bluuebunny/crossref_metadata_2025 huggingface dataset:
Intracranial Relapse in Pediatric Sarcoma
Authors: Smith Danielle E. , Hamby Tyler , Heym Kenneth , Mohamed Ashraf , Vallance Kelly L. , Ray Anish
Published: August 2023

Advances in local control techniques, chemotherapy regimens, and imaging modalities have led to improvements in both morbidity and mortality in pediatric sarcoma patients. However, approximately one-third of patients develop disease relapse and intracranial metastasis was considered rare. The incidence of sarcoma brain metastasis is thought to have increased and is associated with grim outcomes. This was a retrospective study of 3 deidentified patient charts illustrating the possibility of the central nervous system as a potential site for pediatric sarcoma relapse and investigate the patterns of such relapses. We note this is the first report of infantile fibrosarcoma brain metastasis and a rare report of sarcoma lymph node metastasis. In addition, each patient was treated with targeted therapies, including entrectinib, Ruxolitnib, and pazopanib. Caregivers in cases 2 and 3 reported new-onset neurological manifestations before identification of new brain metastasis, indicating a lag in detection of new intracranial relapse in asymptomatic sarcoma patients. We suggest implementing a brief review of systems screening tool focused on concerning neurological manifestations to screen for new brain metastasis.
Clinic Heterogeneity and Management of Pediatric Patients With Germline RET Proto-oncogene Mutation: Single-center Experience
Authors: Şıklar Zeynep , Kontbay Tuğba , Dincaslan Handan , Ünal Emel , Berberoglu Merih
Published: August 2023

Inherited forms of medullary thyroid carcinoma (MTC) can cause serious problems in diagnosis and follow-up. Family screening is performed, and prophylactic thyroidectomy at an appropriate age can be life-saving. This study aimed to investigate the diagnostic, clinical, laboratory characteristics, and treatment methods of cases with rearranged during transfection (RET) mutation in the childhood age group. Patients diagnosed with hereditary MTC and patients who were evaluated by detecting MTC and/or RET mutations in their families were included in this study. Nine cases from 6 families were included in the study. Seven patients were evaluated as a result of screening, whereas 2 patients, one of whom was MEN2B, were symptomatic. Prophylactic thyroidectomy was performed in 7 cases. Medullary microcarcinoma was found in all, and additional papillary thyroid carcinoma in one. An inoperable tumor was detected in one patient, and sorafenib treatment was applied. A very heterogeneous clinical presentation can be seen in a group of pediatric patients with RET mutation. In rare RET mutations, the genotype-phenotype relationship is still unclear, and different clinical pictures can be seen. Although prophylactic thyroidectomy is life-saving, it can cause iatrogenic hypothyroidism and hypoparathyroidism. Concomitant papillary microcarcinomas may occur in very young children with germline RET mutation.
Prevention and treatment of C. difficile in cancer patients
Authors: Puerta-Alcalde Pedro , Garcia-Vidal Carolina , Soriano Alex
Published: August 2023

Purpose of review

We provide an update on the recent literature on Clostridioides difficile infection (CDI) in cancer patients.

Recent findings

Distinguishing between colonization and infection remains challenging in cancer patients. Many patients with negative toxin analysis are still treated for CDI, and some meet criteria for severe cases. The incidence of CDI is high in cancer patients, especially those with haematological malignancies. Disruption of the gut microbiome due to antibiotic consumption, chemotherapy and radiotherapy is the primary factor contributing to CDI development. The severity of CDI in cancer patients is often unclear due to the absence of well-defined severity criteria. Certain microbiome species predominance and specific ribotypes have been associated with worse outcomes. Whole genome sequencing could be helpful for differentiating recurrence from reinfection and exploring potential nosocomial transmission. While certain new drugs such as fidaxomicin or bezlotoxumab show promise, the optimal treatment and prevention strategies for CDI in cancer patients remain uncertain. Faecal microbiota transplantation (FMT) holds potential for reducing CDI recurrence rates.

Further studies are needed to provide robust recommendations for diagnosis, grading severity, and therapeutic management of CDI in cancer patients. Recurrences are particularly concerning due to subsequent exposition to CDI risk factors.
Association of Recipient APOL1 Kidney Risk Alleles With Kidney Transplant Outcomes
Authors: Roy Neil , Morales-Alvarez M. Catalina , Anis Karim H. , Goral Simin , Doria Cataldo , Kopp Jeffrey B. , Winkler Cheryl A. , Feng Rui , Rosas Sylvia E.
Published: August 2023

Background.

Kidney transplant survival in African American recipients is lower compared with non–African American transplant recipients. APOL1 risk alleles (RA) have been postulated as likely contributors. We examined the graft outcomes in kidney transplant recipients (KTRs) stratified by APOL1 RA status in a multicenter observational prospective study.

Methods.

The Renal Transplant Outcome Study recruited a cohort of incident KTRs at 3 transplant centers in the Philadelphia area from 1999–2004. KTRs were genotyped for APOL1 RA. Allograft and patient survival rates were compared by the presence and number of APOL1 RA.

Results.

Among 221 participants, approximately 43% carried 2 APOL1 RA. Recipients carrying 2 APOL1 RA demonstrated lower graft survival compared with recipients with only 1 or none of APOL1 RA at 1 y posttransplant, independently of other donor and recipient characteristics (adjusted hazard ratio 3.2 [95% confidence interval, 1.0-10.4], P = 0.05). There was no significant difference in overall survival or graft survival after 3 y posttransplantation. There was no difference in death by APOL1-risk status (P = 0.11).

