bluuebunny/crossref_metadata_2025_split huggingface dataset:
Utilizing immunotherapy towards achieving a functional cure for HIV-1
Authors: Sugiyama Fabrícia Heloisa Cavicchioli , Dietz Lisa Loksø , Søgaard Ole Schmeltz 
Published: April 2024

Purpose of review
Advancements in antiretroviral therapy (ART) have positively impacted the life expectancy and possibility of living a normal life for people with HIV-1. However, lifelong daily medication is necessary to prevent disease progression. To this end, immunotherapeutic strategies are being tested with the aim of developing a functional cure in which the immune system effectively controls HIV-1 in the absence of ART.

Recent findings
The most promising advances in achieving sustained HIV-1 remission or cure include broadly neutralizing antibodies (bNAbs) that are administered alone or in combination with other agents. Newer and more innovative approaches redirecting T cells or natural killer cells to kill HIV-1 infected cells have also shown promising results. Finally, multiple ongoing trials focus on combining bNAbs with other immune-directed therapies to enhance both innate and adaptive immunity.

Summary
While immunotherapies as an alternative to conventional ART have generally proven to be well tolerated, these therapeutic approaches have largely been unsuccessful in inducing ART-free control of HIV-1. However, promising results from recent trials involving bNAbs that have reported durable HIV-1 control among a subset of participants, provide reason for cautious optimism that we with further optimization of these treatment strategies may be able to achieve functional cure for HIV-1.
Microbiological Profile of Culture-Positive Fungal Keratitis
Authors: Muni Ipsita , Behera Himanshu Sekhar , Sahu Srikant Kumar , Priyadarshini Smruti Rekha , Das Sujata 
Published: April 2024

Purpose:
To examine the microbiological profile of cases of culture-positive fungal keratitis presenting to a tertiary eye care center in eastern India.

Methods:
Microbiology records of all culture-positive microbial keratitis patients presenting to L V Prasad Eye Institute, Bhubaneswar, between January 2020 and December 2021, were retrospectively reviewed. Collected data included smear results of culture-positive fungal or mixed infections, the species isolated, and the time taken for organisms to grow in each media.

Results:
Fungal keratitis formed 36% of all culture-positive microbial keratitis, whereas mixed infections (fungi and other organisms) formed 8.5%. The most common fungal species isolated was Fusarium spp. (25.8%). The most common bacteria involved in mixed infection with fungi was Staphylococcus spp. (54.8%). The positivity of potassium hydroxide+calcofluor white stain in detecting fungal filaments was 89.0% and that of Gram stain was 76.1%. Culture-positive cases of fungal keratitis showed most frequent growth on potato-dextrose agar (77.6%). A similar pattern was observed in culture-positive mixed infections (Sabouraud dextrose agar [SDA]: 84%). Most frequent growth of bacteria in mixed infections was seen in thioglycolate broth (54.7%). The shortest time to achieve significant fungal growth was observed in blood agar (BA) and chocolate agar (CA) (2.2/2.3 days, and 1.8/2 days for fungal keratitis and mixed infections, respectively). Filamentous hyaline fungi took the shortest time to achieve significant growth (2.8 days), whereas yeast forms took the longest (5 days).

Conclusion:
This study highlights the importance of combined use of both solid and liquid culture media, especially potato dextrose agar (PDA)/SDA and CA, to arrive at a definitive diagnosis of fungal keratitis and possible bacterial co-infection, which forms a significant proportion of cases with fungal keratitis. In resource-poor laboratories, two culture media, either SDA or PDA, along with BA, may be plated to detect mixed infections. Examination of stained smears of corneal samples provides an inexpensive method of rapid diagnosis of fungal keratitis when culture media is not available.
Perceived Control, Functional Status, Depressive Symptoms, and Anxiety
Authors: Thapa Ashmita , Kang JungHee , Chung Misook L. , Wu Jia-Rong , Latimer Abigail , Lennie Terry A. , Lin Chin-Yen , Thompson Jessica Harman , Cha Geunyeong , Moser Debra K. 
Published: April 2024

Background
Health-related quality of life (HRQoL) is poor in patients with heart failure. Psychological (ie, depressive symptoms [DS], anxiety, and perceived control) and physical (ie, functional status) factors are associated with HRQoL. The dynamic relationships among these variables and their impact on HRQoL remain unclear, limiting the ability to design effective interventions.

