associated with trauma or stress. The chapter also advocates the following future objectives: The notion of intervention to stop ongoing bullying and other forms of victimization as an integral part of a treatment to alleviate morbidity associated with such victimization; a health intervention to stop ongoing bullying and forms of victimization that is short-term, therapeutic, and includes public health and primary care components; and treatment of morbidity stemming from victimization based on a symptom-targeted approach, instead of treating established diagnoses associated with stress and trauma.
Bullying and Other Forms of Victimization in Tertiary Education
Authors: Srabstein Jorge C.
Published: June 2024

This chapter examines the different forms of victimization occurring in postsecondary or higher education. It reviews what is known about different facets of maltreatment, including bullying, hazing, incivility, sexual harassment, intimidation, and stalking, affecting students or trainees, teachers/instructors, and academic officials studying/working in undergraduate, graduate, and postgraduate education, including military training. It advances the notion of the postsecondary education milieu as a place of work, where all its stakeholders can be affected by workplace bullying and other forms of victimization. Future work should involve research to ascertain the prevalence of all forms of maltreatment affecting university students, military trainees, and their mentors. Furthermore, there is a need to ascertain the health risks linked to exposure to victimization in postsecondary education and training, as well as to advance strategies for its prevention and detection.
Precise timing of solar flare footpoint sources from mid-infrared observations
Authors: Simões Paulo J A , Fletcher Lyndsay , Hudson Hugh S , Kerr Graham S , Penn Matt , Lopez Karla F
Published: June 2024

Solar flares are powerful particle accelerators, and in the accepted standard flare model most of the flare energy is transported from a coronal energy-release region by accelerated electrons that stop collisionally in the chromosphere, heating and ionizing the plasma, producing a broad-band enhancement to the solar radiative output. We present a time-delay analysis of the infrared (IR) emission from two chromospheric sources in the flare SOL2014-09-24T17:50 taken at the McMath–Pierce telescope. By cross-correlating the intensity signals, measured with 1 s cadence, from the two spatially resolved IR sources we find a delay of $0.75\pm 0.07$ s at $8.2\,\mu$m, where the uncertainties are quantified by a Monte Carlo analysis. The sources correlate well in brightness but have a time lag larger than can be reasonably explained by the energy transport dominated by non-thermal electrons precipitating from a single acceleration site in the corona. If interpreted as a time-of-flight difference between electrons travelling to each footpoint, we estimate time delays between 0.14 and 0.42 s, for a reconnection site at the interior quasi-separatrix layer, or at the null-point of the spine-fan topology inferred for this event. We employed modelling of electron transport via time-dependent Fokker–Planck and radiative hydrodynamic simulations to evaluate other possible sources of time-delay in the generation of the IR emission, such as differing ionization time-scales under different chromospheric conditions. Our results demonstrate that they are also unable to account for this discrepancy. This flare appears to require energy transport by some means other than electron beams originating in the corona.
DNA-controlled protein fluorescence: Design of aptamer-split peptide hetero-modulator for GFP to respond to intracellular ATP levels
Authors: Park Ki Sung , Cha Hanvit , Niu Jia , Soh Hyongsok Tom , Lee Jin Hyup , Pack Seung Pil
Published: June 2024

Enabling the precise control of protein functions with artificially programmed reaction patterns is beneficial for investigating biological processes. Although several strategies have been established that employ the programmability of nucleic acid, they have been limited to DNA hybridization without external stimuli or target binding. Here, we report an approach for the DNA-mediated control of the tripartite split-GFP assembly via aptamers with responsiveness to intracellular small molecules as stimuli. We designed a novel structure-switching aptamer-peptide conjugate as a hetero modulator for split GFP in response to ATP. By conjugating two peptides (S10/11) derived from the tripartite split-GFP to ATP aptamer, we achieved GFP reassembly using only ATP as a trigger molecule. The response to ATP at ≥4 mM concentrations indicated that it can be applied to respond to intracellular ATP in live cells. Furthermore, our hetero-modulator exhibited high and long-term stability, with a half-life of approximately four days in a serum stability assay, demonstrating resistance to nuclease degradation. We validated that our aptamer-modulator split GFP was successfully reconstituted in the cell in response to intracellular ATP levels. Our aptamer-modulated split GFP platform can be utilized to monitor a wide range of intracellular metabolites by replacing the aptamer sequence.
Health Benefits of Palm Tocotrienol-Rich Fraction: A Systematic Review of Randomized Controlled Trials
Authors: Looi Aaron Deming , Palanisamy Uma Devi , Moorthy Mohanambal , Radhakrishnan Ammu K
Published: June 2024

Context

Vitamin E, a well-known antioxidant with numerous positive effects on human health, encompasses tocotrienol-rich fraction (TRF), a natural variant abundant in palm oil.