Conclusions.

Recipients with 2 APOL1 high-risk alleles exhibited lower graft survival 1 y posttransplantation compared with recipients with only 1 or 0 APOL1 RA. Further research is required to study the combined role of the recipient and donor APOL1 genotypes in kidney transplantation.
Effects of Amantadine Sulfate on Motor Impairment and Execution of Motor Sequences in Patients With Parkinson Disease
Authors: Müller Thomas , Kuhn Wilfried
Published: August 2023

Background

Intravenous application of amantadine sulfate induces a rapid improvement of motor behavior in patients with Parkinson disease.

Objectives

To determine efficacy of daily infusion of 200 mg amantadine sulfate on scored motor symptoms and performance of standardized movement sequences with components of low and high cognitive efforts.

Methods

Thirty-one participants received infusions of amantadine sulfate in addition to their previous stable drug regimens on 3 consecutive days. Motor symptoms of upper limbs were determined with selected items of the part motor examination of the Unified Parkinson's Disease Rating Scale. Instrumental tasks were executed under cued conditions before and after the infusions.

Results

Scored motor symptoms and components with a need for a higher cognitive load became better. Performance of motion series, characterized by an automated set with low cognitive efforts, did not improve.

Conclusion

Our trial outcomes suggest that the amantadine has a positive impact on cognitive abilities, drive, and vigilance, all of which are necessary for carrying out of higher brain functions.
Pangenomic analyses of antibiotic-resistant Campylobacter jejuni reveal unique lineage distributions and epidemiological associations
Authors: Rodrigues Jose A. , Blankenship Heather M. , Cha Wonhee , Mukherjee Sanjana , Sloup Rebekah E. , Rudrik James T. , Soehnlen Marty , Manning Shannon D.
Published: August 2023

Application of whole-genome sequencing (WGS) to characterize foodborne pathogens has advanced our understanding of circulating genotypes and evolutionary relationships. Herein, we used WGS to investigate the genomic epidemiology of

Campylobacter jejuni

, a leading cause of foodborne disease. Among the 214 strains recovered from patients with gastroenteritis in Michigan, USA, 85 multilocus sequence types (STs) were represented and 135 (63.1 %) were phenotypically resistant to at least one antibiotic. Horizontally acquired antibiotic resistance genes were detected in 128 (59.8 %) strains and the genotypic resistance profiles were mostly consistent with the phenotypes. Core-gene phylogenetic reconstruction identified three sequence clusters that varied in frequency, while a neighbour-net tree detected significant recombination among the genotypes (pairwise homoplasy index P<0.01). Epidemiological analyses revealed that travel was a significant contributor to pangenomic and ST diversity of

C. jejuni

, while some lineages were unique to rural counties and more commonly possessed clinically important resistance determinants. Variation was also observed in the frequency of lineages over the 4 year period with chicken and cattle specialists predominating. Altogether, these findings highlight the importance of geographically specific factors, recombination and horizontal gene transfer in shaping the population structure of

C. jejuni

. They also illustrate the usefulness of WGS data for predicting antibiotic susceptibilities and surveillance, which are important for guiding treatment and prevention strategies.
Microbial Primer: An introduction to biofilms – what they are, why they form and their impact on built and natural environments
Authors: Bamford Natalie C. , MacPhee Cait E. , Stanley-Wall Nicola R.
Published: August 2023

Biofilms are complex communities of microbes that are bound by an extracellular macromolecular matrix produced by the residents. Biofilms are the predominant form of microbial life in the natural environment and although they are the leading cause of chronic infections, they are equally deeply connected to our ability to bioremediate waste and toxic materials. Here we highlight the emergent properties of biofilm communities and explore notable biofilms before concluding by providing examples of their major impact on our health and both natural and built environments.
pyCapsid: Identifying dominant dynamics and quasi-rigid mechanical units in protein shells
Authors: Brown Colin , Agarwal Anuradha , Luque Antoni
Published: August 2023

Structured Abstract

pyCapsid is a Python package developed to facilitate the characterization of the dynamics and mechanical units of protein shells and other protein complexes. The package was developed in response to the rapid increase of high-resolution structures, particularly capsids of viruses, requiring multiscale biophysical analyses. Given a protein shell, pyCapsid generates the collective vibrations of its amino-acid residues, identifies quasi-rigid mechanical regions, and maps the results back to the input proteins for interpretation. pyCapsid summarizes the main results in a report that includes publication-quality figures.

Availability and Implementation

pyCapsid’s source code is available under MIT License on GitHub (https://github.com/luquelab/pycapsid). It is compatible with Python 3.8-3.10 and has been deployed in two leading Python package-management systems, PIP (https://pypi.org/project/pyCapsid/) and Conda (https://anaconda.org/luque_lab/pycapsid). Installation instructions and tutorials are available in the GitHub Page-style online documentation (https://luquelab.github.io/pyCapsid). Additionally, a cloud-based implementation of pyCapsid is available as a Google Colab notebook (https://colab.research.google.com/github/luquelab/pyCapsid/blob/main/notebooks/pyCapsid_colab_notebook.ipynb). pyCapsid Colab does not require installation and generates the same report and outputs as the installable version. Users can post issues regarding pyCapsid in the GitHub repository (https://github.com/luquelab/pyCapsid/issues).
Saponin Nanoparticle Adjuvants Incorporating Toll-Like Receptor Agonists Drive Distinct Immune Signatures and Potent Vaccine Responses
Authors: Ou Ben S. , Baillet Julie , Filsinger Interrante Maria V. , Adamska Julia Z. , Zhou Xueting , Saouaf Olivia M. , Yan Jerry , Klich John H. , Jons Carolyn K. , Meany Emily L. , Valdez Adian S. , Carter Lauren , Pulendran Bali , King Neil P. , Appel Eric A.
Published: August 2023