Purpose
Our aim was to evaluate a moderated mediation model, in which the association between perceived control and HRQoL was hypothesized to be mediated by DS and anxiety in the presence of a moderator, functional status.

Methods
Patients (N = 426) with heart failure completed the Control Attitudes Scale-Revised to measure perceived control, Duke Activity Status Index for functional status, Patient Health Questionnaire-9 for DS, Brief Symptom Inventory for anxiety, and Minnesota Living with Heart Failure Questionnaire for HRQoL. We performed a moderated parallel mediation analysis.

Results
Higher levels of perceived control were associated with better HRQoL through lower levels of anxiety and DS in the presence of functional status (index of moderated mediation for DS, b = 0.029; 95% confidence interval, 0.016–0.045; for anxiety: b = 0.009, 95% confidence interval, 0.002–0.018). The effect of perceived control on psychological symptoms was stronger at low and moderate functional statuses; however, this effect diminished with increasing functional status.

Conclusion
Functional status moderated the indirect effects of perceived control on HRQoL through DS and anxiety in patients with heart failure. Efforts to improve HRQoL by targeting perceived control may be more effective when considering DS and anxiety in patients with low to moderate levels of functional status.
Assessment of species distribution and virulence factors of oral fungal carriage among hospitalized patients with COVID-19: a case-control study
Authors: Ramezanalipour Zahra , Hashemi Seyed Jamal , Daie Ghazvini Roshanak , Shenagari Mohammad , Sharifdini Meysam , Salehiniya Hamid , Keivanlou Mohammad-Hossein , Ashrafi Keyhan , Roostaei Davoud , Mansour Ghanaei Fariborz , Sasani Elahe , Rafat Zahra 
Published: April 2024

Background:
The COVID-19 pandemic highlighted the need to study oral fungal carriage and its potential impact. In oral fungal environments, factors like changes in respiratory epithelium, increased pathogen attachment, local inflammation, and virulence factors could influence COVID-19 severity. The authors conducted a study to explore oral fungal carriage in COVID-19 patients and compare it to a healthy control group.

Methods:
The authors executed a case-control investigation including 144 COVID-19 patients and an equivalent number of 144 healthy controls. The matching criteria encompassed age, sex, body mass index, and the history of antibiotic and antiviral medication intake. This research was performed over a span of 12 months from May 2021 to May 2022. The mouth area was sampled with a cotton-tipped swab. Subsequently, all the samples underwent fungal culture and PCR-sequencing procedures.

Results:
In COVID-19 patients, oral fungal carriage was three times higher compared to healthy controls. Candida was the exclusive genus found in both groups, with Candida albicans being the most frequently isolated species (90.79%). Among COVID-19 patients, Candida species showed significantly higher esterase, proteinase, and hemolysin activity compared to healthy individuals. Both groups exhibited elevated levels of C. albicans virulence factors compared to non-albicans species.

Conclusions:
It is crucial to understand the way that virulence factors of oral fungal carriage act in COVID-19 patients in order to come up with novel antifungal medications, identify the contributing factors to drug resistance, and manage clinical outcomes.
The effects of prehospital TXA on mortality and neurologic outcomes in patients with traumatic intracranial hemorrhage: A subgroup analysis from the prehospital TXA for TBI trial
Authors: Rowell Susan , Meier Eric N. , Hoyos Gomez Tatiana , Fleming Michael , Jui Jon , Morrison Laurie , Bulger Eileen , Sopko George , Weisfeldt Myron , Christenson Jim , Klotz Pat , McMullan Jason , Callum Jeannie , Sheehan Kellie , Tibbs Brian , Aufderheide Tom , Cotton Bryan , Gandhi Rajesh , Idris Ahamed , Frascone Ralph J. , Ferrara Michael , Richmond Neil , Kannas Delores , Schlamp Rob , Robinson Bryce , Dries David , Tallon John , Hendrickson Audrey , Gamber Mark , Garrett John , Simonson Robert , McKinley W. Ian , Schreiber Martin 
Published: April 2024

BACKGROUND
In the prehospital tranexamic acid (TXA) for traumatic brain injury (TBI) trial, TXA administered within 2 hours of injury in the out-of-hospital setting did not reduce mortality in all patients with moderate/severe traumatic brain injury (TBI). We examined the association between TXA dosing arms, neurologic outcome, and mortality in patients with intracranial hemorrhage (ICH) on computed tomography (CT).