Objective

This systematic review analyzed findings from randomized controlled trials published until 2022 to evaluate the health impacts of palm TRF.

Data Sources

A literature search was performed in Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, OVID Medline, SCOPUS, and Web of Science from inception until December 2022. Thirty studies involving 2646 patients, including both healthy individuals and those with underlying conditions, were identified.

Results

This review shows palm TRF to be a promising natural supplement against inflammation and lipid peroxidation and that can significantly enhance overall health. Additionally, the study underscores the necessity for further research to ascertain the optimal dosage, formulation, and duration of supplementation, maximizing the potential health advantages.

Conclusion

This systematic review provides evidence supporting the health benefits associated with palm TRF.

Systematic Review Registration

PROSPERO registration no. CRD42020204070.
Ancient Origin of Acetyltransferases Catalyzing O-acetylation of Plant Cell Wall Polysaccharides
Authors: Zhong Ruiqin , Adams Earle R , Ye Zheng-Hua
Published: June 2024

Members of the domain of unknown function 231/trichome birefringence–like (TBL) family have been shown to be O-acetyltransferases catalyzing the acetylation of plant cell wall polysaccharides, including pectins, mannan, xyloglucan and xylan. However, little is known about the origin and evolution of plant cell wall polysaccharide acetyltransferases. Here, we investigated the biochemical functions of TBL homologs from Klebsormidium nitens, a representative of an early divergent class of charophyte green algae that are considered to be the closest living relatives of land plants, and Marchantia polymorpha, a liverwort that is an extant representative of an ancient lineage of land plants. The genomes of K. nitens and Marchantia polymorpha harbor two and six TBL homologs, respectively. Biochemical characterization of their recombinant proteins expressed in human embryonic kidney 293 cells demonstrated that the two K. nitens TBLs exhibited acetyltransferase activities acetylating the pectin homogalacturonan (HG) and hence were named KnPOAT1 and KnPOAT2. Among the six M. polymorpha TBLs, five (MpPOAT1 to 5) possessed acetyltransferase activities toward pectins and the remaining one (MpMOAT1) catalyzed 2-O- and 3-O-acetylation of mannan. While MpPOAT1,2 specifically acetylated HG, MpPOAT3,4,5 could acetylate both HG and rhamnogalacturonan-I. Consistent with the acetyltransferase activities of these TBLs, pectins isolated from K. nitens and both pectins and mannan from M. polymorpha were shown to be acetylated. These findings indicate that the TBL genes were recruited as cell wall polysaccharide O-acetyltransferases as early as in charophyte green algae with activities toward pectins and they underwent expansion and functional diversification to acetylate various cell wall polysaccharides during evolution of land plants.
Natural variation in response to combined water and nitrogen deficiencies in Arabidopsis
Authors: Xue Zeyun , Ferrand Marina , Gilbault Elodie , Zurfluh Olivier , Clément Gilles , Marmagne Anne , Huguet Stéphanie , Jiménez-Gómez José M , Krapp Anne , Meyer Christian , Loudet Olivier
Published: June 2024

Understanding plant responses to individual stresses does not mean that we understand real-world situations, where stresses usually combine and interact. These interactions arise at different levels, from stress exposure to the molecular networks of the stress response. Here, we built an in-depth multiomic description of plant responses to mild water (W) and nitrogen (N) limitations, either individually or combined, among 5 genetically different Arabidopsis (Arabidopsis thaliana) accessions. We highlight the different dynamics in stress response through integrative traits such as rosette growth and the physiological status of the plants. We also used transcriptomic and metabolomic profiling during a stage when the plant response was stabilized to determine the wide diversity in stress-induced changes among accessions, highlighting the limited reality of a “universal” stress response. The main effect of the W × N interaction was an attenuation of the N-deficiency syndrome when combined with mild drought, but to a variable extent depending on the accession. Other traits subject to W × N interactions are often accession specific. Multiomic analyses identified a subset of transcript–metabolite clusters that are critical to stress responses but essentially variable according to the genotype factor. Including intraspecific diversity in our descriptions of plant stress response places our findings in perspective.
Genome-wide characterization of single-stranded DNA in rice
Authors: Peng Yulian , Zhao Pengtao , Li Zhaoguo , Mu Ning , Tao Shentong , Feng Yilong , Cheng Xuejiao , Zhang Wenli
Published: June 2024

