bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacogenetic interactions of efavirenz or rifampin and isoniazid with levonorgestrel emergency contraception during treatment of HIV or tuberculosis
Authors: Agyemang Nana , Scarsi Kimberly K. , Baker Paxton , Smeaton Laura M. , Podany Anthony T. , Olefsky Maxine , Woolley Elizabeth , Barr Elizabeth , Pham Michelle , Mawlana Sajeeda , Supparatpinyo Khuanchai , Gatechompol Sivaporn , Jalil Emilia M. , Gadama Luis , Badal-Faesen Sharlaa , Van Schalkwyk Marije , Kayama Cecelia , Belaunzaran-Zamudio Pablo F. , Godfrey Catherine , Cohn Susan E. , Mngqibisa Rosie , Haas David W. ,   for the AIDS Clinical Trials Group A5375 Study Team
Published: June 2023

Objective

In AIDS Clinical Trials Group study A5375, a pharmacokinetic trial of levonorgestrel emergency contraception, double-dose levonorgestrel (3 mg, versus standard dose 1.5 mg) offset the induction effects of efavirenz or rifampin on plasma levonorgestrel exposure over 8 h post-dose (AUC0-8h). We characterized the pharmacogenetics of these interactions.

Methods

Cisgender women receiving efavirenz- or dolutegravir-based HIV therapy, or on isoniazid-rifampin for tuberculosis, were followed after a single oral dose of levonorgestrel. Linear regression models, adjusted for BMI and age, characterized associations of CYP2B6 and NAT2 genotypes (which affect plasma efavirenz and isoniazid exposure, respectively) with levonorgestrel pharmacokinetic parameters.

Results

Of 118 evaluable participants, 17 received efavirenz/levonorgestrel 1.5 mg, 35 efavirenz/levonorgestrel 3 mg, 34 isoniazid-rifampin/levonorgestrel 3 mg, and 32 (control group) dolutegravir/levonorgestrel 1.5 mg. There were 73 Black and 33 Asian participants. Regardless of genotype, women on efavirenz and isoniazid-rifampin had higher levonorgestrel clearance. In the efavirenz/levonorgestrel 3 mg group, CYP2B6 normal/intermediate metabolizers had levonorgestrel AUC0-8h values similar to controls, while CYP2B6 poor metabolizers had AUC0-8h values of 40% lower than controls. In the isoniazid-rifampin group, NAT2 rapid/intermediate acetylators had levonorgestrel AUC0-8h values similar to controls, while NAT2 slow acetylators had AUC0-8h values 36% higher than controls.

Conclusion

CYP2B6 poor metabolizer genotypes exacerbate the efavirenz-levonorgestrel interaction, likely by increased CYP3A induction with higher efavirenz exposure, making the interaction more difficult to overcome. NAT2 slow acetylator genotypes attenuate the rifampin-levonorgestrel interaction, likely by increased CYP3A inhibition with higher isoniazid exposure.
Vitamin C in critical illness: end of the story or still a place?
Authors: Radke David I. , Homayr Anna Lulu , Stoppe Christian , Elke Gunnar
Published: June 2023

Purpose of review

Critical illness is associated with decreased micronutrient levels, including vitamin C, an essential antioxidant for systemic inflammation. This review discusses the most recent evidence of high-dose vitamin C monotherapy in critically ill adults.

Recent findings

Three randomized-controlled trials (RCTs) were published in 2022. A pilot study including 40 patients with septic shock could not detect significant differences in outcome parameters after administering vitamin C. A multicenter study with 124 septic patients showed no significant difference in 28-day mortality, while vitamin C was associated with an increased risk of acute kidney dysfunction. The LOVIT trial, an international prospective RCT in 872 septic patients, revealed an increased risk of the composite endpoint persistent organ dysfunction plus death at day 28 in the high-dose vitamin C group. Six systematic reviews and meta-analyses (SRMA), including up to 4740 patients published before and 2 SRMA publications including these RCTs showed divergent results on clinical endpoints including mortality.

The use of high-dose intravenous vitamin C cannot be recommended for the septic critically ill in clinical practice since the LOVIT trial. Further research is needed to evaluate its potential role in other critically ill patients.
Insulin resistance in critical illness: consequences for nutrition therapy and glucose management
Authors: Gunst Jan , Verbruggen Sascha C.
Published: June 2023

Purpose of review:

Critically ill patients usually develop insulin resistance and hyperglycemia, which is aggravated by early parenteral nutrition. In observational studies, the lowest mortality risk associates with glucose concentrations close to the antecedent average glucose level. This review summarizes the most recent evidence regarding glucose control in critical illness.

Recent findings:

Although pioneer randomized controlled trials showed morbidity and mortality benefit by normalizing blood glucose in intensive care, the largest multicenter randomized controlled trial found increased mortality. Differences in glucose targets, the accuracy of the glucose control protocol, and differences in feeding strategy may explain these differences.

Recent randomized controlled trials investigating the impact of individualized glucose control did not show benefits of targeting individualized or looser glucose values in critically ill patients with poorly controlled diabetes.