Over the past few decades, the development of potent and safe immune-activating adjuvant technologies has become the heart of intensive research in the constant fight against highly mutative and immune evasive viruses such as influenza, SARS-CoV-2, and HIV. Herein, we developed a highly modular saponin-based nanoparticle platform incorporating toll-like receptor agonists (TLRas) including TLR1/2a, TLR4a, TLR7/8a adjuvants and their mixtures. These various TLRa-SNP adjuvant constructs induce unique acute cytokine and immune-signaling profiles, leading to specific Th-responses that could be of interest depending on the target disease for prevention. In a murine vaccine study, the adjuvants greatly improved the potency, durability, breadth, and neutralization of both COVID-19 and HIV vaccine candidates, suggesting the potential broad application of these adjuvant constructs to a range of different antigens. Overall, this work demonstrates a modular TLRa-SNP adjuvant platform which could improve the design of vaccines for and dramatically impact modern vaccine development.

Teaser

Saponin-TLRa nanoadjuvants provide distinct immune signatures and drive potent, broad, durable COVID-19 and HIV vaccine responses.
Multimodal Molecular Imaging Reveals Tissue-Based T Cell Activation and Viral RNA Persistence for Up to 2 Years Following COVID-19
Authors: Peluso Michael J. , Ryder Dylan , Flavell Robert , Wang Yingbing , Levi Jelena , LaFranchi Brian H. , Deveau Tyler-Marie , Buck Amanda M. , Munter Sadie E. , Asare Kofi A. , Aslam Maya , Koch Wally , Szabo Gyula , Hoh Rebecca , Deswal Monika , Rodriguez Antonio , Buitrago Melissa , Tai Viva , Shrestha Uttam , Lu Scott , Goldberg Sarah A. , Dalhuisen Thomas , Durstenfeld Matthew S. , Hsue Priscilla Y. , Kelly J. Daniel , Kumar Nitasha , Martin Jeffrey N. , Gambir Aruna , Somsouk Ma , Seo Youngho , Deeks Steven G. , Laszik Zoltan G. , VanBrocklin Henry F. , Henrich Timothy J.
Published: August 2023

The etiologic mechanisms of post-acute medical morbidities and unexplained symptoms (Long COVID) following SARS-CoV-2 infection are incompletely understood. There is growing evidence that viral persistence and immune dysregulation may play a major role. We performed whole-body positron emission tomography (PET) imaging in a cohort of 24 participants at time points ranging from 27 to 910 days following acute SARS-CoV-2 infection using a novel radiopharmaceutical agent, [18F]F-AraG, a highly selective tracer that allows for anatomical quantitation of activated T lymphocytes. Tracer uptake in the post-acute COVID group, which included those with and without Long COVID symptoms, was significantly higher compared to pre-pandemic controls in many anatomical regions, including the brain stem, spinal cord, bone marrow, nasopharyngeal and hilar lymphoid tissue, cardiopulmonary tissues, and gut wall. Although T cell activation tended to be higher in participants imaged closer to the time of the acute illness, tracer uptake was increased in participants imaged up to 2.5 years following SARS-CoV-2 infection. We observed that T cell activation in spinal cord and gut wall was associated with the presence of Long COVID symptoms. In addition, tracer uptake in lung tissue was higher in those with persistent pulmonary symptoms. Notably, increased T cell activation in these tissues was also observed in many individuals without Long COVID. Given the high [18F]F-AraG uptake detected in the gut, we obtained colorectal tissue forin situhybridization SARS-CoV-2 RNA and immunohistochemical studies in a subset of participants with Long COVID symptoms. We identified cellular SARS-CoV-2 RNA in rectosigmoid lamina propria tissue in all these participants, ranging from 158 to 676 days following initial COVID-19 illness, suggesting that tissue viral persistence could be associated with long-term immunological perturbations.
Assessing feasibility and risk to translate, de-identify and summarize medical reports using deep learning
Authors: Gauthier Lucas W. , Willems Marjolaine , Chatron Nicolas , Cenni Camille , Meyer Pierre , Ruault Valentin , Wells Constance , Sabbagh Quentin , Genevieve David , Yauy Kevin
Published: August 2023

Background

Precision medicine requires accurate phenotyping and data sharing, particularly for rare diseases. However, sharing medical reports across language barriers is challenging. Alternatively, inconsistent and incomplete clinical summary provided by physicians using Human Phenotype Ontology (HPO) can lead to a loss of clinical information.

Methods

To assess feasibility and risk of using deep learning methods to translate, de-identify and summarize medical reports, we developed an open-source deep learning multi-language software in line with health data privacy. We conducted a non-inferiority clinical trial using deep learning methods to de-identify protected health information (PHI) targeting a minimum sensitivity of 90% and specificity of 75%, and summarize non-English medical reports in HPO format, aiming a sensitivity of 75% and specificity of 90%.

Results

From March to April 2023, we evaluated 50 non-English medical reports from 8 physicians and 12 different groups of diseases, which included neurodevelopmental disorders, congenital disorders, fetal pathology and oncology. Reports contain in median 15 PHI and 7 HPO terms. Deep learning method achieved a sensitivity of 99% and a specificity of 87% in de-identification, and a sensitivity of 78% and a specificity of 92% in summarizing medical reports, reporting an average number of 6.6 HPO terms per report, which is equivalent to the number of HPO terms provided usually by physicians in databases (6.8 in PhenoDB).