Single-stranded DNA (ssDNA) is essential for various DNA-templated processes in both eukaryotes and prokaryotes. However, comprehensive characterizations of ssDNA still lag in plants compared to nonplant systems. Here, we conducted in situ S1-sequencing, with starting gDNA ranging from 5 µg to 250 ng, followed by comprehensive characterizations of ssDNA in rice (Oryza sativa L.). We found that ssDNA loci were substantially associated with a subset of non-B DNA structures and functional genomic loci. Subtypes of ssDNA loci had distinct epigenetic features. Importantly, ssDNA may act alone or partly coordinate with non-B DNA structures, functional genomic loci, or epigenetic marks to actively or repressively modulate gene transcription, which is genomic region dependent and associated with the distinct accumulation of RNA Pol II. Moreover, distinct types of ssDNA had differential impacts on the activities and evolution of transposable elements (TEs) (especially common or conserved TEs) in the rice genome. Our study showcases an antibody-independent technique for characterizing non-B DNA structures or functional genomic loci in plants. It lays the groundwork and fills a crucial gap for further exploration of ssDNA, non-B DNA structures, or functional genomic loci, thereby advancing our understanding of their biology in plants.
Conspiracy Beliefs and Perceptions of Electoral Integrity: Cross-National Evidence from 29 Countries
Authors: Schnaudt Christian
Published: June 2024

Extant research shows that belief in conspiracy theories and conspiratorial thinking are negatively related to citizens’ perceptions about the fairness and integrity of elections. However, by exclusively focusing on the United States as only one important empirical case, previous studies have left unanswered crucial questions on the scope, generalizability, and context dependency of their empirical findings. In this research note, I aim to fill this void by providing first empirical evidence on the relationship between conspiracy beliefs and electoral-integrity perceptions across twenty-nine countries. Using high-quality individual-level data from the European Social Survey enriched with contextual-level data on the quality of elections taken from the Varieties of Democracy Project, the findings from linear mixed-effects regression models reveal that (1) conspiracy beliefs are negatively related to citizens’ evaluations concerning the integrity of national elections; (2) the specific strength of the observed individual-level relationship varies substantially across countries; and (3) the relationship between conspiracy beliefs and individual electoral-integrity perceptions depends on the contextual-level quality and integrity of elections across countries. Specifically, the results indicate that the negative relationship between conspiracy beliefs and electoral-integrity perceptions is strongest in contexts in which the actual quality of elections is high, and in which citizens have little reason to (seriously) doubt the integrity of the electoral process. These findings provide an important and hitherto missing cross-national and multilevel perspective on the nexus between individual conspiracy beliefs and electoral-integrity perceptions, highlighting that the “conspiratorial challenge” to electoral legitimacy in contemporary democracies is real and more than an “American affliction.”
The New Urban Rebellions: A Review Article
Authors: Goodwin Jeff
Published: June 2024

Mark R. Beissinger's The Revolutionary City is a tour de force that will interest a wide range of readers. It charts both the decline of social revolutions and the rise of a new kind of rebellion, what Beissinger calls the urban civic revolt. Beissinger also analyzes the many ways in which these revolts differ from previous ones. These new rebellions have been minimalist in character, aiming to overthrow despotic regimes but eschewing any effort to redistribute wealth on a large scale or transform class relations. Beissinger's “spatial theory of revolution,” however, only partially illuminates these new urban rebellions, and it leads him to the premature conclusion that social revolutions will never occur again.
A Structural Analysis of Mental Health and Labour Market Trajectories
Authors: Jolivet Grégory , Postel-Vinay Fabien
Published: June 2024

We analyse the joint life-cycle dynamics of labour market and mental health outcomes while allowing for two-way interactions between work and mental health. We model selection into jobs on a labour market with search frictions, accounting for the level of exposure to stress in each job using data on occupational health contents. Taking our model to British data from Understanding Society combined with information from O*NET, we estimate the impact of job characteristics on health dynamics and the effects of health and job stress contents on career choices. We use our model to quantify the effects of job loss, health shocks, or job stress shocks that propagate over the life cycle through both health and work channels. We also estimate the (large) values workers attach to health, employment, or nonstressful jobs.
Excess Capacity and Demand-Driven Business Cycles
Authors: Sun Tiancheng
Published: June 2024

I build a macroeconomic model that features chronic excess capacity. Firms can use their capacity to compete for buyers who are not fully attentive to prices. If one firm expands capacity while other firms do not, it “steals” or attracts profitable demand from others. Theoretically, I show that this capacity competition can cause an over-accumulation of capacity. In the presence of chronic excess capacity, capital resources can be slack, and demand shocks can have large effects on output. The model is consistent with stylized facts about capacity utilization and survey evidence from Switzerland. Quantitatively, when the model is estimated to match the U.S. macro data, demand shocks turn out to be the main driving forces of business cycles.
The bigger your pupils, the better my comprehension: an ERP study of how pupil size and gaze of the speaker affect syntactic processing
Authors: Jiménez-Ortega Laura , Casado-Palacios María , Rubianes Miguel , Martínez-Mejias Mario , Casado Pilar , Fondevila Sabela , Hernández-Gutiérrez David , Muñoz Francisco , Sánchez-García José , Martín-Loeches Manuel
Published: June 2024