METHODS
This was a secondary analysis of the Prehospital Tranexamic Acid for TBI Trial (ClinicalTrials.gov [NCT01990768]) that randomized adults with moderate/severe TBI (Glasgow Coma Scale score < 13) and systolic blood pressure ≥ 90 mm Hg within 2 hours of injury to a 2-g out-of-hospital TXA bolus followed by an in-hospital saline infusion, a 1-g out-of-hospital TXA bolus/1-g in-hospital TXA infusion, or an out-of-hospital saline bolus/in-hospital saline infusion (placebo). This analysis included the subgroup with ICH on initial CT. Primary outcomes included 28-day mortality, 6-month Glasgow Outcome Scale-Extended (GOSE) ≤ 4, and 6-month Disability Rating Scale (DRS). Outcomes were modeled using linear regression with robust standard errors.

RESULTS
The primary trial included 966 patients. Among 541 participants with ICH, 28-day mortality was lower in the 2-g TXA bolus group (17%) compared with the other two groups (1-g bolus/1-g infusion 26%, placebo 27%). The estimated adjusted difference between the 2-g bolus and placebo groups was −8·5 percentage points (95% confidence interval [CI], −15.9 to −1.0) and between the 2-g bolus and 1-g bolus/1-g infusion groups was −10.2 percentage points (95% CI, −17.6 to −2.9). Disability Rating Scale at 6 months was lower in the 2-g TXA bolus group than the 1-g bolus/1-g infusion (estimated difference − 2.1 [95% CI, −4.2 to −0.02]) and placebo groups (−2.2 [95% CI, −4.3, −0.2]). Six-month GOSE did not differ among groups.

CONCLUSION
A 2-g out-of-hospital TXA bolus in patients with moderate/severe TBI and ICH resulted in lower 28-day mortality and lower 6-month DRS than placebo and standard TXA dosing.

LEVEL OF EVIDENCE
Therapeutic/Care Management; Level II.
Late-Onset Findings During Extended EEG Monitoring Are Rare in Critically Ill Children
Authors: Fung France W. , Parikh Darshana S. , Walsh Kathleen , Fitzgerald Mark P. , Massey Shavonne L. , Topjian Alexis A. , Abend Nicholas S. 
Published: April 2024

Purpose:
Electrographic seizures (ES) are common in critically ill children undergoing continuous EEG (CEEG) monitoring, and previous studies have aimed to target limited CEEG resources to children at highest risk of ES. However, previous studies have relied on observational data in which the duration of CEEG was clinically determined. Thus, the incidence of late occurring ES is unknown. The authors aimed to assess the incidence of ES for 24 hours after discontinuation of clinically indicated CEEG.

Methods:
This was a single-center prospective study of nonconsecutive children with acute encephalopathy in the pediatric intensive care unit who underwent 24 hours of extended research EEG after the end of clinical CEEG. The authors assessed whether there were new findings that affected clinical management during the extended research EEG, including new-onset ES.

Results:
Sixty-three subjects underwent extended research EEG. The median duration of the extended research EEG was 24.3 hours (interquartile range 24.0–25.3). Three subjects (5%) had an EEG change during the extended research EEG that resulted in a change in clinical management, including an increase in ES frequency, differential diagnosis of an event, and new interictal epileptiform discharges. No subjects had new-onset ES during the extended research EEG.

Conclusions:
No subjects experienced new-onset ES during the 24-hour extended research EEG period. This finding supports observational data that patients with late-onset ES are rare and suggests that ES prediction models derived from observational data are likely not substantially underrepresenting the incidence of late-onset ES after discontinuation of clinically indicated CEEG.
Noise Stress induces Cardiovascular Metabolic Shifts
Authors: Marques Jair G. , Kuntic Marin , Krishnankutty Roopesh , Blanco Giovanny Rodriguez , Malkov Mykyta , Frenis Katie , Wills Jimi , Shokry Engy , Mow Chee Frederic Li , Taylor Cormac T , Münzel Thomas , Daiber Andreas , von Kriegsheim Alex 
Published: April 2024