It remains unclear whether tight glucose control in critical illness is beneficial or not in the absence of early parenteral nutrition, which is currently being studied in the multicenter TGC-fast randomized controlled trial. Without new evidence, it seems prudent to avoid severe hyperglycemia and hypoglycemia in all patients.
Lateropulsion in Right-Sided Stroke: Brain Anatomical Correlates of Severity and Duration
Authors: Salazar López Elvira , Krewer Carmen , Bergmann Jeannine , Möhwald Ken , Müller Friedemann , Jahn Klaus
Published: June 2023

Background and Purpose:

Lateropulsion (LP) is a profound disorder of postural control that has a significant impact on neurorehabilitation. Knowledge of relevant brain areas could guide decisions on appropriate intervention methods. Although LP severity and duration are highly variable in individuals with LP, imaging studies on LP have not sufficiently considered these aspects. The aim of this study was to investigate the lesion location in individuals after stroke and the correlation with LP duration and severity.

Methods:

A retrospective case-control study using voxel lesion symptom mapping (VLSM) in 74 individuals with right-sided brain lesion (49 with and 25 without LP) was performed to analyze the correlation between lesion location and LP severity. Duration was investigated in a subsample of 22 individuals with LP. LP was diagnosed by means of the Scale for Contraversive Pushing.

Results:

Individuals with LP showed significantly larger lesion sizes compared with the individuals with no LP. VLSM analysis of LP severity did not reveal statistically significant results. VLSM analysis showed a statistically significant association with longer LP duration for the inferior frontal gyrus, the hippocampus, the inferior parietal gyrus, the supramarginal gyrus, the angular gyrus, the temporal cortex, the sagittal stratum, and the superior longitudinal fasciculus.

Discussion and Conclusion:

LP-relevant areas are located in the multisensory network. Areas of the frontoparietal network, which are related to spatial cognition, memory, and attention, were found to be relevant for duration and severity. The findings, especially those regarding duration involving the middle temporal cortex, could explain the better intervention outcomes for methods based more on implicit than on explicit knowledge of verticality.

Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1 available at: http://links.lww.com/JNPT/A433).
Impact of Adjunct Corticosteroid Therapy on Quality of Life for Children With Suspected Pneumonia
Authors: Navanandan Nidhya , Florin Todd A. , Leonard Jan , Ramgopal Sriram , Cotter Jillian M. , Shah Samir S. , Ruddy Richard M. , Ambroggio Lilliam
Published: June 2023

Objective

To determine the association between adjunct corticosteroid therapy and quality of life (QoL) outcomes in children with signs and symptoms of lower respiratory tract infection and clinical suspicion for community-acquired pneumonia (CAP) in the emergency department (ED).

Methods

Secondary analysis from a prospective cohort study of children aged 3 months to 18 years with signs and symptoms of LRTI and a chest radiograph for suspected CAP in the ED, excluding children with recent (within 14 days) systemic corticosteroid use. The primary exposure was receipt of corticosteroids during the ED visit. Outcomes were QoL measures and unplanned visits. Multivariable regression was used to evaluate the association between corticosteroid therapy and outcomes.

Results

Of 898 children, 162 (18%) received corticosteroids. Children who received corticosteroids were more frequently boys (62%), Black (45%), had history of asthma (58%), previous pneumonia (16%), presence of wheeze (74%), and more severe illness at presentation (6%). Ninety-six percent were treated for asthma as defined by report of asthma or receipt of ß-agonist in the ED. Receipt of corticosteroids was not associated with QoL measures: days of activity missed (adjusted incident rate ratio [aIRR], 0.84; 95% confidence interval [CI], 0.63–1.11) and days of work missed (aIRR, 0.88; 95% CI, 0.60–1.27). There was a statistically significant interaction between age (>2 years) and corticosteroids receipt; the patients had fewer days of activity missed (aIRR, 0.62; 95% CI, 0.46–0.83), with no effect on children 2 years or younger (aIRR, 0.83; 95% CI, 0.54–1.27). Corticosteroid treatment was not associated with unplanned visit (odds ratio, 1.37; 95% CI, 0.69–2.75).

Conclusions

In this cohort of children with suspected CAP, receipt of corticosteroids was associated with asthma history and was not associated with missed days of activity or work, except in a subset of children aged older than 2 years.
Creation of the Scaphocephalic Index: Measurement of Global and Regional Severity in Scaphocephaly
Authors: Bins Griffin P. , Zhou Larry Z. , Cull Deborah , Layton Ryan G. , Dunson Blake T. , Kogan Samuel , David Lisa R. , Runyan Christopher M.
Published: June 2023

Background:

The recently described frontal bossing index (FBI) and occipital bullet index (OBI) allow for quantification of scaphocephaly. A similar index examining biparietal narrowing has not been described. Addition of such an index measuring width would allow for direct evaluation of the primary growth restriction in sagittal craniosynostosis and the formation of an optimized global width/length measure.

Methods:

Computed tomography scans and three-dimensional photographs were used to recreate scalp surface anatomy. Equidistant axial, sagittal, and coronal planes were overlaid, creating a Cartesian grid. Points of intersection were analyzed for population trends in biparietal width. Using the most descriptive point coupled with the sellion protrusion to control for head size, the vertex narrowing index is formed. By combining this index with the FBI and OBI, the scaphocephalic index (SCI) is created as a tailored width/length measure.

Results:

Using 221 controls and 360 individuals with sagittal craniosynostosis, the greatest difference occurred superiorly and posteriorly at a point 70% of the head’s height and 60% of the head’s length. This point had an area under the curve of 0.97 and sensitivity and specificity of 91.2% and 92.2%, respectively. The SCI has an area under the curve of 0.9997, sensitivity and specificity greater than 99%, and interrater reliability of 0.995. The correlation coefficient between computed tomography imaging and three-dimensional photography was 0.96.