Gaze direction and pupil dilation play a critical role in communication and social interaction due to their ability to redirect and capture our attention and their relevance for emotional information. The present study aimed to explore whether the pupil size and gaze direction of the speaker affect language comprehension. Participants listened to sentences that could be correct or contain a syntactic anomaly, while the static face of a speaker was manipulated in terms of gaze direction (direct, averted) and pupil size (mydriasis, miosis). Left anterior negativity (LAN) and P600 linguistic event-related potential components were observed in response to syntactic anomalies across all conditions. The speaker’s gaze did not impact syntactic comprehension. However, the amplitude of the LAN component for mydriasis (dilated pupil) was larger than for miosis (constricted pupil) condition. Larger pupils are generally associated with care, trust, interest, and attention, which might facilitate syntactic processing at early automatic stages. The result also supports the permeable and context-dependent nature of syntax. Previous studies also support an automatic nature of syntax (fast and efficient), which combined with the permeability to relevant sources of communicative information, such as pupil size and emotions, is highly adaptive for language comprehension and social interaction.
Multiple sclerosis treatment review for primary care providers
Authors: Hernandez Jeffrey
Published: June 2024

The treatment landscape for multiple sclerosis has dramatically grown in terms of available options and complexity. The various mechanisms of action and safety profiles of these new treatments necessitate that primary care providers remain current in knowledge and practice to provide high-quality care.
Predicting Organ Dysfunction in Septic and Critically Ill Patients: A Prospective Cohort Study Using Rapid Ex Vivo Immune Profiling
Authors: Samuelsen Abigail M. , Halstead E. Scott , Lehman Erik B. , McKeone Daniel J. , Bonavia Anthony S.
Published: June 2024

OBJECTIVES:

While cytokine response patterns are pivotal in mediating immune responses, they are also often dysregulated in sepsis and critical illness. We hypothesized that these immunological deficits, quantifiable through ex vivo whole blood stimulation assays, may be indicative of subsequent organ dysfunction.

DESIGN:

In a prospective observational study, adult septic patients and critically ill but nonseptic controls were identified within 48 hours of critical illness onset. Using a rapid, ex vivo assay based on responses to lipopolysaccharide (LPS), anti-CD3/anti-CD28 antibodies, and phorbol 12-myristate 13-acetate with ionomycin, cytokine responses to immune stimulants were quantified. The primary outcome was the relationship between early cytokine production and subsequent organ dysfunction, as measured by the Sequential Organ Failure Assessment score on day 3 of illness (SOFAd3).

SETTING:

Patients were recruited in an academic medical center and data processing and analysis were done in an academic laboratory setting.

PATIENTS:

Ninety-six adult septic and critically ill nonseptic patients were enrolled.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Elevated levels of tumor necrosis factor and interleukin-6 post-endotoxin challenge were inversely correlated with SOFAd3. Interferon-gamma production per lymphocyte was inversely related to organ dysfunction at day 3 and differed between septic and nonseptic patients. Clustering analysis revealed two distinct immune phenotypes, represented by differential responses to 18 hours of LPS stimulation and 4 hours of anti-CD3/anti-CD28 stimulation.

CONCLUSIONS:

Our rapid immune profiling technique offers a promising tool for early prediction and management of organ dysfunction in critically ill patients. This information could be pivotal for early intervention and for preventing irreversible organ damage during the acute phase of critical illness.
Use of Speckle-Tracking Echocardiography in Septic Cardiomyopathy in Critically Ill Children: A Narrative Review
Authors: Chan J. Charmaine , Menon Anuradha P. , Rotta Alexandre T. , Choo Jonathan T.L. , Hornik Christoph P. , Lee Jan Hau
Published: June 2024

OBJECTIVES:

In critically ill children with severe sepsis, septic cardiomyopathy (SCM) denotes the subset of patients who have myocardial dysfunction with poor response to fluid and inotropic support, and higher mortality risk. The objective of this review was to evaluate the role of speckle-tracking echocardiography (STE) in the diagnosis and prognosis of pediatric SCM in the PICU setting.

DATA SOURCES:

We performed detailed searches using PubMed, Scopus, Web of Science, and Google Scholar. Reference lists of all included studies were also examined for further identification of potentially relevant studies.