Conclusions

De-identification and summarization of non-English medical reports using deep learning methods reports non-inferior performance, providing insights on AI usage to facilitate precision medicine.

Graphical abstract

Illustration of the non-inferiority trial for de-identification and summarization of non-english medical reports and main statistical performances.
Large language model-based information extraction from free-text radiology reports: a scoping review protocol
Authors: Reichenpfader Daniel , Müller Henning , Denecke Kerstin
Published: August 2023

Introduction

Radiological imaging is one of the most frequently performed diagnostic tests worldwide. The free text contained in radiology reports is currently only rarely utilized for secondary use, including research and predictive analysis. However, this data might be made available by means of information extraction (IE), based on natural language processing (NLP). Recently, a new approach to NLP, large language models (LLMs), has gained momentum and continues to improve performance. The objective of this scoping review is to show the state of research regarding IE from free-text radiology reports based on LLMs, to investigate applied methods, and to guide future research by showing open challenges and limitations of current approaches. To our knowledge, no systematic nor scoping review of IE of radiology reports, based on LLMs, has been conducted yet. Existing publications are outdated and do not comprise LLM-based models.

Methods and analysis

This protocol is designed based on the JBI manual for evidence synthesis, chapter 11.2: “Development of a scoping review protocol”. Inclusion criteria and a search strategy comprising four databases (PubMed, IEEE Xplore, Web of Science Core Collection, ACM Digital Library) are defined. Furthermore, we describe the screening process, data charting, analysis and presentation of extracted data.

Ethics and dissemination

This protocol describes the methodology of a scoping literature review and does not comprise research on or with humans, animals or their data. Therefore, no ethical approval is required. After the publication of this protocol and the conduct of the review, its results are going to be published in an open access journal dedicated to biomedical informatics/ digital health.

Strengths and limitations of this study

This scoping review protocol strictly adheres to standardized guidelines for scoping review conduction, including JBI Manual for Evidence Synthesis and the PRISMA-ScR guideline.

The search strategy comprises four databases: PubMed, IEEE Xplore, Web of Science Core Collection, and ACM Digital Library.

This scoping review will close the knowledge gap present in the field of information extraction from radiology reports caused by the recent rapid technical process.

According to the nature of a scoping review, identified sources of evidence are not critically appraised.

The results of the scoping review will serve as a basis for defining further research directions regarding information extraction from radiology reports.
Plasma protein biomarkers distinguish Multisystem Inflammatory Syndrome in Children (MIS-C) from other pediatric infectious and inflammatory diseases
Authors: Yeoh Sophya , Estrada-Rivadeneyra Diego , Jackson Heather , Keren Ilana , Galassini Rachel , Cooray Samantha , Shah Priyen , Agyeman Philipp , Basmaci Romain , Carrol Enitan , Emonts Marieke , Fink Colin , Kuijpers Taco , Torres Federico Martinon- , Mommert-Tripon Marine , Paulus Stephane , Pokorn Marko , Rojo Pablo , Romani Lorenza , Schlapbach Luregn , Schweintzger Nina , Shen Ching-Fen , Tsolia Maria , Usuf Effua , Van der Flier Michiel , Vermont Clementien , Both Ulrich Von , Yeung Shunmay , Zavadska Dace , Coin Lachlan , Cunnington Aubrey , Herberg Jethro , Levin Michael , Kaforou Myrsini , Hamilton Shea ,   UK KD Genetics Consortia
Published: August 2023

Background

Multisystem inflammatory syndrome in children (MIS-C) is a rare but serious hyperinflammatory complication following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The mechanisms underpinning the pathophysiology of MIS-C are poorly understood. Moreover, clinically distinguishing MIS-C from other childhood infectious and inflammatory conditions, such as Kawasaki Disease (KD) or severe bacterial and viral infections is challenging due to overlapping clinical and laboratory features. We aimed to determine a set of plasma protein biomarkers that could discriminate MIS-C from those other diseases.

Methods

Seven candidate protein biomarkers for MIS-C were selected based on literature and from whole blood RNA-Sequencing data from patients with MIS-C and other diseases. Plasma concentrations of ARG1, CCL20, CD163, CORIN, CXCL9, PCSK9 and ADAMTS2 were quantified in MIS-C (n=22), KD (n=23), definite bacterial (DB; n=28) and viral (DV, n=27) disease, and healthy controls (n=8). Logistic regression models were used to determine the discriminatory ability of individual proteins and protein combinations to identify MIS-C, and association with severity of illness.

Results

Plasma levels of CD163, CXCL9, and PCSK9 were significantly elevated in MIS-C with a combined AUC of 86% (95% CI: 76.8%-95.1%) for discriminating MIS-C from other childhood diseases. Lower ARG1 and CORIN plasma levels were significantly associated with severe MIS-C cases requiring oxygen, inotropes or with shock.