Conclusions:

The vertex narrowing index, FBI, and OBI evaluate regional severity, while the SCI is able to describe global morphology in patients with sagittal craniosynostosis. These measures allow for superior diagnosis, surgical planning, and outcome assessment, independent of radiation.
Antivirals vs Antivirals and Steroids for Treatment of Herpes Zoster–Related Ophthalmoplegia: A Case Series and Systematic Review
Authors: Sverdlichenko Irina , Tayeb Safwan , Zaslavsky Kirill , Micieli Jonathan A. , Margolin Edward A.
Published: June 2023

Background:

Up to 1/3 of patients with herpes zoster ophthalmicus (HZO) may develop ophthalmoplegia. Although zoster-related ophthalmoplegia (ZO) is typically treated with antiviral agents, there is controversy regarding the therapeutic role of systemic steroids.

Methods:

This was a retrospective case series and case report–based systematic review. For the case series, participants were recruited from tertiary neuro-ophthalmology clinics. Eligible participants were those who developed cranial nerve palsies (CNP) within 1 month of HZO diagnosis. In the systematic review, all adults with ZO in the literature who were treated with antivirals or steroids only, or combination therapy were included. Main outcomes were initial presentation, investigations, neuroimaging, treatment regimen, and final outcomes of ophthalmoplegia.

Results:

Eleven immunocompetent patients with ZO were included. The most common CNP was CN III (5/11), followed by CN VI (2/11) and CN IV (2/11). One patient had multiple CNPs. All patients were treated with antivirals, and 4 also treated with a short course of oral steroids. At 6-month follow-up, 75% of patients treated with combination therapy and 85.7% treated with antivirals alone had complete recovery of ZO. The systematic review identified 63 studies consisting of 76 cases of ZO. When comparing patients treated with antivirals with those treated with antivirals and steroids, patients on combination therapy had more severe ocular findings, including complete ophthalmoplegia (P < 0.001). Age was the only significant predictor of complete recovery of ophthalmoplegia on multivariable logistic regression (P = 0.037).

Conclusions:

The rate of complete recovery in immunocompetent patients with ZO was similar in patients treated with antivirals alone vs those treated with antivirals and oral steroids. The systematic literature review affirmed these findings. However, age may influence recovery of ophthalmoplegia.
Clinical Knowledge and Reasoning Abilities of AI Large Language Models in Pharmacy: A Comparative Study on the NAPLEX Exam
Authors: Angel Mirana , Patel Anuj , Alachkar Amal , Baldi Pierre
Published: June 2023

Objective

This study aims to evaluate the capabilities and limitations of three large language models (LLMs) – GPT-3, GPT-4, and Bard, in the field of pharmaceutical sciences by assessing their pharmaceutical reasoning abilities on a sample North American Pharmacist Licensure Examination (NAPLEX). We also analyze the potential impacts of LLMs on pharmaceutical education and practice.

Methods

A sample NAPLEX exam consisting of 137 multiple-choice questions was obtained from an online source. GPT-3, GPT-4, and Bard were used to answer the questions by inputting them into the LLMs’ user interface. The answers provided by the LLMs were then compared with the answer key.

Results

GPT-4 exhibited superior performance compared to GPT-3 and Bard, answering 78.8% of the questions correctly. This score was 11% higher than Bard and 27.7% higher than GPT-3. However, when considering questions that required multiple selections, the performance of each LLM decreased significantly. GPT-4, GPT-3, and Bard only correctly answered 53.6%, 13.9%, and 21.4% of these questions, respectively.

Conclusion

Among the three LLMs evaluated, GPT-4 was the only model capable of passing the NAPLEX exam. Nevertheless, given the continuous evolution of LLMs, it is reasonable to anticipate that future models will effortlessly pass the exam. This highlights the significant potential of LLMs to impact the pharmaceutical field. Hence, we must evaluate both the positive and negative implications associated with the integration of LLMs in pharmaceutical education and practice.
High prevalence and risk factors of transmission of hepatitis delta virus in pregnant women in the Center Region of Cameroon
Authors: Ondigui Juliette-Laure Ndzie , Goumkwa Nadège Mafopa , Lobe Cindy , Wandji Brigitte , Awoumou Patrick , Djivida Prisca Voussou , Peyonga Puinta , Atah Solange Manju , Verbe Vivian , Simo Rachel Kamgaing , Moudourou Sylvie Agnès , Gutierrez Ana , Garcia Rosi , Fernandez Isabelle , Riwom Essama Sara Honorine , Mbu Robinson , Torimiro Judith
Published: June 2023

Background

Hepatitis B virus (HBV) and hepatitis delta virus (HDV) co-infection has been described as the most severe form of viral hepatitis, and both can be co-transmitted from mother-to-child. A seroprevalence of 4.0% of HDV infection was reported in pregnant women in Yaoundé, and 11.9% in the general population in Cameroon. Our objective was to describe the rate of HDV infection in pregnant women and to determine risk factors associated with mother-to-child transmission of HDV.