STUDY SELECTION:

Studies with the following medical subject headings and keywords were selected: speckle-tracking echocardiography, strain imaging, global longitudinal strain, echocardiography, sepsis, severe sepsis, septic shock, septic cardiomyopathy, and myocardial dysfunction.

DATA EXTRACTION:

The following data were extracted from all included studies: demographics, diagnoses, echocardiographic parameters, severity of illness, PICU management, and outcomes.

DATA SYNTHESIS:

STE is a relatively new echocardiographic technique that directly quantifies myocardial contractility. It has high sensitivity in diagnosing SCM, correlates well with illness severity, and has good prognosticating value as compared with conventional echocardiographic parameters. Further studies are required to establish its role in evaluating biventricular systolic and diastolic dysfunction, and to investigate whether it has a role in individualizing treatment and improving treatment outcomes in this group of patients.

CONCLUSIONS:

STE is a useful adjunct to conventional measures of cardiac function on 2D-echocardiography in the assessment of pediatric SCM in the PICU.
A systematic review of the role of TREM2 in Alzheimer’s disease
Authors: Yin Yunsi , Yang Hanchen , Li Ruiyang , Wu Guangshan , Qin Qi , Tang Yi
Published: June 2024

Background:

Given the established genetic linkage between triggering receptors expressed on myeloid cells 2 (TREM2) and Alzheimer’s disease (AD), an expanding research body has delved into the intricate role of TREM2 within the AD context. However, a conflicting landscape of outcomes has emerged from both in vivo and in vitro investigations. This study aimed to elucidate the multifaceted nuances and gain a clearer comprehension of the role of TREM2.

Methods:

PubMed database was searched spanning from its inception to January 2022. The search criteria took the form of (“Alzheimer’s disease” OR “AD”) AND (“transgenic mice model” OR “transgenic mouse model”) AND (“Triggering receptor expressed on myeloid cells” OR “TREM2”). Inclusion criteria consisted of the following: (1) publication of original studies in English; (2) utilization of transgenic mouse models for AD research; and (3) reports addressing the subject of TREM2.

Results:

A total of 43 eligible articles were identified. Our analysis addresses four pivotal queries concerning the interrelation of TREM2 with microglial function, Aβ accumulation, tau pathology, and inflammatory processes. However, the diverse inquiries posed yielded inconsistent responses. Nevertheless, the inconsistent roles of TREM2 within these AD mouse models potentially hinge upon factors such as age, sex, brain region, model type, and detection methodologies.

Conclusions:

This review substantiates the evolving understanding of TREM2’s disease progression-dependent impacts. Furthermore, it reviews the interplay between TREM2 and its effects across diverse tissues and temporal stages.
Healthcare provider and patient perspectives on the implementation of pharmacogenetic-guided treatment in routine clinical practice
Authors: Kaur Gurveer , Nwabufo Chukwunonso K.
Published: June 2024

Objective

This study aims to understand patient and healthcare provider perspectives on the integration and application of pharmacogenetics (PGx) testing in routine clinical practice.

Methods

Two anonymous online surveys were distributed globally for healthcare providers and patients respectively on the Qualtrics platform (version 3.24). The surveys were distributed through social platforms, email, and posters with QR codes from 27 October 2023 to 7 March 2024. The surveys evaluated participant familiarity with PGx, previous experience with PGx testing, perceived implementation challenges, and opinions on point-of-care (PoC) PGx testing devices.

Results

This study collected 78 responses from healthcare providers and 98 responses from patients. The results revealed that 64% of healthcare providers had some level of familiarity with PGx, however, PGx testing in clinical practice was low. The primary challenges identified by healthcare providers included limited access to testing and lack of knowledge on PGx test interpretation. In contrast, 52% of patient respondents were aware of PGx testing, with a significant association between awareness and positive opinions toward PGx. Both healthcare providers and patients recognized the value of PoC PGx testing devices, with 98% of healthcare providers and 71% of patients believing PoC devices would improve the accessibility and implementation of PGx testing. Comparative analysis revealed a statistically significant difference in PGx awareness between healthcare providers and patients, with providers being more informed.

Conclusion

Improved PGx awareness, training, clinical guidelines, and PoC PGx testing devices may help promote the implementation of PGx-guided treatments in routine clinical practice.
Development and Validation of a High-Performance Liquid Chromatography Coupled With Ultraviolet Detection Method for Quantification of Bictegravir in Human Plasma
Authors: Xiao Ran , Fu Qiang , Chen Ling , Li Taisheng , Du Xiaoli
Published: June 2024

Background:

To establish a method for determining the bictegravir (BIC) concentration in human plasma using high-performance liquid chromatography coupled with ultraviolet detection.