Conclusion

Our findings demonstrate the feasibility of a host protein biomarker signature for MIS-C and may provide new insight into its pathophysiology.
Population Pharmacokinetics and Target Attainment Analysis of Vancomycin after Intermittent Dosing in Adults with Cystic Fibrosis
Authors: Yellepeddi Venkata K. , Lindley Bryn , Radetich Emi , Kumar Shaun , Bhakta Zubin , Leclair Laurie , Parrot Madison , Young David C.
Published: August 2023

Vancomycin is the first-line agent to treat pulmonary infections caused by methicillin-resistantStaphylococcus aureus(MRSA) in people with cystic fibrosis (PwCF). However, there is no consensus on vancomycin dosing in this population among health institutions, and there is large variability in dosing regimens across the United States. In this study, we characterized the pharmacokinetics (PK) of vancomycin in PwCF using a population PK approach. The clinical PK data to develop the population PK model was obtained from vancomycin therapeutic monitoring data from PwCF undergoing treatment for infections due to MRSA. The population PK model was then used to perform comprehensive Monte Carlo simulations to evaluate the probability of target attainment (PTA) of 12 different dosing scenarios. The area under the curve to minimum inhibitory concentration ratio (AUC/MIC) ≥ 400 mg*h/L was used as a target for PTA analysis. A total of 181 vancomycin plasma concentrations were included in the analysis. A onecompartment model with first-order elimination best described the data. Weight significantly influenced the vancomycin PK (p< 0.05). In the final model, clearance was estimated as 5.52 L/h/70 kg, and the volume of distribution was 31.5 L/70 kg. The PTA analysis showed that at lower MIC levels (MIC = 1), doses greater than and equal to 1000 mg every 8 hours and 1250 mg every 12 hours resulted in >90% PTA. The PTA results from this study may potentially inform the design of vancomycin dosing regimens to treat pulmonary infections due to MRSA in PwCF.
The changes in blood flow velocity in the internal jugular vein under conditions of variable intrapulmonic pressure and gravitational effect
Authors: Kasatkin Anton , Urakov Aleksandr , Kuvshinov Ivan , Zhulkov Nikita
Published: August 2023

Background

We explored the dynamics of changes in the blood flow velocity in the internal jugular vein (IJV) under conditions of changing intrapulmonary pressure and gravitational influence in healthy volunteers.

Methods

Color duplex ultrasonography of the right IJV was performed in 25 healthy volunteers of both genders. The dopplergram of the blood flow spectrum was recorded in the right IJV in the horizontal supine position of the participants, and 3 minutes after the volunteers had attained the new position due to the lifting the bed back section at the 30°. We recorded the maximum (Max) and minimum (Min) linear of blood flow velocity (cm/s). In each position, the measurements were carried out sequentially at positive end-expiratory pressure (PEEP) values of 0, 5, 10 cmH2O after 3 minutes by process of changing the level of PEEP. Quantitative data were presented as arithmetic mean (M), standard deviation (SD) and compared using the Wilcoxon rank-sum test.

Results

Our data demonstrated that negatively related influence of continuous positive airway pressure on IJV blood flow velocity: Max/Min 57.40±13.10/20.68±7.80 cm/s (PEEP 0 cmH2O), 39.00±18.80/14.63±4.90 (PEEP 5 cmH2O), 30.83±7.30/13.25±2.90 (PEEP 10 cmH2O). The blood flow velocity values are increased after 30° head elevation in PEEP 5 and 10 cmH2O in comparison to 0° values.

Conclusions

The constant positive airway pressure 5-10 cmH2O in a person in supine position decreasing blood flow velocity in IJV. The 30° head elevation eliminates this effect.
Magnitude of Psychological Distress among Medical and Non-medical Students during the Late Phase of COVID-19 Pandemic in West Bengal: A Cross-sectional Study
Authors: Das Udisa , Ganguly Arunima , Haldar Dibakar , Mukhopadhyay Asish
Published: August 2023

Background

COVID-19 led to drastic changes worldwide which has affected mental health especially, of the vulnerable student population.

Aim

This study aimed to assess psychological distress due to COVID-19 in students during the late phase of pandemic and to establish correlation of academic course, socio-demographics and knowledge-attitude-practices (KAP) with depression and anxiety. An online cross-sectional survey was conducted among medical and non-medical students in Kolkata, from March to April 2022.

Methods

A cross-sectional survey was done using purposive and snowball sampling methods. Survey questionnaire was circulated via Google forms through social media. It included Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, Fear of COVID-19 scale 2020, KAP regarding COVID-19 and socio-demographics. Data were analyzed using appropriate statistical methods with the Statistical Package for the Social Sciences (Version 22.0). P value of less than 0.05 was considered significant.

Results

Total of 442 responses were received. After excluding incomplete responses, the final sample comprised 219 medical and 202 non-medical students. Majority of the participants were male (58.67%). Overall prevalence of depression was 58.42% in non-MBBS and 81.73% in MBBS students. Whereas, the overall prevalence of anxiety was 50.99% in non-MBBS and 76.25% in MBBS students. MBBS participants had significantly better scores for knowledge and attitude (p=0.000 in both). Depression was higher in those with previous history of psychiatric illness (p=0.015). Anxiety was influenced by residence (p=0.003), mode of travel to college (p=0.002), history of relatives or friends affected by COVID-19 (p= 0.005).

Conclusion

Prevalence of depression and anxiety in college students, especially among medical students, was higher in present study mainly due to long-term indirect effects of the pandemic. This calls for employing student wellness activities and provision of better mental health services across colleges in India.