Materials and Methods

A cross-sectional, descriptive study was conducted from January 2019 to July 2022 among pregnant women attending antenatal contacts in seven health structures in the Centre Region of Cameroon. A consecutive sampling (non-probability sampling) was used to select only women of age over 21 years, who gave a written informed consent. Following an informed consent, an open-ended questionnaire was used for a Knowledge, Attitude and Practice (KAP) survey of these women, and their blood specimens collected and were screened for HBsAg, anti-HIV and anti-HCV antibodies by rapid tests and ELISA. HBsAg-positive samples were further screened for HBeAg, anti-HDV, anti-HBs, and anti HBc antibodies by ELISA, and plasma HDV RNA load measured by RT-qPCR.

Results

Of 1992 pregnant women, a rate of 6.7% of HBsAg (134/1992) with highest rate in the rural areas, and 3.9% of hepatitis vaccination rate were recorded. Of 134, 44 (32.3%) were anti-HDV antibody-positive, and 47.6% had detectable RNA viraemia. Two women of 44 anti-HDV-positive cases (4.5%) were co-infected with HBV and HCV, while 5 (11.4%) with HIV and HBV. Multiple deliveries, the presence of tattoos and/or scarifications were significantly statistically associated with the presence of anti-HDV antibodies. Of note, 80% of women with negative HBeAg and positive anti-HBe serological profile, had plasma HDV RNA load of more than log 3.25 (>10.000 copies/ml).

Conclusion

These results show an intermediate rate of HDV infection among pregnant women with high level of HDV RNA viremia, which suggest an increased risk of vertical and horizontal co-transmission of HDV.
The impact of substance use on tuberculosis treatment adherence among tuberculosis patients in Limpopo Province, South Africa
Authors: Matakanye Hulisani , Tshitangano Takalani
Published: June 2023

Background

Substance use are associated with high discontinuation of tuberculosis treatment which is a barrier to tuberculosis control. Treatment discontinuation significantly increase the risk of poor treatment outcomes in both drug-susceptible and multidrug-resistant tuberculosis patients. This study aimed to explore the impact of substance use on tuberculosis treatment adherence among tuberculosis patients in Limpopo Province, South Africa.

Method

The study employed exploratory qualitative research design. Purposive sampling method was used to sample eight TB focal person and eight facility operational managers who were working in eight community health center within three selected districts in Limpopo province. Data were collected through key informant in-depth interviews and were analysed using Colaizzi’s method.

Results

The study results show four individual major themes that emerged from data analysis: (1) Patients forget to take treatment, (2) Patients miss follow up visit and DOT support appointments (3) Patients refuse social support (4) Patients refuse to attend health education and counselling.

Conclusion

The study highlighted serious impact of substance abuse on TB treatment adherence among TB patients. There is a need to integrate treatment for alcoholism and illicit drug users into primary health care to identify specific group of patients suffering from alcoholism and drug addiction on time, as a component of comprehensive TB treatment strategy.
Observation Of Laryngopharyngeal Reflux During Video-Laryngoscopy Was Common Per Our Single Observer Single Institution Experience
Authors: Suchocki Ewelina , Saasouh Wael , Gupta Deepak
Published: June 2023

Background

Video-laryngoscopy gives an opportunity to objectively document the peri-operative incidence of laryngopharyngeal reflux.

Materials and Methods

To quantify the local real-world incidence of laryngopharyngeal reflux, a single observer observed 100 adult patients undergoing elective video-laryngoscopy for their elective surgical procedures in the operating rooms at a single institution.

Results

Laryngopharynx in 4% of patients demonstrated visible active refluxing of gastroesophageal contents cranially into laryngopharynx during video-laryngoscopy but none of those underwent suctioning to remove the actively refluxing contents before successfully attempting tracheal intubation.

Conclusion

Observed laryngopharyngeal reflux during elective video-laryngoscopy was common among adult patients presenting for elective surgical procedures. The lack of suctioning prior to tracheal intubation warrants consensus discussion and statement regarding whether or not to perform suctioning of visible laryngopharyngeal reflux contents prior to intubation.
Eclipse: A Python package for alignment of two or more nontargeted LC-MS metabolomics datasets
Authors: Hitchcock Daniel S. , Krejci Jesse N. , Sturgeon Chloe E. , Dennis Courtney A. , Jeanfavre Sarah T. , Avila-Pacheco Julian R. , Clish Clary B.
Published: June 2023

Nontargeted LC-MS metabolomics datasets contain a wealth of information but present many challenges during analysis and processing. Often, two or more independently processed datasets must be aligned to form a complete dataset, but no available software meets our needs. For this, we have created an open-source Python package calledEclipse. Eclipseuses a novel graph-based subalignment approach to handle complex matching scenarios that arise fromn>2datasets.Eclipseis open source (https://github.com/broadinstitute/bmxp) and can be installed via “pip install bmxp”.
Homologous chromosome recognition via nonspecific interactions
Authors: Marshall Wallace F. , Fung Jennifer C.
Published: June 2023