Methods:

The analysis was performed on a CLC-octadecylsilane column (150 × 6.0 mm, 5 μm) using a mixture of phosphate buffer and acetonitrile (62:38, v/v) as the mobile phase at the flow rate of 1.4 mL/min. The column temperature was maintained at 40°C. Using triamcinolone acetonide as the internal standard, 100 μL of plasma sample was extracted by methyl tert-butyl ether, followed by evaporating under nitrogen stream, redissolving with 100 μL mobile phase, and injection of 20–40 μL of supernatant into the chromatographic system. Ultraviolet detection was performed at 260 nm, and the total run time for each sample was 14 minutes.

Results:

The method exhibited good linearity within the range from 0.10 to 10.0 mcg/mL (r = 0.9995, n = 5). The intraday and interday relative standard deviations for low-, medium-, and high-concentration quality control samples (0.20, 4.00, 8.00 mcg/mL) and the lower limit of quantification (0.10 mcg/mL) were 1.31%–6.20% (n = 10) and 1.18%–2.87% (n = 5), respectively. The intraday and interday accuracies were 100.53%–102.32% and 97.96%–103.84%, respectively. The extraction recovery rates ranged from 80.00% to 88.09% (n = 3). The stability tests showed that the BIC concentration changed by <15%.

Conclusions:

This study successfully established a high-performance liquid chromatography coupled with ultraviolet detection method for determining plasma BIC concentrations. This method is simple, selective, sensitive, and accurate, making it suitable for clinical monitoring and pharmacokinetic studies of BIC.
A Novel Approach to Safe Patient Handling and Mobility Training in Physical Therapist Education
Authors: Tautonico Michael , Voltmer Christopher , Lee Timothy , DiCandia Erin , Silberman Nicki
Published: June 2024

Background:

Safe patient handling and mobility (SPHM) training is prevalent in health care education and practice. However, there is limited evidence of this training in physical therapist education programs.

Purpose:

To determine if a single training session with a mobile laboratory equipped with SPHM equipment increases the knowledge of SPHM principles and techniques and is valuable to students prior to their first clinical experience.

Methods:

Training included a 1-hour lecture on SPHM principles, research, and techniques, followed by two 50-minute SPHM practice stations. One session was conducted using a mobile laboratory. Students completed a pretest/posttest measuring knowledge of SPHM principles. Students completed a survey regarding the perception and placement of SPHM training within the curriculum.

Results:

A total of 129 students in a physical therapist education program were invited to participate; 59 from first-year cohorts and 70 from second- and third-year cohorts. Eighty-seven students volunteered to participate, including all 59 students from the first-year cohorts receiving training as the experimental group, and 28 from the other cohorts receiving no training as the control group. Seventy students met the criteria for survey data analysis; 42 experimental and 28 control. Of those who received training, 90.5% reported that SPHM training improved their confidence prior to their inpatient clinical experience; 85.5% in the control group would have felt more confident being placed in an inpatient facility if they received SPHM training, and 85.7% of the experimental group and 89.3% of controls agreed that SPHM training should be performed prior to the first clinical experience. A paired t test showed that first-year students reported a statistically significant increase in knowledge of SPHM principles (P < .001).

Conclusions:

Physical therapist education programs should consider SPHM training prior to students’ first clinical experience to increase student confidence in inpatient settings.
Development of a set of measurable outcome indicators for Flemish patients with inflammatory bowel disease
Authors: Fierens Liselotte , Bossuyt Peter , Baert Filip , Baert Didier , Weltens Caroline , Lavaerts Marga , Vanhaecht Kris , Rademakers Frank E. ,   The HERMES Expert Panel, The VznkuL Group, Ferrante Marc
Published: June 2024

Objective

Uniform and standardised quality measurement allows care assessment and improvement. Following a pragmatic consensus method we aimed to agree on a selection of measurable quality indicators that can be used to assess, benchmark and gradually improve inflammatory bowel disease (IBD) care in Flanders.

Methods

Of 49 structures, 135 processes and 37 outcome indicators identified through literature, 58 were preselected and reformulated into measurable outcome indicators by four IBD physicians. A larger expert group scored the 58 indicators on a 10-point importance scale twice, endorsed by patient and expert perspectives in between rounds. Additional items could be suggested. A final selection and subset of indicators with room for improvement were agreed upon during a consensus meeting.