Key Messages

Depression and anxiety was observed to be higher especially among medical students. Previous history of psychiatric illness was found to be a correlate of depression. Anxiety was revealed to be influenced by residence, mode of travel to college, and history of family, friends or relatives affected by COVID-19.
Iron rescues glucose-mediated photosynthesis repression during lipid accumulation in the green algaChromochloris zofingiensis
Authors: Jeffers Tim L. , Purvine Samuel O. , Nicora Carrie D. , McCombs Ryan , Upadhyaya Shivani , Stroumza Adrien , Whang Ken , Gallaher Sean D. , Dohnalkova Alice , Merchant Sabeeha S. , Lipton Mary , Niyogi Krishna K. , Roth Melissa S.
Published: August 2023

Energy status and nutrients regulate photosynthetic protein expression. The unicellular green algaChromochloris zofingiensisswitches off photosynthesis in the presence of exogenous glucose (+Glc) in a process that depends on hexokinase (HXK1). Here, we show that this response requires that cells lack sufficient iron (−Fe). Cells grown in −Fe+Glc accumulate triacylglycerol (TAG) while losing photosynthesis and thylakoid membranes. However, cells with an iron supplement (+Fe+Glc) maintain photosynthesis and thylakoids while still accumulating TAG. Proteomic analysis shows that known photosynthetic proteins are most depleted in heterotrophy, alongside hundreds of uncharacterized, conserved proteins. Photosynthesis repression is associated with enzyme and transporter regulation that redirects iron resources to (a) respiratory instead of photosynthetic complexes and (b) a ferredoxin-dependent desaturase pathway supporting TAG accumulation rather than thylakoid lipid synthesis. Combining insights from diverse organisms from green algae to vascular plants, we show how iron and trophic constraints on metabolism aid gene discovery for photosynthesis and biofuel production.
Extrachromosomal Telomeres Derived from Excessive Strand Displacements
Authors: Lee Junyeop , Lee Jina , Sohn Eric J. , Taglialatela Angelo , O’Sullivan Roderick J. , Ciccia Alberto , Min Jaewon
Published: August 2023

Alternative Lengthening of Telomeres (ALT) is a telomere maintenance mechanism mediated by break-induced replication (BIR), evident in approximately 15% of human cancers. A characteristic feature of ALT cancers is the presence of C-circles, circular single-stranded telomeric DNAs composed of C-rich sequences. Despite the fact that extrachromosomal C-rich single-stranded DNAs (ssDNAs), unique to ALT cells, are considered potential precursors of C-circles, their generation process remains undefined. Here, we introduce a highly sensitive method to detect single stranded telomeric DNA, called 4SET (Strand-Specific Southern-blot for Single-stranded Extrachromosomal Telomeres) assay. Utilizing 4SET, we are able to capture C-rich single stranded DNAs that are near 200 to 1500 nucleotides in size. Both linear C-rich ssDNAs and C-circles are abundant in the fractions of cytoplasm and nucleoplasm, which supports the idea that linear C-rich ssDNA accumulation may indeed precede C-circle formation. We also found that C-rich ssDNAs originate during Okazaki fragment processing during lagging strand DNA synthesis. The generation of C-rich ssDNA requires CST-PP (CTC1/STN1/TEN1-PRIMASE-Polymerase alpha) complex-mediated priming of the C-strand DNA synthesis and subsequent excessive strand displacement of the C-rich strand mediated by the DNA Polymerase delta and the BLM helicase. Our work proposes a new model for the generation of C-rich ssDNAs and C-circles during ALT-mediated telomere elongation.
Dynamics of the adhesion complex of the human pathogensMycoplasma pneumoniae and Mycoplasma genitalium
Authors: Vizarraga David , Kawamoto Akihiro , Marcos-Silva Marina , Martín Jesús , Makino Fumiaki , Miyata Tomoko , Roel-Touris Jorge , Marcos Enrique , Pich Òscar Q. , Aparicio David , Fita Ignacio , Miyata Makoto , Piñol Jaume , Namba Keiichi , Kenri Tsuyoshi
Published: August 2023

Mycoplasma pneumoniaeis a bacterial wall-less human pathogen and the etiological agent of atypical pneumonia and tracheobronchitis in both adults and children.M. pneumoniaeinfectivity, gliding motility and adherence to host target respiratory epithelial cells are mediated by adhesin proteins P1 and P40/P90 forming a transmembrane complex that binds to sialylated oligosaccharides human cell ligands. Here we report the cryo-EM structure of P1 bound to the Fab fragment of monoclonal antibody P1/MCA4, which stops gliding and induces detachment of motileM. pneumoniaecells. On the contrary, polyclonal antibodies generated against the N-domain of P1 or against the whole ectodomain of P40/P90 have little or no effects on adhesion or motility. The epitope of P1/MCA4, centred on loop Thr1426-Asp1438 in the small C-terminal domain of P1, is inaccessible to antibodies in the “open” conformation of the adhesion complex, when ready for attachment to sialylated oligosaccharides. Mutations in the highly conserved Engelman motifs found in the transmembrane helix of P40/P90 also alter adhesion and motility. During the attachment/detachment cycle of the adhesion complex, the C-terminal domain of P1 experiences large conformational rearrangements that are hindered by the antibodies against the domain. Interfering with the gliding of mycoplasma cells suggests new ways to confrontM. pneumoniaeinfections.
Spatiotemporal resonance in mouse primary visual cortex
Authors: Gulbinaite Rasa , Nazari Mojtaba , Rule Michael E. , Bermudez-Contreras Edgar J. , Cohen Michael X , Mohajerani Majid H. , Heimel J. Alexander
Published: August 2023