AbstractEnvironmental stressors present in the modern world can fundamentally affect humans’ physiology and health. Exposure to stressors like air pollution, heat, and traffic noise has been linked to a pronounced increase in non-communicable diseases. Specifically, aircraft noise has been identified as a risk factor for cardiovascular and metabolic diseases, such as arteriosclerosis, heart failure, stroke, and diabetes. Noise stress leads to neuronal activation with subsequent stress hormone release that ultimately leads to activation of the renin-angiotensin-aldosterone system, increasing inflammation and oxidative stress, dramatically affecting the cardiovascular system. However, despite the epidemiological evidence of a link between noise stress and metabolic dysfunction, the consequences of exposure at the molecular, metabolic level of the cardiovascular system are largely unknown. Here we use a murine model system of aircraft noise exposure to show that noise stress profoundly alters heart metabolism. Within days of exposing animals to aircraft noise, the heart has a reduced potential for utilising fatty-acid beta-oxidation, the tricarboxylic acid cycle, and the electron transport chain for generating ATP. This is compensated by shifting energy production towards glycolysis. Intriguingly, the metabolic shift is reminiscent of what is observed in failing and ischaemic hearts. Our results demonstrate that within a relatively short exposure time, the cardiovascular system undergoes a fundamental metabolic shift that bears the hallmarks of cardiovascular disease.Overall, aircraft noise induces rapid, detrimental metabolic shifts in the heart, resembling patterns seen in cardiovascular diseases. These findings underscore the urgent need to comprehend the molecular consequences of environmental stressors, paving the way for targeted interventions aiming at mitigating health risks associated with chronic noise exposure in our modern, noisy environments.
Fiora: Local neighborhood-based prediction of compound mass spectra from single fragmentation events
Authors: Nowatzky Yannek , Russo Francesco , Lisec Jan , Kister Alexander , Reinert Knut , Muth Thilo , Benner Philipp 
Published: April 2024

ABSTRACTNon-targeted metabolomics holds great promise for advancing precision medicine and facilitating the discovery of novel biomarkers. However, the identification of compounds from tandem mass spectra remains a non-trivial task due to the incomplete nature of spectral reference libraries. Augmenting these libraries with simulated mass spectra can provide the necessary reference to resolve unmatched mass spectra, but remains a difficult undertaking to this day. In this study, we introduce Fiora, an innovative open-source algorithm using graph neural networks to simulate tandem mass spectrain silico. Our objective is to improve fragment intensity prediction with an intricate graph model architecture that facilitates edge prediction, thereby modeling fragment ions as the result of singular bond breaks and their local molecular neighborhood. We evaluate the performance on test data from NIST (2017) and the curated MS-Dial spectral library, as well as compounds from the 2016 and 2022 CASMI challenges. Fiora not only surpasses state-of-the-art fragmentation algorithms, ICEBERG and CFM-ID, in terms of prediction quality, but also predicts additional features, such as retention time and collision cross section. In addition, Fiora demonstrates significant speed improvements through the use of GPUs. This enables rapid (re)scoring of putative compound identifications in non-targeted experiments and facilitates large-scale expansion of spectral reference libraries with accurate spectral predictions.Abstract Figure
Neural activity for complex sounds in the marmoset medial prefrontal cortex
Authors: Gilliland Rebekah E. , Selvanayagam Janahan , Zanini Alessandro , Johnston Kevin D. , Everling Stefan 
Published: April 2024

AbstractVocalizations play an important role in the daily life of nonhuman primates and are likely precursors of human language. Recent functional imaging studies in the highly vocal common marmoset (Callithrix jacchus) have suggested that medial prefrontal cortex area 32 may be a part of a vocalization-processing network but the response properties of area 32 neurons to auditory stimuli remain unknown. Here, we performed electrophysiological recordings in area 32 with high-density Neuropixels probes and characterized neuronal responses to a variety of sounds including conspecific vocalizations. More than half of the neurons in area 32 responded to conspecific vocalizations and other complex auditory stimuli. These responses exhibited dynamics consisting of an initially non-selective reduction in neural activity, followed by an increase in activity that immediately conveyed sound selectivity. Our findings demonstrate that primate mPFC area 32 plays a critical role in processing species-specific and biologically relevant sounds.
Sampling Techniques and Genomic Analysis of Biological Material from Artworks
Authors: Roby Rhonda K. , Wiscovitch-Russo Rosana A. , Hart Rebecca , Appel Amanda E. , Kazmi Manija A. , Huber Thomas , Åberg Karina C. , Sakmar Thomas P. , Lorente José A. , Gonzalez-Juarbe Norberto 
Published: April 2024