Results

Fifty indicators received an importance score of 7 or higher by ≥80% of the participants (seven IBD nurses, one abdominal surgeon, one chief medical officer and 31 IBD physicians including two paediatricians). Eight indicators scored highly important by 60–80%, two indicators reintroduced by patients and one newly suggested, were discussed during the consensus meeting. Among 26 participants, eight indicators were agreed to be added to the final selection. Of the 58 selected items, 19 were retained in the improvement subset, related to patient-reported outcomes, use of hospital services and survival, patient characteristics, monitoring of disease activity and remission, endoscopy guidelines, infection prevention, steroid and other medication use.

Conclusion

Fifty-eight indicators were selected to assess IBD care in Flanders and a subset of 19 for use in clinical practice to steer quality improvement initiatives.
False-Positive Bone Lesion With Different PET/CT Tracers
Authors: Moreau Aurélie , Pretet Valentin , Kryza David
Published: June 2024

Collateral circulation is often secondary to a regional thrombosis. This phenomenon can lead to the detection of misleading bone lesions on imaging and is a well-known source of false-positives. Here, we present 2 different tracers PET/CT images, 18F-FDG and 18F-choline, with collateral circulation but without obvious thrombosis. Both cases displayed bone uptake, which mimicked metastasis. However, clinical follow-up ruled out metastasis and revealed false-positive bone lesions related to collateral circulation, even in the lack of acute or chronic underlying thrombotic processes.
Increased 68Ga-FAPI-04 Uptake in Meningioma
Authors: Önner Hasan , Özer Halil , Gezer Burak
Published: June 2024

A 65-year-old woman with long-standing symptoms of COVID-19 participated in our clinical study on the role of 68Ga-FAPI-04 PET/CT in pulmonary fibrosis. Neither sequela parenchymal changes nor 68Ga-FAPI-04 uptake was observed in the lungs. However, focal 68Ga-FAPI-04 uptake was localized in a smoothly circumscribed mass observed in the right frontal region. A meningioma diagnosis was made based on the radiological findings.
Bacterial sepsis triggers stronger transcriptomic immune responses in larger primates
Authors: McMinds Ryan , Jiang Rays H. Y. , Adapa Swamy R. , Cornelius Ruhs Emily , Munds Rachel A. , Leiding Jennifer W. , Downs Cynthia J. , Martin Lynn B.
Published: June 2024

Empirical data relating body mass to immune defence against infections remain limited. Although the metabolic theory of ecology predicts that larger organisms would have weaker immune responses, recent studies have suggested that the opposite may be true. These discoveries have led to the safety factor hypothesis, which proposes that larger organisms have evolved stronger immune defences because they carry greater risks of exposure to pathogens and parasites. In this study, we simulated sepsis by exposing blood from nine primate species to a bacterial lipopolysaccharide (LPS), measured the relative expression of immune and other genes using RNAseq, and fitted phylogenetic models to determine how gene expression was related to body mass. In contrast to non-immune-annotated genes, we discovered hypermetric scaling in the LPS-induced expression of innate immune genes, such that large primates had a disproportionately greater increase in gene expression of immune genes compared to small primates. Hypermetric immune gene expression appears to support the safety factor hypothesis, though this pattern may represent a balanced evolutionary mechanism to compensate for lower per-transcript immunological effectiveness. This study contributes to the growing body of immune allometry research, highlighting its importance in understanding the complex interplay between body size and immunity over evolutionary timescales.
Development and Validation of a Novel FRET-Based IFPP Assay for Hepatitis B Virus Detection in a Diverse Population
Authors: Ede Naga Priyanka , Putatunda Chayanika , Suravaram Swathi , Vanjari Lavanya , Chandela Rahul , Singh Tarun , Mukku Vasu Dev
Published: June 2024

Background

Hepatitis B, a major global health concern, necessitates precise diagnostic methods to manage and mitigate its impact effectively. Traditional real-time PCR techniques, while sensitive, face challenges like false positives and susceptibility to viral mutations. This study introduces a novel Forster Resonance Energy Transfer (FRET)-based approach, the Internal Fluorophore Primer-Primer (IFPP) FRET assay, designed to enhance diagnostic accuracy by optimizing the fluorophore and quencher distances in the assay setup. By doing so, it aims to increase sensitivity and specificity, reduce false results, and improve overall hepatitis B detection capabilities.

Materials and Methods

In the development of the IFPP FRET assay, molecular probes and quenchers are strategically utilized to optimize the detection sensitivity. The assay employs a novel approach where the primers are designed to ensure that the fluorophores and quenchers are placed at a calculated distance, optimizing energy transfer efficiency and reducing the likelihood of quenching anomalies. The diagnostic efficiency of this method is rigorously compared with traditional techniques, emphasizing improvements in sensitivity and specificity due to the refined detection dynamics provided by FRET technology.