Human primary visual cortex (V1) responds more strongly, or resonates, when exposed to ∼10, ∼15-20, ∼40-50 Hz rhythmic flickering light. Full-field flicker also evokes perception of hallucinatory geometric patterns, which mathematical models explain as standing-wave formations emerging from periodic forcing at resonant frequencies of the simulated neural network. However, empirical evidence for such flicker-induced standing waves in the visual cortex was missing. We recorded cortical responses to flicker in awake mice using high spatial resolution widefield imaging in combination with high temporal resolution glutamate-sensing fluorescent reporter (iGluSnFR). The temporal frequency tuning curves in the mouse V1 were similar to those observed in humans, showing a banded structure with multiple resonance peaks (8 Hz, 15 Hz, 33 Hz). Spatially, all flicker frequencies evoked responses in V1 corresponding to retinotopic stimulus location, but some evoked additional peaks. These flicker-induced cortical patterns displayed standing wave characteristics and matched linear wave equation solutions in an area restricted to the visual cortex. Taken together, the interaction of periodic traveling waves with cortical area boundaries leads to spatiotemporal activity patterns that may affect perception.
Sister chromatid cohesion halts DNA loop expansion
Authors: Bastié Nathalie , Chapard Christophe , Nejmi Sanae , Mboumba Henri , Thierry Agnès , Beckouët Frederic , Koszul Romain
Published: August 2023

Eukaryotic genomes are folded into DNA loops mediated by structural maintenance of chromosomes (SMC) complexes such as cohesin, condensin and Smc5/6. This organization regulates different DNA-related processes along the cell cycle such as transcription, recombination, segregation and DNA repair. During G2/M stages, SMC-mediated DNA loops coexist with cohesin complexes involved in sister chromatid cohesion (SCC). However, the articulation between the establishment of SCC and the formation of SMC-mediated DNA loops along the chromatin remains unknown. Here we show that SCC is indeed a barrier to cohesin-mediated DNA loop expansion in G2.
Axon onset remodeling in response to network activity in mouse cortical neurons
Authors: Lehmann Nadja , Markovic Stefan , Thome Christian , Engelhardt Maren
Published: August 2023

In certain subtypes of pyramidal neurons, axons originate from basal dendrites, resulting in an axon-carrying dendrite branch with unique functional characteristics (AcD cells). The number of AcD cells increases during development, however, it is so far unclear whether neurons remodel their axon emergence throughout their lifetime in response to changes in network activity. To test our hypothesis of such large-scale morphological plasticity, we utilizedin vitroandin vivostrategies in mouse primary somatosensory cortex to test whether network activity impacts axon onset. Based on data obtained by immunofluorescence, confocal microscopy and/or live-cell imaging, we show that neurons are indeed capable of changing the onset of their axon origin from somatic to dendritic andvice versawithin a few daysin vitroand that peripheral whisker manipulation and thus changes in sensory input drives large-scale morphological plasticityin vivo.
Exploiting O-GlcNAc transferase promiscuity to dissect site-specific O-GlcNAcylation
Authors: Mitchell Conor W. , Bartual Sergio Galan , Ferenbach Andrew T. , Scavenius Carsten , van Aalten Daan M. F.
Published: August 2023

Protein O-GlcNAcylation is an evolutionary conserved post-translational modification catalysed by the nucleocytoplasmic O-GlcNAc transferase (OGT) and reversed by O-GlcNAcase (OGA). How site-specific O-GlcNAcylation modulates a diverse range of cellular processes is largely unknown. A limiting factor in studying this is the lack of accessible techniques capable of producing homogeneously O-GlcNAcylated proteins, in high yield, forin vitrostudies. Here, we exploit the tolerance of OGT for cysteine instead of serine, combined with a co-expressed OGA to achieve site-specific, highly homogeneous mono-glycosylation. Applying this to DDX3X, TAB1, and CK2α, we demonstrate that near-homogeneous mono-S-GlcNAcylation of these proteins promotes DDX3X and CK2α solubility and enables production of mono-S-GlcNAcylated TAB1 crystals, albeit with limited diffraction. Taken together, this work provides a new approach for functional dissection of protein O-GlcNAcylation.
Regulation of inositol 5-phosphatase activity by the C2 domain of SHIP1 and SHIP2
Authors: Bradshaw William J , Kennedy Emma C , Moreira Tiago , Smith Luke A , Chalk Rod , Katis Vittorio L , Benesch Justin LP , Brennan Paul E , Murphy Emma J , Gileadi Opher
Published: August 2023

SHIP1, an inositol 5-phosphatase, plays a central role in cellular signalling. As such, it has been implicated in many conditions. Exploiting SHIP1 as a drug target will require structural knowledge and the design of selective small molecules. We have determined apo, and magnesium and phosphate-bound structures of the phosphatase and C2 domains of SHIP1. The C2 domains of SHIP1 and the related SHIP2 modulate the activity of the phosphatase domain. To understand the mechanism, we performed activity assays, hydrogen-deuterium-exchange mass spectrometry and molecular dynamics on SHIP1 and SHIP2. Our findings demonstrate that the influence of the C2 domain is more pronounced for SHIP2 than SHIP1. We determined 91 structures of SHIP1 with fragments bound, with some near the interface between the two domains. We performed a mass spectrometry screen and determined four structures with covalent fragments. These structures could act as starting points for the development of potent, selective probes.
Metabolomic changes associated with acquired resistance toIxodes scapularis
Authors: Cui Yingjun , Matias Jaqueline , Tang Xiaotian , Cibichakravarthy Balasubramanian , DePonte Kathleen , Wu Ming-Jie , Fikrig Erol
Published: August 2023