In many organisms, most notablyDrosophila, homologous chromosomes in somatic cells associate with each other, a phenomenon known as somatic homolog pairing. Unlike in meiosis, where homology is read out at the level of DNA sequence complementarity, somatic homolog pairing takes place without double strand breaks or strand invasion, thus requiring some other mechanism for homologs to recognize each other. Several studies have suggested a “specific button” model, in which a series of distinct regions in the genome, known as buttons, can associate with each other, presumably mediated by different proteins that bind to these different regions. Here we consider an alternative model, which we term the “button barcode” model, in which there is only one type of recognition site or adhesion button, present in many copies in the genome, each of which can associate with any of the others with equal affinity. An important component of this model is that the buttons are non-uniformly distributed, such that alignment of a chromosome with its correct homolog, compared with a non-homolog, is energetically favored; since to achieve nonhomologous alignment, chromosomes would be required to mechanically deform in order to bring their buttons into mutual register. We investigated several types of barcodes and examined their effect on pairing fidelity. We found that high fidelity homolog recognition can be achieved by arranging chromosome pairing buttons according to an actual industrial barcode used for warehouse sorting. By simulating randomly generated non-uniform button distributions, many highly effective button barcodes can be easily found, some of which achieve virtually perfect pairing fidelity. This model is consistent with existing literature on the effect of translocations of different sizes on homolog pairing. We conclude that a button barcode model can attain highly specific homolog recognition, comparable to that seen in actual cells undergoing somatic homolog pairing, without the need for specific interactions. This model may have implications for how meiotic pairing is achieved.
Sociodemographic inequalities in COVID-19 booster vaccination in Peru: a GINI index decomposition analysis
Authors: Intimayta-Escalante Claudio , Tapia-Sequeiros Gustavo , Rojas-Bolivar Daniel
Published: June 2023

Background

COVID-19 vaccine coverage, especially in booster doses, remains a significant issue in Peru. This study aimed to analyze the social determinants that affect vaccine coverage and evaluate sociodemographic inequalities in COVID-19 booster dose vaccination in Peru.

Methods

An ecological study was conducted with 196 provinces in Peru. GINI index decomposition analysis was performed to assess the inequality of immunization coverage in these provinces, considering sociodemographic characteristics as sources of inequality (sex, age group, educational level, residence area, and ethnic group). The Oaxaca-Blinder method was utilized to decompose the GINI index into Sk (composition effect), Gk (redistribution effect), Rk (differential effect), share value, and percentage change. Bootstrap method based on percentiles was employed to determine 95% confidence interval values for each GINI index and percentage change in the decomposition analysis.

Results

A total of 196 Peruvian provinces were evaluated. Among these, 59.74% had higher education, while 10.37% had no education or only elementary education. White or mestizo individuals accounted for 51.62% of the population. The GINI index decomposition analysis, six months after the start of the third and fourth dose vaccination campaign, revealed higher Sk values for the white or mestizo ethnic group (Sk= 6.46 vs Sk= 3.03), people living in rural (Sk= 6.63 vs Sk= 2.76) or urban areas (Sk= 5.88 vs Sk= 2.76), and those aged between 30 and 64 years (Sk= 6.84 vs Sk= 3.20). The highest Gk values were observed for the Aymara (Gk= 0.92 vs Gk= 0.92), Afro-Peruvian (Gk= 0.61 vs Gk= 0.61), and Quechua (Gk= 0.53 vs Gk= 0.53) ethnic groups, in contrast to the white or mestizo group (Gk= 0.34 vs Gk= 0.34). Furthermore, Rk exhibited high positive values for individuals with university or postgraduate education (Rk= 0.59 vs Rk= 0.44) and those living in urban areas (Rk= 0.34 vs Rk= 0.28). Conversely, individuals living in rural areas (Rk= -0.34 vs Rk= -0.28), those with elementary education (Rk= -0.46 vs. Rk= -0.36), and those with no education or only preschool education (Rk= -0.41 vs. Rk= -0.32) displayed high negative Rk values.

Conclussion

Sociodemographic inequalities exist in the coverage of third and fourth booster doses against COVID-19 in Peruvian provinces, particularly concerning geographic location, ethnicity, and educational level.
BRAKER3: Fully automated genome annotation using RNA-seq and protein evidence with GeneMark-ETP, AUGUSTUS and TSEBRA
Authors: Gabriel Lars , Brůna Tomáš , Hoff Katharina J. , Ebel Matthis , Lomsadze Alexandre , Borodovsky Mark , Stanke Mario
Published: June 2023

Gene prediction has remained an active area of bioinformatics research for a long time. Still, gene prediction in large eukaryotic genomes presents a challenge that must be addressed by new algorithms. The amount and significance of the evidence available from transcriptomes and proteomes vary across genomes, between genes and even along a single gene. User-friendly and accurate annotation pipelines that can cope with such data heterogeneity are needed. The previously developed annotation pipelines BRAKER1 and BRAKER2 use RNA-seq or protein data, respectively, but not both. A further significant performance improvement was made by the recently released GeneMark-ETP integrating all three data types.