Results

The IFPP Assay demonstrated superior performance compared to the Chip Based Assay with a sensitivity of 96.92% vs. 90.91%, specificity of 95.71% vs. 90.24%, PPV of 95.45% vs. 89.74%, and NPV of 97.10% vs. 91.36%. The assay validation included 110 samples with an additional 160 samples in a prospective study, confirming the assay's robustness and reliability in clinical settings in (Fig 1 & 2 and Table 1).

Conclusion

The novel IFPP FRET Assay shows significant improvements in sensitivity and specificity over traditional methods. It presents a promising alternative for the early and accurate detection of HBV, which is crucial for effective management and treatment strategies.
Antimicrobial resistance patterns among critical priority pathogens in an intensive care unit at a tertiary hospital in Egypt: a descriptive analysis comparing pre- and COVID-19 eras
Authors: Zafer Mai M. , Bassiouny Dina M. , Ghosh Soumya , Bornman Charné , Hussein Amira F. A.
Published: June 2024

Background. The intensified global challenge of antimicrobial resistance, set against the backdrop of the COVID-19 pandemic, is a cause for major concern. Within healthcare settings, intensive care units are recognized as focal points for Gram-negative infections. The study pursued to assess the prevalence and antimicrobial resistance patterns of critical priority pathogens (Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacteriaceae, comprising Klebsiella pneumoniae and Escherichia coli) during both pre- and COVID-19 periods.

Gap Statement. The decision to explore this topic stemmed from the urgent need to understand how the exceptional healthcare crisis of COVID-19 affected AMR patterns.

Methods. This was an observational retrospective analysis of 1056 clinical specimens obtained from 950 patients who were admitted to the Medical Intensive Care Unit at Kasr Al-Aini Hospital, Cairo University, Egypt.

Results. In the period before COVID-19, 342 pathogenic isolates (135 K. pneumoniae, 83 P. aeruginosa, 76 A. baumannii and 48 E. coli) were obtained from samples collected from 450 patients. Conversely, during the COVID-19 period, 714 isolates (237 K. pneumoniae, 205 A. baumannii, 199 P. aeruginosa and 73 E. coli) were collected from the same number of patients. In the course of the pandemic, there is a slight increase in A. baumannii and P. aeruginosa infections, whereas E. coli and K. pneumoniae exhibit a distinct trend with a noticeable reduction in infection rates during COVID-19. During the COVID-19 period, a noticeable rise in resistance rates was observed for all antibiotics utilized. The results from Fisher’s exact test indicated a substantial increase in resistance towards certain antibiotics. Specifically, a significant rise in resistance was observed for E. coli to ciprofloxacin (P = 0.00), gentamicin and P. aeruginosa (P = 0.02), levofloxacin and A. baumannii (P = 0.01), piperacillin-tazobactam and A. baumannii (P = 0.04), and piperacillin-tazobactam and P. aeruginosa (P = 0.01).

Conclusion. Our results display how the pandemic impacted bacterial infections and antibiotic resistance, indicating a general increase in resistance rates. These findings are crucial for guiding healthcare practices, emphasizing the need for continued surveillance and potentially checking antibiotic usage schemes.
Invasive ants fed spinosad collectively recruit to known food faster yet individually abandon food earlier
Authors: Galante Henrique , Forster Moritz , Werneke Cosmina , Czaczkes Tomer J.
Published: June 2024

Current management strategies applied to invasive ants rely on slow-acting insecticides which aim to delay the ant’s ability to detect the poison until its effects are noticeable. Despite this, most control efforts are unsuccessful, likely due to bait abandonment and insufficient sustained consumption. Conditioned taste aversion, a learned avoidance of a particular taste, is a crucial survival mechanism which prevents animals from repeatedly ingesting toxic substances. However, whether ants are capable of this delayed association between food taste and subsequent illness remains largely unexplored. Here, we exposed colonies of the highly invasive Argentine ant,Linepithema humile, to a sublethal dose of the slow-acting insecticide spinosad. We combined measurements of individual-level feeding patterns with quantification of collective preferences and foraging dynamics to investigate the potential effects of the toxicant on behaviour. Collectively, ants preferred an odour associated with a previously experienced food, even if this contained spinosad, over a novel one. However, at the individual-level, previous exposure to spinosad resulted in reduced food consumption, as a consequence of earlier food abandonment. Moreover, while control-treated colonies recruited slower to a food source which tasted like a previously experienced one, spinosad-exposed colonies recruited equally fast to both novel and familiar foods. Although it appears that ants are unable to develop a conditioned taste aversion to sublethal doses of spinosad, ingestion of even small amounts of the toxicant strongly influences foraging behaviour. Understanding the subtle effects of slow-acting pesticides on ant cognition and behaviour can ultimately inspire the development of more efficient control methodologies.