Guinea pigs repeatedly exposed toIxodes scapularisdevelop acquired resistance to the ticks (ATR). The molecular mechanisms of ATR have not been fully elucidated, and partially involve immune responses to proteins in tick saliva. In this study, we examined the metabolome of sera of guinea pigs during the development of ATR. Induction of components of the tyrosine metabolic pathway, including hydroxyphenyllactic acid (HPLA), were associated with ATR. We therefore administered HPLA to mice, an animal that does not develop ATR, and exposed the animals toI. scapularis. We also administered nitisinone, a known inhibitor of tyrosine degradation, to another group of mice. The mortality ofI. scapularisthat fed on mice given HPLA or nitisinone was 26% and 72% respectively, compared with 2% mortality among ticks that fed on control animals. These data indicate that metabolic changes that occur after tick bites contribute to ATR.
Allelic-Exchange Procedure inStaphylococcus aureus
Authors: Zeden Merve S. , Schuster Christopher F. , Gründling Angelika
Published: August 2023

This protocol continues a series of methods for the construction of an in-frame gene deletion inStaphylococcus aureusstrain RN4220. To this end, we describe in this protocol an allelic-exchange procedure forS. aureus. We have previously described how an allelic-exchange plasmid containing a desired gene deletion (in this case, pIMAY*-ΔtagO) can be constructed and isolated fromEscherichia coli, then introduced into electrocompetentS. aureuscells by electroporation. This plasmid contains a temperature-sensitive origin of replication, a counterselectable marker (pheS* gene) and confers chloramphenicol resistance toS. aureus. As a specific example, we present the construction of strain RN4220*ΔtagOfrom strain RN4220 carrying the pIMAY*-ΔtagOplasmid. The protocol can be easily adapted for the construction of other gene deletions and/or allelic-exchange plasmids.
Staphylococcus aureusColony Polymerase Chain Reaction
Authors: Zeden Merve S. , Schuster Christopher F. , Gründling Angelika
Published: August 2023

Here, we describe a protocol for a colony polymerase chain reaction (PCR) method forStaphylococcus aureus. The methodology involves the preparation of smallS. aureuslysates by using the enzyme lysostaphin to degrade the peptidoglycan layer. These lysates are prepared using a small patch of bacteria grown on LB agar plates, and the lysates can subsequently be used for PCR analyses.
4,6-Diferrocenyl-5-(morpholin-4-yl)-1,2,3-triazine
Authors: Aguilar-Lugo Carla , Flores-Alamo Marcos , Sánchez García Jessica J. , Klimova Elena I.
Published: August 2023

The structure of the title Fe complex, [Fe(C5H5)2(C17H16N4O)], was determined at 130 K, and has orthorhombic (Pna21) symmetry. It is of interest with respect to the class of triazine heterocyclic compounds: the triazine ring is substituted by two ferrocenyl and one morpholine groups. The crystal structure features C—H...O and C—H...N non-classical hydrogen bonds.
How performance pressure influences firms’ cross-boundary growth: the moderating effect of managerial discretion
Authors: Yang Lin , Yang Jingyi , Lu Liangliang , Chen Shouming
Published: August 2023

Purpose

In today's complex and rapidly changing business environment, cross-boundary growth is increasingly critical to the survival or even success of organizations. The purpose of this study is to examine the forming mechanism of firm’s cross-boundary growth by integrating the two important antecedent factors of performance pressure and managerial discretion into a united framework and theoretically analyze the direct role of performance pressure on firm’s cross-boundary growth as well as reveal the moderating role of managerial discretion. Also, the authors select listed manufacturing companies in China as samples to empirically test the research hypotheses.

Design/methodology/approach

The authors design a multiple regression model to perform empirical analysis by using a panel of 4,002 year-observations in 1,334 listed manufacturing companies between 2013 and 2016. The sample data sources mainly come from the Wind Database, which is mainland China's leading financial database and software services provider. The hypotheses proposed are tested by adopting a panel data set of the listed manufacturing companies of China.

Findings

Empirical results show that performance pressure has a positive effect on the cross-industry growth and cross-domestic regional growth but a negative effect on the cross-international regional growth, and managerial discretion has a different moderating effect. Specifically, capital intensity strengthens the positive effect of performance pressure on cross-industry growth but weakens the negative effect of performance pressure on cross-international regional growth. State ownership enhances the positive effect of performance pressure on cross-domestic regional growth but decreases the negative effect of performance pressure on cross-international regional growth. CEO duality increases the negative impact of performance pressure on cross-international regional growth.

Practical implications

This study provides several implications for top executives, including how to dialectically consider the double-edged effect of performance pressure on cross-boundary growth of firms, create an appropriate environments of managerial discretion and design the types of cross-boundary growth strategies that top executives can follow in the volatility, uncertainty, complexity and ambiguity era.

Originality/value

Although the relevant literature highlights the importance of performance pressure, it has not been related to the cross-boundary growth of firms. This paper makes an incremental contribution to the literature on the forming mechanisms of firm’s cross-boundary growth by providing an important perspective of performance pressure to firm growth determinants and taking into account the moderating role of managerial discretion.
Socio-emotional competencies as predictors of employability in engineering
Authors: Yepes Zuluaga Sara Maria
Published: August 2023

Purpose

In the current labour context, employability is an important tool for recently graduated who are entering the labour market and must face major challenges that include a decrease in job opportunities, the rapid evolution of technology, and the need for lifelong learning.

Design/methodology/approach

This study analyses the impact of the socio-emotional competencies of 470 senior students and graduates of five engineering majors at a higher education institution in Medellín, Colombia. In the sample examined, the data were analysed using inferential statistics and structural equation modelling (SEM).

Findings

Emotional intelligence (EI) was proven to be a predictor of engineers' employability, which, in turn, depends on three factors: personal strengths that increase employment potential, self-perceived employment opportunities, and career development as a realization of employment potential.

Originality/value

These results show that the higher education system should implement activities to develop students' EI competencies, thus providing them with powerful tools to deal with different situations in the labour market.