We here present the BRAKER3 pipeline that builds on GeneMark-ETP and AUGUSTUS and further improves accuracy using the TSEBRA combiner. BRAKER3 annotates protein-coding genes in eukaryotic genomes using both short-read RNA-seq and a large protein database, along with statistical models learned iteratively and specifically for the target genome. We benchmarked the new pipeline on genomes of 11 species under assumed level of relatedness of the target species proteome to available proteomes. BRAKER3 outperformed BRAKER1 and BRAKER2. The average transcript-level F1-score was increased by∼20 percentage points on average, while the difference was most pronounced for species withlarge and complex genomes. BRAKER3 also outperformed other existing tools, MAKER2, Funannotate and FINDER. The code of BRAKER3 is available on GitHub and as a ready-to-run Docker container for execution with Docker or Singularity. Overall, BRAKER3 is an accurate, easy-to-use tool for eukaryotic genome annotation.
Effect of Dual Leucine Zipper Kinase Inhibitor GNE-3511 on Epileptogenesis and Cognitive and Behavioral Changes in a Temporal Lobe Epilepsy Model in Mice
Authors: Acar Dilan , Tunçcan Emre , Selek Serra Nur , Sayın İrem Ekin , Asaroğlu Can Berk , Tümentemur Gamze , Arslan Devrim Öz , Özdemir Samet , Süyen Güldal Güleç
Published: June 2023

Inflammation and neuronal loss are key factors in the pathophysiology of epilepsy. It is known that activation of Dual Leucine Zipper Kinase (DLK) in chronic neurodegenerative diseases causes neuron death and axon degeneration through apoptotic pathways. Genetic deletion of DLK (dual leucine zipper kinase, MAP3K12) or pharmacological inhibition by GNE-3511 or GNE-8505 was found to have benefits in mouse models of Alzheimer’s and ALS; however, there is no previous study that uses DLK inhibitors in epilepsy models. Therefore, the aim of our study is to suppress the DLK/JNK pathway with the DLK inhibitor GNE-3511 in the temporal lobe epilepsy model induced by pilocarpine and to determine the effect of this inhibition on cognitive and behavioural defects, as well as epileptogenesis. Open field, elevated plus maze, and Morris water maze tests were used to assess locomotor activity, anxiety and learning and memory, respectively. Following decapitation the hippocampi were removed and, histopathological and biochemical analyses were performed. Both treatment groups had less anxiety and locomotor activity as well as decreased impairment in memory and learning performance compared to SE group (p<0.001). Both doses of GNE-3511 prevented the spontaneous recurrent seizures in a dose dependent manner with respect to the SE group (p<0.01 and p<0.001, respectively). Histological examination of the hippocampus revealed a neuroprotective effect of both doses of treatment in the CA1 area and dentate gyrus (p<0.0001). Thus, DLK inhibitor GNE-3511 was found to be effective in preventing epileptogenesis, neuronal loss and cognitive and behavioural deficits due to pilocarpine induced SE.
Experimental testing of two urban stressors on freshwater biofilms
Authors: VRBA Romain , LAVOIE Isabelle , CREUSOT Nicolas , EON Mélissa , MILLAN-NAVARRO Débora , FEURTET-MAZEL Agnès , MAZZELLA Nicolas , MOREIRA Aurélie , PLANAS Dolors , MORIN Soizic
Published: June 2023

Aquatic ecosystems and their communities are exposed to numerous stressors of various natures (chemical and physical), which impacts are often poorly documented. In urban areas, the use of biocides such as dodecyldimethylbenzylammonium chloride (DDBAC) and their subsequent release in wastewater result in their transfer to urban aquatic ecosystems. DDBAC is known to be toxic to most aquatic organisms. Artificial light at night (ALAN) is another stressor that is increasing globally, especially in urban areas. ALAN may have a negative impact on photosynthetic cycles of periphytic biofilms, which in turn may result in changes in their metabolic functioning. Moreover, studies suggest that exposure to artificial light could increase the biocidal effect of DDBAC on biofilms. The present study investigates the individual and combined effects of DDBAC and/or ALAN on the functioning and structure of photosynthetic biofilms. We exposed biofilms in artificial channels to a nominal concentration of 30 mg.L-1of DDBAC and/or ALAN for 10 days. ALAN modified DDBAC exposure, decreasing concentrations in the water but not accumulation in biofilms. DDBAC had negative impacts on biofilm functioning and structure. Photosynthetic activity was inhibited by > 90% after 2 days of exposure, compared to the controls, and did not recover over the duration of the experiment. Biofilm composition was also impacted, with a marked decrease in green algae and the disappearance of microfauna under DDBAC exposure. The integrity of algal cells was compromised where DDBAC exposure altered the chloroplasts and chlorophyll content. Impacts on autotrophs were also observed through a shift in lipid profiles, in particular a strong decrease in glycolipid content was noted. We found no significant interactive effect of ALAN and DDBAC on the studied endpoints.

Graphical abstract
Virtual tissue microstructure reconstruction across species using generative deep learning
Authors: Bettancourt Nicolás , Pérez Cristian , Candia Valeria , Guevara Pamela , Kalaidzidis Yannis , Zerial Marino , Segovia-Miranda Fabián , Morales-Navarrete Hernán
Published: June 2023

Analyzing tissue microstructure is essential for understanding complex biological systems in different species. Tissue functions largely depend on their intrinsic tissue architecture. Therefore, studying the three-dimensional (3D) microstructure of tissues, such as the liver, is particularly fascinating due to its conserved essential roles in metabolic processes and detoxification. Here, we present TiMiGNet, a novel deep learning approach for virtual 3D tissue microstructure reconstruction using Generative Adversarial Networks (GANs) and fluorescence microscopy. TiMiGNet overcomes challenges such as poor antibody penetration and time-intensive procedures by generating accurate, high-resolution predictions of tissue components across large volumes without the need of paired images as input. We applied TiMiGNet to analyze tissue microstructure in mouse and human liver tissue. TiMiGNet shows high performance in predicting structures like bile canaliculi, sinusoids, and Kupffer cell shapes from actin meshwork images. Remarkably, using TiMiGNet we were able to computationally reconstruct tissue structures that cannot be directly imaged due experimental limitations in deep dense tissues, a significant advancement in deep tissue imaging. Our open-source virtual prediction tool facilitates accessible and efficient multi-species tissue microstructure analysis, accommodating researchers with varying expertise levels. TiMiGNet’s simplicity and independence from paired images make it a versatile asset. Overall, our method represents a powerful and efficient approach for studying tissue microstructure, with far-reaching applications in diverse biological contexts and species.
Quantitative comparison of a mobile, tablet-based and two stationary, video-based eye-trackers
Authors: König Aylin , Bremmer Frank , Dowiasch Stefan
Published: June 2023