AbstractThe genomic analysis of biological material obtained from artwork or cultural heritage artifacts can be used to guide curation, preservation and restoration. However, the recovery of biological samples from artworks is dependent on the sampling technique used and the media from which the biological materials are recovered. The ideal sampling method should be non-invasive, yet robust. Only rare examples of direct comparisons among sampling techniques have been reported. To develop a framework for the recovery of biological samples for subsequent microbial DNA analysis, we studied five artworks on paper and compared three sampling methods, each with increasing degrees of invasiveness. Minimally invasive swabbing techniques collect samples from the surface, whereas more aggressive techniques such as wet vacuuming were expected to yield more biological material from within the support media. We report a comparison of collection techniques to generate microbial DNA sequence data from artworks on paper. We observed that wet vacuuming resulted in higher DNA recovery than double swabbing and core punches; however, all three techniques yielded satisfactory microbial DNA sequences. Diverse microbial populations existed to varying degrees on the corners and centers of the five artworks studied, but the distribution of the total biomass was relatively even across the surfaces of the works sampled. Studies of peripheral regions, where sampling is less likely to cause alterations to the artwork, could thus yield useful results in microbiome studies. These results provide a framework for sampling artworks on paper to obtain biological material for microbial genomic analysis. The methods described may provide microbiome identification to facilitate restoration and preservation, and might also contribute to the determination of provenance.
Three dimensionally printed microstructured alginate scaffolds for neural tissue engineering
Authors: Li Jianfeng , Hietel Benjamin , Brunk Michael G.K. , Reimers Armin , Willems Christian , Groth Thomas , Cynis Holger , Adelung Rainer , Schütt Fabian , Sacher Wesley D. , Poon Joyce K.S. 
Published: April 2024

AbstractThe integration of scaffolds, signalling cues, and cellular components is essential in tissue engineering to create anin vivoequivalent environment that supports physiological function. Scaffolds provide mechanical reinforcement for cellular proliferation and differentiation while providing cues that instruct the development of cells during culture. Alginate (Alg) is a versatile biopolymer for scaffold engineering. However, due to a lack of intrinsic cell-binding sites, thus far, Alg must be functionalized for cellular adhesion. Here, we demonstrate proof-of-concept, bioactive additive-free, microstructured Alg (M-Alg) scaffolds for neuron culture. The M-Alg scaffold was formed by introducing tetrapod-shaped ZnO (t-ZnO) microparticles as structural templates in the Alg that were subsequently removed. These transparent, porous, additive-free Alg-based scaffolds with neuron affinity are promising for neuroregenerative and organoid- related research.HighlightsTetrapod-shaped ZnO (t-ZnO) microparticles are used as a template for the fabrication of open interconnected channels and textured surfaces in 3D printed microstructured alginate (M-Alg) scaffolds.Primary mouse cortical neurons seeded on the 3D printed M-Alg scaffolds show improved adhesion and maturation with extensive neural projections forming inside the scaffolds.
Xanthomonas protegenssp. nov., a rice seed-associated probiotic and taxonomic outlier species ofXanthomonas sontii
Authors: Rana Rekha , Sharma Anushika , Madhavan Vishnu Narayanan , Sonti Ramesh V. , Patel Hitendra K. , Patil Prabhu B. 
Published: April 2024

AbstractRice seed microbiota play a vital role throughout their growth and developmental stages.Xanthomonas sontiiis known as an abundant, core-vertically transmitted rice seed endophyte with probiotic properties. Studies reveal a less explored world of non-pathogenicXanthomonas(NPX) species likeX. sontiiandX. indicathat are associated with healthy rice seeds. The present study reports the isolation, biochemical characterization, and in-depth taxonogenomic evidence for a third NPX species,X. protegens, from rice seeds, a taxonomic outlier ofX. sontii. It also highlights the importance of using multiple taxonogenomic indices to identify taxonomic outlier species. Similar to the other two NPX species, the new member species is also non-pathogenic and providesin vivoprotection to rice plants fromXanthomonas oryzaepv.oryzaeupon leaf clip inoculation. The pangenome investigation suggested a set of unique genes to the novel species that might be important in adaptation to rice plants and differentiate it from other NPX species. The study will allow the design of markers for the identification of these NPX members, targeted culturomics of a particular NPX species and in the discovery of other novel NPX species from healthy rice seed microbiome for further exploitation in rice health.