Abstract

The analysis of eye-movements is a non-invasive, reliable and fast method to detect and quantify brain (dys-)functions. Here, we investigated the performance of two novel eye-trackers: the Thomas-Oculus-Motus-research mobile (TOM-rm) and the TOM-research stationary (TOM-rs) and compared it with the performance of a well-established video-based eye-tracker, i.e., the EyeLink 1000 (EL). The TOM-rm is a fully integrated, tablet-based mobile device that presents visual stimuli and records head-unrestrained eye-movements at 30Hz without additional infrared (IR) illumination. The TOM-rs is a stationary, video-based eye-tracker that records eye-movements at either high spatial or high temporal resolution. We compared the performance of all three eye-trackers in two different behavioral tasks: pro– and anti-saccade and free viewing. We collected data from human subjects while running all three eye-tracking devices in parallel. Parameters requiring a high spatial or temporal resolution (e.g., saccade latency or gain), as derived from the data, differed significantly between the EL and the TOM-rm in the pro– and anti-saccade task. In the free viewing task, larger noise and the lower frame rate of the TOM-rm caused deviations of the results with respect to the EL. Differences between results derived from the TOM-rs and the EL were most likely due to experimental conditions, which could not be optimized for both systems simultaneously. We conclude that the TOM-rm can be used for measuring eye-movements reliably at comparably low spatial and temporal resolution. The TOM-rs, on the other hand, can provide high-resolution oculomotor data at least on a par with an established reference system.
In situ neutron diffraction to investigate the solid-state synthesis of Ni-rich cathode materials
Authors: Goonetilleke Damian , Suard Emmanuelle , Bergner Benjamin , Janek Jürgen , Brezesinski Torsten , Bianchini Matteo
Published: June 2023

Studying chemical reactions in real time can provide unparalleled insight into the evolution of intermediate species and can provide guidance to optimize the reaction conditions. For solid-state synthesis reactions, powder diffraction has been demonstrated as an effective tool for resolving the structural evolution taking place upon heating. The synthesis of layered Ni-rich transition-metal oxides at a large scale (grams to kilograms) is highly relevant as these materials are commonly employed as cathodes for Li-ion batteries. In this work, in situ neutron diffraction was used to monitor the reaction mechanism during the high-temperature synthesis of Ni-rich cathode materials with a varying ratio of Ni:Mn from industrially relevant hydroxide precursors. Rietveld refinement was further used to model the observed phase evolution during synthesis and compare the behaviour of the materials as a function of temperature. The results presented herein confirm the suitability of in situ neutron diffraction to investigate the synthesis of batches of several grams of electrode materials with well-controlled stoichiometry. Furthermore, monitoring the structural evolution of the mixtures with varying Ni:Mn content in real time reveals a delayed onset of lithiation as the Mn content is increased, necessitating the use of higher annealing temperatures to achieve layering.
Towards jointin situdetermination of pressure and temperature in the large volume press exclusively from X-ray diffraction
Authors: Farla Robert
Published: June 2023

Since high-pressure devices have been used at synchrotron facilities, accurate determination of pressure and temperature in the sample has been a crucial objective, particularly for experiments that simulate the Earth's interior. However, in some cases using a thermocouple may have a high likelihood of failure or is incompatible with a high-pressure assembly. To address these challenges and similar issues, we aim to expand a previously proposed solution: to jointly estimate pressure and temperature (PT) throughin situX-ray diffraction, to cover a wider range of internalPTcalibrants tested over largerPTranges. A modifiable Python-based software is offered to quickly obtain results. To achieve these aims,in sitularge volume press experiments are performed on pellets of intimately mixed powders of a halide (NaCl, KCl, KBr, CsCl) or MgO and a metal (Pt, Re, Mo, W, Ni) in the pressure range 3–11 GPa and temperature range 300–1800 K. Although the pressure range was chosen for practical reasons, it also covers an equally important depth range in the Earth (down to 350 km) for geoscience studies. A thermocouple was used to validate thePTconditions in the cell assemblies. The key results show that choosing the appropriate calibrant materials and using a jointPTestimation can yield surprisingly small uncertainties (i.e.<±0.1 GPa and <±50 K). This development is expected to benefit current and future research at extreme conditions, as other materials with high compressibility or high thermal pressure, stable over largePTranges, may be discovered and used asPTcalibrants.
Multi-criteria decision-making methods: application in humanitarian operations
Authors: Nain Aniruddh , Jain Deepika , Trivedi Ashish
Published: June 2023

Purpose

This paper aims to examine and compare extant literature on the application of multi-criteria decision-making (MCDM) techniques in humanitarian operations (HOs) and humanitarian supply chains (HSCs). It identifies the status of existing research in the field and suggests a roadmap for academicians to undertake further research in HOs and HSCs using MCDM techniques.

Design/methodology/approach

The paper systematically reviews the research on MCDM applications in HO and HSC domains from 2011 to 2022, as the field gained traction post-2004 Indian Ocean Tsunami phenomena. In the first step, an exhaustive search for journal articles is conducted using 48 keyword searches. To ensure quality, only those articles published in journals featuring in the first quartile of the Scimago Journal Ranking were selected. A total of 103 peer-reviewed articles were selected for the review and then segregated into different categories for analysis.

Findings

The paper highlights insufficient high-quality research in HOs that utilizes MCDM methods. It proposes a roadmap for scholars to enhance the research outcomes by advocating adopting mixed methods. The analysis of various studies revealed a notable absence of contextual reference. A contextual mind map specific to HOs has been developed to assist future research endeavors. This resource can guide researchers in determining the appropriate contextual framework for their studies.

Practical implications

This paper will help practitioners understand the research carried out in the field. The aspiring researchers will identify the gap in the extant research and work on future research directions.

Originality/value

To the best of the authors’ knowledge, this is the first literature review on applying MCDM in HOs and HSCs. It summarises the current status and proposes future research directions.
Investigating the link between socially-responsible HRM and organizational sustainability performance – an HRD perspective
Authors: Nakra Neelam , Kashyap Vaneet
Published: June 2023

Purpose

The paper aims to investigate the impact of socially-responsible human resource (SR-HR) practices on organizational sustainability performance (OSP) in Indian business organizations that are mandated to publish business sustainability and responsibility reporting.

Design/methodology/approach

Data were obtained from 620 working professionals employed in the organizations listed on National Stock Exchange in India. The proposed hypotheses were tested by deploying the statistical technique of multiple regression analysis using SPSS Version-21.

Findings

The results demonstrated that overall, SR-HR practices impact OSP. More precisely, all the dimensions of SR practices are positively associated with the organization’s financial performance, environmental performance and social performance (SP). There was a relatively higher significant impact of legal-oriented human resource management (HRM) on organizational economic and ecological performance. However, in the case of SP, a substantial effect of employee-oriented HRM was found.

Practical implications

Study findings encourage HR practitioners to invest in SR-HR practices to build and strengthen employees’ abilities and contributing to sustainability goals.

Originality/value

This study is one of the few studies conducted in the Indian context that highlights the relevance of the convergence of HRM, human resource development and corporate social responsibility to realize sustainability goals.
Understanding how indoor environmental classroom conditions influence academic performance in higher education
Authors: Brink Henk W. , Lechner Stefan C.M. , Loomans Marcel G.L.C. , Mobach Mark P. , Kort Helianthe S.M.
Published: June 2023

Purpose

This study aims to qualitatively examine the relationship between the indoor environmental quality (IEQ), lecturers’ and students’ perceived internal responses and academic performance.

Design/methodology/approach

To capture user experiences with the IEQ in classrooms, semi-structured interviews with 11 lecturers and three focus group discussions with 24 students were conducted, transcribed, coded and analyzed using direct content analysis.

Findings

The findings show that lecturers and students experience poor thermal, lighting, acoustic and indoor air quality (IAQ) conditions that may influence their ability to teach and learn. Maintaining acceptable thermal and IAQ conditions was difficult for lecturers, as opening windows or doors caused noise disturbances. In uncomfortable conditions, lecturers may decide to give a break earlier or shorten a lecture. When students experienced discomfort, it may affect their ability to concentrate, their emotional status and their quality of learning.

Research limitations/implications

The findings originate from a relatively small sample, which might have limited the number and variety of identified associations between environment and users.

Practical implications

Maintaining acceptable air and thermal conditions will mitigate the need to open windows and doors. Keeping doors and windows closed will prevent noise disturbances and related distractions. This will support the quality of learning in classrooms. This study reveals the end users’ perspectives and preferences, which can inspire designers of new school buildings in higher education.

Originality/value

This study emphasizes the importance of creating and maintaining optimal IEQ conditions to support the quality of teaching and learning. These conditions are particularly relevant when classroom occupancy rates are high or outdoor conditions are unfavourable.
Data literacy training needs of researchers at South African universities
Authors: Moyo Mathew , Bangani Siviwe
Published: June 2023

Purpose

The aim of this study was to determine data literacy (DL) training needs of researchers at South African public universities. The outcome of this study would assist librarians and researchers in developing a DL training programme which addressed identified needs.

Design/methodology/approach

A survey research method was used to gather data from researchers at these universities by convenience. Online questionnaires were distributed to public universities through library directors for further distribution to researchers.

Findings

The results indicate low levels of DL training at the respondent South African public universities with most researchers indicating that they had not received any formal training on DL. A few researchers indicated that they would welcome DL training.

Research limitations/implications

This study was exploratory in nature and data was received from eight universities, which is not representative of all the 26 public universities in South Africa. Nonetheless, the low DL confirmed by the majority in the realised sample is indicative of the need to further investigate the subject.

Practical implications

Librarians and research support personnel should collaborate on the development of DL training courses, workshops and materials used by researchers at institutions of higher learning to enhance DLs on campus.

Originality/value

This study may be novel in South Africa in investigating the DL training needs of researchers at several universities and contributes to the growing body of literature on research data management